Cardiovascular diseases

Research Rates of in-hospital arrests, deaths and intensive care admissions: the effect of a medical emergency team Peter J Bristow, Ken M Hillman, Tien Chey, Kathy Daffurn, Theresa C Jacques, Sandra L Norman, Gillian F Bishop and E Grant Simmons MJA 2000; 173: 236-240 Abstract - Methods - Results - Discussion - Conclusion - Acknowledgements Authors' details - - More articles on Emergency medicine Abstract Objectives: To evaluate the effectiveness of a medical emergency team (MET) in reducing the rates of selected adverse events. Design: Cohort comparison study after casemix adjustment. Patients and setting: All adult (≥ 14 years) patients admitted to three Australian public hospitals from 8 July to 31 December 1996. Intervention studied: At Hospital 1, a medical emergency team (MET) could be called for abnormal physiological parameters or staff concern. Hospitals 2 and 3 had conventional cardiac arrest teams. Main outcome measures: Casemix-adjusted rates of cardiac arrest, unanticipated admission to intensive care unit (ICU), death, and the subgroup of deaths where there was no pre-existing "do not resuscitate" (DNR) order documented. Results: There were 1510 adverse events identified among 50 942 admissions. The rate of unanticipated ICU admissions was less at the intervention hospital in total (casemix-adjusted odds ratios: Hospital 1, 1.00; Hospital 2, 1.59 [95% CI, 1.24-2.04]; Hospital 3, 1.73 [95% CI, 1.37-2.16]). There was no significant difference in the rates of cardiac arrest or total deaths between the three hospitals. However, one of the hospitals with a conventional cardiac arrest team had a higher death rate among patients without a DNR order. Conclusions: The MET hospital had fewer unanticipated ICU/HDU admissions, with no increase in in-hospital arrest rate or total death rate. The non-DNR deaths were lower compared with one of the other hospitals; however, we did not adjust for DNR practices. We suggest that the MET concept is worthy of further study. Certain in-hospital deaths may be preventable.1-3 Nearly 85% of hospital inpatients who suffer a cardiorespiratory arrest have documented observations of deterioration in the eight hours before the arrest.4,5 Recent studies have demonstrated suboptimal care of hospitalised patients before their admission to the intensive care unit (ICU), and that these patients have a higher mortality.6-8 The authors of these studies urge earlier intervention. One approach to providing an early response to at-risk inpatients throughout the hospital is the medical emergency team (MET),9,10 which replaces the conventional cardiac arrest team. The MET responds to specific clinical criteria (such as bradycardia, tachycardia, hypotension and threatened airway) in order to prevent further deterioration. Others have advocated similar approaches to reduce unexpected hospital deaths and morbidity.11,12 In our study, selected outcomes in a hospital with a MET were compared with outcomes in two hospitals with conventional cardiac arrest teams. These outcomes were rates of cardiorespiratory arrest, unanticipated admission to the ICU or high dependency unit (HDU), death, and deaths where there was no prexisting "do not resuscitate" (DNR) order. Methods This study was a prospective cohort comparison of three hospitals, testing whether an early intervention team, the MET, was associated with fewer adverse events among inpatients, after adjusting for casemix differences. The study was approved by the ethics committees of each participating hospital and the University of New South Wales. Setting The hospitals were similarly sized Australian public hospitals, with bed capacities in the range 380-530. At Hospital 1, the cardiac arrest team was replaced by a MET, which any staff member could call for immediate assistance. Staff could summon the MET if concerned about a patient's condition or if the patient's vital signs exceeded certain levels (Box 1).10 An education program explained the MET's role to all new staff. However, calling the MET when criteria were met was not compulsory. The MET consisted of the ICU registrar and senior nurse, and medical registrar. At Hospitals 2 and 3, the arrest team was paged by nursing or medical staff for cardiorespiratory arrest. The arrest team consisted of the ICU registrar, medical registrar, and ICU or coronary care nurse. Data collection We identified all cardiorespiratory arrest calls, deaths, and ICU/HDU admissions at the three hospitals among patients 14 years and over in hospital during the period from 8 July to 31 December 1996. These were designated "events". Soon after an event, the patient's medical record was reviewed for demographic information. In addition, for cardiac arrests and deaths, documentation of a DNR order before arrest or death was recorded. Each ICU/HDU admission was classified as to whether the patient was admitted to ICU/HDU for the same reason he or she was admitted to hospital. If not, the ICU/HDU admission was defined as unanticipated. For example, a patient admitted to ICU with respiratory distress after a cholecystectomy would be unanticipated. Data were collected by three critical care nurses (one at each hospital) trained in the use of a specifically designed form, which was piloted for two weeks before data collection. The nurses were familiar with the medical record at the three hospitals. Where the information contained in the history was unclear, the attending staff were asked for clarification. Data were entered into a database.13 Data cleaning was performed and any anomalies checked by reference to the datasheet or medical record. Data were then exported to SAS14 for analysis. Outcome measures The primary endpoints were the casemix-adjusted rates of ICU/HDU unanticipated admission, cardiac arrest, death, and deaths without a prior DNR order. These were called "total event rates". For any patient, one event could result in additional events (eg, cardiac arrest followed by unanticipated ICU admission and then death). The "index event" was defined as the event the data collectors considered the first in a series of events. The casemix-adjusted rates of index events were compared between the three hospitals as secondary endpoints. To ensure that any decline in the rate of unanticipated admissions was not caused by excess anticipated admissions, the casemix-adjusted rate of all ICU/HDU admissions was calculated as a control measure. Casemix adjustment Demographic and diagnostic data on the patient population (aged ≥ 14 years) admitted to the hospitals for the period were obtained. The study data were merged by medical record number and date of admission with the complete inpatient statistical data to create a dataset with 50 942 records. This enabled us to identify the admissions for which an event occurred and analyse the data at the patient level. Using simple and multiple logistic regression, we modelled the probability of an event occurring during hospitalisation, adjusted for patient demographics and diagnostic characteristics. Models were derived independently for each total event and for each index event. Parameters were added to the model in a stepwise fashion. To prevent overparameterising the models (where minor, non-significant differences cumulatively hide true differences), when C (equivalent to the area under the receiver operator characteristics curve) reached 0.85 no further parameters were added to the model. This always occurred with fewer than six parameters used. Demographic and casemix independent variables that were tested for use in the models are detailed in Box 2. The models developed used groups of diagnostic categories based on ICD-9-CM codes using the principal diagnosis and the stay diagnosis only.15 The ICD-9-CM code groupings used are available from the principal author (PJB). The performance of the models was assessed by Hosmer-Lemeshow goodness-of-fit tests.16 The risk of an event occurring in a hospital compared with the MET hospital was presented as an adjusted odds ratio with 95% confidence intervals. A level of significance of 5% was used in all statistical tests. Results Hospital demographics Characteristics of all patients (aged ≥ 14 years) admitted to the three hospitals during the study period are shown in Box 3. Hospital 2 had fewer admissions than the other hospitals. Hospital 1 had a higher proportion of male patients admitted, and a lower proportion of admissions from the emergency department (ED). This hospital also had a younger patient population, which is reflected in differences in casemix: Hospital 1 had lower proportions of patients with stroke, severe acute heart disease, gastrointestinal disease, and musculoskeletal and connective tissue diseases, but higher proportions with severe trauma and follow-up care without acute diagnosis (eg, dialysis). The rates of DNR orders in dying patients were 77% in Hospital 1, and 64% and 70% in Hospitals 2 and 3, respectively (P = 0.006). Prevalence and characteristics of events A total of 1510 adverse events (unanticipated ICU/HDU admissions, arrest calls, and deaths) were recorded during the study period for the three hospitals. There were 1100 index events. The prevalence and characteristics of events are summarised in Box 4 for total event rates and Box 5 for index rates. There was a significantly reduced rate of unanticipated ICU/HDU admissions at the MET intervention hospital after casemix adjustment (for both the total event rate and the index rate). After adjustment, Hospital 2 had 49 (95% CI, 20-87) more unanticipated ICU/HDU admissions over a six-month period, and Hospital 3 had 92 (95% CI, 47-146) more, compared with Hospital 1. The rate of all ICU/HDU admissions was lower at Hospital 1 than at one control hospital, and trended to lower than at the other. There was no statistically significant difference in cardiac arrest rate or death rate after casemix adjustment. The casemix-adjusted death rate in patients where there was no documentation found of a DNR order was significantly higher at Hospital 2, translating to 27 (95% CI, 7-53) extra non-DNR deaths. Model performance Box 6 presents an example of the odds ratios after addition of the most significant variables in the multiple logistic regression models derived from the data for the total arrest data. It shows the C statistic as each variable was added to the cardiac arrest model. In the cardiac arrest models, the variables that were adjusted for were emergency admissions, age over 74, heart disease, lung disease and infectious disease as diagnoses. In the total death models, the terms adjusted for were emergency admissions, age over 74, single day stay emergency admissions, and cancer and infectious disease. The same demographic variables were used in the index death model, although in the total non-DNR death model both age ≥ 75 and age 65-74 were used in the model. In the unanticipated ICU/HDU models, the variables adjusted for were single day admission, emergency admission, and cancer and gastrointestinal disease diagnoses. The total unanticipated ICU/HDU model also included the variables stroke and infectious disease as diagnoses. All models satisfied the Hosmer- Lemeshow test.16 Discussion Rationale for our methods In this study, we attempted to determine if the MET system was associated with a reduced rate of adverse events among inpatients. To do this, we compared the rates of adverse events between three hospitals after casemix adjustment.17-19 This method was chosen as we decided that randomisation at the patient level was impractical. A random pattern of response to calls would probably have dissuaded staff caring for patients from calling the MET. Randomisation by ward would have risked contamination bias and engendered problems of casemix, as wards differ in the nature of their patients. Historical comparison at Hospital 1 between a period before and a period after introduction of the MET team was impractical, as the team had been trialled and evolved for six years before the study. The models we used appear to adequately fit the data, according to the Hosmer-Lemeshow goodness-of-fit tests, and with good model performance measured by C statistics. However, multiple methods of casemix adjustment are possible, and these may give divergent results. This is a limitation of casemix adjustment methodology.20 To avoid concealing real differences by excessive modelling, parameters were added stepwise by multivariate analysis until the models reasonably represented the data. The terms which appeared in the final models were usually those that could be expected to influence the outcomes. Thus, advanced age and emergency admissions were factors in the death and cardiac arrest models. The cardiac arrest models also included the terms for heart disease, lung and infectious disease. Infectious disease was an unexpected variable and was also significant in the total death model. Other differences (such as levels of hospital funding, ICU/HDU capacity, the number and seniority of medical and nursing staff, and the level of out-of-hours cover) may also have contributed to the results. However, to adjust for these would have been more difficult than for the variables studied, which relate directly to the patients at risk and are easily and reliably obtained. Explanation of findings After casemix adjustment, we found reduced rates of both total and index unanticipated ICU/HDU admissions at the MET intervention hospital. There were no differences in the rates of cardiac arrests or deaths. However, at one hospital without the MET, there was a higher rate of non-DNR deaths, the subset of deaths most likely potentially preventable by a MET. The reduction in unanticipated ICU/HDU admissions that was seen in the MET intervention hospital could result from many factors. One possible explanation is that the MET was effective and able to intervene on the wards and prevent further deterioration. Another possible reason may relate to differences in referral practices: perhaps the presence of MET backup engendered a feeling that ICU/HDU referral was not needed. Misclassification of ICU/HDU admissions as anticipated rather than unanticipated was excluded as an explanation of the difference by the finding that the rate of all ICU/HDU admissions was lower at the intervention hospital than one control hospital and trended to lower at the other. The lack of efficacy of the MET to prevent cardiorespiratory arrest and modify death rate may be related to lack of sensitivity of calling criteria, or because pathophysiological processes (eg, shock) become irreversible. Another possible explanation for the lack of effect of the MET on event rates is underutilisation. Based on a previous study,21 up to 706 MET calls could have been expected, and yet only 150 were made. Frequent education is probably also required to ensure the appropriate calling of a MET.22 No special efforts regarding staff education in the study period were made. The clinical staff of the hospital were unaware of the study, to negate any possible Hawthorne effect.23 Finally, organisational changes such as introduction of a MET are difficult to implement in hospitals.24,25 Our results probably reflect the effectiveness of the implementation of the MET system as much as the concept of early intervention. Future directions Our study cannot answer definitively if the MET was the cause of the benefit we observed; it does show that the MET concept is worthy of further study. The study could be likened to a Phase II trial of a drug comparing three hospitals at one point in time. Further studies of the MET system's efficacy are needed, such as a before-after comparison in several hospitals, or a comparison of a larger sample size of intervention and control hospitals. Such studies should be repeated some time after the intervention. Is the benefit observed useful and worth pursuing? If it is possible to reduce unanticipated ICU admissions without increased mortality this may result in cost saving. It has been estimated that the US spends about 1% of its gross national product on intensive care facilities.26 However, any savings in intensive care would be offset by the cost of establishing and maintaining a MET. The MET may also have unexpected costs and benefits on processes such as staff satisfaction with care provided. Again, these need to be quantified. Conclusion In this study, we found that fewer patients were unexpectedly admitted to ICU or HDU at a hospital with the MET system, and this hospital had fewer non-DNR deaths than one of the other hospitals. There was no significant change in the casemix-adjusted rate of arrests or total deaths. This may be an advantage of an early response team, which could have important implications for patient care in hospitals. We believe that the MET concept should be studied further in a larger sample of institutions. Acknowledgements Funding for the study was provided by a Commonwealth Department of Health and Family Services Research and Development Grant (HS338). Associate Professor Robert Gibberd assisted with the statistical analysis. References Brennan TA, Leape LL, Laird N, et al. Incidence of adverse events and negligence in hospitalised patients: results of the Harvard Medical Practice Study I. N Engl J Med 1991; 324: 370-376. Leape LL, Brennan TA, Laird N, et al. Nature of adverse events in hospitalised patients: results of the Harvard Medical Practice Study II. N Engl J Med 1991; 324: 377-384. Wilson R McL, Runciman WB, Gibberd RW, et al. The Quality in Australian Health Care Study. Med J Aust 1995; 163: 458-471. Schein RMH, Hazday N, Pena M, et al. Clinical antecedents to inhospital cardiopulmonary arrest. Chest 1990; 98: 1388-1392. Franklin C, Mathew J. Developing strategies to prevent inhospital cardiac arrest: analyzing responses of physicians and nurses in the hours before the event. Crit Care Med 1994; 22: 246-247. Lundberg JS, Perl TM, Wiblen T, et al. Septic shock: an analysis of outcomes for patients with onset on hospital wards versus intensive care units. Crit Care Med 1998; 26: 1020-1024. Goldhill DR, Sumner A. Outcome of intensive care patients in a group of British intensive care units. Crit Care Med 1998; 26: 1337-1345. McQuillan P, Pilkington S, Allan A, et al. Confidential inquiry into quality of care before admission to intensive care. BMJ 1998; 316: 1853-1858. Lee A, Bishop G, Hillman KM, Daffurn K. The medical emergency team. Anaesth Intensive Care 1995; 23: 183-186. Hourihan F, Bishop G, Hillman KM, et al. The medical emergency team: a new strategy to identify and intervene in high risk patients. Clin Intensive Care 1995; 6: 269-272. Frank ED. A shock team in a general hospital. Anesth Analg 1967; 46: 740-745. Goldhill DR. Introducing the postoperative care team [editorial]. BMJ 1997; 314: 389. Microsoft Access [computer program]. Version 2.0. Redmond, Wa: Microsoft, 1994. SAS for Windows [computer program]. Version 6.12. Cary, NC: SAS Institute Inc, 1997. Stremple JF, Bross DS, Davis CL, McDonald GO. Comparison of postoperative mortality and morbidity in VA and nonfederal hospitals. J Surg Res 1994; 56: 405-416. Hosmer DW, Lemeshow S. Applied logistic regression. New York: John Wiley and Sons, 1989. Iezzoni LI. The risks of risk adjustment. JAMA 1997; 278: 1600-1607. Dubois RW, Rogers WH, Moxley JH, et al. Hospital inpatient mortality. Is it a predictor of quality? N Engl J Med 1987; 317: 1674-1680. Green J, Passman LJ, Wintfield N. Analyzing hospital mortality. The consequences of diversity in patient mix. JAMA 1991; 265: 1849-1853. Iezzoni LI, Shwartz M, Ash A, et al. Severity measurement methods and judging hospital death rates for pneumonia. Med Care 1996; 34: 11-28. Hillman KM, Bishop G, Lee A, et al. Identifying the general ward patient at high risk of cardiac arrest. Clin Int Care 1996; 7: 242-243. Daffurn KD, Lee A, Hillman KM, et al. Do nurses know when to summon emergency assistance? Intensive Crit Care Nurs 1994; 10: 115-120. Grufferman S. Complexity and the Hawthorne effect in community trials [editorial]. Epidemiology 1999; 10: 209-210. Garside P. Organisational context for quality: lessons from the fields of organisational development and change management. Qual Health Care 1998; 7 Suppl: S8-15. Koeck C. Time for organisational development in healthcare organisations [editorial]. BMJ 1998; 317: 1267-1268. Cerra FB. Healthcare reform: the role of coordinated critical care. Crit Care Med 1993; 21: 457-464. (Received 15 Feb, accepted 10 Jul, 2000) Authors' details Liverpool Hospital, Sydney, NSW. Peter J Bristow, MB BS, FRACP, Staff Specialist, Department of Intensive Care; Ken M Hillman, MB BS, FFICANZCA, Professor, University of New South Wales Clinical School; Kathy Daffurn, RN, MAppSc, Co-Director, Division of Critical Care; Sandra L Norman, MN, BAppSc, Clinical Nurse Specialist, Department of Intensive Care; Gillian F Bishop, MB ChB, FFICANZCA, Director, Department of Intensive Care; Tien Chey, BSc, MAppStat, Statistician, Epidemiology Unit. Department of Intensive Care, St George Hospital, Sydney, NSW. Theresa C Jacques, MB BS, FFICANZCA, Director. Department of Intensive Care, Illawarra Regional Hospital, Wollongong, NSW. E Grant Simmons, MB BS, FFICANZCA, Director. Reprints will not be available from the authors. Correspondence: Dr P J Bristow, Intensive Care Offices, Alfred Hospital, Commercial Road, Prahran, VIC 3181. p.bristowATalfred.org.au Make a comment 1: Criteria for calling the medical emergency team10 Cardiorespiratory arrest Threatened airway Respiratory rate ≤5 breaths per minute ≥36 breaths per minute Pulse rate ≤40 beats per minute ≥140 beats per minute Systolic blood pressure ≤90mmHg Repeated or prolonged seizures Fall in Glasgow Coma Score >2 points Concern about patient status not detailed above Back to text 2: Variables available for calculation of the various models Sex (binary) Seven age categories (14-24, 25-34, 35-44, 45-54, 55-64, 65-74, ≥75) Same-day admission (binary) (ie, admission and discharge occurred on the same calendar day) Referral from emergency department (binary) Australian born (binary) Casemix categories (16 indicator variables, available from author) Hospital (three indicator variables) Back to text 3: Characteristics of admissions at the three study hospitals from 8 July to 31 December 1996 Hospital* Characteristic 1 2 3 Test of Independence† Number of admissions 18338 13059 19545 Male admissions 44.9% 42.9% 42.8% χ2=21.06‡ (2 df) Same-day admissions 47.7% 47.0% 46.7% χ2=4.35 (2 df) Admission via emergency department 29.6% 36.0% 35.1% χ2=186.53‡ (2 df) Australian born Country of birth not stated 49.3% 6.8% 67.2% 0.5% 50.2% 23.2% Not tested Age distribution 14-24 25-34 35-44 45-54 55-64 65-74 ≥75 9.7% 14.9% 14.3% 12.4% 18.1% 20.5% 10.0% 8.6% 15.2% 9.6% 9.8% 18.5% 22.2% 16.0% 7.8% 13.1% 11.1% 10.4% 14.4% 22.1% 21.1% χ2=1146‡ (12 df) Diagnostic category 1. Cancer 2. Stroke 3. Severe acute heart disease 4. Metabolic and electrolyte disorders 5. Pulmonary disease 6. Ophthalmologic disease 7. Low risk heart disease 8. Gastrointestinal disease 9. Urologic disease 10. Musculoskeletal, connective tissue disease 11. Infectious diseases 12. Symptoms and ill-defined conditions 13. Severe trauma 14. Follow-up care without acute diagnosis 15. Pregnancy, childbirth, puerperium 16. Others 4.4% 1.4% 2.6% 1.3% 3.3% 2.0% 3.5% 6.4% 1.9% 1.8% 1.0% 3.2% 2.9% 34.0% 10.8% 19.5% 4.1% 1.8% 3.0% 1.6% 2.9% 1.2% 2.9% 8.9% 1.7% 3.4% 0.7% 3.0% 2.1% 30.1% 14.1% 18.5% 5.3% 1.6% 3.2% 1.1% 4.2% 0.5% 4.6% 10.2% 1.9% 3.2% 1.0% 6.7% 1.8% 23.4% 11.0% 20.5% χ2=1562‡ (50 df) *Hospital 1 had the medical emergency team. †Test for any difference between the three hospitals. ‡P Back to text 4: Comparisons of total event rates by hospitals Event n Crude rates/10000 Unadjusted ORs Adjusted ORs* Cardiac arrest Hospital 1 Hospital 2 Hospital 3 69 66 99 38 51 51 1.00 1.34 (0.96-1.89) 1.35 (0.99-1.83) 1.00 1.14 (0.81-1.61) 1.00 (0.73-1.37) Death Hospital 1 Hospital 2 Hospital 3 243 240 295 133 184 151 1.00 1.39 (1.16-1.67) 1.14 (0.96-1.35) 1.00 1.08 (0.89-1.30) 0.83 (0.70-1.00) Non-DNR death Hospital 1 Hospital 2 Hospital 3 55 86 88 30 66 45 1.00 2.20 (1.57-3.09) 1.50 (1.07-2.11) 1.00 1.68 (1.19-2.36) 0.94 (0.67-1.33) Unanticipated ICU/HDU admission Hospital 1 Hospital 2 Hospital 3 118 146 234 64 112 120 1.00 1.73 (1.36-2.21) 1.86 (1.49-2.32) 1.00 1.59 (1.24-2.04) 1.73 (1.37-2.16) *Odds ratios (ORs) adjusted for patient characteristics and diagnostic categories. Hospital 1 (which has the medical emergency team) is the reference for the ORs. For shaded ORs, 95% CIs do not cross 1.0. DNR="do not resuscitate" order documented. ICU=intensive care unit. HDU=high dependency unit. Back to text 5: Comparisons of index event rates by hospitals Event n Crude rates/10000 Unadjusted ORs Adjusted ORs* Cardiac arrest Hospital 1 Hospital 2 Hospital 3 60 63 84 33 48 43 1.00 1.48 (1.04-2.10) 1.31 (0.94-1.83) 1.00 1.24 (0.87-1.78) 0.96 (0.69-1.35) Death Hospital 1 Hospital 2 Hospital 3 119 139 191 65 106 98 1.00 1.65 (1.29-2.11) 1.51 (1.20-1.90) 1.00 1.24 (0.97-1.60) 1.05 (0.82-1.33) Unanticipated ICU/HDU admission Hospital 1 Hospital 2 Hospital 3 82 140 222 45 107 114 1.00 2.41 (1.83-3.17) 2.56 (1.98-3.30) 1.00 2.17 (1.65-2.87) 2.35 (1.82-3.04) *Odds ratios (ORs) adjusted for patient characteristics and diagnostic categories. Hospital 1 (which has the medical emergency team) is the reference for the ORs. For shaded ORs, 95% CIs do not cross 1.0. ICU=intensive care unit. HDU=high dependency unit. Back to text 6: An example of how the odds ratios and C statistic changed as variables were added stepwise to the model for total cardiac arrests Odds ratio* (95% CI) Hospital 2 Hospital 3 C statistic Crude odds ratio Admission via emergency department Age ≥75 years Severe acute heart disease Low risk heart disease Infectious disease Pulmonary disease 1.34 (0.96-1.89) 1.16 (0.83-1.63) 1.06 (0.75-1.49) 1.06 (0.75-1.49) 1.07 (0.76-1.50) 1.09 (0.77-1.53) 1.14 (0.81-1.61) 1.35 (0.99-1.83) 1.19 (0.87-1.62) 0.98 (0.72-1.34) 0.99 (0.72-1.35) 0.99 (0.72-1.35) 1.00 (0.73-1.37) 1.00 (0.73-1.37) 0.533 0.755 0.798 0.809 0.826 0.833 0.850 *Hospital 1 is the reference for the odds ratios. Back to text

Peter J Bristow · Ken M Hillman · Tien Chey · Kathy Daffurn · Theresa C Jacques · Sandra L Norman · Gillian F Bishop

Editorial Alcohol and cardiovascular disease: still a research priority? MJA 2000; 173: 116-117 More precision in measuring drinking levels and patterns will give a firmer basis for advice about drinking The evidence amassed to date on the link between moderate alcohol intake and reduced risk of dying of cardiovascular disease might be thought already sufficient to bracket sceptics of alcohol's protective effect with doubters of manned lunar missions and members of the Flat Earth Society. Published studies demonstrating this link can now be counted in the hundreds, and no fewer than six plausible underlying biological mechanisms have been identified.1 In this issue of the Journal yet another study reports this link: Simons and colleagues show moderate alcohol intake to be associated with increased survival in elderly people.2 Their study is an elegant example of the genre and drawn from a highly respected prospective study of risk factors for death and illness in the population of Dubbo, New South Wales. The two fields of epidemiology and alcohol studies have much to learn from each other Alternative explanations for the protective effect of moderate alcohol intake, relying on ever more tenuous confounding effects, have been discredited one by one. The apparently protective effect of moderate alcohol consumption has so far survived the use of controls for sociodemographic status,3 for the "sick quitter hypothesis"4 (ie, the suggestion that many abstainers have stopped drinking because of serious illness), for the amount of cholesterol in the diet,5 and even for the degree of social isolation.6 As evidenced in the study by Simons et al,2 the protective effect is fairly specific to cardiovascular disease and does not operate for other major causes of death in older people such as cancer. While a handful of recent studies have failed to find a protective effect for moderate drinking,7,8 these are still heavily outnumbered by those with positive findings.1 In fact, the range of different countries and cultures in which the phenomenon has been documented is also testimony to its robustness, even if different levels of consumption appear to provide the benefit in different drinking cultures.1 So, does medical science need further research on this topic? My contention is that, while the basic protective properties of moderate alcohol consumption appear to have been identified, the precision of the measurement of drinking levels and patterns in these studies needs to be sharpened if we are to have a firmer basis for advising people how to drink to avoid ill-health. The recent major systematic review commissioned by the National Health and Medical Research Council to underpin revisions to Australia's national guidelines on low risk drinking found that nearly all epidemiological studies in this area only attempt to measure one of the important dimensions of alcohol consumption: total volume of drinking, usually expressed as average intake per day.1 Despite recent evidence that pattern of drinking plays a role independent of volume,9 large-scale epidemiological studies rarely include simple items in their questionnaires tapping this dimension, such as frequency of drinking five or more drinks in one day, or maximum amount consumed on one day. Simons et al make a rare contribution to our knowledge by providing an analysis of mortality risk, based not only on average volume of alcohol across all days, but also on usual amount consumed on a drinking day. Clearly, these can be very different measures (eg, seven drinks in a day once a week versus one drink every day of the week).2 While the power of the analyses in Simons et al is limited by sample size, usual consumption of five or more drinks for men and of three or four drinks in a day for women was not associated with a significantly reduced risk of death.2 It should be noted, however, that questions regarding "usual" consumption tend to suffer from a bias towards low-consumption occasions and against less frequent occasions of high intake.10 Forthcoming World Health Organization guidelines on measurement of alcohol consumption advise that a superior method is the "graduated quantity frequency", in which respondents are asked how often they drink at each of different levels of consumption, starting with the highest (eg, "How often do you drink 20 drinks on one day?").10 The same guidelines identify another problem bedevilling attempts to convert the results of alcohol studies into precise advice for drinkers: assumptions about the alcohol content of drinks reported vary between studies and are usually not empirically based. A number of studies from different countries have attempted to document usual-serve sizes employed by random samples of drinkers and found these to vary significantly from those usually assumed by researchers.11,12 One study found that the bias created towards under-reporting of consumption was massive in one particular population subgroup: Afro-American women.13 One striking consequence of a failure to measure pattern of alcohol consumption adequately can be the false identification of special benefits from one type of alcoholic beverage over another. Wine is often reported as being most associated with benefits, but being a wine drinker as opposed to a beer and spirits drinker is a marker for many other things, including a tendency towards a more consistent pattern of daily drinking rather than occasional "bingeing".14 A well known Danish study,3 often cited as evidence for a greater benefit of wine over other drinks, measured alcohol consumption by only asking about how much people usually drank if they drank every day. Because this is a less frequent pattern for heavy drinkers of beer and spirits, many of the latter will have been falsely categorised as light or moderate drinkers, thus significantly biasing against finding protective effects for these beverages. The two fields of epidemiology and alcohol studies have much to learn from each other. If epidemiological studies of risk factors for heart disease do not improve their measurement of patterns and levels of alcohol use, it will remain very hard to give precise advice to drinkers who wish to minimise harms and maximise benefits of alcohol consumption. In reality, despite hundreds of studies into the protective effects of alcohol in relation to heart disease, research into this area has only just begun. Timothy R Stockwell Director National Centre for Research into the Prevention of Drug Abuse Curtin University of Technology, Perth, WA Single E, Ashley MJ, Bondy S, et al. Evidence regarding the level of alcohol consumption considered to be low-risk for men and women. Final report. Canberra: National Health and Medical Research Council, 2000. URL: <http://www.nhmrc.health.gov.au/advice/alc-comp.htm> (accessed 29 June 2000). Simons LA, McCallumJ, Friedlander Y, et al. Moderate alcohol intake is associated with survival in the elderly: the Dubbo Study. Med J Aust 2000; 173: 121-124. Gronbaek M, Deis A, Sorensen TIA, et al. Mortality associated with moderate intakes of wine, beer or spirits. BMJ 1995; 310: 1165-1169. Rehm J, Sempos CT. Alcohol consumption and all-cause mortality: questions about causality, confounding and methodology. Addiction 1995; 90: 493-498. Rehm J, Sempos CT. Alcohol consumption and all-cause mortality. Addiction 1995; 90: 471-480. Murray RP, Rehm J, Shaten J, Connett JE. Does social integration confound the relation between alcohol consumption and mortality in the Multiple Risk Factor Intervention Trial (MRFIT)? J Stud Alcohol 1999; 60: 740-745. Leino EV, Romelsjo A, Shoemaker C, et al. Alcohol consumption and mortality. II. Studies of male populations. Addiction 1998; 93: 205-218. Hart CL, Smith GD, Hole DJ, Hawthorne VM. Alcohol consumption and mortality from all causes, coronary heart disease, and stroke: results from a prospective cohort study of Scottish men with 21 years follow up. BMJ 1999; 318: 1725-1729. Rehm J, Ashley KJ, Room R, et al. On the emerging paradigm of drinking patterns and their social and health consequences. Addiction 1996; 91: 1615-1621. World Health Organization (Substance Abuse Department). International guidelines for monitoring alcohol consumption and harm. Geneva: WHO. In press. Stockwell T. Information provided in Australia about the size of "standard drinks". Med J Aust 1992; 156, 295. Lemmens P. The alcohol content of self-report "standard drinks". Addiction 1994; 89: 593-602. Kaskutas L, Graves K. An alternative to standard drinks as a measure of alcohol consumption. Paper presented at International Conference on the Measurement of Drinking Patterns, Alcohol Problems and the Connection; 2000 April 2-7; University of Stockholm, Sweden. In press. Doll R. One for the heart. BMJ 1997; 315: 1664-1668. Make a comment

Timothy R Stockwell

Research Moderate alcohol intake is associated with survival in the elderly: the Dubbo Study Leon A Simons, John McCallum, Yechiel Friedlander, Michael Ortiz and Judith Simons MJA 2000; 173: 121-124 For editorial comment, see Stockwell Abstract - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Cardiology and cardiac surgery Abstract Objective: To examine the relationship between alcohol intake and survival in elderly people. Design and setting: A prospective study over 116 months of non-institutionalised subjects living in Dubbo, a rural town (population, 34 000) in New South Wales. Participants: 1235 men and 1570 women aged 60 years and over who were first examined in 1988-89. Main outcome measures: All-causes mortality; gross cost of alcohol per life-year gained. Results: Death occurred in 450 men and 392 women. Intake of alcohol was generally moderate (ie, less than 14 drinks/week). Any intake of alcohol was associated with reduced mortality in men up to 75 years and in women over 64 years. In a proportional hazards model, the hazard ratio for mortality in men taking any alcohol was 0.63 (95% CI, 0.47-0.84) and in women was 0.75 (95% CI, 0.60-0.94). Cardiovascular deaths in men were reduced from 20/100 (95% CI, 14-26) to 11/100 (95% CI, 9-13) and in women from 16/100 (95% CI, 13-19) to 8/100 (95% CI, 6-10). The reduction in mortality occurred in men and women taking only 1-7 drinks/week -- hazard ratios, 0.68 (95% CI, 0.49-0.94) and 0.78 (95% CI, 0.61-0.99), respectively, with a similar protective effect from intake of beer or other forms of alcohol. After almost 10 years' follow-up, men taking any alcohol lived on average 7.6 months longer, and women on average 2.7 months longer, compared with non-drinkers. The gross cost for alcohol per life-year gained if consuming 1-7 drinks/week was $5700 in men, and $19 000 in women. Conclusions: Moderate alcohol intake in the elderly appears to be associated with significantly longer survival in men 60-74 years and in all elderly women. The consumption of moderate amounts of alcohol, compared with abstention or with heavy alcohol intake, appears to be associated with reduced all-causes mortality in middle-aged subjects.1-3 This effect may be partially mediated through a reduced risk of coronary heart disease (CHD)4 and stroke.5 Some studies attribute the protection to a specific effect of wine;6,7 other studies attribute it to any type of alcohol.8In elderly people, some of this benefit from moderate alcohol intake may be negated by mortality from other causes.9 In a prospective study of men and women aged 65 years and over in the United States (Established Populations for Epidemiologic Studies of the Elderly), alcohol intake under 21 drinks/week was associated with a 30%-40% lower all-causes mortality in two cohorts, but with no influence in a third cohort.10 In Australian men and women aged 60 years and over with 77 months' follow-up, the intake of 1-7 drinks/week was associated with a 22%-25% reduction in all-causes mortality, although this reduction did not achieve statistical significance.11 We have examined the relationship between alcohol intake and survival in this Australian cohort during a more extended follow-up of 116 months. We present the results and include an economic analysis of moderate alcohol intake. Methods Dubbo Study The Dubbo Study is an ongoing prospective examination of cardiovascular and other diseases in an elderly Australian cohort first examined in 1988-89. All non-institutionalised residents of Dubbo, New South Wales, born before 1930 were eligible; participation rate was 73% (1235 men and 1570 women). Methods and measures have already been described in detail.12,13 The baseline examinations comprised demographic, psychosocial and standard cardiovascular risk assessments, including examination of fasting blood samples. Alcohol usage Questions on alcohol usage were those asked in the National Heart Foundation Risk Factor Prevalence Study,14 and yielded an approximation of usual alcohol intake coded as zero, 1-7, 8-14, 15-28 and more than 28 drinks/week (referring to a standard drink containing 10 g of alcohol). Specific intakes of beer, wine and spirits were not separately sought, but subjects were asked whether they normally drank beer or not, allowing a separation of drinking behaviour into beer and "other". Survival analysis Outcomes from August 1988 to 31 December 1998 were included in the analysis, a median 116 months' follow-up. Hospitalisation and death records were monitored continuously, and postal surveys were conducted every two years to confirm vital status. The survey in 1997 successfully traced more than 98% of surviving participants. Records were coded according to the International classification of diseases, ninth revision, clinical modification (ICD-9-CM). The independent contribution of any risk factor to mortality was examined in a Cox proportional hazards model. Point estimates and 95% CIs for the relative hazard of death were calculated from the regression coefficients (presented as hazard ratio, a measure of relative risk). The models included categories of alcohol intake as described above, and, where relevant, a categorical term describing whether a subject normally drank beer or "other" (ie, wine/spirits). The proportional hazards model assumes constant relative hazard over the length of follow-up. This assumption was confirmed for each model by a plot of log-minus-log survival, demonstrating parallel curves over all categories of alcohol intake. Statistical analyses were conducted using SPSS for Windows NT.15 Economic analysis A weighted alcohol acquisition cost per week using the midpoint of the intake ranges was calculated for each alcohol intake stratum and for each sex using 1999 Dubbo club prices. Individuals were assumed to remain in their initial consumption strata over the whole time period. Survival curve data from the Cox model were used to calculate total expenditure on alcohol, as well as survival benefit for each stratum of intake. An incremental analysis (difference in cost/difference in benefit) was conducted using the no-alcohol-consumption stratum as the reference. This yielded an estimate of the gross cost per life-year gained. Although the study collects hospitalisation records, hospitalisation costs were not available and a net cost per life-year gained could not be estimated. Ethical approval The study was approved by the institutional ethics committees at St Vincent's Hospital, Sydney, the University of New South Wales and the Australian National University. All participants gave informed, written consent. Results Pattern of alcohol intake The pattern of alcohol intake and its clinical associations have been fully documented in an earlier report.11 The pattern of alcohol intake, by quantity and type, is shown in Box 1. On a day when alcohol was consumed, 40% of all men and 45% of all women took one or two drinks, 23% and 7% took three or four drinks, and 15% and 1%, respectively, took five or more drinks. All-causes mortality Death occurred in 450 men (36%) and 392 women (25%). Consumption of more than 14 drinks/week was uncommon. Hence, where relevant, the use of alcohol has been grouped into zero use and any use. Alcohol intake: Age-specific all-causes mortality by alcohol intake is presented in Box 2. Alcohol use in men appeared to be associated with reduced mortality up to age 74 years, but not beyond. In women, its use was associated with reduced mortality in all groups older than 64 years. Predictors of all-causes mortality: The independent contribution of alcohol to all-causes mortality was explored in men 60-74 years and in all women in proportional hazards models which adjusted for the presence of major demographic, psychosocial and cardiovascular variables at study entry. The significant predictors of all-causes mortality are summarised in Box 3. (Alcohol intake was not a significant predictor of mortality in men aged more than 74 years.) Any alcohol intake was significantly associated with reduced all-causes mortality in both sexes. Quantity or type of alcohol intake: The relationship between quantity or type of alcohol intake and all-causes mortality in the proportional hazards model is presented in Box 3. The risk of mortality was significantly reduced at all levels of alcohol intake, except in women taking 15-28 drinks/week (representing only 3% of women in the study). A similar degree of reduction in all-causes mortality was observed at all levels of alcohol intake. The protection observed was broadly similar in those using beer versus wine/spirits, although this only reached statistical significance for beer consumption. Pattern of alcohol intake: In a subsequent model, the quantity of alcohol consumed per week was replaced by a variable denoting the usual number of drinks taken on a given day, a measure of the pattern of drinking. Using zero intake as the reference group, the hazard ratio in men with a consumption of one or two drinks on a given day was 0.64 (95% CI, 0.46-0.89), with three or four drinks 0.68 (95% CI, 0.47-0.98), and with five or more drinks 0.69 (95% CI, 0.45-1.06). The corresponding hazard ratios in women were 0.74 (95% CI, 0.59-0.93), 0.68 (95% CI, 0.38-1.22) and 1.38 (95% CI, 0.58-3.29) (there were only 17 women in this group). Hazard curves: The hazard curves calculated from the proportional hazards models in men and women are presented in Box 4. By the end of almost 10 years' follow-up, men taking any alcohol lived on average 7.6 months longer, and women on average 2.7 months longer, than their counterparts taking no alcohol. Specific causes of death: Cardiovascular death (ie, CHD and stroke) was reduced from 20/100 (95% CI, 14-26) in non-drinkers to 11/100 (95% CI, 9-13) in men taking any alcohol. The corresponding reduction in cardiovascular death in women was from 16/100 (95% CI, 13-19) to 8/100 (95% CI, 6-10). Deaths attributed to any cancer were unchanged in men (6/100 [95% CI, 3-9] versus 7/100 [95% CI, 5-9]) and in women (4/100 [95% CI, 2-6] versus 5/100 [95% CI, 3-7]). Gross cost for alcohol per life-year gained From the number of life-years added to survival for each quantity of intake, we have estimated the gross cost for alcohol per life-year gained. In men 60-74 years and in women 60 years and over taking 1-28 drinks/week, the respective costs were $13 000 and $31 000 per life-year gained. Since much of the benefit from alcohol intake was observed at a moderate intake of only 1-7 drinks/week, the respective costs at this intake were $5700 and $19 000 per life-year gained. Discussion In this well-defined, community-based sample of rural elderly Australians, alcohol intake could be described as moderate rather than heavy.11 Our results confirm that any intake of alcohol is associated with significantly reduced all-causes mortality in men 60-74 years and in all elderly women, consistent with our previous report at 77 months' follow-up.11 Statistical significance has now been reached due to the greater number of deaths and increased statistical power. Absolute death rates in men were substantially higher than in women, especially in the "young old". This would account for the greater average survival advantage shown in Box 4 (7.6 months versus 2.7 months). Equivalent reductions in mortality occurred at 1-7 drinks/week and at higher intakes. In men there was no evidence of a differential effect between 1-2 drinks on a given day and an intake of five or more drinks on a given day. Not all studies have documented an association between all-causes mortality and alcohol intake.16,17 The reduction in CHD and stroke mortality associated with alcohol use we observed is consistent with findings of previous reports,8,18,19 as well as those of recent reports in large middle-aged cohorts from the United States.4,5,20 These data are gradually causing health authorities to reconsider public policy on moderate alcohol intake, say 1-7 drinks/week, in the prevention of future morbidity and mortality.21 Studies in younger populations indicate a "U"- or "J"-shaped relationship between alcohol intake and all-causes mortality.2 This has not been a general finding in the elderly, possibly because these cohorts contain an excess of "healthy survivors".10 It is surprising that we could find no relationship between alcohol intake and mortality in men aged over 74 years, but it is plausible that very elderly men lose the benefit of alcohol intake because they become subject to competing causes of mortality.9 There is a potential for misclassification of alcohol intake between zero and low intake because of under-reporting. This would diminish any apparent relative benefit of alcohol intake on all-causes mortality. Hence, our statistically significant findings may represent a minimum estimate of the benefit of moderate alcohol intake. We have demonstrated essentially a "threshold effect" between alcohol intake and all-causes mortality in either sex. Protection does not improve greatly as alcohol intake increases further (Box 3). Thus, under-reporting would then have less impact on our findings. This threshold effect is important, particularly if we were to move to a public health position of suggesting that abstainers should begin to imbibe! The economic findings take no account of any changes in healthcare costs arising downstream through the benefits or otherwise of alcohol intake. What we regard as an acceptable cost per life-year gained is arbitrary, but it is informative to compare our calculated costs with, for example, recently published gross costs for the use of simvastatin in patients with established CHD, with survival increased by around 20%.22 Assuming such patients receive lifetime therapy with simvastatin from their mid-50s, the gross cost per life-year gained in the UK population would be £5100 (or about $13 000). Although one is comparing unrelated "therapy", moderate alcohol intake, at least in older men, may turn out to be a popular and cost-effective means of improving survival which does not require government subsidy! The relative merits of wine versus other forms of alcohol consumption remain controversial. Data from France6 and Denmark7 highlight specific benefits of wine, and this has generated a new research effort to identify which components of wine, apart from alcohol, may be the most beneficial. Antioxidants are among the most prominent suggestions.23 Others consider that alcohol in any form gives protection against cardiovascular disease,8 largely through its effect in raising high density lipoprotein (HDL) cholesterol levels.11 In Dubbo, the quantity of alcohol intake was highly correlated with HDL cholesterol (r = 0.32, P < 0.001 and r = 0.23, P < 0.001 in men and women, respectively). Other suggested mechanisms for cardiovascular protection include favourable effects of alcohol on thrombotic and fibrinolytic pathways, reduced insulin resistance and improved endothelial function through increased nitric oxide production.5 Alcohol may also influence survival in ways which currently defy measurement: regular alcohol intake may reflect a special lifestyle integrated with less tangible factors.21 Although excess alcohol intake is undoubtedly toxic to the central nervous system, recent studies suggest that a moderate intake may reduce the risk of dementia. In a study of elderly French people 65 years and over, appropriately from Bordeaux, the rate of hospitalisation for dementia in non-drinkers over three years was 4.9/100, but only 3.9/100 in those taking any alcohol (with a more striking effect on the risk of Alzheimer's disease).24 During 116 months' follow-up in the Dubbo population, the respective rates of hospitalisation for dementia were 4.3/100 and 2.5/100 (P < 0.01). It is premature to promote the use of alcohol for prevention of dementia, but the 21st century may witness a completely new role for alcohol in health. Acknowledgements The Dubbo Study is supported in part by grants from the National Health and Medical Research Council of Australia, Astra Pharmaceuticals Pty Ltd, Amrad Pharmaceuticals Pty Ltd, Bristol-Myers Squibb Australia Pty Ltd, Merck Sharp & Dohme Australia Pty Ltd, Parke Davis Pty Ltd and Pfizer Pty Ltd. We acknowledge the dedication of the Dubbo Nurse-Manager Kerrie Pearson, the assistance of Gina Brinsmead in economic analysis and Helen Adams in preparation of the manuscript. References Klatsky AL, Armstrong MA, Friedman DD. Alcohol and mortality. Ann Intern Med 1992; 117: 646-654. Holman CDJ, English DR, Milne E, Winter MG. Meta-analysis of alcohol and all-cause mortality: a validation of NHMRC recommendations. Med J Aust 1996; 164: 141-145. Thun MJ, Peto R, Lopez AD, et al. Alcohol consumption and mortality among middle-aged and elderly US adults. N Engl J Med 1997; 337: 1705-1714. Albert CM, Manson JE, Cook NR, et al. Moderate alcohol consumption and the risk of sudden cardiac death among US male physicians. Circulation 1999; 100: 944-950. Berger K, Ajani UA, Kase CS, et al. Light-to-moderate alcohol consumption and the risk of stroke among US male physicians. N Engl J Med 1999; 341: 1557-1564. Renaud S, Geuguen R, Siest G, Salamon R. Wine, beer, and mortality in middle-aged men from Eastern France. Arch Intern Med 1999; 159: 1865-1870. Gronbaek M, Deis A, Sorensen TIA, et al. Mortality associated with moderate intakes of wine, beer or spirits. BMJ 1995; 310: 1165-1169. Rimm EB, Klatsky A, Grobbee D, Stampfer MJ. Review of moderate alcohol consumption and reduced risk of coronary heart disease: is the effect due to beer, wine or spirits? BMJ 1996; 312: 731-735. Van de Water HA, Boshuizen HC. The impact of substitute morbidity and mortality on public health policies. Leiden: TNO Prevention and Health, Division of Public Health and Prevention, 1995. Scherr PA, LaCroix AZ, Wallace RB, et al. Light to moderate alcohol consumption and mortality in the elderly. J Am Geriatr Soc 1992; 40: 651-657. Simons LA, Friedlander Y, McCallum J, Simons J. Alcohol intake and survival in the elderly: a 77 month follow-up in the Dubbo Study. Aust N Z J Med 1996; 26: 662-670. Simons LA, McCallum J, Friedlander Y, et al. Dubbo Study of the elderly: sociological and cardiovascular risk factors at entry. Aust N Z J Med 1991; 21: 701-709. Simons LA, McCallum J, Friedlander Y, Simons J. Predictors of mortality in the prospective Dubbo Study of Australian elderly. Aust N Z J Med 1996; 26: 40-48. Risk Factor Prevalence Study Management Committee. Risk Factor Prevalence Study: Survey No 3 1989. Canberra: National Heart Foundation Australia and Australian Institute of Health, 1990. SPSS for Windows NT [computer program], version 9.0. Chicago, Ill: SPSS Inc, 1999. Leino EV, Romelsjo A, Shoemaker C, et al. Alcohol consumption and mortality. II. Studies of male populations. Addiction 1998; 93: 205-218. Hart CL, Smith GD, Hole DJ, Hawthorne VM. Alcohol consumption and mortality from all causes, coronary heart disease, and stroke: results from a prospective cohort study of Scottish men with 21 years follow up. BMJ 1999; 318: 1725-1729. Hennekens CH, Willett W, Rosner B, et al. Effects of beer, wine and liquor in coronary deaths. JAMA 1979; 242: 1973-1974. Stampfer MJ, Colditz GA, Willett WC, et al. A prospective study of moderate alcohol consumption and the risk of coronary disease and stroke in women. N Engl J Med 1988; 319: 267-273. Sacco RL, Elkind M, Boden-Albala B, et al. The protective effect of moderate alcohol consumption on ischemic stroke. JAMA 1999; 281: 53-60. Hommel M, Jaillard A. Alcohol for stroke prevention? N Engl J Med 1999; 341: 1605-1606. Pickin DM, McCabe CJ, Ramsay LE, et al. Cost effectiveness of HMG-CoA reductase inhibitor (statin) treatment related to the risk of coronary heart disease and cost of treatment. Heart 1999; 82: 325-332. Frankel EN, Kanner J, Germann JB, et al. Inhibition of oxidation of human low-density lipoprotein by phenolic substances in red wine. Lancet 1993; 341: 454-457. Orgogozo J-M, Dartigues J-F, Lafont S, et al. Wine consumption and dementia in the elderly: a prospective community study in the Bordeaux area. Rev Neurol (Paris) 1997; 153: 185-192. (Received 23 Dec 1999, accepted 10 Apr 2000) Authors' details University of New South Wales Lipid Research Department, St Vincent's Hospital, Sydney, NSW. Leon A Simons, MD, FRACP, Associate Professor of Medicine; Judith Simons, MACS, Analyst-Programmer. Faculty of Health, University of Western Sydney MacArthur, Sydney, NSW. John McCallum, DPhil, Professor and Dean. Department of Social Medicine, Hebrew University - Hadassah Hospital, Jerusalem, Israel. Yechiel Friedlander, PhD, Associate Professor in Epidemiology. Pfizer Pty Ltd, Sydney, NSW. Michael Ortiz, PhD, Health Outcomes Manager. Reprints will not be available from the authors. Correspondence: Professor L A Simons, Lipid Research Department, St Vincent's Hospital, Darlinghurst, NSW 2010. l.simonsATnotes.med.unsw.edu.au Make a comment Back to text 2: Age-specific all-causes mortality rate and alcohol intake during 116 months' follow-up of subjects 60 years and over. Data are mortality rates per 100 subjects (95% CI and number of subjects in each group in parentheses) Men Women Zero alcohol Any alcohol Zero alcohol Any alcohol 60-64 y 65-69 y 70-74 y 75-79 y 80+ y All ages 26 (17-35) (88) 37 (24-50) (54) 57 (45-69) (65) 51 (35-67) (37) 83 (68-98) (23) 44 (38-50) (267) 17 (13-21) (326) 26 (21-31) (266) 41 (34-48) (184) 64 (55-73)(120) 83 (74-92) (63) 34 (31-37) (959) 9 (5-13) (193) 22 (16-28) (172) 31 (24-38) (154) 45 (36-54) (121) 72 (63-81) (104) 31 (28-34) (744) 10 (7-13) (288) 14 (9-19) (191) 11 (6-16) (166) 36 (27-45) (107) 54 (42-66) (68) 20 (17-23) (820) Back to text 3: Proportional hazards model of all-causes mortality and alcohol intake in elderly subjects Hazard ratio (95% CI) Men 60-74 years Women 60+ years Significant predictors of all-causes mortality Any alcohol intake Age (/year) Current smoker Ex-smoker Prior stroke Blood pressure medication Diabetes Atrial fibrillation Poor expiratory flow 0.63 (0.47-0.84) 1.07 (1.04-1.11) 2.81 (1.90-4.16) 1.76 (1.26-2.46) 1.58 (1.03-2.42) 1.54 (1.16-2.06) 1.99 (1.38-2.87) -- 1.53 (1.09-2.17) 0.75 (0.60-0.94) 1.08 (1.06-1.10) 1.74 (1.22-2.49) -- -- -- 2.06 (1.46-2.92) 2.77 (1.65-4.64) 2.00 (1.43-2.79) Relationship of quantity or type of alcohol to all-causes mortality Drinks/week Nil 1-7 8-14 15-28 >28 1.00 0.68 (0.49-0.94) 0.58 (0.39-0.85) 0.62 (0.40-0.95) 0.56 (0.33-0.96) 1.00 0.78(0.61-0.99) 0.66 (0.45-0.97) 0.67 (0.29-1.55) Alcohol type Nil Beer Wine/spirits 1.00 0.62 (0.46-0.84) 0.70 (0.44-1.12) 1.00 0.64 (0.47-0.86) 0.85 (0.66-1.11) The reference category for alcohol usage was zero intake. Other variables in the models were body mass index, family history of coronary heart disease (CHD), prevalent CHD, blood pressure, lipid levels, self-rated health, and physical disability. Poor expiratory flow refers to peak expiratory flow tertile I. Back to text Back to text

Leon A Simons · John McCallum · Yechiel Friedlander · Michael Ortiz · Judith Simons

Fitness And Health Physical activity and cardiovascular risk factors: effect of advice from an exercise specialist in Australian general practice Julie A Halbert, Christopher A Silagy, Paul M Finucane, Robert T Withers and Phil A Hamdorf MJA 2000; 173: 84-87 Abstract - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on General practice and primary care Abstract Objective: To determine whether provision of individualised physical activity advice by an exercise specialist in general practice is effective in modifying physical activity and cardiovascular risk factors in older adults. Design: Randomised controlled trial of individualised physical activity advice, reinforced at three and six months (intervention) versus no advice (control). Setting: Two general practices in Adelaide, South Australia, 1996. Participants: 299 adults aged 60 years or more who were healthy, sedentary and living in the community. Main outcome measures: Changes to physical activity (frequency and duration of walking and vigorous exercise), selected cardiovascular risk factors (blood pressure, body weight, serum lipid levels) and quality of life over 12 months. Results: Self-reported physical activity increased over the 12 months in both groups (P < 0.001). The increase was greater for the intervention than the control group for all measures except time spent walking (P < 0.05). More intervention than control participants increased their intention to exercise (P < 0.001). Serum levels of total and low-density lipoprotein cholesterol and triglycerides fell significantly over the 12 months to a similar extent in the two groups. No other significant changes in cardiovascular risk factors were seen. Quality-of-life scores decreased over the 12 months. The decrease was significantly greater among intervention than control women, but not men, for emotional well-being (P = 0.02), physical well-being (P = 0.04) and social functioning (P = 0.04). Discussion: Provision of general practice-based physical activity advice reinforced three-monthly produced a sustained increase in self-reported physical activity. However, there were no associated changes in clinical measures of cardiovascular risk factors and minimal changes in quality-of-life measures. A large body of evidence shows that all-cause mortality and death and disability from cardiovascular disease decrease with regular physical activity1 and physical fitness.2 Leisure-time activity also reduces coronary risk factors,3 and the greatest decrease is achieved by moving individuals from the sedentary, low-fitness category.4,5Among Australians aged over 60 years, 55% of men and 61% of women are not sufficiently active to maintain general health.6 Encouragingly, a Western Australian survey found that 93% of general practitioners (GPs) reported asking about physical activity when a patient presented with a condition that might benefit from exercise, and 50% asked new patients about current physical activity patterns.7 However, GPs comment on a lack of skill in assessing and guiding activity and a lack of guidelines.8 Although many believe referral to a qualified fitness professional is desirable, fewer than 15% make these referrals.9 Previous studies of interventions to increase provision of advice and patients' physical activity in primary care have had mixed results and are of varying methodological quality.10 To reduce the demand on GPs, several groups have examined the effectiveness of advice from practice staff. Results of advice from a health visitor were initially favourable but were not sustained,11 while advice from practice nurses produced no increases in objectively measured12 or self-reported13 exercise levels in the short term. Therefore, we designed a properly powered study to determine the effectiveness of individualised advice from an exercise specialist in a general practice setting on changing physical activity levels and cardiovascular risk factors at 12-month follow-up. Methods The study was a randomised, controlled trial. Ethics approval was granted by the Committee on Clinical Investigation, Flinders Medical Centre, Adelaide. Recruitment and baseline measures Sedentary adults aged 60 years or over who lived in the community were recruited from two general practices in the southern region of Adelaide, South Australia, in 1996, as described previously.14 Briefly, 2878 people who met the above criteria were invited to a screening appointment; 913 attended and completed a questionnaire on demographic characteristics, medical history, medication use and physical activity levels. Exclusion criteria included a cerebrovascular or ischaemic cardiac event in the previous six months, malignancy or other life-threatening disease, inability to comply with the requirements of the study, a condition for which physical activity was contraindicated, use of β-blocker medication, and regular physical activity, leaving 351 people eligible. These 351 were invited to attend a baseline appointment at which they signed a consent form and were randomly allocated to the intervention or control groups using sealed opaque envelopes. They also answered a written questionnaire about current physical activity levels, intention-to-exercise,15 quality of life (assessed by the Short Form 3616) and demographic information. Blood pressure, body weight and height were measured, and a blood sample was taken for lipid studies. Interventions Both groups had a 20-minute session with an exercise specialist (with a master's degree in exercise physiology; J A H). Spouses were invited to attend these and follow-up sessions, which were held at the participants' usual GP surgeries. The intervention group received individualised advice about the benefits of physical activity and a pamphlet containing a plan for physical activity for the next three months. This plan, based on current position statements,17,18 involved aerobic activities at moderate intensity for a minimum of three sessions per week for at least 20 minutes per session, with self-monitoring of heart rate. The exercise plan, potential barriers to exercise and strategies to overcome these were discussed. The focus was on incorporating physical activity into the individual's usual activities and on increasing "self-efficacy" (belief in one's ability to perform the activity) by recommending a preferred, familiar activity and setting modest targets for the first three months. These targets were to be progressively increased, depending on progress, enthusiasm and health. The control group received a pamphlet promoting good nutrition for older adults, which was discussed for 20 minutes. Follow-up At three and six months, all participants were mailed a follow-up questionnaire to be returned in a postage paid envelope (control participants) or at an interview (intervention participants). This interview was arranged by telephone, and intervention participants were encouraged to attend whatever their adherence to the exercise plan. Participants were also asked to complete a seven-day physical activity log as a prompt for discussion, which included physical activity levels and benefits, reasons for success or failure, injuries, heart-rate monitoring and changes to the plan. At 12 months, all participants were invited to a follow-up interview, at which they completed a questionnaire, and clinical characteristics (except height) were remeasured. Energy expenditure was measured for 59 participants (31 intervention and 28 control participants) over four days (two weekends and two weekdays) using a Caltrac portable, vertical accelerometer.19 These 59 were recruited by telephoning randomly selected participants until six volunteers per week were obtained (a total of 88 were telephoned). Statistical analyses Sample size calculations indicated that 212 people were required to detect a 5 mm Hg difference in systolic blood pressure between the intervention and control group using a parallel group design (assuming a power of 0.9 and type I error rate of 0.05). Targeting 300 subjects allowed for a 40% dropout and non-compliance rate. Assumptions for parametric analysis were investigated. Repeated-measures analyses of variance were used to examine data for physical activity and five quality-of-life scores, using time as the within-subject variable, and time, intervention and sex as the between-subject variables. As data for three quality-of-life scales (roles physical and emotional and social functioning) were non-continuous and skewed, they were dichotomised (score of 100 = 0, score < 100 = 1) and then analysed with generalised estimating equations -- an extension of generalised linear models -- to examine time, intervention and sex interactions.20 Twelve-month changes in clinical characteristics, quality-of-life and accelerometer results were analysed with Student's t tests (independent samples). Intention-to-exercise data were analysed with χ2 statistics. All data were analysed on an intention-to-treat basis. In the event of missing responses, data were entered at the previous follow-up, thereby assuming no change. Results Participants Of the 351 people eligible for the study, 299 attended the baseline interview and were randomised (149 to the intervention group and 150 to the control group). Their characteristics have been reported previously.14 There were no statistically significant differences between the intervention and control groups in age (mean age, 67.3 years [SD, 7.9 years] versus 67.8 years [SD, 5.5 years]), sex distribution (48% versus 44% men), current and past medical history and current medication use or clinical parameters at baseline (Box 1). Three- and six-month follow-up questionnaires were returned by 274 (92%) and 269 (90%) participants, respectively, while 264 (88%) attended the 12-month follow-up interview (123 in the intervention and 141 in the control group). Of the 35 who did not attend, two had died, six were on holidays, seven were ill, and 20 were not interested. There were no statistically significant differences in baseline clinical and sociodemographic measures between participants who attended the 12-month follow-up interview and those who did not. Physical activity At all three follow-ups, all self-reported measures of physical activity had increased significantly from baseline levels in both the intervention and control groups (P < 0.05; Box 2). However, the intervention group reported significantly more physical activity than the control group for all measures except time spent walking (P < 0.05). Men reported significantly more minutes of walking per session (P = 0.02) and more frequent vigorous exercise (P = 0.02) than women at all follow-ups. In addition, the difference in frequency of vigorous exercise between the intervention and control groups was significantly greater for men than for women (P < 0.001). Energy expenditure data were available for 59 participants who wore an accelerometer (31 intervention and 28 control participants). The intervention and control groups did not differ significantly in any measured parameter of energy expenditure -- total per day, per day as a percentage of total energy expenditure, during activity per day, or during activity per kg body weight. At all follow-ups, there were significant differences between the intervention and control groups for change in intention to exercise (P < 0.001). At 12-month follow-up, more intervention than control participants increased their intention to exercise (Box 3). Cardiovascular risk factors Over the 12 months, there were no statistically significant changes in body weight, resting heart rate, blood pressure or serum high-density lipoprotein levels in either the control or intervention group (Box 1). However, there were significant decreases in serum levels of total and low-density lipoprotein cholesterol and triglycerides in both groups; the decreases did not differ significantly between the two. In addition, body weight decreased for all men and for control-group women, but increased for intervention-group women (P = 0.01). Quality of life Quality-of-life scores decreased between baseline and 12-month follow-up in both the intervention and control groups. These score decreases were significant in both groups for bodily pain (P = 0.001), general health (P < 0.001), physical functioning (P < 0.001), vitality (P = 0.04) and role physical (odds ratio [OR], 1.80; 95% CI, 1.33-2.43). Women in the intervention group had significantly greater score decreases than women in the control group for the scales role emotional (P = 0.02), role physical (P = 0.04) and social functioning (P = 0.04). In addition, women reported worse scores at 12-month follow-up than men for bodily pain (P = 0.02), mental health (P = 0.03), physical functioning (P = 0.04) and vitality (P = 0.01), and were 1.5 times more likely to report some difficulty with role physical (OR, 1.43; 95% CI, 1.03-1.99) and social functioning (OR 1.53; 95% CI, 1.06-2.21). Discussion This randomised controlled trial showed that provision of physical activity advice by an exercise specialist was effective in increasing the intention to exercise and self-reported physical activity among patients 60 years and over in two general practices. Other studies have also found increased intention to exercise14 and increased physical activity levels12,21 as a consequence of physical activity advice. However, our study differs from most others in that it had a large number of participants and high retention rate (88% at 12 months), and calculated results on an intention-to-treat basis. The high retention rate possibly resulted from participants' strong association with their GPs, who were aware and possibly encouraging of their participation, and the fact that all visits were conducted at the GPs' practices. The success of the intervention may be attributed to the enthusiastic volunteer population, who, while sedentary, were keen to start regular activity. Another possible contributor was the strong emphasis on walking as the preferred activity. The physical activity advice had the characteristics of successful physical activity interventions -- a home-based program, comprising unsupervised, informal exercise (generally walking), of moderate intensity and comparatively low frequency (which is associated with better maintenance), as well as frequent professional contact.22 The major limitation of this study was its reliance on self-report, as patients over 65 years tend to overestimate their physical activity.12 The number of participants and limited resources precluded general use of more objective measures of physical activity or fitness. Objective measurements of energy expenditure by accelerometer in 59 volunteers did not detect a difference between the control and intervention groups, possibly because of the small sample size. Other possible reasons are that people in each group who had established regular physical activity volunteered preferentially for accelerometer measurement, or that the self-reported increase in physical activity in the intervention group was not real. We were also unable to detect any differences between the intervention and control groups in cardiovascular risk factors after 12 months. This is consistent with results of others. For example, patients referred by their GPs to a local leisure centre had increased self-reported physical activity after 37 weeks, but no changes in systolic or diastolic blood pressures or body mass index.23 In our study, the increase in self-reported physical activity in the intervention group was possibly not large enough to increase physical fitness. Previous investigators have shown that cardiovascular risk factors are more strongly related to physical fitness than to physical activity,4,5and that, in individuals with low levels of fitness, increased physical activity without a change in fitness does not modify cardiovascular risk factors.24 Further, although the difference in physical activity between the intervention and control groups reached statistical significance, it was modest in absolute terms. Finally, all participants remained under the usual care of their GPs, who were free to initiate or cease prescribing medications that might modify cardiovascular risk factors. We found declines in quality of life from baseline to 12 months in both groups, with the greatest change in the first three months. We hypothesise that quality of life was more accurately reported at three months than at baseline, when scores were much higher than the Australian norms for the participants' age. It is possible that participants were initially keen to present themselves as healthy in all respects or that they were expressing high hopes for the study. In conclusion, this study showed that, for a specific population of general practice patients, providing physical activity advice three-monthly for six months resulted in increases to both self-reported physical activity and intention to exercise, which were maintained at 12-month follow-up. Further research in primary care is needed to determine whether these changes apply to other groups and whether they confer significant health benefits. Acknowledgements This project was funded by a Public Health Research and Development Project Grant from the National Health and Medical Research Council and Department of Health, Housing, Local Government and Community Services. We wish to thank the GPs and staff from Blackwood and Flinders Clinics, Adelaide, SA, for their assistance and Lynne Giles (Flinders University, Adelaide, SA) for statistical advice. Conflict of interest: None. References Paffenbarger RS, Hyde RT, Wing AL, et al. The association of changes in physical-activity level and other lifestyle characteristics with mortality among men. N Engl J Med 1993; 328: 538-545. Blair SN, Kohl HW, Paffenbarger RS, et al. Physical fitness and all-cause mortality. A prospective study of healthy men and women. JAMA 1989; 262: 2395-2401. Folsom AR, Caspersen CJ, Taylor HL, et al. Leisure time physical activity and its relationship to coronary risk factors in a population-based sample. Am J Epidemiol 1985; 121: 570-579. Eaton CB, Lapane KL, Garber CE, et al. Physical activity, physical fitness and coronary heart disease risk factors. Med Sci Sports Exerc 1995; 27: 340-346. Lochen M-L, Rasmussen K. The Tromso study: physical fitness, self-reported physical activity, and their relationship to other coronary risk factors. J Epidemiol Community Health 1992; 26: 103-107. Active Australia. Physical activity levels of Australians. Results of the Active Australia baseline survey 1997. Available at <www.ausport.gov.au/ partic/actozfr.html> Bull FCL, Schipper ECC, Jamrozik K, Blanksby BA. Beliefs and behaviour of general practitioners regarding promotion of physical activity. Aust J Public Health 1995; 19: 300-304. Murphy B, Ruth D. GPs role in CVD Prevention. A report on focus group discussions with general practitioners for the RISK study in general practice. Melbourne: Monash University, 1991. Bull FCL, Schipper ECC, Jamrozik K, Blanksby BA. How can and do Australian doctors promote physical activity? Prev Med 1997; 26: 866-873. Eaton CB, Menard LM. A systematic review of physical activity promotion in primary care settings. Br J Sports Med 1998; 32: 11-16. Harland J, White M, Drinkwater C, et al. The Newcastle exercise project: a randomised controlled trial of methods to promote physical activity in primary care. BMJ 1999; 319: 828-832. Sims J, Smith F, Duffy A, Hilton S. The vagaries of self-report of physical activity: a problem revisited and addressed in a study of exercise promotion in the over 65s in general practice. Fam Prac 1999; 16: 152-157. Simmonds GJ, Naylor P-J, Riddoch CJ, Velleman G. Stage-based counselling for exercise in primary care -- a controlled trial. Presented at the Scientific Basis of Health Services Conference. 1995 Oct; London. Halbert JA, Silagy CA, Finucane P, et al. Recruitment of older adults for a randomized, controlled trial of exercise advice in a general practice setting. J Am Geriat Soc 1999; 47: 477-481. Marcus BH, Banspach SW. Using the stages of change model to increase the adoption of physical activity among community participants. Am J Health Promot 1992; 6: 424-429. Ware JE, Snow KK, Kosinski M, Gandek B. SF-36 health survey manual and interpretation guide. Boston: New England Medical Center, 1993. National Institutes of Health Consensus Development Panel on Physical Activity and Cardiovascular Health. Physical activity and cardiovascular health. JAMA 1996; 276: 241-246. American College of Sports Medicine. The recommended quantity and quality of exercise for developing and maintaining cardiorespiratory and muscular fitness in healthy adults. Position Stand. Med Sci Sports Exerc 1990; 22: 265-274. Jacobs DR, Ainsworth BE, Hartman TJ, Leon AS. A simultaneous evaluation of 10 commonly used physical activity questionnaires. Med Sci Sports Exerc 1993; 25: 81. Liang K-Y, Zeger S. Longitudinal data analysis using generalized linear models. Biometrika 1986; 73: 13-22. Stevens W, Hillsdon M, Thorogood M, McArdle D. Cost-effectiveness of a primary care based physical activity intervention in 45-74 year old men and women: a randomised controlled trial. Br J Sports Med 1998; 32: 236-241. Hillsdon M, Thorogood M, Anstiss T, Morris J. Randomized controlled trials of physical activity promotion in free living populations: a review. J Epidemiol Community Health 1995; 49: 448-453. Taylor AH, Doust J, Webborn N. Randomised controlled trial to examine the effects of a GP exercise referral programme in Halisham, East Sussex, on modifiable coronary heart disease risk factors. J Epidemiol Community Health 1998; 52: 595-601. McMurray RG, Ainsworth BE, Harrell JS, et al. Is physical activity or aerobic power more influential on reducing cardiovascular disease risk factors? Med Sci Sports Exerc 1998; 30: 1521-1529. (Received 4 Feb, accepted 4 May, 2000) Authors' details Department of Rehabilitation and Aged Care, Flinders University of South Australia, Adelaide, SA. Julie A Halbert, MSc, Research Manager; Paul M Finucane, FRCPI, FRACP, Head. Monash Medical Centre, Melbourne, VIC. Christopher A Silagy, PhD, FRACGP, FAFPHM, Head of Institute of Public Health and Health Services Research. School of Education, Flinders University of South Australia, Adelaide, SA. Robert T Withers, PhD, FASMF, FACSM, Senior Lecturer in Rehabilitation. Hampstead Centre, Royal Adelaide Hospital, Adelaide, SA. Phil A Hamdorf, PhD, Head of Centre for Physical Activity in Ageing. Reprints will not be available from the authors. Correspondence: Ms J A Halbert, Department of Rehabilitation and Aged Care, Repatriation General Hospital, Daw Park, SA 5041. julie.halbertATflinders.edu.au Make a comment 1: Clinical measures at baseline and 12-month follow-up (mean and 95% confidence interval) Control group (n=150) Intervention group (n=149) Baseline 12 months Baseline 12 months Body weight (kg) Height (cm) Resting heart rate (bpm) 74.0 (71.8-76.1) 165.8 (164.4-167.2) 71.3 (69.7-72.9) 73.6 (71.5-75.8) ND 71.6 (70.0-73.2) 75.9 (73.8-78.0) 166.9 (165.5-168.4) 70.9 (69.1-72.6) 76.0 (73.9-78.1) ND 71.1 (69.6-72.6) Blood pressure (mm Hg) Systolic Diastolic 148.1 (145.1-151.0) 85.7 (84.2-87.1) 146.6 (143.4-149.6) 86.3 (84.9-87.7) 148.6 (145.9-151.4) 85.6 (84.1-87.1) 147.4 (144.4-150.5) 86.1 (84.6-87.7) Serum levels (mmol/L) Total cholesterol Triglycerides HDL cholesterol LDL cholesterol 5.88 (5.73-6.03) 1.64 (1.50-1.78) 1.34 (1.27-1.40) 3.81 (3.67-3.95) 5.70 (5.55-5.85)* 1.57 (1.43-1.70)* 1.34 (1.28-1.41) 3.65 (3.52-3.80)* 5.85 (5.68-6.02) 1.70 (1.50-1.89) 1.30 (1.24-1.37) 3.78 (3.65-3.95) 5.63 (5.47-5.80)* 1.57 (1.42-1.73)* 1.29 (1.23-1.35) 3.64 (3.50-3.79)* *Significant decrease from baseline level (P<0.05). HDL=high-density lipoprotein. LDL=low-density lipoprotein. ND=measurement not done. Back to text 2: Self-reported physical activity at baseline and follow-up (median value and 25th-75th percentile) Control group (n=150) Intervention group (n=149) Baseline 3 months 6 months 12 months Walking Frequency (sessions/week) Time (mins/session) 0 (0-2) 0 (0-20) 2 (0-3)* 30 (0-49)* 2 (0-4)* 30 (0-60)* 2 (1-3)* 30 (10-60)* Vigorous exercise Frequency (sessions/week) Time (mins/sessions) 0 (0-0) 0 (0-0) 0 (0-1)* 0 (0-16)* 0 (0-2)* 0 (0-21)* 0 (0-1)* 0 (0-15)* Walking Frequency (sessions/week) Time (mins/session) 0 (0-1) 0 (0-25) 3 (1-4)*† 30 (19-50)* 3 (2-4)*† 30 (20-60)* 3 (1-4)*† 30 (10-60)* Vigorous exercise Frequency (sessions/week) Time (mins/sessions) 0 (0-0) 0 (0-0) 2 (0-3)*† 20 (0-35)*† 2 (0-3)*† 20 (0-40)*† 2 (0-3)*† 20 (0-35)*† *Statistically significant increase from baseline level (P<0.05). †Values significantly higher than for control group (P<0.05). Back to text Back to text

Julie A Halbert · Christopher A Silagy · Paul M Finucane · Robert T Withers · Phil A Hamdorf

Indigenous Health Research Reducing premature death and renal failure in Australian Aboriginals A community-based cardiovascular and renal protective program Wendy E Hoy, Philip R Baker, Angela M Kelly and Zhiqiang Wang MJA 2000; 172: 473-478 Abstract - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Aboriginal health Abstract Objective: To describe results of a systematic treatment program to modify renal and cardiovascular disease in an Aboriginal community whose rates of renal failure and cardiovascular deaths are among the highest in Australia. Design: Longitudinal survey of people during treatment, and comparison of rates of natural death and renal failure with those in a historical control group. Setting: Tiwi Islands (population, about 1800), November 1995 to December 1998. Participants: All adults with blood pressure ≥ 140/90, with diabetes and urinary albumin/creatinine ratio (ACR) ≥ 3.4 g/mol (microalbuminuria threshold), or with progressive overt albuminuria (ACR ≥ 34 g/mol) were eligible for treatment. The historical control group comprised 229 people who satisfied these criteria in the pretreatment period 1992-1995. Interventions: Perindopril, combined with calcium-channel blockers and diuretics if needed to achieve blood pressure goals; attempts to improve control of blood glucose and lipid levels; health education. Main outcome measures: Blood pressure, ACR, serum creatinine level and glomerular filtration rate (GFR) over two years of treatment; rates of renal failure and natural death compared with control group (analysed on intention-to-treat basis). Results: 258 people enrolled in the program, and 118 had complete data for two years of treatment. In these 118, blood pressures fell significantly, while ACR and GFR stabilised. Rates of the combined endpoints of renal failure and natural death per 100 person-years were 2.9 for the treatment group (95% CI, 1.7-4.6) and 4.8 for the control group (95% CI, 3.3-7.0). After adjustment for baseline ACR category, the relative risk of the treatment group versus the control group for these combined endpoints was 0.47 (95% CI, 0.25-0.86; P = 0.013). Treatment benefit was especially marked in people with overt albuminuria or hypertension and in non-diabetic people. The estimates of benefit were supported by a fall in community rates of death and renal failure. Conclusions: Aboriginal people can participate enthusiastically in chronic disease management, with rapid, dramatic improvement in clinical profiles and mortality. Similar programs should be introduced urgently into other Aboriginal communities nationwide. Aboriginal people in the Northern Territory are experiencing an epidemic of cardiovascular disease (CVD) and end-stage renal disease (ESRD). Age-standardised CVD death rates are three times those of non-Aboriginal people,1 while the incidence of treated ESRD in Aboriginal people is approaching 1000 per million, and doubling every four years.2 ESRD treatment costs, at $100 000 per person annually, are becoming a huge burden,3 but premature death is the greater human catastrophe. These problems are especially serious in the communities of the Tiwi Islands, north of Darwin (population, about 1800) (Box 1). The incidence of ESRD among Tiwi people recently reached 2700 per million, and they have one of the highest CVD mortality rates in Australia.2,4In a community-wide screening program starting in the early 1990s, we found a high prevalence of cardiovascular risk factors, including type 2 diabetes and hypertension, and albuminuria (measured by the albumin/creatinine ratio (ACR) of a random urine specimen).5 Albuminuria correlated inversely with glomerular filtration rate (GFR), and its intensity predicted not only renal failure, but also cardiovascular deaths and all-cause natural deaths.6-9 In the early 1990s, use of antihypertensive drugs was increasing gradually in the Tiwi communities, but systematic management of the huge burden of morbidity identified by the screening program was beyond the capacity of the existing health services. In November 1995, we therefore introduced a systematic treatment program to reduce blood pressure and to modify the expression and progression of renal and cardiovascular disease. We describe the results of this program to the end of 1998. Methods The study was a longitudinal survey of people in the Tiwi Islands communities during treatment, and comparison of endpoints with a historical control group. Treatment was offered to eligible people as part of improved standard care. All participants gave informed consent to have their course followed up for the projects The epidemiology and prevention of Aboriginal renal disease, Parts 1 and 2. These projects were approved by the Joint Institutional Ethics Committee of the Menzies School of Health Research and Territory Health Services, Darwin, and its Aboriginal subcommittee, and by the Tiwi Land Council (Part 1) and the Tiwi Health Board (Part 2). Treatment program The program relied considerably on screening and treatment algorithms. Interventions included education about diet, exercise, health behaviours and medical treatment. Medical treatment centred around use of a long-acting angiotensin-converting enzyme inhibitor (ACEi) (perindopril; Coversyl [Servier]), aggressive blood pressure control,10,11 and, where appropriate, oral hypoglycaemic and lipid-lowering drugs. The choice of an ACEi was based on the well recognised antihypertensive and cardiovascular-protective effects of this class of drug12 and several reports, subsequently substantiated, of an additional renal protective effect.13-23 If antihypertensive drugs had been prescribed before entry into the study, they were discontinued or tapered when perindopril was started. Objectives were to achieve a minimum daily dose of 4 mg perindopril and to lower blood pressure, initially to < 130/85, but more recently to < 120/75.10 A stepped approach to achieve these blood pressures included increasing perindopril to 8 mg, with addition of long-acting calcium-channel blockers and/or diuretics if needed. Participants were seen at least monthly while medications were introduced or changed, then at least every three months for the first year, and at least every six months thereafter. Each examination included a minimum of a brief history, medication review, and measurement of weight, blood pressure, urinary ACR and serum creatinine level and, in diabetics, evaluation of blood glucose control. After a start-up period, the day-to-day program was largely conducted by local health workers and community project officers, who were supported by telephone contacts and regular visits by nurse coordinators from Darwin. Doctors, who reviewed eligibility assessments, supported or made treatment decisions and modified the protocols, were less intensively involved. The program has run in parallel with other clinic activities in Nguiu, Bathurst Island, but has been integrated into regular clinic activities at the Melville Island communities of Milikapiti and Pirlangimpi. Participants Treatment group: People eligible for ACEi therapy were those with: hypertension (blood pressure ≥ 140/90 mmHg); diabetes and ACR ≥ 3.4 g/mol (microalbuminuria threshold), regardless of blood pressure; or progressive overt albuminuria (ACR ≥ 34 g/mol on first testing and increasing over time), regardless of blood pressure or diabetes status. All qualifying features needed to be confirmed on at least two occasions. People with past adverse reactions and breastfeeding women were ineligible for ACEi therapy. Fertile women were advised about teratogenic risks and the options of contraception or discontinuation of ACEi medication early in unplanned pregnancy. People with serum creatinine levels over 250 µmol/L were considered ineligible for long-acting ACEi therapy in the first six months of the program, but were later enrolled when treatment proved safe and effective in people with mild and moderate renal insufficiency. To some extent, enrolment was prioritised by disease severity. Thus, most people with overt albuminuria, uncontrolled blood pressure and renal insufficiency were enrolled in the first year of the program. Control group: In the absence of a parallel control group, rates of renal failure and natural death in participants were compared with those of a historical control group from the pre-program period. This control group comprised adults whose results on a single screening examination between July 1992 and September 1995 met the eligibility criteria later used for the treatment program. Selection was blinded to their future course, which was followed to 30 October 1995. Data analyses Analyses were performed using STATA statistical software.24 Clinical profiles in the treatment group were described at baseline, six, 12, and 24 months of treatment, regardless of compliance, and were compared by analysis of variance, using geometric means for ACR and serum creatinine level to normalise their distribution. All endpoint data in the treatment group were analysed on an intention-to-treat basis. Rates of natural death and renal failure were calculated by baseline ACR category for the intention-to-treat and control groups, and the risk ratios for the intention-to-treat group calculated in stratified analysis by ACR category by the Mantel-Haenszel method for cohort studies. Kaplan-Meier survival curves for both groups were derived, and survivals compared by the non-parametric Wilcoxon technique. Results Enrolment By 31 December 1998, 258 people had enrolled in the program (29% of all adults in the island communities) and 227 were still participating. Of these, 39 had completed over three years of treatment, 137 over two years, 168 over one year, and 192 over six months. Of 31 dropouts, nine had died, seven had begun dialysis (two of whom later died), seven had stopped taking the medication because of side effects (cough in four; angioedema, itching and dizziness in one each), four became normotensive without treatment, two chose to quit, one moved, and one entered palliative care with osteomyelitis of the skull. Characteristics of people who enrolled are shown in Box 2: 42% had diabetes, almost two-thirds had hypertension, with a quarter already prescribed enalapril, and almost two-thirds had overt albuminuria. Medications and participation Doses of perindopril prescribed for the 227 people participating at the end of 1998 were 2 mg (5 people; 2%), 4 mg (72; 32%), and 8 mg (150; 66%). Calcium-channel blockers were being taken by 37 people (16%), diuretics by 15 (7%), and both by 13 (6%). Participation was enthusiastic, and compliance increased over time; 65% were taking ≥ 70% of their prescribed dose (assessed by pill counts and interview), 27% were taking medicine occasionally, and 7% were taking little or no medication at the end of 1998. Two-year clinical profiles Of the 137 people who had been treated for at least two years, 118 had largely complete follow-up data and were included in the two-year profile. These 118 were well matched with participants not included in this profile for age, BMI, and blood pressure, but were more likely to have diabetes, overt albuminuria, and to have been taking prior ACEi therapy (Box 2). These differences reflected prioritisation of sicker people for early entry into the program. Two-year clinical profiles for the 118 people are shown in Box 3. Treatment was associated with a swift and sustained fall in blood pressure, as well as stabilisation of ACR and GFR. Results are presented according to participants' clinical categories at baseline in Box 4. The fall in blood pressure was marked in people with hypertension at baseline and less marked but still apparent in those who had been normotensive, as well as in those previously prescribed an ACEi. Good blood pressure responses were seen in people both with and without diabetes, those with micro- and overt albuminuria and those with "normal" and raised levels of serum creatinine. Stabilisation of ACR and GFR was seen in all clinical categories. Indeed, serum creatinine level tended to fall and GFR to rise in all categories. Baseline weight did not change (mean, 74 kg; SD, 16 kg), while mean serum potassium level rose non-significantly from 4.04 mmol/L (SD, 0.46 mmol/L) to 4.14 mmol/L (SD, 0.49 mmol/L). No one developed significant hyperkalaemia. There was no evidence that ACEi therapy accelerated progression to renal insufficiency. Comparisons with control group Two hundred and twenty-nine people qualified as controls from the pre-program period, comprising 123 people who subsequently went onto the treatment program and 106 people who did not. Reasons for not going onto the program included death, dialysis, failure to qualify on subsequent examinations, presence of exclusion criteria (eg, pregnancy, breastfeeding), declining treatment, or moving. Baseline characteristics of the control and intention-to-treat groups are compared in Box 2. The control group was younger at enrolment, had lower BMI, and included fewer people with diabetes or overt albuminuria. The control group was followed up for a total of 564 years (individual mean, 2.5 years; range, 1 month to 3.3 years) and the intention-to-treat group for 560 years (individual mean, 2.2 years; range, 2 weeks to 3.1 years). Endpoints of the two groups are compared in Box 5. The treatment group as a whole had lower rates of dialysis, natural death and the combined endpoint (dialysis or death) than the control group, although the differences were not significant. However, rates of endpoints were strongly correlated with baseline ACR category. Indeed, renal failure necessitating dialysis was confined to people with ACR ≥ 100 g/mol at baseline, and in these people the treatment group had an estimated 57% lower dialysis rate than the control group. In contrast, rates of natural death and of the combined endpoint were lower in the treatment group than in the control group for all categories of baseline overt albuminuria. After adjustment for ACR category, the treatment group had an estimated 45% lower rate of natural death and an estimated 53% lower rate of the combined endpoint. Box 6 shows estimates of the survival advantage in people with various baseline clinical profiles after adjustment for ACR category. Treatment benefit was strong in people with overt albuminuria, non-diabetic people and people with hypertension. It was less marked in diabetic or normotensive people. Survival estimates for people with overt albuminuria at baseline are shown in Box 7. Although the intention-to-treat group showed attrition during the first year (representing ESRD and deaths of seriously ill people prioritised for early entry), a survival advantage over the control group was clear by two years of the treatment program. Discussion This study found that the introduction of a systematic treatment program to the Tiwi Island communities was associated with marked improvements in blood pressure and stabilisation of renal function in people receiving treatment. These changes contrasted sharply with the increase in blood pressure and ACR and fall in GFR noted previously in people matched for ACR category in the pretreatment status quo.10 The treatment program was also associated with a swift and dramatic decrease in rates of renal failure and natural death in the treated group compared with a historical control group, suggesting that the program prevented or at least delayed these outcomes. Further evidence for the existence of this estimated survival benefit was the decrease in community-wide rates of ESRD and natural death -- previously increasing -- after introduction of the program (Box 8). In contrast, ESRD continued to increase among non-Tiwi Aboriginal people in the Top End (Box 9), arguing against a chance background effect. Preliminary estimates of cost effectiveness of the program, based solely on avoidance or delay of dialysis, are already startling.3,25 These results show that Aboriginal people are interested in health issues and receptive to health messages, and will take medications over the long term to protect against future health risk, with excellent response. They also show that a systematic approach, with testing and treatment algorithms and clear goals, is superior to the previous approach of gradually improving medical management. While we cannot apportion relative benefit to individual elements of the treatment program, the observed fall in blood pressures alone would be expected to markedly reduce cardiovascular deaths and progression of renal disease,10,11 compatible with the effects we found. Our intention-to-treat analyses probably underestimate the therapeutic efficacy of treatment, as a third of the intention-to-treat group took the prescribed medications only occasionally or not at all. Use of the historical control group was also a potential source of bias. On the one hand, it may have also led to underestimates of treatment benefit because of the group's potentially better survival prospects, based on its younger mean age, milder disease and the probable inclusion of people with borderline blood pressure or ACR readings, as eligibility for the group was not confirmed by a second examination. On the other hand, the 123 controls who subsequently entered the treatment program might have had superior survival characteristics to the controls who did not enter the program, potentially inflating the apparent benefit of the program. Another source of bias was the prioritisation of the sickest people for early enrolment in the treatment program, many of whom were failing previous management regimens. This predisposes to poor short term outcomes of the program and underestimates of its benefits. Analyses of program results at four and five years, when more people have passed through one to two years of treatment, will dilute the impact of these early events. Longer-term analyses will also be needed to evaluate any survival effect of treatment in people without overt albuminuria, and the extent to which treatment has delayed rather than prevented ESRD and death in people with overt albuminuria. The program could still be improved. Blood pressure control should be better; at two-year follow-up, 31% of people had blood pressures ≥ 140/90, and 50% had blood pressures ≥ 120/75.10 Hypertension, and therefore eligibility for treatment even in the absence of albuminuria, should probably be redefined as blood pressures ≥ 130/80 in this high-risk population.10 Control of blood glucose and lipid levels needs to improve. Finally, we might reassess the notions of the maximally renal-protective dose of ACEi and/or add other renal-protective drugs, such as angiotensin II receptor blocking agents,26,27 for poor responders. Much of the success of this particular program derives from a strong sense of community ownership and control, a non-judgemental, non-authoritarian style, and respect for competing personal and community perspectives and priorities. Individuals appreciate personalisation of their health goals, and many are slowly adopting lifestyle changes. This program is now being integrated into normal clinic activities at Nguiu. Its protocols have also been incorporated into standard care guidelines for Aboriginal adults in the Top End of the NT.28 Extension of its principles to other Aboriginal communities with high burdens of disease nationwide is a matter of urgency.29 Allocation of adequate resources is a challenge, but the clinical benefit and cost-effectiveness mandate the short- and intermediate-term investment. Acknowledgements This study was supported by Servier Australia, the Australian Kidney Foundation, Rio Tinto, the National Health and Medical Research Council, the Stanley Tipiloura Fund, and Territory Health Services. We gratefully acknowledge the support, enthusiasm and participation of the Tiwi community and the staff of the Tiwi Island clinics at Nguiu, Milikapiti and Pirlangimpi. We especially thank the Tiwi Health Board for review of this manuscript, and Treatment Program Coordinators Susan Jacups and Kiernan McKendry, Aboriginal Health Workers Jerome Kerinauia and Nellie Punguatji, and Community Project Officers Eric Tipiloura and Elizabeth Tipiloura for their dedicated work. Finally, we thank Resident Medical Officer, Dr Chris Harrison, for his support and participation. Dr Alan Cass updated the Top End ESRD rates. References Cunningham J, Condon J. Premature mortality in Aboriginal adults in the Northern Territory. Med J Aust 1996; 165: 309-312. Spencer JS, Silva D, Hoy WE. An epidemic of renal failure among Australian Aborigines. Med J Aust 1998; 168: 537-541. You J, Hoy W, Beaver C, Zhao Y. Costs of hemodialysis and hospitalisations for patients with end stage renal disease in the Top End of the Northern Territory. Presented at the 35th Annual Scientific Meeting of the Australian and New Zealand Society of Nephrology; 1999 Mar 3-5; Brisbane (Qld). Jain SK, editor. Trends in mortality by causes of death in Australia, the States and Territories during 1971-1992, and in statistical subdivisions during 1991-1992. Canberra: National Center for Epidemiology and Population Health and Australian Bureau of Statistics, 1994. (ABS catalogue no. 3313.0)Hoy WE, Pugsley DJ, Normal RJ, Hayhurst BG. A brief heath profile of adults in a Northern Territory Aboriginal community: with an emphasis on preventable morbidities. Aust N Z J Public Health 1997; 21: 121-126. Hoy WE, Mathews JD, Pugsley DJ, et al. The multidimensional nature of renal disease: rates and associations of albuminuria in a high risk Aboriginal community. Kidney Int 1998; 54: 1296-1304. Cockcroft D, Gault MK. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31-41. Hoy WE, Wang Z, Baker P, et al. The natural history of renal disease in an Australian Aboriginal community. Presented at the 35th Annual Scientific Meeting of the Australian and New Zealand Society of Nephrology; 1999 Mar 3-5; Brisbane (Qld). McDonald S, Wang Z, Hoy WE. Physical and biochemical predictors of death in an Australian Aboriginal cohort. Clin Exp Pharmacol Physiol 1999; 26: 618-621. The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC VI). Arch Intern Med 1997; 157: 2413-2446. Collins R, Peto R, MacMahon S. Blood pressure, stroke and coronary artery disease. Part 2. Short term reductions in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet 1990; 335: 827-838. Lonn EM, Yusuf S, Jha P. Emerging role of angiotensin converting enzyme inhibitors in cardiac and vascular protection. Circulation 1994; 90: 2056-2068. Mogensen CE. Angiotensin converting enzyme inhibitors and diabetic nephropathy. BMJ 1992; 304: 327-328. Ravid M, Savin H, Lang R, et al. Proteinuria, renal impairment, metabolic control, and blood pressure in type 2 diabetes mellitus. A 14-year follow up report on 195 patients. Arch Intern Med 1992; 152: 1225-1229. Ravid M, Savin H, Jutrin I, et al. Long term stabilizing effect of angiotensin converting enzyme inhibition on plasma creatinine and on proteinuria in normotensive type 2 diabetic patients. Ann Intern Med 1993; 118: 577-581. Gansevoort RT, de Zeeuw D, de Jong PE. Long term benefits of the antiproteinuric effect of angiotensin converting enzyme inhibition in nondiabetic renal disease. Am J Kidney Dis 1993; 22: 202-206. Lewis EJ, Hunsicker LG, Bain RP, et al. The effect of angiotensin converting enzyme inhibition on diabetic nephropathy. N Engl J Med 1993; 329: 1456-1462. Bedogna V, Valvo E, Casagrande P, et al. Effect of ACE inhibition in normotensive patients with chronic glomerular disease and normal renal function. Kidney Int 1994; 38: 101-107. Cattran DC, Greenwood C, Ritchie S. Long term benefits of angiotensin converting enzyme inhibitor therapy in patients with severe immunoglobulin A nephopathy: a comparison to patients receiving treatment with other antihypertensive agents and patients receiving no therapy. Am J Kidney Dis 1994; 23: 247-254. Mogensen CE, Keane WF, Bennett PH, et al. Prevention of diabetic renal disease with special reference to microalbuminuria. Lancet 1995; 346: 1080-1084. Maschio G, Alberti D, Janin G, et al. Effect of angiotensin converting enzyme inhibitor benazapril on the progression of chronic renal insufficiency. N Engl J Med 1996; 334: 939-945. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, nondiabetic nephropathy. Lancet 1997; 349: 1857-1863. Ruggenenti P, Perna A, Gheradi G, et al. Renoprotective properties of ACE inhibition in nondiabetic nonnephrotic proteinuria. Lancet 1999; 354: 359-364. Statcorp. Stata statistical software, release 6.0. College Station (TX): Stata Corporation, 1999. Baker P, Hoy WE, Wang Z, et al. Towards evaluation of the cost-effectiveness of a treatment program for renal disease in Australian Aborigines. Presented at the 35th Annual Scientific Meeting of the Australian and New Zealand Society of Nephrology; 1999 Mar 3-5; Brisbane (Qld). Mackenzie HS, Ziai F, Omer SA, et al. Angiotensin receptor blockers in chronic renal disease: the promise of a bright future. J Amer Soc Nephrol 1999; 10 Suppl 12: S283-S286. Mimran A, Ribstein J. Angiotensin receptor blockers: pharmacology and clinical significance. J Amer Soc Nephrol 1999; 10 Suppl 12: S273-S277. Hoy WE. Screening and treatment for renal disease: the community model. Nephrology 1998; 4 Suppl iii-iv: S90-S95. Minutes of the Inaugural Meeting of the National Aboriginal and Torres Strait Islander Renal Disease Scientific Working Group and its Guidelines Subcommittee. Office of Aboriginal and Torres Strait Islander Health. 1999; Nov 16 Alice Springs (NT). (Received 14 Jul 1999, accepted 6 Apr 2000) Authors' details Menzies School of Health Research, Darwin, NT. Wendy E Hoy, FRACP, Senior Renal Consultant; Philip R Baker, BSc, NHMRC PhD Student, Menzies School of Health Research, and Department of Social and Preventive Medicine, University of Queensland, Brisbane, QLD; Angela M Kelly, RN, BAppSc, Senior Program Coordinator; Zhiqiang Wang, PhD, Epidemiologist and Statistician, and Senior Research Officer. Reprints will not be available from the authors. Correspondence: Dr W E Hoy, Menzies School of Health Research, PO Box 41096, Casuarina, NT, 0811. wendyATmenzies.su.edu.au Make a comment Back to text 2: Baseline characteristics of participants in the treatment program and the historical control group All participantsIncluded in 2-year profiles Historical control group (n=258)Yes (n=118)No* (n=140)(n=229)P?% Men43%47%40%51%0.13Mean age in years (SD)43.4 (11.1)43.5 (10.4)43.4 (11.7)40.8 (12.8)0.02Mean body mass index27.0 (5.7)27.1 (5.7)27.0 (5.8)25.2 (5.4)< 0.001(kg/m2) (SD) Blood pressure (mm Hg) Mean systolic (SD)135 (20)135 (20)135 (21)134 (20)0.58Mean diastolic (SD)82 (14)81 (13)82 (15)85 (15)0.01% With hypertension?65%66%63%65%0.91% With diabetes42%46%37%26%0.001% With ACR ≥34g/mol65%74%58%58%0.02% With raised serum creatinine level§12%13%11%12%0.62Previous ACEi25%33%16%NR ACR=urinary albumin/creatinine ratio. ACEi=angiotensin-converting enzyme inhibitor. NR=no result. *90 had been enrolled less than 2 years, 19 had been enrolled ≥ 2 years but did not have complete data for all visits, and 31 had dropped out. ?For test of significance of difference between all participants (intention-to-treat group) and control group. ?Blood pressure ≥140/90 or taking antihypertensive treatment. §Serum creatinine level > 106µmol/L (women), > 120µmol/L (men). Back to text 3: Clinical profiles over two years of treatment in 118 Tiwi people VariableBaseline6 months12 months24 monthsP*Blood pressure (mm Hg) Mean systolic (SD)135 (20)126 (21)124 (20)122 (22)< 0.001Mean diastolic (SD)81 (13)75 (14)77 (14)74 (14)< 0.001Mean? ACR (g/mol) (95% CI)55 (43-70)50 (39-64)53 (41-69)55 (43-69)0.36Mean? serum creatinine level (µmol/L) (95% CI)89 (85-93)88 (84-92)88 (84-92)84 (79-89)0.44Mean GFR (mL/min/1.73m2) (SD)89 (26)91 (28)89 (26)93 (29)0.54ACR=urinary albumin/creatinine ratio. GFR=glomerular filtration rate. *Test for significance of difference in values among the four intervals by analysis of variance. ?Geometric mean. Back to text 4: Clinical profiles over two years of treatment in 118 Tiwi people, by clinical category at baseline Blood pressure PreviousDiabetes < 140/90 (n=69)≥ 140/90 (n=49)ACEi (n=39)No (n=64)Yes (n=54)BP (mm Hg) Mean systolicBaseline123 (11)152 (17)136 (19)135 (21)136 (19)(SD)24 months117 (20)130 (22)128 (23)122 (15)122 (23)Mean diastolicBaseline75 (9)90 (12)83 (11)81 (15)81 (10)(SD)24 months72 (14)77 (13)78 (14)76 (15)72 (11)Mean ACRBaseline66 (50-87)43 (27-61)62 (40-97)48 (34-68)62 (45-91)(g/mol) (95% CI)24 months75 (57-98)35 (23-54)66 (45-98)50 (36-70)60 (41-87)Mean serumBaseline88 (82-94)90 (85-95)94 (85-103)90 (85-95)87 (81-93)creatinine level (µmol/L) (95% CI)24 months84 (77-92)84 (77-91)93 (82-105)83 (77-89)86 (78-94)Mean GFR (SD)Baseline91 (29)86 (21)91 (31)90 (26)88 (26)(mL/min/1.73m2)24 months95 (32)91 (25)92 (32)96 (28)90 (24) Albuminuria Serum creatinine level Micro-* (n=28)Overt? (n=86)Normal (n=98§)Raised? (n=15§)BP (mm Hg)Mean systolicBaseline 134 (24)135 (18)135 (20)139 (19)(SD)24 months 123 (23)120 (21)123 (22)118 (20)Mean diastolicBaseline 82 (15)81 (12)82 (13)78 (13)(SD)24 months 73 (15)74 (14)75 (14)71 (13)Mean ¶ ACRBaseline 16 (13-19)104 (90-121)49 (38-65)125 (83-187)(g/mol) (95% CI)24 months 19 (15-25)90 (72-112)50 (38-66)88 (45-174)Mean¶ serumBaseline 85 (79-92)90 (85-95)83 (82-88)137 (123-153)creatinine level (µmol/L) (95% CI)24 months 75 (70-81)88 (82-95)78 (75-81)119 (98-144)Mean GFR (SD)Baseline 88 (23)89 (28)95 (23)55 (18)(mL/min/1.73m2)24 months 102 (24)91 (28)99 (24)57 (30) ACEi=angiotensin-converting enzyme inhibitor. BP=blood pressure. ACR=urinary albumin/creatinine ratio. GFR=glomerular filtration rate. *ACR, 3.4-33g/mol. ?ACR >34g/mol. ?Serum creatinine level >106µmol/L (women), >120µmol/L (men). §Data not available for all participants. ¶Geometric mean. Back to text 5: Rates of endpoints in historical control and intention-to-treat groups Historical control group (n=229) BaselineEndpointACR (g/mol)CasesPerson-yearsRate per 100 person-years (95% CI)DialysisAll ≥ 1009 9564 1201.6 (0.8-3.1) 7.5 (3.9-14.4)Natural deathAll < 34 34-99 ≥ 10018 2 9 7555 226 205 1243.2 (1.0-5.1) 0.9 (0.2-3.5) 4.4 (2.2-8.4) 5.6 (2.7-11.2)Combined (dialysis or natural death)All < 34 34-99 100-199 ≥ 20026? 2 9 6 9543 227 205 74 374.8 (3.3-7.0) 0.9 (0.2-3.5) 4.4 (2.3-8.4) 8.1 (3.6-18.0) 24.2 (12.6-46.5) Intention-to-treat group (n=258) Endpoint CasesPerson-yearsRate per 100 person-years (95% CI)Dialysis 7 7548 1971.3 (0.6-2.6) 3.6 (1.7-7.0)Natural death 11 3 3 5560 178 194 1882.0 (1.1-3.4) 1.7 (0.5-5.2) 1.5 (0.4-4.8) 2.7 (1.1-6.4)Combined (dialysis or natural death) 16 3 3 3 7549 178 193 104 732.9 (1.7-4.6) 1.7 (0.5-5.2) 1.6 (0.5-4.8) 2.9 (0.9-8.9) 9.6 (4.6-20.2) Relative risk (RR) (95% CI) Endpoint Crude*Adjusted?P (for adjusted RR)Dialysis 0.77 (0.24-2.33)0.43 (0.17-1.12)0.08Natural death 0.59 (0.25-1.31)0.55 (0.26-1.16)0.11Combined (dialysis or natural death) 0.59 (0.30-1.14)0.47 (0.25-0.86)0.01 ACR=urinary albumin/creatinine ratio. *Overall estimate for treatment group versus control group. ?Relative risk adjusted for baseline ACRcategory. ?People who underwent dialysis and later died were counted only once for the combined endpoint. Back to text 6: Estimated survival advantage for intention-to-treat versus control group, adjusted for ACR category Clinical category at baselineRelative risk (95% CI)?PAll0.47 (0.25-0.86)0.01Overt albuminuria0.36 (0.18-0.72)0.004DiabetesNo0.28 (0.09-0.93)0.02Yes0.65 (0.28-1.51)0.31HypertensionNo0.59 (0.25-1.44)0.24Yes0.38 (0.15-0.98)0.04* ACR=urinary albumin/creatinine ratio. Categories: < 3.4 3.4-33, 34-99, 100-199, ≥ 200 g/mol. ? For combined endpoints of natural death and renal failure, intention-to-treat versus control group. Back to text Back to text Back to text Back to text

Wendy E Hoy · Philip R Baker · Angela M Kelly · Zhiqiang Wang

Abstract Objectives: To compare rates of mortality from coronary heart disease (CHD) between populations living within and outside Australian capital city statistical divisions. Design and setting: Descriptive epidemiological study based on data for all residents of Australia aged 30-69 years who died between 1986 and 1996 in all States and Territories of Australia. Main outcome measures: Standardised mortality rates from all causes and coronary heart disease as coded by the Australian Bureau of Statistics, and estimated excess deaths in populations living outside capital city statistical divisions. Results: Between 1986 and 1996, mortality from CHD declined by 46% in men and 51% in women, and accounted for 61% of the decline in mortality from all causes in men and 48% in women. More deaths than expected from acute myocardial infarction resulted in mortality rates from CHD up to 30% higher in men and 21% higher in women living outside the capital city statistical divisions, and accounted for an overall estimated excess of 3835 deaths from CHD in men (32% of excess deaths from all causes), and 1385 deaths from CHD in women (27% of excess deaths from all causes) over the 11-year study period. Conclusions: Although there were impressive declines in coronary mortality in all Australian States and Territories from 1986 to 1996, populations living outside capital cities continue to have higher death rates from CHD. These differences in mortality rates indicate a need for further research into factors which may influence mortality rates for CHD in rural and remote areas, and immediate measures to ensure optimal treatment of coronary risk factors and acute coronary events in such populations. Coronary heart disease (CHD) remains the largest single cause of death in Australia.1 Although there has been a steady decline in the death rate associated with CHD over the past 30 years, rates of decline have not been equal throughout Australia.2,3 A study of coronary mortality in Tasmania showed higher rates of mortality outside the capital city region.4 We examined official data for Australian men and women aged 30-69 years between 1986 and 1996 for evidence of differences in rates of death from CHD between capital city and regional populations. Methods The Australian Bureau of Statistics (ABS) collects and disseminates social, demographic and economic statistics for 66 Statistical Divisions based on an Australian Standard Geographical Classification (ASGC).5 The boundaries of capital city statistical divisions are determined by the anticipated development of the city for a period of at least 20 years, and delimit an area that is stable for general statistical purposes. Statistical divisions outside a capital city are relatively homogeneous regions characterised by identifiable social and economic links between the inhabitants and between the economic units within the region, under the unifying influence of one or more major towns or cities. We obtained ABS estimates of the size of the Australian population aged 30-69 years, and its distribution between capital city and other statistical divisions for the years 1986 and 1996. We also obtained ABS data for mortality from all causes, and from CHD, acute myocardial infarction (AMI) and subacute and chronic myocardial ischaemia for men and women aged 30-69 years living within and outside capital city statistical divisions for each year from 1986 to 1996. We excluded deaths at 70 or more years because certification of the cause of death in older people may be unreliable.6 We defined mortality from CHD as deaths with an underlying cause classified under rubrics 410, 411, 413 and 414 of the International classification of diseases, ninth revision (ICD-9-CM),7 with mortality from AMI classified under ICD-9-CM rubric 410, and mortality from subacute and chronic myocardial ischaemia classified under rubrics 411, 413, 414. Statistical methods Annual age-standardised rates for mortality from all causes, CHD, AMI and subacute and chronic myocardial ischaemia were calculated as follows: The number of deaths in each age group (30-39, 40-49, 50-59 and 60-69 years), coded to each cause of death category, were summed. Age-specific rates were calculated and then standardised with weightings obtained from Segi's "world population" (World Health Organization standard population).8 The normal approximation for the distribution was used to calculate 95% confidence intervals. For each State and the Northern Territory, we calculated expected numbers of deaths in each age group for populations living outside capital city statistical divisions by applying age-specific mortality rates from populations living within the capital city statistical division. Differences between the actual (observed) number of deaths and the expected number of deaths were then summed across 10-year age strata to give total expected numbers of deaths. Excess deaths were calculated as the difference between the sum of the observed and the sum of the expected number of deaths for all States and the Northern Territory. The population of the Australian Capital Territory living outside the Canberra Statistical Division was less than 0.1% of the total population of the ACT and was not included in the calculation. Results Population size and distribution Unpublished regional population data from the ABS estimated that, in 1986, there were 7 174 246 Australians aged 30-69 years, 64.4% of whom lived in capital city statistical divisions. The sex distribution in capital cities was 49.9% men and 50.1% women, compared with 51.0% men and 49.0% women outside capital cities. By 1996, the estimated population of Australians aged 30-69 years had increased to 8 793 107, 63.5% of whom lived in capital city statistical divisions. The sex distribution in capital cities was 49.8% men and 50.2% women, compared with 50.7% men and 49.3% women outside capital cities. Trends in mortality rates among men Between 1986 and 1996, mortality from all causes in all 30-69-year-old Australian men declined by 23%; this decline within capital city statistical divisions was 25%, compared with 21% among men living outside capital city statistical divisions (Box 1). Mortality from all causes in populations outside the capital cities remained higher than in capital city populations, with the difference increasing from 12% in 1986 to 18% in 1996. Between 1986 and 1996, mortality from CHD in Australian men aged 30-69 years declined by 46% and accounted for 61% of the decline in all-cause mortality. Mortality among men living within capital city statistical divisions declined by 49%, compared with 41% among men living outside capital city statistical divisions (Box 1). Mortality from CHD in populations outside the capital cities remained higher than in capital city populations, with the difference increasing from 13% in 1986 to 30% in 1996. Mortality from AMI among men living within capital city statistical divisions declined by 62%, compared with 50% among men living outside capital city statistical divisions (Box 1). Mortality from AMI in men living outside the capital cities remained higher than in capital city populations, with the difference increasing from 24% in 1986 to 63% in 1996. Excess mortality outside capital city statistical divisions Box 2 shows that, among men, CHD accounts for 32% of the excess deaths from all causes from 1986 to 1996 occurring outside the capital city statistical divisions. Among those deaths coded as CHD, observed deaths from AMI exceeded expected deaths by 5487. The number of excess deaths from CHD is smaller than that from AMI, as there was a higher rate of death from subacute and chronic myocardial ischaemia in capital city populations. Observed deaths from AMI among men aged 30-39 years living outside capital city statistical divisions exceeded expected deaths by 79%; corresponding figures for the remaining age groups were 72% (40-49 years), 51% (50-59 years), and 25% (60-69 years). Trends in mortality rates among women Between 1986 and 1996, mortality from all causes in all 30-69-year-old Australian women declined by 21%; this decline within capital city statistical divisions was 24%, compared with 18% among women living outside capital city statistical divisions (Box 1). Mortality from all causes in populations outside the capital cities remained higher than in capital city populations, with the difference increasing from 6% in 1986 to 15% in 1996. Between 1986 and 1996, mortality from CHD in Australian women aged 30-69 years declined by 51% and accounted for 48% of the decline in all-cause mortality. Mortality among women living within capital city statistical divisions declined by 54%, compared with 50% among women living outside capital city statistical divisions (Box 1). Mortality from CHD in populations outside the capital cities remained higher than in capital city populations, with the difference increasing from 13% in 1986 to 21% in 1996. Mortality from AMI among women living within capital city statistical divisions declined by 59%, compared with 54% among women living outside capital city statistical divisions (Box 1). Mortality from AMI in women living outside the capital cities remained higher than in capital city populations, with the difference increasing from 24% in 1986 to 38% in 1996. Excess mortality outside capital city statistical divisions Box 2 shows that, among women, CHD accounts for 27% of the excess mortality from all causes occurring outside the capital city statistical divisions. Observed deaths from AMI exceeded expected deaths by 1479. Observed deaths from AMI among women aged 30-39 years living outside capital city statistical divisions exceeded expected deaths by 108%; corresponding figures for the remaining age groups were 75% (40-49 years), 44% (50-59 years), and 20% (60-69 years). Overall mortality Box 3 shows that death rates from CHD outside capital cities are consistently higher than within capital cities in all Australian States and the Northern Territory, the only exception being mortality from CHD among women in the Northern Territory in 1986. Discussion The contribution of reduced CHD mortality to the overall decline in all-cause mortality in Australia from 1986 to 1996 was 61% for men and 48% for women. However, our findings show that CHD mortality rates were higher outside capital cities, and that discrepancies increased from 1986 to 1996 and were largest in younger age groups. It is likely that the differences we found in CHD mortality are real, as they are matched by parallel trends in all-cause mortality rates, and at least two studies have confirmed the validity of deaths coded by the ABS to CHD.9,10 While a study based on 1979 data questioned the validity of subcategories of CHD such as rubric 410 (AMI),11 we found consistently higher death rates from AMI in populations outside capital cities in all Australian States and the Northern Territory (data not shown), despite variations in medical certification requirements between States. The apparent higher rates of mortality in capital city populations from subacute and chronic CHD may be the result of a coding anomaly or of deaths occurring in large population centres after patients were moved there for the management of their subacute or chronic CHD. Our study was limited to documenting the difference in CHD mortality between capital cities and other areas. Clearly, an understanding of the factors associated with higher CHD mortality outside capital cities has implications for prevention and improved treatment of CHD. This would require detailed examination of population characteristics to determine which populations outside capital cities, including subpopulations such as Indigenous people, are most at risk of higher mortality. It is also necessary to consider factors such as differences in socioeconomic status, in risk factors for CHD, and in access to medical care. Previous reports showed that the decline in mortality from CHD in NSW was slower in lower income populations, many of which were in rural or regional areas.12,13 Also, sudden cardiac death in Tasmanian men was found to occur twice as frequently in unemployed men compared with employed men.14 While the association between populations with lower socioeconomic status and higher risk for CHD is recognised, the actual factors that influence this association have not been well delineated. Risk factors for CHD clearly have an influence on mortality. Much of the decline in mortality from CHD in Finland from 1972 to 1992 can be explained by changes in the three main coronary risk factors: serum cholesterol level, blood pressure and smoking.15 In Australia, the National Heart Foundation (NHF) Risk Factor Prevalence Surveys found significant declines between 1980 and 1989 in the prevalence of hypertension and cigarette smoking, but no overall favourable trend in lipid levels.16 However, these surveys are limited to capital cities, and it is not known whether regional areas of Australia have seen the same trends in risk factor prevalence. In 1992, a major risk factor prevalence survey based on the 1989 NHF Risk Factor Prevalence Survey was undertaken in two rural regions of Tasmania. The prevalence of major coronary risk factors was consistent with the high rate of mortality from CHD among men in North-West Tasmania, but did not explain variation in rates of mortality in women across the three regions of Tasmania.17 Differences in mortality from CHD may be the result of differential incidences of CHD or differences in case-fatality rates. A detailed study of sudden cardiac death among previously asymptomatic men found that the higher rate of deaths in the two rural regions of Tasmania occurred mostly among men for whom symptomatic CHD could have been diagnosed, implying a higher case-fatality rate for CHD.14 This finding was supported by higher rates of coronary deaths occurring after hospitalisation in the two rural regions of Tasmania from 1986 to 1989,4 and in Newcastle in 1984.18 A higher case-fatality rate may result from differences in risk of death from factors such as previous infarction, delays in reaching medical care, or differences in medical care.19 While the relative geographic isolation of most populations outside the capital cities may be expected to result in delays in reaching secondary and tertiary medical centres, the findings of the MONICA study did not support changes in time to medical care (including ambulance staff) having a significant effect on deaths before hospitalisation in major population centres.18 A significant decline in case fatality after hospitalisation did, however, make an important contribution to the overall decline in coronary deaths in the MONICA centres of Auckland (New Zealand), Newcastle (Australia) and Perth (Australia) from 1984 to1993. Medical management of acute coronary events has changed substantially over the past 20 years. The use of aspirin, thrombolytic therapy and coronary angioplasty as first-line treatments for AMI has resulted in reductions in mortality of up to 43%.20,21 The use of thrombolytic therapy in the MONICA centres increased from being rare in the early 1980s, to being used in approximately 50% of hospitalised patients with non-fatal definite myocardial infarction or coronary death by the early 1990s.22,23 The benefits of such treatments are dependent on them being given soon after the event,24 and it is not clear whether populations living at any distance from secondary or tertiary medical centres experience delays in access to new treatment methods for symptomatic CHD. In southern Tasmania between 1992 and 1996, 849 doses of streptokinase and tissue plasminogen activator were administered for AMI. No thrombolytic therapy was administered outside the capital city of Hobart (Royal Hobart Hospital Pharmacy Supplies Report), despite 15% of the population of the Southern Region living outside the capital city and having mortality rates approximately 40% higher than the capital city population. In conclusion, although there have been impressive declines in mortality from CHD in all Australian States and Territories over the past 30 years, the 35% of the Australian population living outside the capital cities continue to have higher coronary mortality. Our results indicate the need for increased research into factors which may influence mortality rates for CHD in rural and remote areas. Acknowledgements This study was supported by funding from Roche Products Pty Ltd and the Tasmanian branch of the AMA, and by assistance in-kind from the Hobart City Council and Australian Hospital Care Ltd. We are grateful to Chris Sweeney from the Australian Bureau of Statistics and to the Pharmacy Department of the Royal Hobart Hospital. References Tonkin AM, Bennett S. Cardiovascular disease at the turn of the century. Med J Aust 1999; 170: 408-409. Gibberd RW, Dobson AJ, Florey C du Ve, Leeder SR. Differences and comparative declines in ischaemic heart disease mortality among sub-populations of Australia 1969-1978. Int J Epidemiol 1984; 13: 25-31. Sexton PT, Woodward DR, Gilbert N, Jamrozik K. Interstate differences in trends in coronary mortality and risk factors in Australia. Med J Aust 1990; 152: 531-534. Sexton PT, Jamrozik K, Walsh J, et al. Regional variation in coronary mortality within Tasmania. Med J Aust 1992; 157: 449-451. Australian Bureau of Statistics. Australian Standard Geographical Classification. Canberra: ABS, 1998. Christie D. Mortality from cardiovascular disease. Med J Aust 1974; 1: 390-393. National Coding Centre, Faculty of Health Sciences, University of Sydney. Australian version of the international classification of diseases. 9th revision, clinical modification (ICD-9-CM). 2nd ed. Vol.1: Tabular list of diseases. Sydney: NCC, University of Sydney, July 1996. Doll R. Comparison between registers, age-standardised rates. IARC Sci Publ 1976; 3: 453-459. Martin CA, Hobbs MST, Armstrong BK. Estimation of myocardial infarction mortality from routinely collected data in Western Australia. J Chron Dis 1987; 40: 661-669. Sexton PT, Jamrozik K, Walsh J. Death certification and coding for ischaemic heart disease in Tasmania. Aust N Z J Med 1992; 22: 114-118. Dobson AJ, Gibberd RW, Leeder SR. Death certification and coding for ischaemic heart disease in Australia. Am J Epidemiol 1983; 117: 397-405. Burnley IH. Inequalities in the transition of ischaemic heart disease mortality in New South Wales, Australia. Soc Sci Med 1998; 47: 1209-1222. Taylor R, Chey T, Bauman A, Webster I. Socio-economic, migrant and geographic differentials in coronary heart disease occurrence in New South Wales. Aust N Z J Public Health 1999; 23: 20-26. Sexton PT, Jamrozik K, Walsh J. Sudden unexpected cardiac death among Tasmanian men. Med J Aust 1993; 159: 467-470. Vartiainen E, Puska P, Pekkanen J, et al. Changes in risk factors explain changes in mortality from ischaemic heart disease in Finland. BMJ 1994; 309: 23-27. Bennett SA, Magnus P. Trends in cardiovascular risk factors in Australia. Results from the National Heart Foundation's Risk Factor Prevalence Study, 1980-1989. Med J Aust 1994; 161: 519-527. Thomson A, Rundle S, Singh BB, et al. Regional differences in cardiovascular risk factor prevalence in Tasmania: are they consistent with the increased cardiovascular mortality. Aust N Z J Med 1995; 25: 290-296. Beaglehole R, Stewart AW, Jackson R, et al. Declining rates of coronary heart disease in New Zealand and Australia, 1983-1993. Am J Epidemiol 1997; 145: 707-713. Beaglehole R. Medical management and the decline in mortality from coronary heart disease. BMJ 1986; 292: 33-35. Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI). Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986; 1: 397-402. Second International Study of Infarct Survival Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17 187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988; 2: 349-360. Doggen CJM, van der Palen J, Beaglehole R. Trends in medical management of acute myocardial infarction. N Z Med J 1993; 106: 278-281. Dobson AJ, Jamrozik KD, Hobbs MST, et al. Medical care and case fatality from myocardial infarction and coronary death in Newcastle and Perth. Aust N Z J Med 1993; 23: 12-18. Bett JHN. LATE assessment of thrombolytic efficacy with alteplase (rt-PA) six-24 hours after onset of acute myocardial infarction. Aust N Z J Med 1993; 23: 745-748. (Received 23 Sep 1999, accepted 31 Jan 2000) Authors' details The Hobart Private Hospital, Hobart, TAS. Peter T Sexton, PhD, FAFPHM, Director of Medical Services; Tiina-Liisa H Sexton, BCom, CA, Research Assistant. Reprints: Dr P T Sexton, The Hobart Private Hospital, Cnr Argyle and Collins Streets, Hobart, TAS 7000. 1: Comparison of mortality rates between populations aged 30-69 years living within and outside capital cities in Australia Back to text 2: Estimated excess deaths from all causes, CHD and AMI among men and women living outside capital city statistical divisions from 1986 to 1996 Age group (years) 30-3940-4950-5960-69Total Men Mortality from all causes Observed deaths8599126982622760856108380 Expected deaths736310718216195672596425 Excess deaths123619804608413111955 Mortality from CHD (ICD-9-CM 410, 411, 413, 414) Observed deaths682270372391824128865 Expected deaths493209959021653625030 Excess deaths189604 133717053835 Mortality from AMI (ICD-9-CM 410) Observed deaths470197253341328721063 Expected deaths263114435411062815576 Excess deaths207828 179326595487 Women Mortality from all causes Observed deaths38877021138633146756238 Expected deaths32025998119722991851090 Excess deaths6851023189115495148 Mortality from CHD (ICD-9-CM 410, 411, 413, 414) Observed deaths143537 187869379495 Expected deaths91381 150361358110 Excess deaths52156 3758021385 Mortality from AMI (ICD-9-CM 410) Observed deaths102391 140050736966 Expected deaths49223 97242435487 Excess deaths53168 4288301479 CHD=coronary heart disease. AMI=acute myocardial infarction Back to text 3: Mortality within and outside capital city statistical divisions by Australian States and Territories Men Age-standardised mortality rate per 100000 (95% CI) % changeEstimated excess 1986 1996 per yeardeaths from CHD All causesCHDAll causesCHDfrom CHD1986-1996 New South Wales Capital722 (702-741)223 (212-234)511 (496-527)106 (99-113)-4.8 Balance761 (736-786)232 (218-246)601 (581-622)143 (133-153)-3.51506 Victoria Capital658 (638-678)199 (188-210)487 (470-503)97 (90-105)-4.7 Balance755 (722-789)242 (223-261)583 (556-611)131 (118-144)-4.21015 Queensland Capital691 (657-724)226 (207-245)549 (523-575)122 (109-134)-4.2 Balance754 (723-785)227 (210-245)585 (562-609)136 (125-147)-3.6444 South Australia Capital653 (619-687)213 (194-232)528 (499-557)125 (110-139)-3.8 Balance707 (650-764)234 (201-267)633 (583-683)160 (135-186)-2.9291 Western Australia Capital638 (603-673)183 (164-202)498 (471-525)102 (89-114)-4.0 Balance779 (716-841)249 (214-285)594 (546-642)121 (100-143)-4.7203 Tasmania Capital605 (526-684)141 (103-179)595 (520-669)102 (71-133)-2.5 Balance758 (685-831)276 (232-320)619 (558-680)144 (115-174)-4.3243 Northern Territory Capital640 (463-817)115 (46-185)716 (569-863)97 (36-158)-1.4 Balance1443 (1206-1679)233 (138-329)1030 (862-1199)132 (73-191)-3.9133 Australian Capital Territory 598 (521-675)205 (159-251)428 (372-484) 111 (82-140)-4.2 All of Australia Capital679 (668-690)209 (203-215)510 (501-519)107 (103-111)-4.4 Balance763 (747-778)237 (228-245)602 (590-614)139 (133-145)-3.83835 Women Age-standardised mortality rate per 100000 (95% CI) % changeEstimated excess 1986 1996 per yeardeaths from CHD All causesCHDAll causesCHDfrom CHD1986-1996 New South Wales Capital391 (377-405)82 (76-88)284 (273-296)32 (28-36)-5.5 Balance420 (401-439)89 (80-97)335 (319-350)45 (39-51)-4.5564 Victoria Capital360 (346-375)65 (59-72)274 (262-286)31 (27-35)-4.8 Balance361 (338-384)68 (58-77)307 (287-327)35 (28-41)-4.4277 Queensland Capital371 (347-395)67 (57-78)308 (288-328)39 (32-46)-3.8 Balance378 (355-400)75 (65-85)299 (282-316)36 (30-42)-4.7171 South Australia Capital347 (323-371)69 (58-79)285 (264-306)31 (24-38)-5.0 Balance291 (317-400)83 (64-103)339 (301-377)39 (26-52)-4.8143 Western Australia Capital349 (324-374)59 (49-70)275 (255-295)37 (30-45)-3.4 Balance386 (339-433)78 (296-372)334 (57-99)36 (24-49)-4.9105 Tasmania Capital424 (360-488)68 (42-93)365 (308-422)49 (28-70)22.5 Balance421 (367-475)87 (62-111)385 (336-434)54 (36-72)-3.462 Northern Territory Capital434 (271-597)46 (-10-103)392 (261-523)41 (-3-86)-1.0 Balance911 (702-1120)37 (-6-81)762 (593-932)88 (28-148)+12.563 Australian Capital Territory 380 (319-440)56 (32-80)267 (223-311)41 (23-59)-2.4 All of Australia Capital372 (363-380)71 (68-75)284 (278-291)33 (31-36)-4.9 Balance396 (384-407)80 (75-85)326 (317-335)40 (37-44)24.51385 CHD=coronary heart disease. Capital=within capital city statistical divisions. Balance=outside capital city statistical divisions. Back to Text

Peter T Sexton · Tiina-Liisa H Sexton

Editorial Mortality from cardiovascular disease is too high outside capital cities Do we accept this situation or look for ways of changing it? MJA 2000; 172: 360-361 The report by Sexton and Sexton1 in this issue of the Journal updates our knowledge about geographic differences in death rates from cardiovascular disease (CVD) in Australia. Their major finding is that deaths from coronary heart disease (CHD) in 1996 were 30% higher for men and 21% higher for women who live outside our capital cities than for those who live in capital cities. The gap widened over the period of study -- in 1986 the CHD mortality difference (in both men and women) was 13%. The gratifying decline in deaths from CVD over the last number of years has been greater for those who live in capital cities, and this has led to a widening of the geographic gradient in CVD deaths. Of particular concern in the report is that the excess mortality outside capital cities is greater among younger age groups. The demonstration of social and geographic gradients in death rates is not new.2,3 The findings of Sexton and Sexton are disturbing -- what could be the explanation? What can we do about them? There are two reasons for excess CHD deaths -- risk factors among the population and inadequacies in the level of medical care provided. A combination of changes in these factors has been found to be the explanation for the recent decline in CHD deaths seen in Australia.4Sexton and Sexton allude to differences in socioeconomic status between urban and rural areas, which together with higher levels of unemployment outside capital cities may be part of the "explanation" of the higher CHD mortality. Their report does not examine separately death rates in Aboriginal people, and, while these are likely to contribute to the overall picture, Indigenous people constitute too small a proportion of the total population for this to be the whole explanation. Data on risk factor levels are scarce outside capital cities, but some limited data discussed in the report suggest that differences in risk factor levels mirror the excess rural mortality. The strength of the article by Sexton and Sexton is the demonstration of a widening of the mortality gap over time. There have been major changes in the provision of medical care for patients with heart disease between 1986 and 1996, and it seems most appropriate to focus here on the level of healthcare provided in and outside capital cities. The data from Sexton and Sexton do not allow us to distinguish between disease incidence and case fatality, but other data indicate that there are differences in case fatality and in medical care for acute myocardial infarction (AMI) between metropolitan and non-metropolitan hospitals.5,6 There are differences in the types of hospital in and outside capital cities and in the distribution of specialist cardiologists. There is ample evidence that hospital type and size and the speciality of the treating physician are related to the outcome and the practice of evidence-based care for patients with CHD.7-10 A recent report in this Journal found that the evidence-based use of drugs after AMI was lower among doctors in smaller non-metropolitan hospitals in New South Wales.7 It is not beyond credibility to suggest that at least part of the reason for the widening geographic gradient in CHD deaths in Australia is differential levels of care for those with the disease. Rural areas have smaller hospitals and fewer cardiologists (who prefer to have access to investigative facilities, which have become such an important part of their speciality). We must find solutions to the need to practise evidence-based care and prevention throughout the Australian healthcare system, irrespective of access to specialist services and tertiary care facilities. Guidelines and clinical pathways have been promulgated as a response to the demonstration of variations in medical care, and may have an impact on changing patterns of care.11,12 However, the solution to the structural inequalities in the provision of care is likely to be much more complex than the use of these clinical decision aids, especially given the relatively small impact they might be expected to have.12 Do we just accept that people who live outside capital cities in a large country where the population is thinly spread will inevitably have less access to high quality medical care (as they have less access to many other resources such as the arts and retail outlets)? These are fundamental questions about societal expectations. Where is the consumer pressure for change? What is the responsibility of the health professions for the health of the whole of the population, and how is this expressed? A number of these questions were discussed at the recent Federal Government Regional Australia Summit, at which, despite the comment that "There are no easy solutions facing regional Australia", a number of key priorities and proposed strategies were identified.13 For example, two of the key priorities under the health theme are: "Regional, rural and remote communities require improved and expanded access to healthcare services . . ." and "Resource allocation for regional, rural and remote communities must be equitable in terms of health need relative to the urban population." One of the proposed strategies to achieve this latter priority is "A health services plan will be established to set optimal levels of services for communities of different sizes. The Commonwealth Health Department will act as broker for funding to any community which wishes to invoke those benchmarks." Maybe the demonstration of a reduced geographic gradient for CVD deaths could be a future marker of the success of this and other interventions. Richard F Heller Professor of Community Medicine and Clinical Epidemiology Centre for Clinical Epidemiology and Biostatistics Faculty of Medicine and Health Sciences The University of Newcastle, Newcastle, NSW Sexton PT, Sexton T-L H. Excess coronary mortality among Australian men and women living outside the capital city statistical divisions. Med J Aust 2000; 172: 370-374. Taylor R, Chey T, Bauman A, Webster I. Socio-economic, migrant and geographic differentials in coronary heart disease occurrence in New South Wales, Australia. Aust N Z J Public Health 1999; 23: 20-26. Marmot M, Ryff CD, Bumpass LL, et al. Social inequalities in health: next questions and converging evidence. Soc Sci Med 1997; 44: 901-910. Dobson AJ, McElduff P, Heller R, et al. Changing patterns of coronary heart disease in the Hunter Region of New South Wales, Australia. J Clin Epidemiol 1999; 52: 761-771. Huy Dinh Vu, Heller RF, Lim LLY, et al. Hospital mortality after acute myocardial infarction is lower in metropolitan than non-metropolitan regions. J Epidemiol Commun Health. In press. Lim L, O'Connell R, Heller R. Differences in management of heart attack patients between metropolitan and regional hospitals in the Hunter Region of Australia. Aust N Z J Public Health 1999; 23: 61-66. Lim LLY, Heller RF, O'Connell R, D'Este C. Stated and actual management of acute myocardial infarction among different specialties. Med J Aust 2000; 172: 208-212. Chen J, Radford MJ, Wang Y, et al. Do "America's best hospitals" perform better for acute myocardial infarction? N Engl J Med 1999; 340: 286-292. Jollis JG, Delong ER, Peterson ED, et al. Outcome of acute myocardial infarction according to the speciality of the admitting physician. N Engl J Med 1996; 335: 1880-1887. Weitzman S, Cooper L, Chambless L, et al. Gender, racial, and geographic differences in the performance of cardiac diagnostic and therapeutic procedures for hospitalised acute myocardial infarction in four states. Am J Cardiol 1997; 79: 722-726. Kitchiner DJ, Bundred PE. Clinical pathways [editorial]. Med J Aust 1999; 170: 54-55. Gupta L, Ward JE, Hayward RS. Clinical practice guidelines in general practice: a national survey of recall, attitudes and impact. Med J Aust 1997; 166: 69-72. Regional Australia Summit communiquŽ. Presentation of the summit recommendations. <http://www.dotrs.gov.au/regional/summit/communique.htm> (Accessed 23 March 2000). Make a comment

Richard F Heller

Abstract Cardiovascular risk factors are commonly associated with erectile dysfunction and should be identified and treated. Patients with cardiovascular diseases should be assessed and counselled regarding their fitness for sexual activity. The danger of concurrent use of sildenafil and nitrates under any circumstances, regardless of age and sex, must be highlighted at all levels of the community. Sildenafil is absolutely contraindicated in patients receiving treatment with long-acting nitrates for ischaemic heart disease. Patients who need sublingual short-acting nitrates infrequently should not be precluded from taking sildenafil, provided they are aware that sildenafil is not to be taken within 24 h of taking the nitrate. There has been concern about the use of sildenafil (Viagra; Pfizer) for the treatment of erectile dysfunction (ED), particularly with regard to its possible role in the reported deaths and other serious cardiovascular events. Although sildenafil attracted considerable free media publicity in its debut in Australia and ranks as the most publicised new product this decade,1,2 consumer interest has been subdued and partly overshadowed by reports of 130 deaths involving sildenafil users in the United States between late March and mid-November 1998.3 It is therefore important that the association between sildenafil and these deaths be examined critically, so that the nature and the degree of risk may be identified and proper guidelines may evolve for the use of sildenafil. Cardiovascular disease and erectile dysfunction Cardiovascular disease and ED are known to be associated. In the Massachusetts Male Ageing Study,4 moderate or complete ED was 31% more prevalent among people with heart disease than in an age-matched cohort without heart disease. In a study in Perth, WA, the prevalence of complete ED among patients with hypertension, ischaemic heart disease and peripheral vascular disease was 26%, 38% and 57%, respectively, compared with 18.6% for the whole study.5 Reported ED in patients hospitalised for myocardial infarct or coronary artery surgery is of the order of 57%-64%.6,7 Conversely, in patients with severe ED, there is a 16% risk of severe, clinically occult ischaemic heart disease.8 Indeed, a statistically significant correlation has been shown between ED and the number of occluded coronary vessels.9 A significant number of patients requesting treatment for ED will have known or undiagnosed ischaemic heart disease, leading to considerable potential for adverse cardiovascular events. Moreover, many medications used for the treatment of cardiovascular disease may aggravate ED or complicate its treatment.10 Sildenafil and erectile dysfunction Sexual stimulation leads to the release of nitric oxide in the corpus cavernosum and results in an increase of cyclic guanosine monophosphate (cGMP), which produces smooth muscle relaxation and increased blood flow. Sildenafil is a selective inhibitor of cGMP-specific type 5 phosphodiesterase (PDE), the enzyme responsible for the degradation of cGMP in the corpus cavernosum. Thus, it enhances the effects of cGMP and permits an erectile response to be achieved or sustained (Box 1). The relevant pharmacodynamic and pharmacokinetic characteristics of sildenafil are summarised in Box 2.11-13 The efficacy of sildenafil in the treatment of ED has been demonstrated in 21 randomised, double-blind, placebo-controlled trials involving more than 3000 patients aged 19-87 years with ED of various aetiology.11 Sildenafil has been studied in men with ischaemic heart disease and with a wide range of other risk factors.14 A low incidence of serious or clinically significant adverse events, including cardiovascular events, was reported, comparable to that in patients with no known history of cardiovascular disorders. In Phase II-III studies involving 349 placebo patient-years and 693 sildenafil patient-years in randomised studies and 4220 patient-years in open-label studies, the incidence of myocardial infarction was lower in the sildenafil group than in the placebo group, although the difference was not statistically significant. The incidence of adverse events attributable to lowering of blood pressure in patients taking sildenafil was also low and no higher than in those receiving placebo. It was similar in patients taking concomitant antihypertensives and in those not taking these medications.14 There were reports of 26 deaths in about 5000 sildenafil patient-years, including 14 people with myocardial infarction and sudden death. None of the deaths was considered to be treatment related.14 Sildenafil and adverse cardiovascular events The unprecedented hype generated by the launch of sildenafil in the United States was dampened by reports of cardiovascular events, including deaths, allegedly associated with its use. A summary of reports of death among sildenafil users was posted by the Food and Drug Administration (FDA), with the pertinent remark that, in interpreting these reports, consideration should be given to the limitations of spontaneous reporting, such as under-reporting, duplication, marketing and medicolegal factors, incomplete or inaccurate clinical information, and the assumption of a cause-effect relationship.3 An overview of the FDA's updated summary of 130 reports of death between late March and mid-November 1998 is shown in Box 3. Deaths have also been reported in the Netherlands15 and Australia.16 Did sildenafil cause or contribute to the reported deaths? Sexual activity remains a potential trigger for myocardial infarction and sudden death may result from ischaemia or arrhythmia, although the relative and absolute risks are apparently low (Box 4). In the US general population with an age distribution similar to that of sildenafil users, there are about 400 deaths per million per week, and about 150 of these have a cardiovascular cause.29 In Australia, there are about 250 myocardial infarctions (50 fatal) per week affecting men aged 35 to 69 years.30,31 More than 70% of the deceased subjects in the FDA summary had overt or occult cardiovascular disease. Considering the high prevalence of risk factors for sudden cardiac death in users of sildenafil, the reported 130 deaths need to be viewed in the context of patient exposure to about 50 million sildenafil tablets, or more than 6 million prescriptions, during the same period. Pharmacologically, the action of sildenafil as a type 5 PDE inhibitor is highly specific. Potential for disaster seems to lie in the concurrent use of sildenafil and organic nitrates, as sildenafil potentiates the effect of nitrates and may lead to life-threatening hypotension (Box 1). Among the deaths reported in the FDA summary, there were 16-19 sildenafil users who had allegedly used or received glyceryl trinitrate or a nitrate-containing medication. In this subset of individuals, the concurrent use of nitrates would provide the possible causal link between sildenafil and death. Therefore, it is not unlikely that sexual activity in a vulnerable person and adverse drug interaction caused or contributed to the reported deaths. Recommendations Box 5 shows the recommended strategy for treating ED. To minimise adverse consequences, it is important that a patient's fitness for sexual and physical activity be assessed when treatment of ED is considered, and that the patient be appropriately counselled if sexual activity is inadvisable. In general, sexual intercourse should be safe if a patient can perform an activity equal to 5-6 metabolic equivalents (METS), such as climbing 20 stairs in 10-15 seconds without distress.32 Postinfarction patients who reach 5-6 METS on stress testing without ischaemia or arrhythmia can resume their normal sexual activity without risk.33 In one study, patients with a negative exercise test result did not demonstrate ischaemia on Holter monitoring during sexual intercourse.26 The frequent use of short-acting nitrates and ongoing therapy with long-acting nitrates are absolute contraindications to the use of sildenafil. The only option for patients in this situation is to avoid the use of sildenafil. A policy of refraining totally from the use of sildenafil in all patients receiving nitrates in whatever form and regardless of frequency would, of course, quarantine patients from the risk of drug interaction. Nevertheless, patients who have only an infrequent need for short-acting nitrates, such as sublingual glyceryl trinitrate, should not be precluded from the use of sildenafil. However, doctors need to ensure that patients fully understand the implications of the potential interaction of these therapies. Patients whose only exposure to nitrate therapy is infrequent use of sublingual glyceryl trinitrate tablets or spray should be advised that at least 24 hours from the last use of the short-acting nitrates should be allowed to elapse before the use of sildenafil. It is not definitely known when nitrates can be safely administered after a dose of sildenafil. Certainly, patients should be cautioned against the use of any form of nitrates for at least 24 hours after sildenafil. In elderly patients, and in those with hepatic and renal impairment or receiving medications which may inhibit the cytochrome P450 3A4 isoenzyme (eg, erythromycin, fluconazole, fluoxetine, cimetidine), consideration must be given to decreased sildenafil clearance. If a patient should develop angina within 24 hours of taking sildenafil, nitrates should be totally avoided. Doctors should ensure that their patients follow this advice carefully. If necessary, an increase in the dose of alternative anti-anginal agents should be considered. If a patient requires hospital admission, non-nitrate anti-anginal preparations such as ß-blockers or calcium-channel blockers can be used with due regard to the risk of hypotension. If complications should develop from the inadvertent concurrent use of a nitrate, the recommendations of the American College of Cardiology and the American Heart Association34 should be followed. These include resuscitative measures such as fluid infusion and judicious use of intravenous vasopressors to maintain blood pressure, as well as appropriate non-nitrate anti-anginal agents. If adherence to such guidelines is difficult, the alternative is to avoid sildenafil in favour of other therapeutic options for ED. Clinical judgement and discretion must prevail over generalisation, bearing in mind the risk and benefit and the priority of the therapeutic interventions involved. There are no established data on the safety and efficacy of sildenafil in patients with myocardial infarction or life-threatening arrhythmia within the preceding six months; patients with systolic blood pressure < 90 mmHg; or patients with cardiac failure or coronary artery disease causing unstable angina. Caution must be exercised in prescribing sildenafil for these patients and for patients receiving complicated multidrug antihypertensive therapy.34 Where appropriate, monitoring of blood pressure at the initiation of sildenafil therapy would identify patients with a hypotensive response to sildenafil. An appropriate educational program will reduce the risk of drug interaction by alerting pharmacists and doctors to the potential danger. Pharmaceutical companies marketing nitrate-containing medications should specify sildenafil as a contraindication in their product information. Paramedics, nursing staff, patients and the community at large should be instructed on the danger of the concurrent use of sildenafil and nitrates, and of the undesirable practice of sharing medication with relatives and friends (Box 6). It is important that a warning be given to every patient, regardless of sex or age. Women have been known to use sildenafil to heighten sexual arousal and young people may use amyl nitrite inhalation for recreational pursuit. Cardiovascular diseases affect an estimated 2.3 million Australians.35 The risk of angina increases with age, affecting 12.4% of men and 11.7% of women aged 65-69 years.36 These proportions are likely to be greater among patients with ED. A request for treatment of ED provides a window of opportunity to assess the patient for cardiovascular and other risk factors, including diabetes and abnormal lipid profile. Cardiovascular risk factors, if identified, should be vigorously treated according to established guidelines.37,38 The sildenafil controversy continues.39 It has been reported that the FDA continues to believe that sildenafil remains safe.39 However, continuing postmarketing surveillance is essential for sildenafil, as for any recently marketed drug. Disclosure B G A Stuckey has served as a principal investigator in clinical studies of sildenafil. K K Chew and B G A Stuckey have received sponsorship to attend conferences from Pfizer Aust Pty Ltd. P L Thompson serves on the international steering committee of a Pfizer-sponsored clinical trial of lipid lowering in the elderly. K K Chew, B G A Stuckey and P L Thompson have been invited to present papers at Pfizer-sponsored meetings. References Kiely M. Viagra saturates media. Marketing Globe. Marketing 1998; Dec: 58. Jones A. When the thrill has gone. Business Rev Weekly 1999; June 25: 90-95. US Department of Health, Food and Drug Administration. Postmarketing safety of sildenafil citrate (Viagra) and summary of reports of death in Viagra users received from marketing (late March through mid-November 1988). 24 November 1988. Feldman HA, McKinlay JB, Goldstein I, Longcope C. Erectile dysfunction, cardiovascular disease and cardiovascular risk factors: prospective results in a large random sample of Massachusetts men. J Urol 1998; 159 Suppl 5: 91 abstract 347. Chew KK, Earle CM, Stuckey BGA, et al. Erectile dysfunction in general medical practice: prevalence and clinical correlates. Int J Impot Res 2000; 12: 1-5. Wabrek AJ, Burchell RC. Male sexual dysfunction associated with coronary heart disease. Arch Sex Behav 1980; 9: 69-75. Gundle MJ, Reeves BR, Tate S, et al. Psychosocial outcome after aortocoronary artery surgery. Am J Psychiatry 1980; 137: 1591-1594. Anderson M, Nicholson B, Louie E, Mulhall JP. An analysis of vasculogenic erectile dysfunction as a potential predictor of occult cardiac disease. J Urol 1998; 159 Suppl 5: 30 abstract 118. Greenstein A, Chen J, Miller H, et al. Does severity of ischaemic coronary disease correlate with erectile function? Int J Impot Res 1997; 9: 123-126. Slag MF, Morley JE, Elson MK, et al. Impotence in medical clinic outpatients. JAMA 1983; 249: 1736-1740. Morales A, Gingell G, Collins M, et al. Clinical safety of sildenafil citrate (Viagra) in the treatment of erectile dysfunction. Int J Impot Res 1998; 10: 69-74. Viagra -- approved product information. Pfizer, 1998. Boolell M, Allen MJ, Ballard SA, et al. Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Int J Impot Res 1996; 8: 47-52. Zusman RM, editor. Cardiovascular data on sildenafil citrate. Am J Cardiol 1999; 83(5A). Feenstra J, van Drie-Pierik RJHM, Lacle CF, Stricker BHC. Acute myocardial infarction associated with sildenafil. Lancet 1998; 352: 957-958. Viagra is here! Australian Adverse Drug Reactions Bulletin 1998; 17(4). Hellerstein HK, Friedman EH. Sexual activity and the postcoronary patient. Arch Intern Med 1970; 125: 987-999. Bohlen Y, Held JP, Sanderson MO, Paterson RP. Heart rate, rate-pressure product, and oxygen uptake during four sexual activities. Arch Intern Med 1974; 144: 1745-1748. Willich SN, Klatt S, Arntz HR. Circadian variation and triggers of acute coronary syndromes. Eur Heart J 1998; 19 Suppl C: C12-23. Nalbangtil I, Yigitbasi O, Kiliccioglu B. Sudden death in sexual activity. Am Heart J 1976; 91: 405-406. Ueno M. The so-called coital death. Jpn J Legal Med 1963; 17: 330-340. Renshaw DC, Karstaedt A. Is there (sex) life after coronary bypass? Comp Ther 1988; 14: 61-66. Lecomte D, Fornes P, Nicolas G. Stressful events as a trigger of sudden death: a study of 43 medico-legal autopsy cases. Forensic Sci Int 1996; 79: 1-10. Muller JE, Mittleman MA, Maclure M, et al. Triggering myocardial infarction by sexual activity. JAMA 1996; 275: 1405-1409. Johnston BL, Fletcher GF. Dynamic electrocardiographic recording during sexual activity in recent post-myocardial infarction and revascularization patients. Am Heart J 1979; 98: 736-741. Drory Y, Shapira I, Fisman EZ, Pines A. Myocardial ischaemia during sexual activity in patients with coronary artery disease. Am J Cardiol 1995; 75: 835-837. Kavanagh T, Shephard RJ. Sexual activity after myocardial infarction CMAJ 1977; 116: 1250-1253. Paolillo V, Marra S, Spadaccini F, Angelino PF. Dynamic electrocardiographic recording during sexual activity in recent post-myocardial infarction and revascularization patients [letter]. Am Heart J 1980; 100: 763. Health United States. 1998. Hyattsville, Maryland: US National Center for Health Statistics, 1998. Australian Institute of Health and Welfare. Heart, stroke and vascular diseases, Australian facts. Canberra: AIHW and the Heart Foundation of Australia, 1999. (Cardiovascular Disease Series No. 10. AIHW Cat. No. CVD 7.) Australian Bureau of Statistics. Causes of death, Australia. Canberra: ABS, 1997. (Cat No. 3303.0.) Cardiac rehabilitation: sex after a heart attack. In: Zaret BL, Moser M, Cohen LS, editors. Yale University School of Medicine Heart Book. New York: Hearst Books, 1992; 351. Tardif GS. Sexual activity after a myocardial infarction. Arch Phys Med Rehabil 1989; 70: 763-766. Summary statement of the American College of Cardiology and the American Heart Association on the use of sildenafil (Viagra) in patients at clinical risk from cardiovascular effects. 10 August 1998. <http://www.americanheart.org/ Whats_News/AHA_Science_Advisories/viagra.html>. Accessed 18 February 2000. Fact sheet for prevention of myocardial infarction. National Heart Foundation of Australia. Curr Ther 1999; 39: 52. Fact sheet for angina. National Heart Foundation of Australia. Curr Ther 1999; 39: 63. Grundy SM, Balady GJ, Criqui MH, et al. Guide to primary prevention of cardiovascular diseases. A statement for healthcare professionals from the Task Force on Risk Reduction. Circulation 1997; 95: 2329-2331. Heart Foundation of Australia. Guide for the use of lipid lowering drugs in adults. Canberra: Heart Foundation of Australia, 1999. Available at <http://www. heartfoundation.com.au/include/defaultStory.asp?OwnerUID=200&Content Type=tblcategory>. Mitka M. Some men who take Viagra die -- why? [news]. JAMA 2000; 283(5). <http://jama.ama-assn.org/issues/v283n5/full/jmn0202-2.html>. Accessed 18 February 2000. (Received 8 Oct 1999, accepted 14 Feb 2000) Authors' details Keogh Institute for Medical Research, Perth, WA. K Kim Chew, FRCP(Edin), FRCP(Glas), Senior Clinical Fellow; Bronwyn G A Stuckey, MB BS, FRACP, Medical Director, and Consultant Endocrinologist, Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Perth, WA. University of Western Australia, Perth, WA. Peter L Thompson, FRACP, FACP, Clinical Professor of Medicine, University of Western Australia, and Consultant Cardiologist, Sir Charles Gairdner Hospital, Perth, WA. Reprints will not be available from the authors. Correspondence: Dr B G A Stuckey, Keogh Institute for Medical Research, 3rd Floor A Block, Queen Elizabeth II Medical Centre, 2 Verdun Street, Nedlands, WA 6009. rmriATwt.com.au 2: Pharmacodynamic and pharmacokinetic characteristics of sildenafil11-13 Sildenafil is about 4000-fold more selective for type 5 phosphodiesterase (PDE5) than for PDE3, which is involved in cardiac contractility. In healthy volunteers, sildenafil produced a modest decrease in blood pressure (up to 8.4 mmHg systolic and 5.5 mmHg diastolic), but no consistent orthostatic effects and no clinically relevant electrocardiographic changes. In patients receiving medications containing nitrates, the hypotensive effects of sildenafil can be severe. In a US study with isosorbide mononitrate 20 mg twice daily, 50 mg sildenafil produced maximal blood pressure reductions of 40.9 mmHg systolic sitting and 51.6 mmHg systolic standing, and 25.8 mmHg diastolic sitting and 29.3 mmHg diastolic standing, about one hour after dosing and lasting up to 6 h. Similar haemodynamic interaction occurred for about two hours after a dose of 500 µg sublingual glyceryl trinitrate (maximum reductions: systolic, 36.0 mmHg sitting; diastolic, 20.5 mmHg sitting). Sildenafil has a half-life of about 4 h. After an oral dose of 100 mg, the plasma level peaks at about 440 ng/mL within 30-120 min, and drops to about 2 ng/mL at 24 h. Sildenafil is predominantly metabolised in the liver by the cytochrome P450 3A4 system, and 18% of the dose is excreted in the urine. Increased plasma levels may result from concomitant use of a cytochrome P450 3A4 inhibitor (eg, erythromycin, fluconazole, fluoxetine, cimetidine) or reduced clearance in elderly persons (>65 years) and in those with significant hepatic and renal impairment (creatine clearance <30 mL/min). 3: US Food and Drug Administration summary of reports of death in sildenafil users Number of deaths reported130Number with cause not mentioned or unknown48Number from homicide or drowning2Number from stroke3Number from cardiovascular events Definite or suspected myocardial infarction Cardiac arrest Cardiac symptoms Coronary artery disease77 41 27 6 3Use of nitrates Took or were administered a nitrate medication Found with nitrate in their possession16 3Time of death after use of sildenafil Not stated or unknown Within 4-5 hours of using sildenafil (includes 27 during or immediately after sexual intercourse) Later the same day Next day Two days later Three to seven days later61 44 6 8 5 4Cardiovascular risk factors One or more risk factors No identified risk factors, but severe coronary artery disease found at autopsy No history of cardiac disease or risk factors No risk factors and no sexual activity Not specified 90 3 12 2 23 4: Sexual activity and adverse cardiovascular events Sexual activity, like any other physical effort, increases cardiac work and myocardial oxygen demand.17 Heart rate and blood pressure rise to an energy expenditure of 2.0-5.4 metabolic equivalents.18 Sexual activity may trigger an adverse cardiovascular event.19,20 Coital death has been reported to account for 0.6% of sudden deaths,21 although it is said to be rare in a stable sexual relationship.22 In a study of 43 cases, sudden death was found to occur primarily in patients with severe heart disease, especially coronary heart disease, and in only three cases was sexual activity involved.23 In another study, 9% of patients reported having had sexual activity in the 24 hours, and 3% in the two hours, preceding myocardial infarction. The relative risk of myocardial infarction occurring in the two hours after sexual activity was estimated to be 2.5, and was not increased in patients with a history of previous angina pectoris or myocardial infarction. The absolute risk increase was low, at one chance in a million for a healthy individual.24 Electrocardiographic abnormalities during sexual activity have been reported in 12 of 24 patients with recent myocardial infarction or revascularisation.25 In another study, 31% of men with ischaemic heart disease had ischaemia on Holter monitoring during sexual intercourse, although only 7% were symptomatic.26 However, the frequency of angina pectoris and ventricular premature beats is less during sexual intercourse than during standard laboratory exercise, and sexual relations are thought to carry no special risk for the average postinfarction patient.27 Sexual activity in the early posthospital phase of myocardial infarction is not a stronger stimulus than other activities for cardiac electrical instability.28 Anxious sexual preoccupation, frustration and avoidance may actually be greater risk factors than coitus or coital alternatives.22

Peter L Thompson

Editorial Mood disturbances and coronary heart disease: progress in the past decade Psychological factors are increasingly being identified as important contributors to the onset and course of coronary heart disease MJA 2000; 172: 151-152 Psychological conditions, such as life event stress, mood disturbance and personality disorders, are believed to be important risk factors for coronary heart disease (CHD).1-3 Building on the work of the past decade, growing evidence is emerging that mood disturbances can contribute substantially to CHD. This work has studied the effect of a range of emotional conditions, including hostility and anger, but we will focus here on anxiety and depressed mood. Anxiety Studies of patients with pre-existing CHD show that anxiety, independently of conventional risk factors, can be predictive of recurrent acute CHD events.4 Moreover, prospective studies of anxiety in normal populations show that there is an association between anxiety assessed at enlistment and subsequent CHD mortality over many years, even when conventional risk factors are controlled for -- the relative risks are significant, being of the order of 5-6 for sudden death and 2-3 for fatal acute myocardial infarction (AMI).5 Impressive data also come from prospective studies of panic disorder, which show that CHD mortality risk may be doubled in people with the disorder.6,7 There has been strong supportive psychophysiological evidence -- for example, in patients with pre-existing CHD undergoing ventriculography and exposed to trivial experimental stressful tasks, a significant but transient reduction (of up to 50%) in coronary muscle perfusion can occur.2,8 At the other end of the evidence hierarchy are the clinical case reports of patients with panic disorder, found to be free of CHD at angiography, who have had an acute AMI or ongoing angina following panic attacks.9 It has furthermore been shown that patients with panic disorder, while lacking any demonstrable peripheral elevation in serum catecholamine levels, nonetheless have significant release of adrenaline from the coronary sinus during panic attacks.10 This may in turn adversely affect coronary perfusion, cardiac rhythm, shear forces on atheromatous plaques, and platelet function.11 States of severe emotional arousal can also affect underlying pathophysiological risk factors for CHD, including platelet function and haemostasis.12,13 Longer-term effects of anxiety on cardiovascular pathophysiology are also possible; it has been shown that subjects with an exaggerated blood pressure response to mental stress may experience more rapid progression of carotid atherosclerosis.14 Depressed mood Depressed mood is emerging as an important risk factor for CHD. Depressed mood in CHD patients is associated with increased mortality.15 The increased risk is not trivial (relative risk > 3), being of the same order as other risk factors such as prior AMI and impaired left ventricular function after infarction. Even in long-term studies of normal CHD-free populations, depression at enlistment doubles the risk of subsequent acute coronary events16 and increases mortality risk.17 States resembling depression, such as "vital exhaustion" (characterised by fatigue, irritability and demoralisation),18 have been shown to be associated with acute myocardial events in normal populations even when conventional risk factors are controlled. Unlike the more acute effects of anxiety, the effects of depression are not immediate. Indeed, in one prospective study, mortality rates in women with depression did not begin to increase until after 16 months of follow-up.19 Thus, depression may well have a prolonged mode of action on CHD risk. One study found that one component of depression (ie, hopelessness) was associated with more rapid progression of atherosclerosis.20 The CHD risk of a person with chronic depression or dysphoric mood, either as an induced state or an enduring trait of "depressive" personality, needs further study. Personality Recently the "type D ('distressed') personality" has been described by Denollet et al as a result of finding significant differences in CHD outcome in those with certain personality traits. The type D personality is identified by two components: the continual experience of negative emotions, including depression, and the inhibition of social expression of these emotions. In a sample of patients undergoing cardiac rehabilitation, deaths from cardiac causes were increased fourfold in those with type D personality even after controlling for conventional risk factors.21 This suggests that type D personality (whether as a biological construct of temperament or a constellation of habitual behaviours) is a risk factor at least equivalent in importance to the other, "conventional" coronary heart disease prognostic factors. Implications It is possible that the association between mood and CHD risk is not causal, but that the two are linked by some common underlying genetic factor, perhaps associated with vascular disease in general. Weighted against this interpretation are the experimental findings showing the effect of emotions on cardiovascular pathophysiology. To explore the possibility of covariance, prospective aetiological and interventional studies are necessary to examine both mood state (which is episodic) and the personality-based predisposition (trait) to depression. Intervention studies are now in progress to assess whether antidepressants may reduce CHD events in those with depression following AMI.22 In the meantime, in patients with pre-existing CHD or those at increased risk of CHD, the identification and treatment of mood disorders, including anxiety and depression, is important for improving quality of life and for reducing the risk of CHD events and mortality. Christopher C Tennant Professor, Department of Academic Psychiatry Loyola McLean Lilly Psychiatry Research Training Fellow Department of Academic Psychiatry Royal North Shore Hospital, St Leonards, NSW tennantATmed.usyd.edu.au Hemingway H, Marmot M. Evidence-based cardiology: psychosocial factors in the aetiology and prognosis of coronary heart disease. Systematic review of prospective cohort studies. BMJ 1999; 318: 1460-1467. Rozanski A, Blumenthal JA, Kaplan J. Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy. Circulation 1999; 99: 2192-2217. Tennant CC, Palmer KJ, Langeluddecke PM, et al. Life event stress and myocardial reinfarction: a prospective study. Eur Heart J 1994; 15: 472-478. Moser DK, Dracup K. Is anxiety early after myocardial infarction associated with subsequent ischemic and arrhythmic events? Psychosom Med 1996; 58: 395-401. Kawachi I, Gollditz G, Ascherio A, et al. Prospective study of phobic anxiety and risk of coronary heart disease in men. Circulation 1994; 89: 1992-1997. Coryell W, Noyes R, House JD. Mortality among outpatients with anxiety disorder. Am J Psychiatry 1986; 143: 508-510. Weissman MM, Markowitz JS, Ouellette R, et al. Panic disorder and cardiovascular/cerebrovascular problems: results from a community survey. Am J Psychiatry 1990; 147: 1504-1508. Tennant C. Experimental stress and cardiac function. J Psychosom Res 1996; 40(6): 569-583. Mansour VM, Wilkinson DJ, Jennings GL, et al. Panic disorder: coronary spasm as a basis for cardiac risk? Med J Aust 1998; 168: 390-392. Wilkinson DJ, Thompson JM, Lambert GW, et al. Sympathetic activity in patients with panic disorder at rest, under laboratory mental stress, and during panic attacks. Arch Gen Psychiatry 1998; 55: 511-520. Deedwania PC. Hemodynamic changes as triggers of cardiovascular events. Cardiol Clin 1996; 14: 229-238. Grignani G, Pacchiarini L, Zucchella M, et al. Effect of mental stress on platelet function in normal subjects and in patients with coronary artery disease. Haemostasis 1992; 22: 138-146. Malkoff SB, Muldoon MF, Zeigler ZR, Manuck SB. Blood platelet responsivity to acute mental stress. Psychosom Med 1993; 55: 477-482. Kamarck TW, Everson SA, Kaplan GA, et al. Exaggerated blood pressure responses during mental stress are associated with enhanced carotid atherosclerosis in middle-aged Finnish men: findings from the Kuopio Ischaemic Heart Disease Study. Circulation 1997; 96: 3842-3848. Frasure-Smith N, Lesperance F, Talajic M. Depression and 18-month prognosis after myocardial infarction. Circulation 1995; 91: 999-1005. Ford DE, Mead LA, Chang PP, et al. Depression is a risk factor for coronary artery diease in men: the precursors study. Arch Intern Med 1998; 158: 1422-1426. Simonsick EM, Wallace RB, Blazer DG, Berkman LF. Depressive symptomatology and hypertension-associated morbidity and mortality in older adults. Psychosom Med 1995; 57: 427-435. Appels A, Otten F. Exhaustion as precursor of cardiac death. Br J Clin Psychol 1992; 31: 351-356. Whooley MA, Browner WS. Association between depressive symptoms and mortality in older women. Arch Intern Med 1998; 158: 2129-2135. Everson SA, Kaplan GA, Goldberg DE, et al. Hopelessness and 4-year progression of carotid atherosclerosis. The Kuopio Ischaemic Heart Disease Risk Factor Study. Arterioscler Thromb Vasc Biol 1997; 17: 1490-1495. Denollet J, Stanislas US, Stroobant N, et al. Personality as independent predictor of long-term mortality in patients with coronary heart disease. Lancet 1996; 347: 417-421. Shapiro PA, Lesperance F, Frasure-Smith N, et al. An open-label preliminary trial of sertraline for treatment of major depression after acute myocardial infarction (the SADHAT Trial). Sertraline Anti-Depressant Heart Attack Trial. Am Heart J 1999; 137: 1100-1106. Make a comment

Christopher C Tennant · Loyola McLean

Editorial Defibrillation for out-of-hospital cardiac arrest Strengthening that most important link in the "chain of survival" MJA 2000; 172: 53-54 Cardiac arrest outside hospital is a common mode of unexpected death in our society. The arrest is usually caused by coronary artery disease, and indeed may be its first manifestation, occurring in apparently fit and well individuals. The causative arrhythmia is usually ventricular fibrillation, but by the time help arrives and the rhythm is recorded it has often degenerated into asystole. In this issue of the Journal, Meyer et al1 present a detailed medical perspective of this problem, and outline the steps we need to take to improve the survival rate for victims of out-of-hospital cardiac arrest, particularly the "chain of survival" -- the critical links in the resuscitation process. When a cardiac arrest is witnessed, the first priority is defibrillation, but in most situations cardiopulmonary resuscitation (CPR) needs be undertaken before defibrillation. The spectacular success of implantable defibrillators in terminating lethal arrhythmias2 in patients known to be at extreme risk of ventricular fibrillation raised the possibility that the same sensing technology and defibrillator waveforms might be incorporated into an external defibrillator, without the need for rhythm interpretation by a medical or paramedical attendant. Such devices were introduced over 10 years ago, and have been widely implemented, with results for successful defibrillation by junior ambulance officers that were as good as those of paramedics.3 By 1990, the New South Wales Ambulance Service had introduced semiautomatic defibrillators into all its frontline ambulances (ie, those not used for routine transport) to complement the care given by paramedics with manual defibrillators. Similar systems have since been initiated in other Australian States. By 1991, the concept of public access defibrillation (PAD) was re-emerging. This idea was first conceived by the pioneer of prehospital coronary care, Frank Pantridge of Belfast,4 who developed a small but primitive defibrillator in the late 1960s which could be installed next to every fire extinguisher and used in the same way, simply and easily, and by whoever was closest. Pantridge asked the question "Is property more important than life?". With the re-emergence of this concept within the American Heart Association, the aim was to have semiautomatic defibrillators so widely available, and sufficient members of the public trained, that a person who suffered a cardiac arrest in a public place might have the benefit of a defibrillator before the arrival of an ambulance and when the chance of a successful outcome may be well over, rather than well under, 50%.5 Semiautomatic defibrillators are now deployed in what may seem to be the most unlikely places,5 and Australia has played a leading role. They were first installed in the QANTAS International fleet and in Australian airports during 1991.6 The long-term survival rate for people treated on the ground or in the air by QANTAS International staff is 32%,7 now exceeded by the seven of 14 (50%) for people treated by American Airlines staff over the past 18 months.8 Defibrillators are deployed widely in Chicago's O'Hare Airport and are available for public access. Deployment of public access defibrillators in airports is becoming commonplace, and Sydney's international and domestic terminals will be equipped with a system similar to Chicago's within months. Installation in airliners is becoming the industry standard throughout the world,8 with programs completed or under way for most major international and domestic airlines (including QANTAS and Ansett Domestic). Use in airports and airliners has followed awareness of the fact that deaths from cardiac arrest in the air are far more common than deaths from aircraft crashes,7,8 while deaths in terminals of people undergoing unaccustomed exercise are more common than at other locations9 (except at sporting venues, where deaths in older spectators are common). Survival rates of 70% have been reported from the Melbourne Cricket Ground10 and in Las Vegas casinos:11 in both situations remote monitoring of crowd activity enables quick recognition, which, together with appropriate placement of personnel and devices, ensures a prompt response. Deployment of defibrillators in police cars, complementing the ambulance service in the environs of the Mayo Clinic, has increased community survival after cardiac arrest in Rochester, Minnesota, to near 50%.12 St John Ambulance, as the leading teacher of community resuscitation and first aid in Australia, has endorsed training in defibrillation with CPR, and is embarking on an ambitious program, through its training and operational arms, to make public access defibrillation widely available throughout the nation. Such a program must mesh with the existing professional ambulance service, and complement this by strengthening that most important earliest link in the "chain of survival" -- the prompt reversal of ventricular fibrillation by whoever can do so first, and fastest. In strife-torn Belfast, Pantridge's idea lapsed because no system was available at the time for automatic recognition of ventricular defibrillation, so the device had to be used in the manual mode, and could have been used as a weapon. The introduction of safe semiautomatic defibrillators which will only operate in the presence of ventricular fibrillation has changed this situation. A satisfactory answer can now be given to Pantridge's question. As peace emerges in Ulster, the concept proposed by Pantridge and Geddes4 has taken firm root throughout the whole world. Michael F O'Rourke Professor of Medicine University of New South Wales and St Vincent's Hospital and Clinic, Sydney, NSW Meyer ADMcR, Cameron PA, Smith KL, McNeil JJ. Out-of-hospital cardiac arrest. Med J Aust 2000; 172: 73-76. Moss AJ, Hall WJ, Cannon DS, et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. N Engl J Med 1996; 335: 1933-1940. O'Rourke MF, Hall J. Pre-hospital cardiac arrest in New South Wales (1992). Aust N Z J Med 1994; 24: 619. Geddes JS, editor. The management of the acute coronary attack: the J Frank Pantridge Festschrift. London: Academic Press, 1986. Nichol G, Hallstrom AP, Kerber R, et al. American Heart Association Report on the Second Public Access Defibrillation Conference, April 17-19, 1997. Circulation 1998; 97: 1309-1314. Donaldson E, O'Rourke MF. Defibrillators on QANTAS aircraft. Med J Aust 1992; 156: 293. O'Rourke MF, Donaldson E, Geddes JS. An airline cardiac arrest program. Circulation 1997; 96: 2849-2853. Crewdson J. Code blue: survival in the sky. Chicago Tribune Aug 1, 1999: C1-C3. Becker L, Eisenberg M, Fahrenbruch C, Cobb L. Public locations of cardiac arrest: implication for public access defibrillation. Circulation 1998; 97: 2106-2109. Wassertheil J, Keane G, Fisher N, Leditschke JF. Cardiac arrest outcomes at the Melbourne Cricket Ground and Shrine of Remembrance using a tiered response strategy -- a forerunner to Public Access Defibrillation. Resuscitation 2000. In press. Valenzuela TD, Bjerke HS, Clark LL, et al. Rapid defibrillation by non-traditional responders. The Casino project. Acad Emerg Med 1998; 5: 414-415. White RD, Hankins DG, Bugliosi TF. Seven years' experience with early defibrillation by police and paramedics in an emergency medical services system. Resuscitation 1998; 30: 145-151. Make a comment

Michael F O'Rourke

Clinical Update Out-of-hospital cardiac arrest Out-of-hospital cardiac arrest (OHCA), with its high fatality rate, is a significant public health issue. The aetiology of OHCA is reviewed, and management strategies are discussed, including the "chain of survival", the Utstein method of data collection, and recent developments in advanced cardiac life support emphasising defibrillation. Alastair D McR Meyer, Peter A Cameron, Karen L Smith and John J McNeil MJA 2000; 172: 73-76 Background - Recent advances in management of OHCA - Improving survival rates after OHCA in Australia - References - Authors' details - - More articles on Emergency medicine Out-of-hospital cardiac arrest (OHCA) is a leading cause of death in First World countries. The estimated incidence in the United States is about 1/1000 population per year (15%-20% of all deaths).1 Current Australian data based on ambulance attendances in metropolitan Melbourne suggest that about 2000 lives are lost from OHCA per year.2OHCA is often the first presentation of ischaemic heart disease. If victims of OHCA can receive immediate and appropriate treatment, they have a 30%-70% chance of survival.3 There is a paucity of data on survival from OHCA in Australia (Box 1). The Melbourne report of cardiac arrest victims mentioned above, which included all patients with arrhythmia of presumed cardiac cause, suggests that the survival rate may be as low as 3%.2 The management of OHCA is presently the only area of pre-hospital emergency care where there is clear evidence that appropriate intervention leads to improved survival.10 We present a clinical update on the management of OHCA. Background The usual cause of sudden cardiac death is coronary artery disease, which accounts for up to 90% of all victims;11 most have major pathological changes in two or more coronary arteries.11An arrhythmia is the most common cause of cardiac arrest, with ventricular fibrillation (VF) being more common12,13 than asystole, pulseless ventricular tachycardia (VT) and other arrhythmias. VF generally has a better prognosis than the other arrhythmias.12,13 Ischaemia, electrolyte imbalance, stress, and neurochemical transmitters (eg, adrenaline, noradrenaline), as well as clotting disorders (eg, massive pulmonary emboli), may trigger arrhythmia.12 VF rarely reverts spontaneously, and the definitive treatment is defibrillation.10 Hypoxic brain injury occurs at four minutes, and death will occur within 12 minutes if no therapy is offered.3,10 It has been predicted that with ideal pre-hospital care, survival rates would be of the order of 70%.3 Recent advances in management of OHCA The "chain of survival" Successful resuscitation of victims of OHCA depends on each individual's unique features (eg, prior medical condition, cardiac rhythm associated with the collapse, collapse witnessed or not witnessed), and the system in the community to deal with such problems. The system must provide a "chain of survival". This concept, initially described by Cummins et al in 1991, and adopted by the American Heart Association, focuses attention on four critical links in the resuscitation process of a victim of OHCA:14 Early recognition and access to emergency medical services Early cardiopulmonary resuscitation Early defibrillation Early advanced cardiac life support. Communities with integrated links along this chain have higher survival rates after OHCA than those with deficiencies in these links.15 Analysing emergency medical services (EMS) in different countries has been difficult, but, in 1990, an international Consensus Conference established uniform terms and definitions for out-of-hospital resuscitation.15 The Consensus Conference recommended that a template approach, the Utstein template, be used for reporting data from out-of-hospital resuscitations.16 This allows comparison and benchmarking between EMS in different countries (Box 2). Early access Recognition of cardiac arrest is often difficult, as it may be confused with fitting or fainting. Cardiac arrest is assumed in an unconscious patient who has no palpable pulse. Spontaneous breathing and pupil size are irrelevant to the diagnosis. Early access to EMS in Australia needs improvement. Two studies of OHCA found that bystanders do not know who to call and have trouble describing the victim.2,5 Education and training programs have been used to raise community awareness and response to OHCA. The "Phone first" campaign in rural Iowa (USA) decreased access times by over a minute. This simple campaign emphasised the need for citizens witnessing a collapse to call the EMS without delay.17 Early cardiopulmonary resuscitation (CPR) The available evidence shows that the earlier patients receive CPR, the greater their chance of survival.18-20For resuscitative efforts to be effective, the patient must be supine, and on a flat, firm surface. Chest compressions are performed in the lower part of the sternum, 4-6 cm in depth and at a rate of 80-100 compressions per minute. During cardiac arrest, properly performed chest compressions can produce systolic blood pressure peaks of 60-80 mmHg. Cardiac output is only 25%-30% of normal.21 Bystander CPR is seldom practised in Australia. Despite there being witnesses to 54% of OHCAs presenting as VF in the Melbourne report, only 22% received bystander CPR and it was often of questionable quality.2 Family members who witness their own relative's OHCA are less likely to perform CPR than a stranger who happens by a victim of OHCA in the street.22,23 Early defibrillation Defibrillation is the definitive treatment for VF.24 The chance of success deteriorates with each minute.3 Such is the importance of defibrillation that Wei and Tang have suggested the appropriate sequence to follow in resuscitation from cardiac arrest is D (defibrillation), C (circulation), B (breathing) and A (airway), rather than the more familiar ABC.25New technology has allowed defibrillators to become more user friendly. Automated external defibrillators (AEDs) can analyse patients' electrical rhythm and can proceed to deliver pre-programmed shocks without further decisions by the rescuer. These machines are simple to operate and are ideal for use by unskilled first responders. This technology is suitable for health clinics and general practitioners' surgeries.26 Members of the public may soon have access to such devices. In the United States, they have been deployed in public buildings, sporting venues and are carried by police. They have also been successfully used by family members of patients known to be at high risk of OHCA.26 New developments in the defibrillating shock may increase the efficacy and safety of defibrillation.26,27 Kerber et al have described a dual-pulse defibrillating shock.27 Different energy waveforms during defibrillation have been described by Bardy et al.28 A damped sinusoidal pattern is most often used for traditional transthoracic defibrillation. These authors have shown that during transthoracic defibrillation, a biphasic shock at 130 J is as effective as a (traditional) monophasic shock at 200 J. The shock also produces less myocardial injury and is potentially safer for bystander use.28 Current-based defibrillation is another promising alternative to traditional energy-based defibrillation. Current-based defibrillation requires the operator to select the electrical dose (amperes) rather than the energy (joules). In this way, delivery of low energy in the face of high transthoracic impedance is avoided. The defibrillator measures the transthoracic impedance, then delivers the exact current requested.26 Early advanced cardiac life support (ACLS) ACLS has traditionally been described as having three interventions: defibrillation, endotracheal intubation and intravenous medications. Defibrillation now stands alone as the single most vital intervention of resuscitation from OHCA, and must be delivered as early as possible. Consequently, it is now rightly the responsibility of primary responders. Endotracheal intubation Endotracheal intubation isolates the airway, keeps it patent, permits tracheal toileting, ensures delivery of a high concentration of oxygen and provides a route for administration of certain drugs. However, no randomised controlled studies have yet been published that demonstrate a significant survival difference with this intervention when compared with basic airway management.18 Intravenous medications Intravenous medications can be administered by a variety of routes (eg, central vein, peripheral vein). The ideal route for administering drugs to a patient in cardiac arrest is one which delivers the drug to the target organ, is simple and rapid to perform with minimal expertise, and has minimal complications. At present, no single route has all of these features.29 A large antecubital fossa vein is recommended for the initial intravenous access. Intravenous medications are discussed in Box 3. Improving survival rates after OHCA in Australia To improve the chance of surviving an OHCA in Australia, data must be collected according to the Utstein template. From this, all aspects of the "chain of survival" can be clearly studied and benchmarked, and developments such as public education programs and public access defibrillators can then be implemented and accurately evaluated (Box 4). Future modification of ACLS management protocols should only be made on the basis of controlled studies. References Becker LB, Smith DW, Rhodes KV. Incidence of cardiac arrest: a neglected factor in evaluating survival rates. Ann Emerg Med 1993; 22: 86-91. Bernard S. Outcome from prehospital cardiac arrest in Melbourne, Australia. Emerg Med 1998; 10: 25-29. Larson MP, Eisenberg MS, Cummins RO, et al. Predicting survival from out-of-hospital cardiac arrest. Ann Emerg Med 1993; 22: 1652-1658. Bett JHN. Experience with a mobile coronary care unit in Brisbane. Ann Emerg Med 1989; 18: 969-974. Jacobs IG, Oxer HF. A review of pre-hospital defibrillation by ambulance officers in Perth, Western Australia. Med J Aust 1990; 153: 662-664. Scott IA, Fitzgerald GJ. Early defibrillation in out-of-hospital sudden cardiac death: an Australian experience. Arch Emerg Med 1992; 10: 1-7. Brennan RJ, Luke C. Failed hospital resuscitation following out-of-hospital cardiac arrest: are further efforts in the emergency department warranted? Emerg Med 1995; 7: 131-138. Jackson T, Cameron PA. Prehospital defibrillation in Geelong. Emerg Med 1993; 5: 184-187. Sammel NL, Taylor K, Selig M, O'Rourke M. New South Wales intensive care ambulance system: outcome of patients with ventricular fibrillation. Med J Aust 1981; 2: 546-550. American Heart Association. Emergency Cardiac Care Committee and Subcommittees. Guidelines for cardiopulmonary resuscitation and emergency care. JAMA 1992; 268: 2171. Reichenbach DD, Moss NS, Meyer E. Pathology of the heart in sudden cardiac death. Am J Cardiol 1977; 39: 865. Eisenberg MS, Horwood BT, Cummins RO, et al. Cardiac arrest and resuscitation: a tale of 29 cities. Ann Emerg Med 1990; 19: 179-186. Eisenberg MS. Prehospital care. In: Skinner D, Swain A, Peyton R, Robertson C, editors. Cambridge textbook of accident and emergency medicine. Cambridge: Cambridge University Press, 1997: 288-298. Cummins RO, Ornato JP, Theis W, et al. Improving survival from cardiac arrest: the chain of survival concept. Circulation 1991; 83: 1832-1847. Cummins RO and Graves. Prehospital care II: European and American perspectives. In: Skinner D, Swain A, Peyton R, Robertson C, editors. Cambridge textbook of accident and emergency medicine. Cambridge University Press, 1977: 298-303. AHA Medical/Scientific Statement. Recommended Guidelines for Uniform Reporting of Data from Out-of-Hospital Cardiac Arrest: The Utstein Style. Circulation 1991; 84: 960-975. Montgomery WH, Brown DD, Hazinski MF, et al. Citizen response to cardiopulmonary emergencies. Ann Emerg Med 1993; 22: 428-434. Maguire JE. Advances in cardiac life support: sorting the science from the dogma. Emerg Med 1997; 9 Suppl: 1-8. Callahan M, Madsen CD. Relationship of timeliness of paramedic Advanced Life Support interventions to outcome in out-of hospital cardiac arrest treated by first responders with defibrillators. Ann Emerg Med 1996; 27: 638-648. Weaver WD, Cobb LA, Hallstrom AP, et al. Considerations for improving survival from out-of-hospital cardiac arrest. Ann Emerg Med 1986; 10: 1181-1186. Varon J, Marik PE, Fromm RE Jr. Cardiopulmonary resuscitation: a review for clinicians. Resuscitation 1998; 36: 133-145. De Vreede-Swagamakers JJ, Gorgels AP, Dubois-Arbouw WI, et al. Out of hospital cardiac arrest in the 1990s: a population-based study in the Maastricht area on incidence, characteristics and survival. J Am Coll Cardiol 1997; 30: 1500-1505. Jackson RE, Swor RA. Who gets bystander cardiopulmonary resuscitation in a witnessed arrest? Acad Emerg Med 1997; 4: 540-544. Pantridge JF, Geddes JS. A mobile intensive care unit in the management of myocardial infarction. Lancet 1967; 2: 271-273. Wei MH, Tang W. Science challenges the dogma of ACLS [editorial]. Chest 1996; 109: 597-598. Robertson CE, Nichol NM. Recent advances in defibrillation therapy. Curr Opin Crit Care 1997; 3: 214-217. Kerber RE, Spencer KT, Kallok MJ, et al. Overlapping sequential pulses: a new wave form for transthoracic defibrillation. Circulation 1994; 89: 2369-2379. Bardy GH, Marchlinski FE, Sharma AD, et al. Multicentre comparison of truncated biphasic shocks and standard damped sinewave monophasic shocks for transthoracic ventricular defibrillation. Circulation 1996; 94: 2508-2514. ALS Working Party of the ERC. Guidelines for advanced life support. Resuscitation 1992; 22: 191-195. Hapnes SA, Robertson CE. CPR-drug delivery routes and systems. Resuscitation 1992; 24: 137-142. Linder KH, Koster R. Vasopressor drugs during cardiopulmonary resuscitation. Resuscitation 1992; 24: 147-154. Stiell IG, Herbert PC, Weitzman BN, et al. High grade epinephrine in adult cardiac arrest. N Engl J Med 1992; 327: 1045-1049. Brown CG, Martin DR, Pepe PE, et al. A comparison of standard dose and high dose epinephrine in cardiac arrest outside hospital. N Engl J Med 1992; 327: 1051-1055. Callahan M, Madsen CD, Barton CW, et al. A randomised clinical trial of high dose epinephrine and norepinephrine and standard dose epinephrine in prehospital cardiac arrest. JAMA 1992; 268: 2667-2672. Woodhouse SP, Case C, Cox S, et al. Trial of large dose adrenaline vs placebo in cardiac arrest [abstract]. Resuscitation 1993; 25: 89. Woodhouse SP, Cox S, Boyd P, et al. High dose and standard dose adrenaline do not alter survival compared with placebo in cardiac arrest. Resuscitation 1995; 30: 243-249. Linder KH, Dirks B, Strohmenger HU, et al. Randomised comparison of epinephrine and vasopressin in patients with out-of-hospital ventricular fibrillation. Lancet 1997; 349: 535-537. Stahmer SA, Varon J, Fromm RE. Controversies in cardiopulmonary resuscitation pharmacotherapy. Hosp Physician 1994; 30: 23-30. Steedman DJ, Robertson CE. Acid-base changes in arterial and central venous blood during cardiopulmonary resuscitation. Arch Emerg Med 1990; 9: 169-176. Steuven HA, Thomson BM, Aprahamian C, et al. Calcium chloride: reassessment of use in asystole. Ann Emerg Med 1984; 13: 820-822. Authors' details Emergency Department, Royal Melbourne Hospital, Melbourne, VIC. Alastair D McR Meyer, BSc(Hons), MB BS, FACEM, Research Fellow in Emergency Medicine; and PhD Scholar, Department of Epidemiology and Preventive Medicine, Monash University. Peter A Cameron, MD, FACEM, Director of Emergency Medicine. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC. Karen L Smith, BSc(Hons), GradDipEpiBiostats, PhD Scholar. John J McNeil, PhD, FRACP, Professor; and Head of Department. Reprints will not be available from the authors. Correspondence: Dr A D McR Meyer, Research Fellow in Emergency Medicine, Emergency Department, Royal Melbourne Hospital, Grattan Street, Parkville, VIC 3050. Make a comment 1: Survival from out-of-hospital cardiac arrest - Australian studies StudyPatients/presenting rhythmSurvival (%) to dischargeBett (1989)4 Ventricular fibrillation110 (9%)Jacobs and Oxer (1990)5Ventricular fibrillation231 (22%)*Scott and Fitzgerald (1992)6All patients with OHCA103 (17%)Brennan and Luke (1995)7All patients with presumed cardiac arrest, arriving at hospital274 (5%)Bernard (1998)2All OHCA victims, presumed cardiac cause, all rhythms 361 (3%)Jackson and Cameron (1993)8Ventricular fibrillation/pulseless ventricular tachycardia79 (18%)Sammel et al (1981)9Ventricular fibrillation/pulseless ventricular tachycardia434 (21%)*28 days after discharge. OHCA=Out-of-hospital cardiac arrest. Back to text 2: The Utstein Consensus Conference Two meetings in 1990 with representatives from the American Heart Association, the European Resuscitation Council, the Heart and Stroke Foundation of Canada, and the Australian Resuscitation Council: Established uniform terms and definitions for out-of-hospital resuscitation; Established a reporting template for resuscitation studies to ensure comparability; Defined time points and time intervals relating to cardiac resuscitation; Defined clinical items and outcomes that the emergency medical service should gather; and Developed guidelines for describing resuscitation systems. Back to text 3: Intravenous medications in early advanced cardiac life support Adrenaline Catecholamines, such as adrenaline and noradrenaline, are vasopressors and have long been used as adjuncts to improve the success rate in CPR. These catecholamines increase aortic diastolic pressure by producing arteriolar vasoconstriction and improve blood delivery to the central circulation. If exogenous catecholamines are administered, improved myocardial and cerebral perfusion occurs. The optimal dose range for humans in both the prehospital and hospital stage remains unclear.30 Three large North American multicentre trials have failed to show any benefit from the administration of high-dose adrenaline or noradrenaline in the prehospital or inhospital setting.31-33 The recommended dose is 1mg intravenously repeated at 2-3-minute intervals.34 There is evidence, however, that the use of adrenaline may make absolutely no difference to the outcome of VF cardiac arrest.35,36 Vasopressin There are encouraging results with the use of vasopressin in OHCA.37 In cardiac arrest of long duration, vasopressin seems to have greater efficacy in restoring spontaneous cardiovascular function compared with adrenaline alone.37 More evidence is required before this drug can be recommended. Antiarrhythmics There are many agents which have antiarrhythmic properties in patients with a cardiac output. However, the overwhelming evidence is that antiarrhythmic drug therapy has very little, if any, role to play in the treatment of OHCA.38 Acidaemia When cardiac arrest occurs, anaerobic metabolism occurs in tissues and this results in the production of large amounts of lactic and other organic acids. Good quality CPR and adequate alveolar ventilation limits the development of acidaemia.39 Significant falls in arterial pH do not occur for the first 20 minutes after cardiac arrest. Correction of the acidosis through measures other than ventilation and restoration of circulation has not been shown to improve outcome.38 Calcium Calcium ions play a role in myocardial contractility. A deficiency of calcium is associated with cardiac arrest. However, there is no benefit for the use of calcium in patients with asystole or VF.40 There may be some use for this agent in specific situations of pulseless electrical activity secondary to hyperkalaemia, calcium channel blocker overdose, or hypocalcaemia.40 Back to text 4: Strategies to improve survival from out-of-hospital cardiac arrest in Australia Improved education of the public and healthcare providers in recognising cardiac arrest and accessing emergency medical services (EMS) Improved training of laypersons in cardiopulmonary resuscitation Increased deployment of automatic external defibrillators Public access defibrillation Improved ambulance response times Improved data collection by the EMS throughout Australia Improved communication between units researching pre-hospital resuscitation An evidence-based approach to allocating resources for pre-hospital early advanced cardiac life support protocols Back to text

Peter A Cameron · Karen L Smith · John J McNeil

The Weight Debate The sources of risk factor information for general practitioners: is physical activity under-recognised? Fiona Dupen, Adrian E Bauman and Rose Lin MJA 1999; 171: 601-603 For editorial comment, see Caterson Abstract - Introduction - Methods - Results - Discussion - Acknowledgement - References - Authors' details - - More articles on General practice and primary care

Fiona Dupen · Adrian E Bauman · Rose Lin

Editorial Erectile dysfunction in the Australian community This problem is both increasingly recognised and increasing in prevalence with the ageing of our population MJA 1999; 171: 342-343 Erectile dysfunction (ED) is the persistent inability to achieve and/or maintain an erection sufficient for satisfactory sexual activity.1 Worldwide, 100 million men are estimated to have some degree of ED, with around 30 million men in the United States1 and around one million men in Australia affected. With our ageing, but relatively fit, population the incidence of ED is certain to escalate. The first major community-based study on ED was the Massachusetts Male Aging Study (MMAS),2 an observational study (conducted from 1987 to 1989) of a random sample of men aged between 40-70 years living in and around Boston, Massachusetts. This study yielded, for the first time, an understandable concept of ED; comparable studies in Australia have been singularly lacking. The first report on the prevalence of ED in our community was a study by Chew et al from the Keogh Institute for Medical Research in Perth3 (formerly the Reproductive Medicine Research Institute). The generalisability of this 1996 study was limited as it only included men who presented to general practices in Perth. The South Australian community study by Pinnock and colleagues in this issue of the Journal,4 which recruited men from the general community through a 1997 household survey, provides data that are, firstly, drawn from a more general community sample than the one in the Perth study, and secondly, more suited to our own demographic situation than data from overseas surveys. The South Australian study confirms that age is the strongest contributing demographic factor to ED, with 60 years of age being the turning point where desire exceeds potency and sexual frequency diminishes.4 The MMAS found that 52% of men aged between 40 and 70 years had some form of ED, with almost 60% of 60-year-old men having this complaint.2 Both studies found that sexual function was also affected by risk factors such as smoking, hypertension, obesity and a high total cholesterol level with a low concentration of high density lipoprotein. Vigorous exercise was found to be protective. The Perth study also found diabetes mellitus (types 1 and 2) to be significant contributors to ED. It should be noted that Pinnock et al used a questionnaire based on the UCLA Prostate Cancer Index that covered sexual function parameters including desire and orgasm, frequency of intercourse, prostate surgery and erectile function. As this index has not been validated in patients who do not have prostate cancer, its use in a randomly based population study represents a methodological flaw. A more appropriate questionnaire for this study would have been the better-known International Index of Erectile Function (IIEF),5 a 15-question survey that includes similar parameters, assesses intercourse and overall satisfaction, but excludes questions related to prostate cancer. The higher incidence of ED reported in the South Australian study4 compared with the MMAS2 probably reflects improvements in public awareness and keenness to discuss and report ED over the past 10 years. The study by Pinnock et al4 clearly shows that cardiovascular disease and ED have similar risk factors and present in a similar age group. Thus, it seems possible that, by improving their risk factor profile, men may benefit both their cardiovascular health and their sexual function. Pinnock et al also suggest non-cancer prostate surgery appears a more important contributor to ED than previously recognised. Erectile dysfunction is clearly an established and recognised male health problem -- one that is decreasingly being regarded as an inevitable consequence of ageing. The estimated 10% of men currently seeking help will increase, as more men will seek help in the future. Doctors will need to improve their skills in obtaining patients' sexual histories as more men request help. A full assessment of men, with emphasis on cardiovascular risk factors, will help direct the consultation to discussion of sexual matters -- it makes good sense to combine cardiac and sexual issues. Sildenafil is the first effective oral medication for ED, and its arrival on the market was well timed with the increasing interest in ED and the increasing numbers of men wanting a simpler treatment. Initial media interest over coital deaths associated with sildenafil has abated, and the drug is now accepted as a safe treatment when prescribed within the recommended guidelines. These guidelines advise caution when prescribing sildenafil to male cardiac patients who may not be fit enough to engage in sexual activity. Sildenafil is also absolutely contraindicated in men receiving nitrate therapy and those who use amyl nitrite "poppers". When sildenafil is contraindicated or fails to achieve the desired result, the use of injectable vasoactive agents is appropriate. Penile injection therapy is still considered the "gold standard", having been used for over 10 years. Alprostadil is the only approved injectable prostaglandin medication available on the Pharmaceutical Benefits Scheme. Alprostadil is also available as an intra-urethral pellet. Vacuum erection devices have been available for over 20 years and are still an acceptable choice for some men. Penile prostheses may be used in more difficult cases. The Australian community-based studies on male sexual function show a pattern similar to that in overseas studies, and highlights two important points in this era of increasing demand for treatment for ED: Doctors need to understand "normal" sexual function for men at different age groups, as knowing the effects of ageing on sexuality is important when counselling patients and advising on treatment; and Knowing that an apparently healthy patient presenting with ED may have underlying cardiovascular disease can advantage the patient's health outcome, and conversely, reducing a patient's cardiovascular risk factors may benefit both cardiovascular health and sexual function; the implications for sexual function may add weight to the arguments against obesity, smoking and excessive alcohol intake. Michael P Lowy Sexual Health Physician Australian Centre for Sexual Health St Luke's Hospital Complex, Sydney, NSW NIH Consensus Conference. Impotence. NIH Consensus Development Panel on Impotence. JAMA 1993; 270: 83-88. Feldman HA, Goldstein I, Hatzichristou DG, et al. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 1994; 151: 54-61. Chew KK, Earle CM, Stuckey BGA, et al. Erectile dysfunction in general medical practice. A study in Perth, Australia. Int J Impotence Res 1997; 9 (Suppl 1): A17. Pinnock CB, Stapleton AMF, Marshall VR. Erectile dysfunction in the community: a prevalence study. Med J Aust 1999; 171: 353-357. Rosen RC, Riley A, Wagner G, et al. The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction. J Urol 1997; 49: 822-830.

Michael P Lowy

Research Erectile dysfunction in the community: a prevalence study Carole B Pinnock, Alan M F Stapleton and Villis R Marshall MJA 1999; 171: 353-357 For editorial comment see Lowy Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Urology Abstract Objective: To investigate the prevalence of erectile dysfunction (ED) in the South Australian community, and the influence of demographic and other risk factors. Design: Survey by mailed questionnaire (based on the University of California, Los Angeles prostate cancer index) of a subset (men who agreed to participate) of a probability sample of the South Australian community who completed a multiuser interview survey. Participants and setting: Men over the age of 40 in South Australia. Main outcome measures: Sexual desire, orgasm, ability to have an erection, adequacy (firmness) of erections for intercourse, frequency of erections when wanted, frequency of intercourse, nocturnal or morning erections, and history of prostate surgery; total sexual function score based on these. Results: 612 men (86.7%) agreed to answer the sexual function survey; 427 (69.8%) returned questionnaires. ED was strongly correlated with age in all seven domains of sexual function. Erections inadequate for intercourse affected 3% of 40-49-year-olds, increasing to 64% of 70-79-year-olds. The frequency of intercourse considered normal for age by men 50-69 years was 1-6 times weekly; the disparity between this and reported frequency increased in men over 60 years, as did the difference between sexual desire and potency. A history of vigorous exercise was protective across all ages. High triglyceride levels, blood pressure medication and non-cancer surgery for prostate disease were independent predictors of poor sexual function at older ages. High cholesterol level was an independent predictor of impotence. Conclusions: We found similar or higher levels of ED than in comparable overseas studies. Disparity between potency and desire was greatest, and hence the age group in whom demand for treatment may be highest, in those 60 years and older. Cardiovascular risk factors were predictors of ED in these older men, suggesting that prevention may benefit sexual function. Non-cancer prostate surgery may be a greater contributor to ED than previously realised. Introduction Establishing the prevalence of erectile dysfunction (ED) in the community is difficult,1 but important for understanding the need for services, establishing functional expectations of men as they age and for determining the influence of demographic and preventable risk factors. An understanding of community prevalence of ED is useful when evaluating treatments for prostate disease which carry high risks of ED. Community prevalence has been examined in international, but not Australian, studies.1-4 One Australian study of ED prevalence in a Perth general practice population has been reported in conference proceedings.5 We undertook this study to establish the prevalence of erectile dysfunction among Australian men, and to investigate the influence of risk factors. Methods Questions were included in the spring 1997 Omnibus survey, a multiple-user household interview survey which provides a representative sample of the South Australian population. We have reported the methods of and results from this annual survey previously.6-8 The Omnibus survey included questions about age, educational attainment, marital status, household income, area of residence, blood pressure group (low, normal, borderline, high), cholesterol group (low, normal, high), alcohol intake by frequency (days per week) and volume (standard drinks per day when drinking), doctor's report of high triglyceride levels, body mass index (BMI), whether vigorous exercise was undertaken in the past two weeks, current and previous smoking status, and number of cigarettes per day usually smoked. Also included were questions about the presence of lower urinary tract symptoms (LUTS) such as nocturia, frequency, urgency, and a visit to a doctor for LUTS, as reported previously.6 In addition, men aged 40 years and over were asked if they would be prepared to answer a further, mailed questionnaire on urological issues. This comprised an introductory letter explaining the purpose of the survey,7 questions on sexual function and one on history of prostate surgery. To provide an indication of men's expectations of intercourse frequency across age groups, the first question asked what frequency of intercourse the respondent considered normal for a man of his age. Respondents were then offered the opportunity to return the questionnaire without answering further questions if they considered these too intrusive. Sexual function questions were derived from the UCLA (University of California, Los Angeles) prostate cancer index developed by Litwin et al.9,10 These applied to the previous three months and covered seven domains: (i) sexual desire, (ii) orgasm, (iii) ability to have an erection, (iv) frequency of erections when wanted, (v) frequency of intercourse, (vi) frequency of morning or nocturnal erections, and (vii) firmness of erections. The first six of these had five response options ("nil", "poor", "fair", "good", "very good" for domains i-iii; "never had an erection when I wanted one", "less than half the time when I wanted one", "about half the time I wanted one", "whenever I wanted one" for domain iv; "once or more daily", "1-6 times weekly", "1-3 times monthly", "less than once a month", "not at all" for domain v; "never", "seldom [less than a quarter of the time]", "not often [less than half the time]", "often [more than half the time]", "very often [more than 75% of the time]" for domain vi), while the seventh had four ("no erections at all", "not firm enough for any sexual activity", "firm enough for masturbation and foreplay only", "firm enough for intercourse"). Additional questions involved history of prostate surgery (for cancer and for non-cancerous conditions). Ethical consideration for the study was by Repatriation General Hospital's Research Ethics Committee. Analysis We defined sexual dysfunction as a response of one of the two lowest response categories (eg, "nil" or "poor") in each of the first six domains. Confidence intervals were adjusted for a design effect of 1.1 to allow for clustering.11 Dysfunction in the seventh domain (firmness of erections) was termed "impotence", defined as "usual quality of erections during the past three months not firm enough for intercourse" (corresponds with National Institutes of Health definition)12 -- one of the three lowest response options for this domain. A total erectile function score was derived by adding scores for each of the seven domains. The resulting score out of a possible 34 was expressed as a percentage; a score of 0 indicated worst possible function and 100% indicated best possible function in all domains. The reliability coefficient (Cronbach's alpha) of this seven-item score was 0.940. The association of demographic and cardiovascular risk factors with total sexual function (expressed as a continuous variable) and with impotence (a dichotomous variable) was examined after allowing for the effects of age by means of analysis of variance and logistic regression. For analysis, data were weighted by household size, age, sex and geographic region to benchmarks derived from the resident South Australian population in August 1996. We used SPSS for Windows13 for statistical analysis. Results The numbers and age breakdown of respondents are shown in Box 1. The mean age of respondents was 57.5 years (standard error, 0.58). Of the 745 men aged 40 years and over who responded to the Omnibus survey (representing a response rate of 70.8%), 612 (82.1%) agreed to complete a further, mailed questionnaire on urological issues. These questionnaires were returned by 427 respondents (69.8%), 371 (86.9%) of whom agreed to answer the full questionnaire. Box 1 shows that the age distribution was the same in all of these groups. We weighted further analyses to reflect the age distribution in the South Australian community; marginal totals thus do not correspond to the totals in Box 1. A comparison of respondents who agreed to answer the sexual function questions with those who did not agree to a further survey, did not respond to the mailed form or did not agree to answer the sexual function questions showed no significant differences in age, marital status, blood pressure, cholesterol and triglyceride levels, blood pressure medication or visit to a doctor for LUTS. Men who answered the sexual function questions were more likely to report vigorous exercise in the past two weeks (25.0% v 15.4%; P = 0.001), and more likely to drink alcohol five or more times per week (34.2% v 25.3%; P = 0.026) than those who did not answer these questions. Frequency of intercourse The frequency of intercourse considered by respondents as normal for their age, shown in Box 2(a), and actual reported frequency of intercourse were strongly correlated (Spearman's correlation coefficient, 0.62; P < 0.0001). Most 40-60-year-olds considered that intercourse 1-6 times per week was normal for their age and most reported this frequency of intercourse. In older men, however, a discrepancy emerged: most 70-79-year-olds considered 1-3 times per month to be normal for their age, but most reported an actual frequency of less than once per month. Box 2(b) illustrates this more clearly. In younger age groups, the reported frequency approximated that considered normal for age, but in older age groups it was substantially lower. Similarly, Box 2(c) shows that, while potency exceeds desire in men aged 40-59 years, after age 60 years desire exceeds potency. Prevalence of erectile dysfunction Erectile dysfunction was strongly correlated with age across all seven domains (Box 3). The prevalence of impotence (defined above) increased sharply from 3% in 40-49-year-olds to 42% in 60-69-year-olds and 64% in 70-79-year-olds. Other domains of sexual function, including morning or nocturnal erections, followed this pattern of steep decline in the fifth and sixth decades. Total sexual function scores ranged from 17% to 97%, with a mean of 68.1% (standard error, 1.1); 21% of respondents had a score of 50% or less. The sexual function score was also strongly correlated with age (Pearson's correlation coefficient, 0.63; P < 0.0001). Demographic risk factors Age, income, education, marital status, area of residence, occupation and country of birth were examined for their association with total sexual function and impotence. By far the strongest contributor to total sexual function score was age, and so the contribution of other factors was examined singly after first accounting for the effects of age in analysis of variance models, including first-order interactions (sexual function) and logistic regression (impotence). Where factors or their first-order interactions were significant, a combined model was examined. A summary of these analyses is given in Box 4. Men with lower socioeconomic status (income, education, occupation) tended to have lower sexual function, and this association was seen particularly in older men. In the 70-79 years age group, the total sexual function score varied from 47.1 in the lowest education category to 61.7 in the highest. Sexual function tended to be lower in Australian-born than overseas-born respondents. When tested in a model containing cardiovascular risk factors, this association remained. No demographic factors, apart from age, were significant contributors to impotence. Cardiovascular and other risk factors The cardiovascular risk factors shown in Box 4, as well as presence of LUTS, doctor visit for LUTS and surgery for prostate disease (cancer or non-cancer), were examined for their effects on total sexual function and impotence, as described for demographic factors. A number of factors were significantly (P < 0.05) associated with decreased sexual function after controlling for the effects of age. For total sexual function, these were ever having smoked, taking blood pressure medication and having had surgery for non-cancer prostate disease. A history of vigorous exercise was protective. Risk factors for impotence were high body mass index, high levels of triglycerides and cholesterol, and surgery for non-cancer prostate disease. Again, a history of vigorous exercise was protective. When combined models were constructed with these factors, the number that remained independently significant was reduced (Box 4). For total sexual function, these were vigorous exercise, high triglyceride levels, blood pressure medication, and surgery for non-cancer prostate disease. The combined model for total sexual function explained 55% of the variance. The observed power was low for all non-significant factors. The effects of cardiovascular risk factors were stronger in older age groups. For example, men in their 60s with high triglyceride levels had a total sexual function score of 41% (95% CI, 31%-52%), compared with 64% (95% CI, 59%-70%) for men of the same age who did not have this risk factor. Discussion Few international or Australian studies of the prevalence of sexual dysfunction have surveyed the general community.1 Our study was based on a representative sample of the South Australian community, and employed rigorous methods which have been previously used in other prevalence studies.1,8 The study was undertaken before the recent introduction of the drug oral sildenafil for erectile dysfunction. The subsample who answered questions on sexual function were similar in terms of most demographic and risk factor variables tested, but did report undertaking more vigorous exercise, and more frequent alcohol consumption. They may therefore reflect a more physically active subgroup, and our estimates of erectile dysfunction are likely to be conservative. Relative to other studies with comparable methods and measures of sexual dysfunction, the prevalences we found were similar or higher. For example, a study of frequency of sexual activity reported that 34.7% of married 60-65-year-old people did not have sexual intercourse within the preceding month,14 while we found that 34.3% of 60-69-year-old men reported having intercourse "less than once a month". A survey of 1240 men attending general practices in Perth found a 45% prevalence of "complete ED [erectile dysfunction]" in 70-79-year-old men,5 compared with our finding of impotence in 64.2%, and 64.3% in a study by Diokno et al.15 The frequently quoted Massachusetts Male Aging Study reports a prevalence of complete impotence of 9.6% for a 40-70-year-old population;2 the corresponding figure in our study was 16%. As expected, frequency of intercourse considered normal for age was strongly correlated with the frequency of intercourse reported (Figure 2). Solstad and Hertoft found that, while 40% of interviewed Danish men reported some kind of sexual dysfunction, only 7% considered their problems abnormal for their age,16 implying that men tend to see their own functional level as normal. Nevertheless, in our study, the discrepancy between reported frequency of intercourse and that considered normal for age increased with age. It was greatest in men 70 years and older, suggesting that it is older men who may be most concerned about their sexual function. Consistent with this, potency exceeded desire in younger age groups, but the relationship was reversed in men aged 60 years and over. About one in five men over the age of 50 experience good to very good sexual desire, but nil to poor erectile function; these men may be more likely to seek treatment. If the goal of treatment is to achieve perceived "normal function for this age", this may be a frequency of intercourse of 1-3 times monthly for 70-79-year-olds and weekly in the case of 40-69-year-olds. The effects of demographic risk factors such as income and education were more apparent in older age groups and were consistent with lower sexual function in lower socioeconomic groups. No reason is immediately apparent for the lower sexual function of Australian-born men compared with their overseas-born counterparts. Cardiovascular and medical risk factors reflected a conventional pattern.1,17 Predictors of low total sexual function scores after controlling for age only were smoking, blood pressure medication, high triglyceride levels and non-cancer prostate surgery, while a history of vigorous exercise provided a protective effect. In a combined model, smoking was no longer significant. Predictors of impotence after controlling for age only were high body mass index, high triglyceride levels, high cholesterol level, surgery for non-cancer prostate disease, while vigorous exercise was again protective. In a combined model, only high cholesterol remained significant. However, it is likely that small numbers of respondents limited the power of our study to investigate all these factors simultaneously. Our findings suggest that men experience poor sexual function as a deficit in the same age ranges in which cardiovascular risk factors are major determinants of that function, raising the possibility of prevention. It would be interesting to know whether, for men 60 years and over, improving cardiovascular risk factor profile would also reduce the prevalence of sexual dysfunction. Also of interest is the consistent and independent effect of non-cancer prostate surgery on sexual function. While its effects are small relative to age, it may point to a higher impotence rate than is commonly believed to result from this type of surgery,18 and this warrants further investigation. Acknowledgements We thank Living Health and Quitline for generously sharing their data on cardiovascular risk factors, and the AntiCancer Foundation for funding the prostate cancer questions. We would also like to thank the Behavioural Epidemiology Unit, South Australian Department of Human Services, and Lynne Giles, Flinders University, for assistance with aspects of the statistical analyses. References Bortolotti A, Parazzini F, Colli E, Landoni M. The epidemiology of erectile dysfunction and its risk factors. Int J Androl 1997; 20: 323-334. Feldman HA, Goldstein I, Hatzichristou DG, et al. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 1994; 151: 54-61. Helgason AR, Adolfsson J, Dickman P, et al. Factors associated with waning sexual function among elderly men and prostate cancer patients. J Urol 1997; 158: 155-159. Jonler M, Moon T, Brannan W, et al. The effect of age, ethnicity and geographical location on impotence and quality of life. Br J Urol 1995; 75: 651-655. Chew K, Burio C, Stuckey B, Jamrozik K. Erectile dysfunction in general medical practice. A study in Perth, Australia. Int J Impotence Res 1997; 9 (Suppl 1): S36. Pinnock C, Marshall V. Troublesome urinary symptoms in the community: a prevalence study. Med J Aust 1997; 167: 72-75. Weller D, Pinnock C, Silagy C, et al. Prostate cancer testing in South Australian men: influence of sociodemographic factors, health beliefs and lower urinary tract symptoms. Aust N Z J Public Health 1998; 22: 400-402. Pinnock C, Weller D, Marshall V. Self-reported prevalence of prostate specific antigen (PSA) testing in South Australia: a community study. Med J Aust 1998; 169: 25-28. Litwin MS, Hays RD, Fink A, et al. Quality-of-life outcomes in men treated for localized prostate cancer. JAMA 1995; 273(2): 129-35. [See comments.] Litwin MS, Nied RJ, Dhanani N. Health-related quality of life in men with erectile dysfunction. J General Intern Med 1998; 13: 159-166. Kish L. Estimates of unit variance: design effect. Survey sampling. New York: John Wiley and Sons, 1965: 257-263. NIH Consensus Conference. Impotence. NIH Consensus Development Panel on Impotence. JAMA 1993; 270: 83-88. SPSS for Windows [computer program], version 6.1. Chicago, Ill: SPSS Inc, 1996. Marsiglio W, Donnelly D. Sexual relations in later life: a national study of married persons. J Gerontol 1991; 46(6): S338-S344. Diokno AC, Brown MB, Herzog AR. Sexual function in the elderly. Arch Intern Med 1990; 150: 197-200. Solstad K, Hertoft P. Frequency of sexual problems and sexual dysfunction in middle-aged Danish men. Arch Sexual Behavior 1993; 22: 51-58. Helgason AR, Adolfsson J, Dickman P, et al. Waning sexual function -- the most important disease-specific distress for patients with prostate cancer. Br J Cancer 1996; 73: 1417-1421. Clinical practice guidelines for the management of uncomplicated lower urinary tract symptoms in men. Canberra: National Health and Medical Research Council, 1997. (Received 30 Nov 1998, accepted 28 Jun 1999) Authors' details Repatriation General Hospital, Daw Park, Adelaide, SA. Carole B Pinnock, PhD, Principal Research Scientist, Division of Surgery; Alan M F Stapleton, PhD, FRACS, Director, Urology Unit; Villis R Marshall, MD, FRACS, Head, Division of Surgery, and Head, Department of Surgery, Flinders Medical Centre. Reprints will not be available from the authors. Correspondence: Dr C B Pinnock, Division of Surgery, Repatriation General Hospital, Daws Road, Daw Park, SA 5041. carole.pinnockAThealth.sa.gov.au Back to text Back to text Back to text Back to text

Carole B Pinnock · Villis R Marshall

Research Impact of written information on knowledge and preferences for cardiopulmonary resuscitation Ian H Kerridge, Sallie-Anne Pearson, Isobel E Rolfe, Michael Lowe and John R McPhee MJA 1999; 171: 239-242 Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Ethics Abstract Aim: To investigate knowledge about and attitudes to cardiopulmonary resuscitation (CPR), and to determine whether written information about CPR alters knowledge and choices made. Design: Questionnaire-based survey before and immediately after provision of written information describing CPR and its risks and benefits. Subjects and setting: All health professionals (803) and competent inpatients (260) in a tertiary care hospital (John Hunter Hospital, Newcastle, New South Wales, Australia) in June 1994. Main outcome measures: CPR knowledge scores and choice scores (number of hypothetical clinical scenarios in which CPR would be chosen) before and after provision of information about CPR. Results: Response rates were 64% (health professionals) and 58% (patients). Patients had limited awareness of procedures involved in CPR, while both patients and health professionals overestimated its success rates. Mean knowledge scores increased after provision of information: for patients, from 6.4 out of 18 (95% confidence interval [CI], 6.0-6.9) to 10.4 (95% CI, 9.9-11.1); and for health professionals, from 11.9 (95% CI, 11.7-12.1) to 13.9 (95% CI, 13.7-14.2). In contrast, mean choice scores decreased after provision of information: for patients, from 5.3 out of 12 (95% CI, 4.7-5.7) to 4.4 (95% CI, 3.9-4.8); and for health professionals, from 4.1 (95% CI, 3.9-4.2) to 3.5 (95% CI, 3.3-3.7). Conclusion: Our results imply that people understand and use prognostic information to make decisions about CPR. To make autonomous judgements, patients and health professionals need better education on CPR outcomes. Introduction While cardiopulmonary resuscitation (CPR) can be lifesaving, success rates (survival to discharge) are less than 5% in some types of patients, particularly those with chronic illness or multiple comorbidities.1 Among those who survive, quality of life is often poor and life expectancy often short.2 In the mid-1970s, growing concern about inappropriate application of CPR and increased awareness of patient rights led to the development of "do-not-resuscitate" (DNR) orders.3 Health professionals are now increasingly encouraged to discuss DNR decisions with patients and their families.4 However, for decision-making about CPR to be appropriate, patients and their surrogates must have some understanding of the likelihood of surviving CPR and the possible adverse effects. Previous research has found that 50%-80% of patients claimed awareness of CPR, but their knowledge was very limited and derived mainly from television dramas. Most patients believed erroneously that CPR is generally successful,5,6 and both patients and health professionals were found to overestimate its success by up to 300%.7 We aimed to investigate knowledge of and attitudes to CPR among hospital inpatients and health professionals and to determine whether written information about CPR alters knowledge and preference for CPR. We have previously reported the opinions of patients and health professionals on the process of decision-making about CPR.8 Methods Subjects and setting The study was conducted at the John Hunter Hospital, Newcastle, New South Wales (a 530-bed tertiary care hospital), over a four-day period in June 1994. Subjects comprised all health professionals working in the hospital (doctors, nurses and allied health professionals) and all eligible (competent) inpatients, as described previously.8 Informed consent was obtained by trained interviewers, and a Mini Mental State Examination (MMSE) performed on patients. Those with MMSE scores < 24 were excluded. A questionnaire for self-completion was administered before and immediately after provision of written information about CPR. Questionnaire The questionnaire asked about: sociodemographic characteristics; sources of information on CPR (respondents could nominate as many as applied from a list of 11); whether each of 10 procedures is part of CPR (possible answers: yes, no or don't know); how successful CPR is in eight clinical scenarios, using a five-point scale: rarely (< 5%), seldom (5%-30%), sometimes (31%-60%), mostly (61%-90%) or almost always (> 91%); and whether respondents would like CPR performed on themselves in 12 specific clinical scenarios (possible answers: yes or no). On completing the questionnaire, respondents were given a one-page information sheet that explained various aspects of CPR, including its definition, procedures that may or may not be considered part of CPR, risks and benefits, success rates, and prognostic indicators (good prognosis: after acute myocardial infarction; poor prognosis: cancer, severe infection, organ failure). Respondents were then asked to repeat the questions on knowledge and choices. Statistical analyses Data were analysed with SPSS version 6.0 for Windows.9 Sociodemographic characteristics of patients and health professionals were compared using continuity-corrected χ2 analyses. All other analyses were performed for patients and health professionals separately. Knowledge of CPR was scored by allocating a point for each correct response. We assessed the relationship between this score and sociodemographic characteristics by standard multiple linear regression, with knowledge score as the dependent variable. For this analysis, we converted the discrete sociodemographic variable (health professional background) into a set of dichotomous independent variables using dummy variable coding (ie, doctors versus all other health professionals, and nurses versus all other health professionals). Significance of change in knowledge scores after provision of information was examined by one-way repeated-measures analysis-of-variance (ANOVA). As answers to some of the knowledge questions may be contentious (whether CPR involves intravenous drugs, intubation and defibrillation), analyses were repeated using scores with these questions omitted. Composite "choice scores" about CPR were calculated by allocating a point for each condition in which the subject would choose to have CPR. The relationship between choice score, sociodemographic characteristics and knowledge score after provision of information was assessed by standard multiple linear regression, with choice score as the dependent variable and knowledge score and sociodemographic factors as independent variables. Significance of change in choice scores after provision of information was examined by ANOVA. Ethical approval The study was approved by the Hunter Area Health Service Research Ethics Committee and the University of Newcastle Human Research Ethics Committee. Results Subjects Of the 803 questionnaires delivered to health professionals, 511 (64%) were returned (148 from doctors, 312 from nurses and 51 from allied health professionals). Of the 443 adult patients in the hospital during the study, 183 were excluded (because of dementia, neurological impairment or delirium [110], incompetence as assessed by MMSE [35], visual or language problems [24], psychiatric illness [9], or as they were undergoing procedures [5]); 153 (58%) of the remaining 260 completed the questionnaire. Sociodemographic characteristics of respondents are shown in Box 1. Knowledge about CPR Sources of information about CPR most commonly identified by health professionals were first aid or in-service courses (33% of responses); school, college or university (27%); and other health professionals (17%). Sources most commonly identified by patients were television (28% of responses), books or magazines (15%), first aid classes (15%), and school (10%). Knowledge before provision of information is shown in Box 2. Patients' knowledge scores were low (mean, 6.4 out of 18; 95% confidence interval [CI], 6.0-6.9), mainly because of lack of awareness of success rates of CPR, with 90% overestimating success for the "all patients" category. Health professionals' knowledge scores were higher than patients' (mean, 11.9; 95% CI, 11.7-12.1), but health professionals also overestimated success of CPR, with 65% overestimating success for "all patients". ANOVA showed that knowledge scores improved significantly after provision of written information for both patients and health professionals (patients: mean, 10.4; 95% CI, 9.9-11.1; health professionals: mean, 13.9; 95% CI, 13.7-14.2). The only sociodemographic characteristics that significantly predicted knowledge scores before provision of information were age (for patients) and professional background (for health professionals): younger patients achieved higher scores than older patients, while doctors and nurses achieved higher scores than allied health professionals. Repeat analysis of the data after omission of contentious questions did not affect the relationship between sociodemographic variables and knowledge scores or the change in knowledge scores after provision of information. Choices about CPR Percentages of patients and health professionals who chose CPR are shown in Box 3. Percentages varied between clinical scenarios, but decreased after provision of information for almost all. ANOVA showed that choice scores also decreased significantly for both patients and health professionals. Mean choice scores decreased for patients from 5.3 out of 12 (95% CI, 4.7-5.7) to 4.4 (95% CI, 3.9-4.8), and for health professionals, from 4.1 (95% CI, 3.9-4.2) to 3.5 (95% CI, 3.3-3.7). CPR was chosen for more scenarios by patients who were younger or had lower knowledge scores and by health professionals who were younger, male, tertiary educated or had better self-reported health status. Discussion We found that patients in an Australian teaching hospital had poor knowledge of CPR, and that both they and, to a lesser extent, hospital staff had unrealistic expectations about its success rates. We also found that provision of written information about CPR risks, benefits and success rates had a clear impact on whether patients and health professionals reported wanting CPR performed on themselves in hypothetical clinical scenarios, decreasing their preference for CPR. Other studies have also found that patients are unaware of the procedures involved in CPR and, along with their relatives, generally overestimate success rates.10 This is not surprising, as television, books and magazines are often their most common sources of information. In addition, community education tends to be positive about CPR, often failing to describe its real success rates. Several previous studies have investigated the relationship between choices about CPR and estimated probability of survival.5,11 They found, similarly to us, that many patients change their minds about wanting CPR when they learn the true probability of survival. Furthermore, formal processes of information disclosure, including discussion of the likely outcome of resuscitation in specific clinical situations, has been shown to modify preferences for CPR.12 In our study, the change in preference followed provision of a one-page information sheet. It is possible that a more optimal form of education (eg, repeated explanations tailored to the individual, with time for reflection and questions) would have produced a greater change in preferences. Perceived morbidity after CPR also strongly influences many people's choices. A survey of 200 medical inpatients found that choice of CPR or DNR status was strongly influenced by anticipated outcome; 90% of patients desired CPR if they were to be restored to their normal health, 30% if the likely outcome after recovery was dependence, 15% if it was perceived as "hopeless", and 6% if it was coma.13 Other studies from the United States14 and United Kingdom15 have found that senile dementia, more than any other condition, is associated with a preference for DNR status. We found similarly that patients and health professionals would be unlikely to opt for CPR in the presence of brain injury or severe dementia. Nevertheless, as found by others,6,10 some patients continued to opt for CPR even if they were likely to have a serious disability, such as coma or terminal illness. We also found, in common with others overseas, that health professionals vastly overestimate the success rates of CPR. These rates (3%-30% in general hospitals) have not changed significantly in the past 30 years.1,16 However, they are well below the rates perceived by physicians and nurses, who are responsible for making decisions about resuscitation status and informing patients and their surrogates.17,18 There are several limitations to our study. Subjects included hospitalised patients with acute illness, and the findings may not be generalisable to other patient populations. The study instrument was a self-report questionnaire using hypothetical clinical scenarios; answers may not accurately reflect what individuals would choose in reality. However, the study has strengths; it assessed both knowledge of and attitudes to CPR in variable clinical contexts and included a formal assessment of competence (the MMSE). The study also used trained interviewers rather than clinicians to distribute questionnaires and so was less likely to introduce bias and perhaps more likely to elicit patients' true preferences. As factors such as likelihood of survival and functional status after resuscitation may contribute to patients' wishes for CPR, it is ethically and clinically desirable that patients be provided with this information. Furthermore, the High Court of Australia has reaffirmed that patients must be given adequate information when making decisions concerning their healthcare.19,20 It is also essential that health professionals who advise patients are aware of the real success rates of CPR. Otherwise, they have failed to meet the standards required both for ethical medical care and by law.21 Respect for autonomy demands that the views of patients or their surrogates should be sought in decision-making about CPR. Our study implies that patients understand and use prognostic information in their decision-making. For truly autonomous judgements, patients and health professionals clearly need better education on risks and benefits of CPR. Acknowledgements We would like to thank the interviewers and patients and staff of the John Hunter Hospital for their generous participation in this study. References Robinson GR, Hess D. Post-discharge survival and functional status following in-hospital cardiopulmonary resuscitation. Chest 1994; 105: 991-994. Landry FJ, Parker JM, Phillips YY. Outcome of cardiopulmonary resuscitation in the intensive care setting. Arch Intern Med 1992; 152: 2305-2308. Rabkin MT, Gillerman JD, Rice NR. Orders not to resuscitate. N Engl J Med 1976; 295: 364-366. Decisions relating to cardiopulmonary resuscitation. A statement from the British Medical Association and the Royal College of Nursing in association with the Resuscitation Council (UK). London: BMA, 1993. Miller DL, Jahnigen DW, Gorbien MJ, Simbarti L. Cardiopulmonary resuscitation: how useful? Attitudes and knowledge of an elderly population. Arch Intern Med 1992; 152: 578-582. Schonwefter RS, Walker RM, Kramer DR, Robinson BE. Resuscitation decision-making in the elderly: the value of outcome data. J Gen Intern Med 1993; 8: 295-300. Potter JM, Stewart D, Duncan G. Living wills: would sick people change their minds? Postgrad Med J 1994; 70: 818-820. Kerridge IH, Pearson SA, Rolfe IE, Lowe M. Decision making in CPR: attitudes of hospital patients and health care professionals. Med J Aust 1998; 169: 128-131. SPSS. Statistical package for the social sciences. Version 6.0 for Windows. Chicago, Ill: SPSS Inc, 1990. Schmerling RH, Bedell SE, Lilienfeld A, Delbanco TL. Discussing cardiopulmonary resuscitation: a study of elderly outpatients. J Gen lntern Med 1988; 3: 317-321. Murphy DJ, Burrows MD, Santilli S, et al. The influence of the probability of survival on patients' preferences regarding cardiopulmonary resuscitation. N Engl J Med 1994; 330: 545-549. Schonwetter RS, Teasdale TA, Taffet G, et al. Educating the elderly: cardiopulmonary resuscitation decisions before and after intervention. J Am Geriatr Soc 1991; 39: 372-377. Frankl D, Oye RK, Bellamy PE. Attitudes of hospitalised patients toward life support: a survey of 200 medical inpatients. Am J Med 1989; 6: 645-648. Ebell MH, Doukas DJ, Smith MA. The do-not-resuscitate order: a comparison of physician and patient preferences and decision-making. Am J Med 1991; 91: 255-260. Robertson GS. Resuscitation and senility: a study of patients' opinions. J Med Ethics 1993; 19: 104-107. Bedell SE, Delbanco TL, Cook EF, Epstein FH. Survival after cardiopulmonary resuscitation. Crit Care Med 1983; 309: 569-576. Miller DL, Gorbien MJ, Simbarti LA, Jahnigen DW. Factors influencing physicians in recommending in-hospital cardiopulmonary resuscitation. Arch Intern Med 1993; 153: 1999-2003. Wagg A, Kinirons M, Stewart K. Cardiopulmonary resuscitation: doctors and nurses expect too much. J R Coll Physicians Lond 1995; 29: 20-24. Rogers v Whitaker (1992) 175 CLR 479. Chappel v Hart [1998] HCA 55. Wyong Shire Council v Shirf (1980) 146 CLR 40. (Received 13 Jan, accepted 7 Jul, 1999) Authors' details Faculty of Medicine and Health Sciences, University of Newcastle, Newcastle, NSW. Ian H Kerridge, MPhil, Lecturer in Clinical Ethics; Sallie-Anne Pearson, PhD, Research Academic; Isobel E Rolfe, MMedEd, Senior Lecturer in Medical Education; Michael Lowe, FRACP, Tutor in Clinical Ethics; John R McPhee, BCom(Hons) (Legal Studies), Consultant in Health Law. Reprints will not be available from the authors. Correspondence: Dr I H Kerridge, Clinical Unit in Ethics and Health Law, Locked Bag 1, Hunter Region Mail Centre, Newcastle, NSW 2310. Email: ikerridgATmail.newcastle.edu.au 1: Sociodemographic characteristics of patients and health professionals surveyed about cardiopulmonary resuscitationPatients (n =153)Healthcare professionals (n =511)PAge > 35 years*90 (59%)235 (46%) 0.007Female98 (65%)373 (73%)< 0.001Marital status† Married/de facto97 (64%)328 (64%) Single/divorced/widowed55 (36%)183 (36%) 0.99Education† Secondary or less117 (77%)72 (14%) Tertiary35 (23%)438 (86%) < 0.001Religion† Religious‡127 (84%)401 (79%) Not religious25 (16%)109 (21%) 0.18Ethnic background† Australian/British144 (95%)463 (91%) Other7 (5%)45 (9%) 0.09Self-reported health status Good68 (45%)493 (97%) Fair/poor/very poor84 (55%)17 (3%)< 0.001CI = confidence interval. * Median split. †Data were missing for some respondents. ‡Any belief system: Christian, Jewish, Islamic, Hindu or Buddhist. Back to text 2: Percentages of 153 patients and 511 health professionals who replied correctly to questions about cardiopulmonary resuscitation (CPR) before provision of written information% Correct (95% confidence interval)QuestionCorrect responsePatientsHealthcare professionalsWhat is involved in CPR?Chest compression (external cardiac massage)Yes*84% (77%-90%)100%Kidney machine (dialysis)No62% (54%-70%)99% (98%-100%)Intravenous drugsYes*25% (18%-33%)84% (80%-87%)Mouth-to-mouth (artificial respiration) Yes86% (80%-91%)99% (98%-100%)Feeding tube into the nose (nasogastric tube)No48% (40%-56%)96% (94%-98%)AntibioticsNo56% (48%-64%)98% (93%-97%)Tube into the throat to assist breathing (intubation)Yes*35% (27%-43%)85% (82%-88%)External electric shock to the heart (defibrillation)Yes*60% (51%-68%)91% (88%-93%)SurgeryNo48% (40%-56%)98% (96%-99%)Breathing machine (ventilator)No27% (20%-35%)57% (53%-61%)How successful is CPR?All patients5%-30%1% (0-4%)26% (22%-30%)Nursing home patients< 5%8% (4%-13%)62% (58%-66%)Patients who have had recent heart attack31%-60%40% (32%-48%)40% (36%-44%)Patients with widespread cancer< 5%42% (34%-50%)61% (57%-65%)Patients with severe infections (eg, pneumonia)< 5%17% (11%-24%)28% (24%-32%)Patients with kidney failure< 5%25% (18%-33%) 39% (35%-43%)Patients under 60 years5%-30%5% (2%-10%)22% (18%-26%)Patients over 70 years5%-30%15% (10%-22%)34% (30%-38%)* As these answers are contentious, analyses were performed using both responses. 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Ian H Kerridge · Sallie-Anne Pearson · Isobel E Rolfe · Michael Lowe · John R McPhee

Editorial Primary stenting in acute myocardial infarction: paving the way to arterial patency No matter how enticing the data may be, all the answers are not in MJA 1999; 170: 518-519 Acute myocardial infarction (AMI) remains a major cause of morbidity and the single most common cause of mortality among adult Australians.1 It has been estimated that there is one AMI every half hour and one fatal event every hour among men and women under 70 years of age.1 Despite a decade of remarkable insights into the pathobiology of AMI and innumerable randomised clinical trials evaluating therapeutic approaches, the optimal acute management strategy still remains unclear. It is widely accepted that the primary objective in AMI is early reperfusion,2 which, by preserving myocardial cell viability and contractility, results in improved survival.3-6 However, the main mechanism of achieving coronary artery reperfusion -- intravenous thrombolytic therapy -- is not without its limitations: up to half the patients may be ineligible on clinical grounds, and it is only moderately effective in reinstituting the level of coronary flow necessary for improved survival.7 Other problems include recurrent ischaemia, reinfarction and a small but significant chance of life-threatening haemorrhagic complications.8 Because of these drawbacks, interest in mechanical reperfusion by primary coronary balloon angioplasty (without prior thrombolysis) has steadily increased. Despite its 17-year history, balloon angioplasty is not as widely available or as frequently used9 as perhaps it should be (for reasons beyond the scope of this editorial). However, current evidence for its use in primary treatment of AMI is quite encouraging. A review of 10 randomised clinical trials comparing primary coronary balloon angioplasty with thrombolytic therapy in 2606 patients with AMI found those treated with balloon angioplasty had a 34% lower mortality rate, a lower rate of death and/or non-fatal reinfarction and a significantly lower rate of total and haemorrhagic stroke.10 Other randomised trials have indicated that, by reducing early and late recurrent ischaemia, primary balloon angioplasty may expedite early discharge and thus reduce costs.11,12 Promising as these data might be, they are far from conclusive, in part because of the size of the dataset and the unblinded nature of the clinical trials. Almost 13 000 patients would need to be enrolled in a trial to detect a 20% advantage in 30-day mortality rates of primary coronary balloon angioplasty over thrombolytic therapy (assuming a 7% mortality rate in the thrombolytic therapy group).13 Equally concerning are the incidence of no reflow due to distal thrombus embolisation at the time of balloon dilatation; early recurrent ischaemia and/or reinfarction (5%-10% of patients14) due to elastic vascular recoil and/or platelet and thrombus deposition at the site of balloon-induced intimal disruption (dissection); and late restenosis (30%-50% of patients14) due to a varying mix of neointimal proliferation, unopposed recoil and vascular remodelling. While there have been substantial improvements in operator skills, procedural techniques, equipment design and adjunctive antiplatelet therapies, the issues mentioned above continue to frustrate the proponents of primary coronary balloon angioplasty. It is not surprising, therefore, that they should have become infected and intoxicated by the euphoria surrounding coronary stenting in elective angioplasty. Compared with simple balloon angioplasty, coronary stenting in elective (non-infarct-related) coronary angioplasty has been shown to reduce the rate of periprocedural complications and late restenosis, and to be beneficial in the management of saphenous vein graft lesions and restenotic lesions after balloon angioplasty. The thought of in-situ coronary thrombus and the likely consequences of deploying a metal stent into such an environment in a patient with AMI initially struck fear into the hearts of even the most ardent supporters of primary balloon angioplasty. However, the realisation that antiplatelet therapy could prevent stent-related thrombotic complications and the publication of a bold study of primary infarct stenting without conventional anticoagulation therapy15 strengthened the advocates' resolve. This first study, although small and non-randomised, paved the way for larger feasibility trials,16 and, more recently, randomised controlled trials of primary stenting in AMI.17,18 These studies demonstrate a substantially lower rate of recurrent ischaemia, reinfarction, angiographic restenosis and a reduced need for target-vessel revascularisation compared with good old balloon angioplasty. Unfortunately, neither of the randomised trials had sufficient power to assess effects on mortality. As is often the case with provocative new data, these observations on primary stenting in AMI provide many more questions than answers. Clearly, it is now important to establish in whom and by whom primary stenting should be done. What patient, vessel or lesion characteristics respond best to primary stenting? For example, should primary stenting be the treatment of choice in diabetic patients, who tend to have more diffuse atherosclerotic disease and a higher risk of restenosis? Should only experienced operators attempt primary stenting in AMI? Coronary stenting may add to the complexity and risks of the procedure rather than lessen them, and most of the recently published data16-18 emanate from centres with unparalleled resources and expertise. Furthermore, what if the lesion is not amenable to primary stenting, or, for that matter, even primary angioplasty? The question of a second-line strategy is often not addressed. In this issue of the Journal, Hansen and colleagues19 indeed address some of these important practical issues. In a pilot study, they assessed the feasibility, safety and short term clinical outcomes of a primary stenting strategy (embracing several critical contingency plans) in a consecutive group of patients with AMI and eligible for fibrinolysis. The authors observed that primary stenting was possible in 71% of their cohort, and, by adopting a strategy that included the "fall-back" options of simple balloon angioplasty, emergency or semiurgent coronary artery bypass grafting (CABG) and medical therapy, they achieved successful early revascularisation of the infarct-related artery in 95% of their patients, with a remarkably low rate of early, six-week and six-month cardiovascular events. The immediate questions that come to mind concern, firstly, the costs, and what well-timed thrombolytic therapy might have achieved in this cohort, and, secondly, whether these results can be extrapolated to centres where resources such as CABG might not be as readily available. The study by Hansen et al is limited by being non-randomised and observational and the experience of a single centre. Nonetheless, it provides important local insight into primary stenting in AMI and indicates that this strategy is safe and feasible and can be delivered in a timely fashion in an appropriately equipped Australian hospital. Whether this holds true for patients at remote centres is unknown, and it is not clear whether patients should be denied early lytic therapy at one institution so they may be transferred to another to obtain primary coronary balloon angioplasty/primary stenting. Thrombolytic therapy has an inherent time delay of approximately 45-60 minutes. A modest delay in obtaining primary angioplasty/primary stenting may therefore be acceptable, but has not been formally tested. In summary, there is a growing body of evidence which suggests that primary stenting in AMI may be preferable to primary coronary balloon angioplasty and possibly more efficacious than conventional thrombolytic therapies. However, no matter how enticing the data may be, all the answers are not in. Does it save lives? Is it cost effective? Is it widely applicable? Does it improve myocardial salvage? Are all stents equal or are some more equal than others? Is it better than primary coronary balloon angioplasty with adjunctive glycoprotein IIb/IIIa platelet receptor blockade? These are but a few of the questions that need addressing, and until these issues are resolved primary stenting must be viewed as a procedure undertaken with the best of intentions. And need I mention where the road paved with good intentions might lead? Ian T Meredith Associate Professor; and Director, Cardiac Catheterisation and Interventional Cardiology, Centre for Heart and Chest Research Monash Medical Centre, Melbourne, VIC Email: ian.meredithATmed.monash.edu.au National Heart Foundation of Australia. Heart and stroke facts. Canberra: NHF, 1996: 1. Lange RA, Hillis LD. Thrombolysis -- the preferred treatment. N Engl J Med 1996; 335: 1311-1312. White HD, Norris RM, Brown MA, et al. Effects of intravenous streptokinase on left ventricular function and early survival after acute myocardial infarction. N Engl J Med 1987; 317: 850-855. O'Rourke M, Baron D, Keogh A, et al. Limitation of myocardial infarction by early infusion of recombinant tissue-type plasminogen activator. Circulation 1988; 77: 1311-1315. Gruppo Italiano per lo Studio della Streptochinasi nell' Infarto Miocardico, GISSI. Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986; 1: 397-401. ISIS-2 Collaborative Group. A randomized trial of intravenous streptokinase, oral aspirin, both or neither among 17187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988; 2: 349-360. The GUSTO Angiographic Investigators. The effects of tissue plasminogen activator, streptokinase or both on coronary artery patency, ventricular function and survival after acute myocardial infarction. N Engl J Med 1993; 329: 1615-1622. Grines CL. Primary angioplasty -- the strategy of choice. N Engl J Med 1996; 335: 1313-1315. Coronary angioplasty in Australia 1995. Canberra: Australian Institute of Health and Welfare, 1995. (Cardiovascular Disease Series No. 8.) Weaver WD, Simes RJ, Betriu A, et al. Comparison of primary coronary angioplasty and intravenous thrombolytic therapy for acute myocardial infarction. A quantitative review. JAMA 1997; 278: 2093-2098. Stone GW, Grines CL, Rothbaum D, et al. Analysis of the relative costs and effectiveness of primary angioplasty versus tissue-type plasminogen activator: The Primary Angioplasty Myocardial Infarction (PAMI) Trial. J Am Coll Cardiol 1997; 29: 901-907. De Boer MJ, van Hout BA, Liem AL, et al. A cost-effective analysis of primary coronary angioplasty versus thrombolysis for acute myocardial infarction. Am J Cardiol 1995; 76: 830-833. Yusuf S, Pogue J. Primary angioplasty compared with thrombolytic therapy for acute myocardial infarction. JAMA 1997; 278: 2110-2111. Stone GW, Grines CL, Topol EJ. Update on percutaneous transluminal coronary angioplasty for acute myocardial infarction. In: Topol E, Serruys P, editors. Current review of interventional cardiology. 2nd edition. Philadelphia, Pa: Churchill Livingstone, 1995: 1-56. Saito S, Hosokawa G, Kim K, et al. Primary stent implantation without coumadin in acute myocardial infarction. J Am Coll Cardiol 1996; 28: 74-81. Stone GW, Brodie BR, Griffin JL, et al. Clinical and angiographic follow-up after primary stenting in acute myocardial infarction. The primary angioplasty in myocardial infarction (PAMI) Stent Pilot Trial. Circulation 1999; 99: 1548-1554. Suryapranata H, van't Hof AWJ, Hoorntje JCA, et al. Randomised comparison of coronary stenting with balloon angioplasty in selected patients with acute myocardial infarction. Circulation 1998; 27: 2502-2505. Antonucci D, Santoro GM, Bolognese L, et al. A clinical trial comparing primary stenting of the infarct-related artery with optimal primary angioplasty for acute myocardial infarction. Results from the Florence randomized elective stenting in acute coronary occlusions (FRESCO) trial. J Am Coll Cardiol 1998; 31: 1234-1239. Hansen PS, Rasmussen HH, Vinen J, Nelson GIC. A primary stenting strategy as an alternative to fibrinolytic therapy in acute myocardial infarction. An analysis of results in hospital and at 6 weeks and 6 months. Med J Aust 1999; 170: 537-540. Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Ian T Meredith

Healthcare A primary stenting strategy as an alternative to fibrinolytic therapy in acute myocardial infarction An analysis of results in hospital and at 6 weeks and 6 months Peter S Hansen, Helge H Rasmussen, John Vinen and Gregory I C Nelson MJA 1999; 170: 537-540 For editorial comment, see Meredith Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Cardiology and cardiac surgery Abstract Objective: To report the feasibility and results to 6 months of a primary stenting strategy in patients with acute myocardial infarction (AMI). Design: Prospective, single-centre, observational study. Setting: A tertiary referral teaching hospital (Royal North Shore Hospital, Sydney), July 1997 to November 1998. Subjects: 102 (of 194) consecutive patients presenting to the emergency department with AMI who were eligible for fibrinolytic therapy, and for a primary stenting strategy. The first 50 patients were under 70 years of age, and had not had previous coronary artery bypass grafting (CABG). The following 52 patients included patients up to 80 years and with previous CABG. Outcome measures: Major adverse cardiac and cerebrovascular events: death, reinfarction, cerebrovascular accident (CVA) and repeat target lesion revascularisation, in hospital, and at 6 weeks and 6 months. Minor inhospital adverse events: bleeding requiring blood transfusion, vascular complications and new-onset heart failure. Time delays to treatment, and duration of hospital stay. Results: Normal flow was established in the infarct-related artery in 97/102 patients (95%). Stenting, percutaneous transluminal coronary angioplasty (PTCA), CABG or medical therapy was performed in 74, 11, 9 and 8 patients, respectively. Minor inhospital events, time delays and hospital stay were similar to those reported previously. At 6 weeks, major adverse cardiac and cerebrovascular events had occurred in 5% of patients (four repeat target lesion revascularisation and one reinfarction). By 6 months, repeat target lesion revascularisation had been performed in an additional 10% of patients. No deaths had occurred. Conclusions: A primary stenting strategy can be performed safely, without significant delays and with excellent short and intermediate term outcomes. Introduction Early patency of the infarct-related artery after acute myocardial infarction (AMI) (defined as patency 90 minutes after the start of fibrinolytic therapy) improves early and late survival.1-3 With fibrinolytic therapy, the key treatment of AMI for the past 12 years,4,5 at best only about half the patients treated achieve early patency, the proportion varying with the fibrinolytic agent used (29% with streptokinase and 54% with tissue plasminogen activator [t-PA]).1 Moreover, in up to 30% of patients the artery reoccludes within 3 months.6 Prospective randomised trials of primary percutaneous transluminal coronary angioplasty (PTCA) have shown improved early patency and short-term clinical outcomes in comparison with fibrinolytic therapy.7-10 However, the benefits of primary PTCA are attenuated, as reocclusion occurs in 5%-10% of patients, reinfarction in 3%-5%, angiographic restenosis in 35%-45%, and recurrent ischaemia requiring repeat target lesion revascularisation in about 20% of patients.7-13Primary stenting in selected patients with AMI appears to be more effective than PTCA or fibrinolytic therapy,2,3,6-18 but not all infarct-related arteries are suitable for stenting. A primary stenting strategy incorporating primary stenting, PTCA, coronary artery bypass grafting (CABG) or medical treatment (except fibrinolytic therapy) is expected to cater for all patients. We examined prospectively the feasibility and clinical outcomes to 6 months of a primary stenting strategy in patients with AMI who were eligible for fibrinolysis. Methods During the period July 1997 to November 1998, we studied prospectively 194 consecutive patients who presented with AMI to the emergency department at Royal North Shore Hospital. Patients with contraindications to heparin, aspirin, ticlopidine or fibrinolytic therapy, and those with established cardiogenic shock, were not eligible for the study. Patient selection Patients included: 102 patients fulfilled GUSTO criteria for AMI,5 and were eligible for fibrinolysis. A lower age limit was imposed during the first half of the study (during the learning curve for the stenting team), and patients with previous CABG were excluded because stenting was initially thought to be less effective in vein-graft occlusion. Accordingly, the first 50 patients were under 70 years and had not had CABG. The following 52 patients, two of whom had had CABG, were under 80 years. Patients excluded: Reasons for non-entry to the study in 92 patients were age limit exceeded (over 70 years, 47 patients; over 80 years, 23 patients); transfer from other hospitals for primary intervention (5 patients); not eligible for fibrinolysis, including two with cardiogenic shock (8 patients); no vascular access (2 patients); prior CABG (2 patients); cardiogenic shock (1 patient); eligible but refused (2 patients); and eligible but interventional cardiologist unavailable (2 patients). Ethical approval The protocol was approved by the hospital's Human Research and Ethics Committee. All patients gave informed consent. Study protocol Patients were given aspirin (300 mg), ticlopidine (500 mg) and an intravenous heparin bolus (150 U/kg), and transferred immediately to the catheterisation laboratory, or, out of working hours, as soon as the interventional team arrived. Low-osmolar ionic contrast medium (sodium ioxaglate) was used to minimise thromboembolic complications.19 Blood flow was re-established in the occluded infarct-related arteries with Magnum (Schneider, Bulach, Switzerland) 0.014 inch wire through a 6 French (2 mm diameter) guide. Placement of a stainless steel stent (the majority were GFX (Arterial Vascular Engineering, Santa Rosa, Calif, USA) by high pressure balloon inflation (> 10 atmospheres) was attempted in vessels with a reference segment diameter of more than 2.5 mm and a lesion length of less than 32 mm. Thrombus was not considered a contraindication to stenting. Fibrinolytic therapy was not given. Medical treatment only was given (aspirin, heparin, β-blockers) if, after cardiac catheterisation, the infarct-related artery was patent with normal brisk flow (ie, grade 3 flow as defined by the Thrombolysis in Myocardial Infarction [TIMI] trial20), and had residual stenosis of less than 50% of vessel diameter. Emergency (immediate) or inhospital CABG was performed for left main coronary artery and/or severe triple-vessel disease, and PTCA was performed when the diameter of the infarct-related artery was less than 2.5 mm. A glycoprotein IIb/IIIa receptor antagonist (abciximab) was given to 23 of the 102 patients: 11 patients having primary PTCA, 3 patients in whom reflow did not occur, and 9 patients with persistent filling defects or a long stented segment (> 18 mm). Further heparin was given if activated clotting time (for monitoring high dose heparin) was under 300 seconds. No further heparin was given after the procedure and patients were mobilised 12 hours after femoral sheath removal. Ticlopidine (250 mg daily) was administered for 4 weeks and patients were monitored for side effects (neutropenia, thrombocytopenia). All patients were followed up by their general practitioner and specialist physician. Follow-up for the trial was at 6 weeks and 6 months; patients completed questionnaires or, if necessary, were interviewed by phone. Outcome measures Study outcome measures were major adverse cardiac and cerebrovascular events: death, reinfarction, cerebrovascular accident (CVA) and repeat target lesion revascularisation, in hospital, and at 6 weeks and 6 months. Reinfarction was defined as recurrent ischaemic symptoms with changes noted on the electrocardiogram (ECG) (ST-segment elevation or new Q waves) and elevation in the level of creatine kinase (MB fraction) to more than twice the upper limit (normal range, 0-7 µg/L) or any rise above a previously elevated level. CVA was defined as new persistent (> 24 hours) neurological deficit consistent with a stroke, confirmed by a physician or by computed tomography scan of the brain. Patency of the infarct-related artery was determined by TIMI classification.20 Minor inhospital adverse events included bleeding requiring blood transfusion, vascular complications and new-onset heart failure. Successful procedural outcome was a patent infarct-related artery with residual stenosis of less than 30% of vessel diameter (without major adverse cardiac and cerebrovascular events in hospital), or uncomplicated CABG. Results The baseline clinical characteristics of the 102 consecutive eligible patients with AMI are shown in Box 1, and their treatment and outcome in hospital are shown in the Figure. Overall, TIMI 3 flow in the infarct-related artery was restored in 97/102 (95%) patients within a mean of 64 minutes (range, 30-130 minutes) of notifying the interventional team. There were no inhospital deaths, reinfarctions or CVAs. Four patients (4%) required repeat target lesion revascularisation (three had been treated initially with PTCA and one with stenting). Unscheduled recatheterisation was performed in another four patients with chest pain, without ECG changes. All showed a widely patent stent. No patient developed recurrent chest pain with ECG changes while in hospital. Minor inhospital events included blood transfusion, all after CABG (7/102; 7%), new-onset heart failure (2/102; 2%), and femoral artery pseudoaneurysm requiring surgical repair (2/102; 2%). For more information see flow chart Six-week and 6-month follow-up Follow-up was completed for all patients due for follow-up at 6 weeks (n = 102) and at 6 months (n = 58). At 6 weeks no deaths or CVAs had occurred. One patient had had a reinfarction after a subacute stent thrombosis on Day 10. He underwent successful repeat PTCA (reperfusion at sites other than the target lesion was not performed). Major adverse cardiac or cerebrovascular events had occurred in 5/102 patients: one had a reinfarction after discharge and four required repeat target lesion reperfusion. At 6 months, still no deaths had occurred, and there had been no further reinfarctions or CVAs. Clinical restenosis requiring repeat target lesion revascularisation occurred in an additional 6/58 patients (10%). Revascularisation at a new site of stenosis was performed in 1/58 patients (2%). No deaths, reinfarctions or CVAs had occurred since discharge, and at 6 months there had not been any requirement for revascularisation in 51/58 patients (88%). Hospital stay Mean hospital stay was 5.0 days (95% confidence interval (CI), 4.5-5.5 days). Mean coronary care, intensive care and general ward stays were 1.5 (95% CI, 1.4-1.6), 0.5 (95% CI, 0.3-0.7) and 3.0 days (95% CI, 2.7-3.3), respectively. Median hospital stay was 3 days. Time delays Time delays between the onset of chest pain and re-establishment of TIMI 3 flow of the infarct-related artery are shown in Box 2. Although 58% of patients presented out of working hours, only 10% of "call-backs" for the intervention team took place between 23:00 and 04:00. Discussion We examined the feasibility and clinical outcomes to 6 months of a primary stenting strategy. Expected advantages of such an approach, compared with fibrinolytic therapy, are greater patency of the infarct-related artery with improved outcome, early recognition of high risk patients for surgical revascularisation and low risk patients for early discharge, reduced rate of CVA, and lower acute complication rate and need for reperfusion of the target lesion compared with primary PTCA.14 Our results support these expectations. Coronary artery patency with the primary stenting strategy was achieved in 95% of patients, similar to reports for primary stenting in selected patients,14-18 but higher than reported for primary PTCA (73%-87%) and fibrinolysis with t-PA (54%).1,3,7-9 Interestingly, 25% of patients in our study had TIMI 3 flow at cardiac catheterisation, a rate higher than reported by some investigators (7%-11%)14 and similar to rates after fibrinolysis with streptokinase (29%-32%). We gave a 150 U/kg bolus dose of intravenous heparin, which may explain this difference.21 Our results compare favourably with those of other primary stenting studies.14-18 A 30-day rate of 3% for major adverse cardiac and cerebrovascular events has been reported for patients undergoing primary stenting.14,15 However, in one of these studies,14 up to 15% of patients screened were excluded, owing to unsuitable anatomy of the infarct-related artery (eg, diffuse disease), and events in such patients were not included. Several studies report outcomes of patients treated by primary PTCA separately to those treated by stenting,14-18 making it difficult to directly compare the results with those of trials of fibrinolytic therapy in which all patients are included. We included all patients eligible for fibrinolysis who fulfilled the inclusion criteria in our analysis. This allows a more realistic impression of the benefits of a primary stenting strategy, as our data can be compared with data from trials of fibrinolytic therapy (the alternative treatment offered to all patients at enrolment). Feasibility In order to test the feasibility of a primary stenting strategy (our main aim), our emergency department had to triage patients without delay and the interventional team had to respond swiftly at all hours. Time delays (mean and median) from arrival at the emergency department to notification of the interventional team (42 and 35 minutes), from notification of the team to TIMI 3 flow (64 and 60 minutes), and from arrival at the emergency department to TIMI 3 flow (106 and 95 minutes), compare well with time delays from trials of fibrinolysis and angioplasty. The GUSTO investigators reported a median interval of 64 minutes from randomisation to administration of fibrinolytic therapy,5 and the GUSTO IIb investigators reported a median interval of 114 minutes from emergency department arrival to first balloon inflation in the primary PTCA group.10 Patency rates are reported 90 minutes after starting fibrinolytic therapy.1 Assuming a mean delay of 42 minutes in the emergency department to administration of fibrinolytic therapy, the equivalent inhospital delay from emergency department arrival to TIMI 3 flow with fibrinolytic therapy would be a mean of 132 minutes (but TIMI 3 flow would actually be achieved in only 54% of patients). We achieved TIMI 3 flow in 95% of patients within a mean of 106 minutes of arrival at the emergency department. Limitations of the study This study was a non-randomised, single-centre study with a small sample size. For the first half of the study, enrolment was restricted to a relatively low risk group under 70 years of age without previous CABG. Interventions were performed by two experienced operators. Thus, comparison of our data with results from much larger trials of fibrinolytic therapy must be performed with caution. Conclusions A primary stenting strategy is feasible and safe, with an excellent clinical outcome to 6 months. We are now planning a larger, randomised phase of this study, with patients from the Northern Sydney Area Health Region (which includes four district hospitals) outside the Royal North Shore Hospital (RNSH) catchment area being allocated at random to either conventional treatment with fibrinolytic therapy at the district hospital or a primary stenting strategy at RNSH. We hypothesise that mechanical reperfusion therapy will prove the superior strategy because of its higher early patency rate3 and offset any disadvantages of the small time difference imposed by a longer ambulance journey. Acknowledgements This study was supported by the North Shore Heart Research Foundation (NSHRF). GFX (AVE) stents and Magnum (Schneider) guide wires were donated. Dr P S Hansen received a Cordis-Johnson & Johnson Interventional Fellowship (1997) and a NSHRF Fellowship (1998). The study would not have been possible without the unselfish support from radiographers, technicians and nursing staff of the Royal North Shore Hospital cardiac catheterisation laboratories as well as all staff involved from the Cardiology, Emergency and Cardiothoracic departments. References The GUSTO Angiographic Investigators. The effects of tissue plasminogen activator, streptokinase, or both on coronary-artery patency, ventricular function, and survival after acute myocardial infarction. N Engl J Med 1993; 329: 1615-1622. Califf RM, White H, Van de Werf F, et al. One-year results from the global utilization of streptokinase and TPA for occluded coronary arteries (GUSTO-I) trial. Circulation 1996; 94: 1233-1238. Ross AM, Coyne KS, Moreyra E, et al, for the GUSTO-I Angiographic Investigators. Extended mortality benefit of early postinfarction reperfusion. Circulation 1998; 97: 1549-1556. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomized trials of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988; 2: 349-360. The GUSTO investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 1993; 329: 673-682. Meijer A, Verheugt FWA, Werter CJPJ, et al. Aspirin versus coumadin in the prevention of reocclusion and recurrent ischemia after successful thrombolysis: a prospective placebo-controlled angiographic study. Circulation 1993; 87: 1524-1530. Grines CL, Browne KF, Marco J, et al. A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. N Engl J Med 1993; 328: 673-679. Zijlstra F, de Boer JM, Hoorntje JC, et al. A comparison of immediate coronary angioplasty with intravenous streptokinase in acute myocardial infarction. N Engl J Med 1993; 328: 680-684. Gibbons RJ, Holmes DR, Reeder GS, et al. Immediate angioplasty compared with the administration of a thrombolytic agent followed by conservative treatment for myocardial infarction. N Engl J Med 1993; 328: 685-691. The GUSTO-IIb angioplasty substudy investigators. A clinical trial comparing primary coronary angioplasty with tissue plasminogen activator for acute myocardial infarction. N Engl J Med 1997; 336: 1621-1628. Stone GW, Grines CL, Browne KF, et al. Predictors of in-hospital and 6 month outcome after acute myocardial infarction in the reperfusion era: the Primary Angioplasty in Myocardial Infarction (PAMI) trial. J Am Coll Cardiol 1995; 25: 370-377. Ohman EM, Califf RM, Topol EJ, et al. Consequences of reocclusion after successful reperfusion therapy in acute myocardial infarction. Circulation 1990; 82: 781-791. Weaver WD, Simes J, Amadeo B, et al. Comparison of primary coronary angioplasty and intravenous thrombolytic therapy for acute myocardial infarction. A quantitative review. JAMA 1997; 278: 2093-2098. Stone GW, Brodie B, Griffin J, et al. Prospective, multicentre study of the safety and feasibility of primary stenting in acute myocardial infarction: In-hospital and 30-day results of the PAMI Stent Pilot Trial. J Am Coll Cardiol 1998; 31: 23-30. Suryapranata H, van't Hof AWJ, Hoorntje JCA, et al. Randomized comparison of coronary stenting with balloon angioplasty in selected patients with acute myocardial infarction. Circulation 1998; 97: 2502-2505. Antoniucci D, Santoro GM, Bolognese L, et al. A clinical trial comparing primary stenting of the infarct-related artery with optimal primary angioplasty for acute myocardial infarction. Results from the Florence Randomized Elective Stenting in Acute Coronary Occlusions (FRESCO) Trial. J Am Coll Cardiol 1998; 31: 1234-1239. Saito S, Hosokawa G. Primary Palmaz-Schatz stent implantation for acute myocardial infarction: the final results of Japanese PASTA (Primary Angioplasty vs Stent Implantation in AMI in Japan) trial [abstract]. Circulation 1997; 96: A3320. Serruys PW, Garcia-Fernandez E, Kiemeney F, et al. Stenting in acute MI: A pilot study as preamble to a randomized trial comparing balloon angioplasty and stenting [abstract]. Circulation 1997; 96: A1822. Grines CL, Schreiber TL, Savas V, et al. A randomized trial of low osmolar ionic versus nonionic contrast media in patients with myocardial infarction or unstable angina undergoing percutaneous transluminal coronary angioplasty. J Am Coll Cardiol 1996; 27: 1381-1386. The TIMI Study Group. The Thrombolysis in Myocardial Infarction (TIMI) Trial: Phase 1 findings. N Engl J Med 1985; 312: 1073-1092. Verheugt FWA, Liem A, Zijlstra F, et al. High dose bolus heparin as initial therapy before primary angioplasty for acute myocardial infarction: results of the heparin in early patency (HEAP) pilot study. J Am Coll Cardiol 1998; 31: 289-293. (Received 3 Jul 1998, accepted 15 Feb 1999) Authors' details Department of Cardiology, Royal North Shore Hospital, Sydney, NSW. Peter S Hansen, FRACP, Interventional Fellow. Helge H Rasmussen, DMSc, FRACP, Professor of Cardiology. John Vinen, FACEM, Director, Emergency Department. Gregory I C Nelson, FRACP, Director, Cardiac Catheterisation Laboratory and Coronary Care Unit. Reprints: Dr G I C Nelson, Department of Cardiology, Royal North Shore Hospital, St Leonards, NSW 2065. Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/> 1: Baseline clinical and angiographic characteristics of the study population (n = 102)Age in years, median (range) 60 (35-79)Women18 (18%)Hypertension (< 160/190 mmHg) 46 (45%)Diabetes mellitus13 (13%)Current cigarette smoking28 (27%)Hypercholesterolaemia (< 5.5 mmol/L)62 (61%)Family history of IHD47 (46%)Prior AMI14 (14%)Prior PTCA2 (2%)Prior CVA or transient ischaemic attack7 (7%)Infarct-related artery: Left anterior descending artery (40), diagonal branch of left anterior descending artery (1), left main coronary artery (1) 42 (41%) Right coronary artery40 (39%) Left circumflex artery (12), obtuse marginal artery (2)14 (14%) Saphenous vein graft2 (2%)No infarct-related artery identified (3), normal coronary arteries (1) 4 (4%)Multivessel disease48 (47%)Admission Killip class < I6 (6%)Killip class > I = the presence of either lung crepitations and a third heart sound gallop, frank pulmonary oedema or cardiogenic shock. PTCA = percutaneous transluminal coronary angioplasty. CVA = cerebrovascular accident. IHD = ischaemic heart disease. AMI = acute myocardial infarction. Back to textBack to textBack to text

Peter S Hansen · Helge H Rasmussen · John Vinen

For Debate The 100-year conflict: salt intake and cardiovascular disease MJA 1998; 169: 174-180 The health effects of dietary salt have long been debated. As early as the beginning of the 20th century, salt restriction was used as a therapeutic measure, first for oedema and then for hypertension, particularly in France.1 Later, in the United States, the benefits of low salt diets for patients with hypertension and renal disease were championed by Allen in the 1920s and 30s and by Kempner in the late 1930s and 40s.1 However, not all investigators were convinced of the value of these diets, and the hazards of overzealous and prolonged salt restriction were also appreciated.1 By the 1960s and 70s, studies linking an increase in blood pressure of indigenous populations with the introduction of salty Western diets persuaded government bodies to recommend reduced salt as part of healthy dietary guidelines. One of the eight Dietary Goals for Australia, announced in 1979 by the then Commonwealth Department of Health, was "Decrease consumption of salt".2 There are, however, many researchers who maintain that there is insufficient evidence of benefit to recommend universal salt restriction. A summary of this controversy, described as "a philosophical clash between the requirements of public health policy and the requirements of good science", appeared in Science last year.3 In the MJA the salt controversy is alive and well. A study by Beard et al published in 1997 showing a low level of conformity with the year 2000 dietary salt target for Australians (<100mmol/day)4 brought an immediate response from Kincaid-Smith, reminding readers of the possible dangers of low salt intake.5 Then, in March 1998, a study by Alderman et al in the Lancet, claiming to have found an inverse association between dietary salt intake and all-cause and cardiovascular disease mortality,6 revived the international controversy, to which the Lancet's letters columns attest.7-10 Here, we present our own salt debate, with three views of the value (or otherwise) of salt restriction as part of a healthy diet. Universal recommendations for sodium intake should be avoided Restriction of salt intake is needed too ameliorate the cardiovascular disease epidemic The salt dilemma: some answers, many questions Link to salt debate references Dr Derek Denton showed unequivocally that increased salt intake causes a substantial rise in blood pressure in chimpanzees.11 Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

At the end of the 20th century, the good news about rheumatic fever is that it has become so rare in most of Australia that many medical practitioners will never see a case. This is a dramatic change from the first half of the century; in Melbourne during the 1930s, more than 50% of paediatric hospital medical beds were occupied by children with acute rheumatic fever or acute poststreptococcal glomerulonephritis, with rheumatic fever patients outnumbering those with glomerulonephritis (Dr Howard E Williams, previously In-Patient Physician, Royal Children's Hospital, Melbourne, personal communication). The decline of rheumatic fever in affluent populations occurred largely as a result of economic development and improved living conditions, with perhaps a small contribution from antibiotics and the possibly altered virulence of circulating group A streptococcal strains.1 The bad news is that socially and economically disadvantaged populations worldwide, including some indigenous and minority populations living in affluent countries, continue to have high rates of rheumatic fever and rheumatic heart disease. The highest published incidence of acute rheumatic fever in the world is in Aboriginal people living in the "Top End" of the Northern Territory.2 In this population the annual incidence of acute rheumatic fever (1989-1993) is between two and seven cases for every 1000 children aged 5 to 14 years, while up to three per cent of all people in some of the remote Aboriginal communities have established rheumatic heart disease. In contrast, the prevalence of rheumatic heart disease in the non-Aboriginal population is 0.014 per cent, and no non-Aboriginal children had acute rheumatic fever over this five-year period.2 While rheumatic fever appears to occur in only a subset of any given population, there are no data to support any major predisposition based on ethnicity. Similar high rates were documented in non-Aboriginal people in Melbourne during the 1930s and 1940s.3 The current high rates of rheumatic fever in the Aboriginal population are not related to ethnicity, but are likely to reflect high levels of exposure to group A streptococci, which, in turn, are related to overcrowding and continuing poor living conditions.4,5 The World Health Organization has promoted the use of rheumatic fever registers in developing countries,6 with the major aims of coordinating individual patient management and improving adherence to secondary prophylaxis to prevent recurrent rheumatic fever and the associated cumul ative valve damage. Registers are useful not only for developing countries: a register-based program in New Zealand, with acute rheumatic fever as a notifiable disease, helped reduce from 22% to 6% the proportion of hospitalised cases of rheumatic fever which were recurrences.7 The Commonwealth Department of Health and Family Services, together with the Australian Institute of Health and Welfare, has taken the commendable step of funding a register-based control program in the Top End of the Northern Territory (Dr Vicki Krause, Director, Centre for Disease Control, Territory Health Services, Darwin, personal communication). This program will also involve new health promotion strategies in Aboriginal communities -- directed at both health and education staff and at people with rheumatic fever and rheumatic heart disease and their families. Videos, booklets and treatment charts have been developed by indigenous educators and researchers.8 The program will attempt to create a partnership for change, involving indigenous and non-indigenous health professionals and government and non-government health services. Secondary prophylaxis will reduce the number of people developing rheumatic heart disease or requiring intervention for worsening valvular damage, but it will not stop initial episodes of acute rheumatic fever. This is where rheumatic fever control becomes difficult. While efforts to address social and economic inequities, particularly living conditions and overcrowding in Aboriginal communities, cannot be overemphasised,4,5 in some remote communities substantial change in these areas has not been evident over the past two decades and, in the current economic climate, is unlikely, we believe, to occur for some time. Conventionally, primary prevention relies on the accurate diagnosis and timely treatment with penicillin of group A streptococcal pharyngitis. However, most developing countries do not have the finances, skilled staff or laboratory facilities to do this well. Furthermore, more than two-thirds of cases of acute rheumatic fever may not follow symptomatic pharyngitis,9 so concentrating only on sore throats probably will not prevent most cases of rheumatic fever. Important progress is being made towards the development of a group A streptococcal vaccine, including current Australian initiatives,10 but in the shorter term other approaches are needed. In one such approach, a program of regular throat swabbing and treatment of streptococcal carriers in one Aboriginal community appeared to coincide with fewer cases of rheumatic fever,11 although the program was not sustained over the long term.12 This program appears to be the sole published effort to improve primary prevention of acute rheumatic fever in an Aboriginal community. While an association between streptococcal skin sores and acute rheumatic fever remains speculative, clues to further primary prevention strategies may come from understanding the epidemiology of group A streptococcal diseases in Aboriginal communities -- where the prevalence of streptococcal pyoderma (skin sores) may be up to 70% in children, but throat carriage rates of group A streptococci are often low.13 The ongoing epidemic of scabies in Aboriginal communities must underlie much of the streptococcal skin disease. More research is needed to better understand the epidemiology and best management of sore throats, streptococcal pharyngitis and skin sores in Aboriginal communities, as well as the relationship between streptococcal throat and skin infections and rheumatic fever. In the meantime, primary prevention strategies should include measures to reduce the reservoir of circulating streptococci found in skin sores; coordinated programs to control skin sores and underlying scabies can be effective in Aboriginal communities.13 Successful primary prevention strategies developed in Australia could have global implications for rheumatic fever control. Rheumatic heart disease in Aboriginal communities can be controlled in the short term through the use of comprehensive strategies to improve adherence to secondary prophylaxis regimens and to reduce exposure to group A streptococci, and possibly, in the longer term, with a vaccine. However, the ultimate aim must be improved living conditions for Aboriginal people, including emphasis on water supply, taps and showers, the disposal of sewage and solid waste, and resources to support better hygiene.

Jonathan R Carapetis · Bart J Currie

Panic disorder and coronary artery spasm Whatever the causative mechanism, prolonged chest pain during panic attacks requires investigation MJA 1998; 168: 376-377 The three cases reported by Mansour et al1 in this issue of the Journal add to the evidence for increased risk of adverse cardiovascular events in people with severe anxiety. The existing evidence derives from both prospective epidemiological studies2,3 and controlled longitudinal clinical studies.4 In the latter, mortality was related to severity of emotional arousal; panic disorder patients were at greater risk of sudden cardiac death than patients with lesser forms of anxiety, such as generalised anxiety disorder. Two of the cases reported by Mansour et al (Patients 1 and 3) showed a close temporal association between panic attacks and ischaemic chest pain. In the absence of severe obstructive coronary disease, might the ischaemia be due to coronary artery spasm? Patient 1 presented with severe chest pain accompanying episodes of panic. An electrocardiogram (ECG) showed mild tachycardia and ST-segment depression, but no cardiac enzymes were released, and the coronary angiogram was normal. With subsequent panic attacks, the patient continued to experience anginal pain, which resolved completely after prescription of amlodipine (a potent dihydropyridine calcium antagonist known to prevent epicardial coronary spasm). Patient 3 had long-standing panic disorder and mild hypertension. He had acute ischaemic chest pain during a panic attack; cardiac enzyme levels were raised, and infarction was diagnosed. Angiography showed no underlying atherosclerosis. Angina-like chest pain occurred during subsequent panic attacks, but once again resolved completely after amlodipine therapy. The other patient (Patient 2) experienced an infarct associated with exercise rather than with an acute panic attack. Coronary angiography during the acute stage showed that the infarct-related artery was occluded, while the other coronary arteries were normal. The patient had a nine-year history of panic disorder, and previous panic attacks had been accompanied by chest pain. However, no chest pain occurred during post-infarction panic attacks, and there was no temporal relationship between panic attacks and the major ischaemic episode. Although coronary artery spasm is one of the plausible mechanisms for the cardiac ischaemia, none of these patients had convincing evidence of spasm during panic attacks. Spasm of an epicardial coronary artery usually results in ST-segment elevation, which accompanies transmural ischaemia. A definitive diagnosis of coronary spasm requires demonstration of ST-segment elevation, or spasm at angiography, during spontaneous angina or after provocation with ergonovine, acetylcholine or hyperventilation. In Patient 1, the ECG during chest pain showed ST-segment depression, while in Patient 3 no ECG changes were seen. While coronary spasm with ST-segment depression or even no ST changes has been reported, this is very uncommon. In Patient 1, the presence of tachycardia along with ST-segment depression raises the possibility of Syndrome X (angina-like chest pain with ST-segment depression, no demonstrable myocardial ischaemia and normal coronary arteries,5 which is not to be confused with the endocrinological Syndrome X, or insulin resistance metabolic syndrome6 ). Another possible explanation is the coronary "slow flow" phenomenon, which may be caused by microvascular spasm, although slow flow was not mentioned in the angiography report. Nevertheless, the complete resolution of angina in Patients 1 and 3 after treatment with amlodipine provides circumstantial evidence that spasm was involved. Radionuclide studies shed some light on a possible link between mental stress and coronary vasoconstriction. Subjects exposed to minor experimental stress have been shown to develop significantly reduced coronary perfusion and ischaemic abnormalities of left ventricular wall motion. These abnormalities are due to coronary vasoconstriction, but are limited to subjects with at least minor degrees of underlying coronary artery disease, and are more pronounced when this disease is more severe. Subjects with normal arteries do not show such changes.7 Similarly, coronary spasm in the setting of emotional problems was described in nine women with normal or near-normal arteries,8 but it was likely that most had at least minor atherosclerosis (ie, <25% narrowing). In two of the patients reported by Mansour et al, coronary vessels were normal (and possibly also in Patient 2 before occlusion), so induction of spasm or vasoconstriction with ischaemia seems inconsistent with the experimental studies. However, angiographically "normal" arteries may harbour minor atherosclerotic lesions that do not encroach on the lumen. In addition, the severe and overwhelming emotional stress and arousal typical of panic, which these patients doubtless experienced, contrasts with the relatively minor tasks with minimal emotional responses to which the experimental subjects were exposed. The coronary vascular responses to severe and minor stress may be quite different. For example, extreme rage induced myocardial infarction in dogs, although after a critical stenosis had been created in a coronary artery.9 Severe emotional arousal deserves further investigation. Wilkinson et al showed that patients with panic disorder have dramatic increases in epinephrine secretion and cardiac epinephrine spillover during panic, but that baseline levels and responses to mild experimental stress differ little from those of control subjects.10 Cardiac perfusion and functional studies during panic would be of interest, but would require panic attacks to be artificially induced in the laboratory. The absence of ECG changes in Patient 3, despite severe chest pain and significantly raised cardiac enzyme levels, raises an important issue about myocardial ischaemia. In the radionuclide studies mentioned above, significant decreases in perfusion or abnormalities in wall motion often occurred without ischaemic pain or ECG changes. Ischaemia can be electrocardiographically "silent", particularly in certain vascular distributions, such as that of the left circumflex coronary artery. Nevertheless, it must be unusual that ischaemia sufficient to produce necrosis should produce no ECG changes. These cases should raise clinician awareness of the potential association between severe anxiety and myocardial ischaemia, so that patients with chest discomfort and panic disorder are appropriately investigated. All patients with severe panic accompanied by prolonged chest pain should have cardiac enzyme levels measured, irrespective of ECG findings. While epicardial coronary artery spasm is a plausible explanation, further investigations are needed into the mechanisms of ischaemia in panic disorder. S Ben Freedman Professor, and Head, Department of Cardiology Concord Repatriation General Hospital, University of Sydney, NSW Christopher C Tennant Professor and Head, Department of Academic Psychiatry Royal North Shore Hospital, University of Sydney, Sydney, NSW Mansour VM, Dominic JC, Jennings GL, et al. Panic disorder: coronary spasm as a basis for cardiac risk? Med J Aust 1997; 168: 390-392. Kawachi I, Sparrow D, Vokonas PS, Weiss ST. Symptoms of anxiety and risk of coronary heart disease. Circulation 1994; 90: 2225-2229. Kawachi I, Colditz GA, Ascherio A, et al. Prospective study of phobic anxiety and risk of coronary heart disease in men. Circulation 1994; 89: 1992-1997. Coryell W, Noyes R, Clancy J. Excess mortality in panic disorder. A comparison with primary unipolar depression. Arch Gen Psychiatry 1982; 39: 701-703. Cannon RO. Does coronary endothelial dysfunction cause myocardial ischemia in the absence of obstructive coronary artery disease? Circulation 1997; 96: 3251-3254. Alford FP. Syndrome X (insulin resistance metabolic syndrome): a deadly quartet or an awesome foursome? Med J Aust 1996; 164: 4-5. Tennant C. Experimental stress and cardiac function. J Psychosom Res 1996; 40: 569-583. Bashour T, Hakim O, Cheng TO. Coronary spastic angina in middle-aged women: a psychosomatic disorder? Am Heart J 1983; 106: 609-613. Verrier RL, Hagestad EL, Lown B. Delayed myocardial ischemia induced by anger. Circulation 1987; 75: 249-254. Wilkinson DJC, Thompson JM, Lambert GW, et al. Sympathetic activity in patients with panic disorders at rest, under laboratory mental stress and during panic attacks. Arch Gen Psychiatry 1998. In press. Reprints: Professor S Ben Freedman, Department of Cardiology, Concord Repatriation General Hospital, Hospital Road, Concord, Sydney, 2137. - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Christopher C Tennant

Panic disorder: coronary spasm as a basis for cardiac risk? Virginia M Mansour, Dominic J C Wilkinson, Garry L Jennings, Rosemary G Schwarz, Jane M Thompson and Murray D Esler For editorial comment see Freedman & Tennant Patients with panic disorder often complain of angina-like chest pain during panic attacks, but this is not usually considered life-threatening. We describe three patients with panic disorder and documented cardiac ischaemia during episodes of chest pain. In two, it progressed to myocardial infarction. As none had atherosclerosis evident at coronary angiography, the mechanism was presumed to be coronary artery spasm. These cases illustrate that pain typical of angina during panic attacks may have an organic cause. (MJA 1998: 168; 390-392) Introduction - Case records - Discussion - Acknowledgement - References - Authors' details - - ©MJA1998 Introduction Panic disorder is characterised by unpredictable and overwhelming feelings of fear accompanied by various symptoms of sympathetic nervous system arousal, such as sweating, palpitations, diarrhoea, and tremor.1 Often, angina-like chest pain is also present, but detailed cardiac "workup" in patients with panic disorder typically shows no abnormalities. Thus, although panic disorder is distressing and disabling, it has not been thought life-threatening. However, recent well conducted, prospective epidemiological studies show substantially increased risk of myocardial infarction and sudden death in patients with panic disorder (three- to six-fold increase).2,3 These patients sit at the crossroads of cardiology and neuropsychiatry, and provide a clinical model for investigation of the relationship between stress and heart disease. The mechanism by which cardiac risk is increased in panic disorder is not known, but has been thought to involve activation of the sympathetic nerves of the heart, predisposing to ventricular arrhythmias. We present three patients with panic disorder and chest pain whose cases suggest coronary artery spasm as a pos sible mechanism. Case records All three patients met the diagnostic criteria for panic disorder of the Diagnostic and statistical manual of mental disorders (4th edition),4 and all were non-smokers. Patient 1 A 34-year-old woman presented to a hospital casualty department in November 1996 with severe chest pain radiating to her left arm and shortness of breath after having taken cocaine. She also complained of palpitations, dizziness, tremor, and an overwhelming sense of doom and fear. She had taken cocaine occasionally over the previous two years without panic symptoms. An electrocardiogram (ECG) showed inferolateral ST-segment depression suggesting ischaemia. The pain eased with sublingual nitroglycerine and intramuscular morphine. A thallium exercise stress test two weeks later gave normal results. The patient presented again a month later with recurrent episodes of severe chest pain accompanying panic attack symptoms. She had stopped using cocaine after the first panic attack. An ECG taken during persisting pain again showed inferolateral ST-segment depression (Figure 1, below). Serum creatine kinase (CK) levels were normal. Coronary angiography during subsequent hospital admission (when the patient was free of pain) showed a normal coronary arterial tree (Figure 1). The patient was prescribed the selective serotonin reuptake inhibitor paroxetine (20 mg, increasing to 40 mg, daily), low dose aspirin (100 mg daily) and alprazolam (0.5 mg daily). Over two months' follow-up, panic attacks were less frequent, but chest pain recurred with each. After the addition of the slow calcium-channel blocker amlodipine (5 mg daily), her infrequent panic attacks were pain-free. Patient 2 A 42-year-old woman suffered anteroseptal infarction in November 1996 after exercise. Although she had no antecedent panic attack, she had a nine-year history of panic disorder, with panic attacks commonly associated with chest pain. She had been jogging as usual that morning without any symptoms, and presented later in the day with chest tightness and left-arm pain. A 12-lead ECG (Figure 2, below) showed anteroseptal ST-segment elevation consistent with acute myocardial infarction. Acute coronary angiography (Figure 2) showed total occlusion of the left anterior descending coronary artery in its mid portion. Treatment with balloon angioplasty and abciximab (an inhibitor of platelet aggregation) achieved complete recanalisation, and the pain resolved. No atherosclerosis was evident in the coronary arterial tree. Although a vasodilator was not given during angiography, the treating cardiologist described the angiogram as indicating development of fresh thrombus at a site of spasm in an otherwise normal coronary artery. Low dose aspirin and amlodipine (5 mg daily) were prescribed. The patient had further panic attacks (without chest pain) until paroxetine (20 mg daily) was also prescribed. Patient 3 A 46-year-old man presented to a casualty department in October 1996 with severe chest pain during a panic attack. He had long-standing panic disorder and a 15-year history of mild essential hypertension treated by propranolol (40 mg daily). His ECG was normal in the casualty department, and he was not admitted. The chest pain failed to resolve over the next 10 hours and he attended his family doctor, who found a raised serum CK level and arranged urgent hospital admission. His serum CK level rose progressively in hospital, peaking at 518 U/L (normal range [NR], 0-130 U/L), with CK MB isoenzyme level 66 U/L (NR, 0-10 U/L), leading to a diagnosis of myocardial infarction. Coronary angiography 14 days later, when the patient was free of pain, gave normal results, with no evidence of atherosclerosis. Over the ensuing eight months, the patient had increasingly frequent panic attacks accompanied by angina-like pain. He was prescribed paroxetine (20 mg, increasing to 40 mg, daily) and alprazolam (0.5 mg daily). Although the panic attacks became less frequent when the daily paroxetine dose was increased to 40 mg, chest pain persisted until amlodipine (5 mg daily) and aspirin (100 mg daily) were added to the regimen. Discussion These three patients with panic disorder had otherwise inexplicable episodes of cardiac ischaemia. In all three, the panic attacks were typically accompanied by chest pain. In two, the documented ischaemic events (angina with ST-segment depression in one and myocardial infarction in the other) occurred during a panic attack. In the third, while myocardial infarction was associated with exercise rather than a panic attack, there was a long prior history of panic attacks with chest pain. None of the three had atherosclerosis evident on coronary angiography, and two were women with no classical cardiac risk factors. Coronary artery spasm was thought to be the underlying mechanism of the ischaemia in all three cases. In some circumstances, patients with primary cardiac arrhythmias can be misdiagnosed as having panic disorder.5 Similarly, it might perhaps be argued that our patients had variant angina, with the anxiety disorder developing after a period of misdiagnosis of the cause of the chest pain, so that the myocardial ischaemia was a cause rather than a consequence of the panic disorder. However, in Patients 2 and 3 the diagnosis of panic disorder antedated the development of chest pain during panic attacks, while in Patient 1 angina-like pain was a feature of the first and of most subsequent panic attacks. The mechanism by which coronary spasm develops in panic disorder is not clear. Cigarette smoking can underlie coronary spasm, but our three patients were non-smokers. Hyperventilation, often a concomitant of a panic attack, can precipitate coronary spasm in the presence of atheroma6 and even in coronary arteries free of atherosclerosis.7 Patients who had spontaneous panic attacks in the research laboratory have shown a substantial increase in adrenaline secretion and sympathetic nervous system activity. 8 However, adrenaline typically increases, rather than decreases, coronary blood flow by means of b -adrenergic coronary vasodilatation.9 Similarly, sympathetic nervous system stimulation usually causes coronary vasodilatation and increases flow, partly through the attendant metabolic myocardial stimulation, but also through direct effects on the vasculature.9 In some circumstances, disorders of coronary vasomotion have been linked to dysfunction of the vascular endothelium. Endothelial function was not assessed in our patients, but such tests would be relevant for future prospective studies given that the mechanism of presumed spasm remains elusive. We suspect that coronary spasm is not uncommon during panic attacks, particularly in patients with typical angina-like pain, and that panic disorder may be an undetected cause of otherwise inexplicable coronary heart disease, especially in premenopausal women, who are otherwise at low cardiac risk. It may possibly overlap clinically with "Syndrome X", a poorly understood condition in which recurrent myocardial ischaemia occurs despite the presence of structurally normal coronary arteries. This condition, not to be confused with the endocrinological Syndrome X (insulin metabolic resistance syndrome),11 seems to result, not from coronary spasm, but from reduced myocardial flow reserve caused by a functional abnormality in the cardiac microcirculation.10 Formal testing involving measurements of coronary blood flow under conditions which increase it reflexly, such as exercise, would be needed to exclude this syndrome. An understanding of the mechanism of coronary spasm in panic disorder would facilitate therapeutic intervention. At present, we treat patients with panic disorder and clinical evidence of coronary spasm with drugs and other measures aimed at preventing or minimising their panic attacks,1 a slow calcium-channel blocker as a non-specific antispasm measure, and low dose aspirin as prophylaxis against coronary thrombosis during spasm. It is difficult to know how far to pursue cardiac testing in patients with panic disorder. As we believe their level of cardiac risk is low overall, we recommend selective investigation of those with typical angina-like pain during panic attacks. Capturing ECG evidence of myocardial ischaemia during a panic attack, either during clinic or emergency department attendance or on Holter monitoring, is of central clinical relevance. While it is important to exclude the presence of fixed coronary artery stenosis (which may coexist, particularly in older patients), standard provocative ischaemia testing is not entirely satisfactory; exercise or vasodilator pharmacological challenges are inappropriate for behaviourally induced ischaemia. Panic attacks can be induced in some patients by breathing a mixture of carbon dioxide (10%-15%) and oxygen.12 ECG or thallium stress testing using this stimulus as a challenge is worth future research evaluation. Panic disorder may provide a useful clinical model for studying the possible link between stress and heart disease. A direct relationship between mental stress and sudden death has been seen in special circumstances, such as inherited long-QT-interval syndromes, in which there is electrical instability of the heart muscle.13 In addition, rates of non-traumatic sudden death were markedly increased in people with underlying coronary disease during the 1994 Los Angeles earthquake.14 However, research on stress and heart disease has been hampered by disagreement over what constitutes stress and how to measure it. In panic disorder, the episodes of recurring, often inexplicable, anxiety can be regarded as repeated mental stress reactions. The study of cardiac risk during panic attacks may be a valid method for testing the general proposition that the clinical endpoints of ischaemic heart disease can be "triggered" by stressful events. Acknowledgement This work was supported by a Project Grant from the National Heart Foundation of Australia and an Institute Grant to the Baker Medical Research Institute from the National Health and Medical Research Council of Australia. The contributions of Dr David Prior and Sister Leonie Johnston in the research cardiac catheter laboratory are gratefully acknowledged. The authors also wish to thank Dr Emmanuel G Manolas for provision, through the Epworth Hospital, of clinical and angiographic findings on his patient. References Agras WS. The diagnosis and treatment of panic disorder. Annu Rev Med 1993; 44: 39-51. Kawachi I, Colditz GA, Ascherio A, et al. Prospective study of phobic anxiety and risk of coronary heart disease in men. Circulation 1994; 89: 1992-1997. Kawachi I, Sparrow D, Vokonas PS, Weiss ST. Symptoms of anxiety and risk of coronary heart disease. Circulation 1994; 90: 2225-2229. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994: 394-403. Lessmeier TJ, Gamperling D, Johnson-Liddon V, et al. Unrecognized paroxysmal supraventricular tachycardia. Potential for misdiagnosis as panic disorder. Arch Intern Med 1997; 157: 537-543. Girotti LA, Crosatto JR, Messuti H, et al. The hyperventilation test as a method for developing successful therapy in Prinzmetal angina. Am J Cardiol 1982; 49: 834-841. Yasue H, Nagao M, Omote S, et al. Coronary arterial spasm and Prinzmetal's variant form of angina induced by hyperventilation and Tris-buffer infusion. Circulation 1978; 58: 56-62. Wilkinson DJC, Thompson JM, Lambert GW, et al. Sympathetic activity in patients with panic disorder at rest, under laboratory mental stress and during panic attacks. Arch Gen Psychiatry 1998. In press. Hjemdahl P. Physiology of the autonomic nervous system as related to cardio vascular function: implications for stress research. In: Byrne DG, Rosenman RH, editors. Anxiety and the heart. New York: Hemisphere Publishing, 1990: 95-158. Fragasso G, Rossetti E, Dosio F, et al. High prevalence of the thallium-201 reverse redistribution phenomenon in patients with Syndrome X. Eur Heart J 1996; 17: 1482-1461. Alford FP. Syndrome X (insulin resistance metabolic syndrome): a deadly quartet or an awesome foursome? Med J Aust 1996; 164: 4-5. Battaglia M, Perna G. The 35% CO 2 challenge in panic disorder: optimization by receiver operating characteristics (ROC) analysis. J Psychiatr Res 1995; 29: 111-119. Zipes DP. The long QT interval syndrome. A rosetta stone for sympathetically mediated ventricular tachyarrhythmias. Circulation 1991; 84: 1414-1419. Leor J, Poole WK, Kloner RA. Sudden cardiac death triggered by an earthquake. N Engl J Med 1996; 334: 413-419. (Received 28 Aug 1997, accepted 21 Jan 1998) Authors' details Baker Medical Research Institute, Melbourne, VIC. Virginia M Mansour, MB BS, Clinical Research Associate; Jane M Thompson, MB BS, Clinical Research Associate; Murray D Esler, PhD, FRACP, Associate Director. Melbourne University, Melbourne, VIC. Dominic J C Wilkinson, BMedSci, Medical Student. Alfred Hospital Heart Centre, Melbourne, VIC. Garry L Jennings, MD, FRACP, Director. Medical Advisory Committee, The Melbourne Clinic, Melbourne, VIC. Rosemary G Schwarz, FRANZCP, Chair. Reprints: Professor M D Esler, Human Neurotransmitter Research Laboratory, Baker Medical Research Institute, PO Box 348, Prahran, VIC 3181. E-mail: Esler AT Baker.edu.au Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Virginia M Mansour · Garry L Jennings · Rosemary G Schwarz · Jane M Thompson · Murray D Esler

Apolipoprotein screening in Australian children: feasibility and the effect of age, sex, and ethnicity Judith F Lynch, Michelle D Marshall, Xing L Wang and David E L Wilcken MJA 1998; 168: 61-64 Abstract - Introduction - Methods - Results - Discussion - References - Authors' details - - ©MJA1998 Abstract Objectives: (i) To evaluate the feasibility of detecting adverse lipid profiles in schoolchildren by measuring capillary dried blood spot apolipoprotein levels, and (ii) to assess the effect of age, sex and ethnicity on apolipoprotein levels. Design: We measured capillary dried blood spot apolipoproteins B and A-I (apo B and apo A-I); assessed levels in relation to age, sex and ethnicity; and recalled children with elevated levels for a full lipid profile measurement. Participants and setting: 6992 children (3501 boys and 3491 girls), aged 5-13 years, from schools in eastern Sydney, 1991-1995. Main outcome measures: Capillary blood levels of apolipoproteins B and A-I, and serum total cholesterol level. Results: Of the 6951 children who provided an adequate fingerprick blood sample, we recalled 1465 children (21.1%) (640 boys [43.7%] and 825 girls [56.3%]) with elevated apo B levels and/or apo B : apo A-I ratios for further testing, either by us or by their family doctor (overall estimated compliance rate up to 70%). Among the 458 children who returned to us, there was a 90% positive predictive value for a total cholesterol level of over 4.5 mmol/L in those with both elevated apo B levels and high apo B : apo A-I ratios. Girls had higher apo B levels and apo B : apo A-I ratios than boys (P < 0.00001 for both), and in both sexes there was a trend downwards for apo B and upwards for apo B : apo A-I ratio over the age range tested, but levels were relatively stable between the ages of 6 and 10 years. Indian children (1.5% of the screened population) had the highest apo B levels, followed by white children (71.1%); Asian children (9.2%) had the lowest (P < 0.00001 compared with Indian and white children). Conclusions: The high positive predictive value of capillary blood apolipoprotein levels for an adverse lipid profile in children suggests that measuring apolipoprotein levels by this method is a useful initial approach to cardiovascular risk assessment. Introduction Despite a recent decline in cardiac deaths, coronary disease is still the largest single cause of premature death in Australia.1 It is known that atherogenesis, the underlying pathological process, may begin in childhood;2,3 that relevant risk factors may track from childhood to adulthood (particularly elevated levels of total and low-density lipoprotein [LDL] cholesterol and increased body weight); and that these factors tend to aggregate within families.4,5 With these considerations in mind, we explored the feasibility of screening for adverse lipid profiles in a target group of primary schoolchildren, with the aim of implementing family-based coronary prevention by secondarily identifying any parents at risk. We measured levels of apolipoprotein B (apo B), the carrier protein for the atherogenic LDL cholesterol, and apolipoprotein A-I (apo A-I), the principal carrier protein for the antiatherogenic high density lipoprotein (HDL) cholesterol, in capillary dried blood spots from 6992 primary schoolchildren aged 5-13 years. There is increasing evidence that high apo B and low apo A-I levels are as reflective of cardiovascular risk as are their respective lipoproteins.6 We describe here the positive predictive value of high apo B and/or apo B : apo A-I ratio for elevated total cholesterol levels and the effects of age, sex and eth nicity on lipid levels in Australian children. Methods School and population demographics We received permission from 70 schools in eastern Sydney (public primary schools, 45%; Catholic primary schools, 29%; and private fee-paying schools, 26%) to contact parents and offer them the option of their child participating in a "Heart Health Screening Program". Children were given consent forms to take home to their parents. On the forms, we asked for the country of origin of each family, and this information was confirmed by a family history questionnaire (sent to all parents within a week of the testing at school) asking each parent to identify their country of origin. Only 1% of the total declined to answer this question (the "unknown" group) (Table 1). Blood collection and apolipoprotein measurement Testing took place between 1991 and 1995. From each child we obtained a capillary blood sample by fingerprick, which was spotted directly onto filter paper (No. 903: Schleicher & Schuell Inc., Keene, NH, USA), allowed to air dry and stored at 2 70¡C until analysis. Concentrations of dried blood spot apo B, apo A-I and lipoprotein (a) (Lp(a)) were measured within two weeks by our previously described enzyme-linked immunosorbent assay methods,7-9 and from these results an apo B : apo A-I ratio was also calculated. These methods allowed us to carry out all three measurements on one small (minimum, 20 µL sample) capillary dried blood spot. We report here the results obtained for measurement of apo B and apo A-I only. Recall In the first school tested, we established the frequency distribution for apo B levels and apo B : apo A-I ratios and set the level for recall for each of these as at or above the 90th percentile. These cut-off points were adjusted from the apo lipoprotein results obtained from each of the next seven schools. However, a stable cut-off level was reached by the third school. We defined three categories of children for recall: those with an ele vated apo B level only (Criterion 1), those with a combination of elevated apo B level and apo B : apo A-I ratio (Criterion 2), and finally those with an elevated apo B : apo A-I ratio only (Criterion 3). We notified the parents of the children for recall by letter, explaining the results and suggesting that both parents, the child, and any other siblings might come to us for further lipid testing, or attend their family doctor. In those who returned to us, we measured total cholesterol level, as well as HDL cholesterol and triglyceride levels, in a venous blood sample by standard methods. LDL cholesterol level was calculated by the Friedewald formula,10 and we also measured serum apo B, apo A-I and Lp(a) by the methods outlined above.7-9 The parents of children with apo B levels and apo B : apo A-I ratios below the established cut-off points were also sent a letter explaining that their children's levels currently fell below the recall criteria. These families were sent a healthy lifestyle pamphlet specifically directed to maintaining a low level of cardiovascular risk; they were also asked if they would like to volunteer as a healthy control family and have complete lipid profiles measured as above. Statistical analysis As the distributions of age, apo B and apo A-I levels, and apo B : apo A-I ratios were normal, analyses by parametric methods were appropriate. We used one-way analysis of variance (ANOVA) for comparisons of measured quantitative variables when there were more than two groups; for example, when children were divided according to high apo B, high apo B : apo A-I ratio, or both, as categorical variables, and levels of total cholesterol and LDL cholesterol, and total cholesterol to HDL cholesterol ratio as the continuous outcome variables. When the comparison was between two groups -- for example, when lipid values were compared in girls and boys as categorical determinants -- Student's t test was used.11 We employed a chi-squared comparison for assessing associations between categorical variables, and used the SPSS statistical software package for all analyses.12 Ethical approval The study was approved by the ethics committee of the University of New South Wales. Results Initial testing The parental consent rate to initial testing was 63.9%. There were 6992 children aged 5-13 years available for testing, 3501 (50.1%) boys and 3491 (49.9%) girls. Only 41 children (0.6%) failed to provide an adequate finger-prick blood sample on the day, leaving a total population of 6951 children tested. Recall population The cut-off point for apo B level was set at 0.550 g/L or more and for the apo B : apo A-I ratio 1.200 or more. We recalled 1465 children (or 21.1% of the population tested). Of these recalls, 65.3% were for elevated apo B only (Criterion 1), 19.6% for elevated apo B and apo B : apo A-I ratio (Criterion 2), and 15.1% for elevated apo B : apo A-I ratio only (Criterion 3). In all, 458 of the children recalled returned with their families to our laboratory for lipid studies (31.2% compliance rate). To obtain an assessment of how many may have been seen by their family doctor (the other option we suggested), we contacted 205 of the remaining 1007 families. Among these, 118 had seen their family doctor for follow-up, and 89 had either moved or were not interested in further testing. This suggested an overall compliance rate of about 70%, if this sample was representative. Of the non-recalled "normal" population of 5486 (78.9%), only 151 families (2.7%) volunteered for lipid testing, an insufficient number for meaningful statistical analysis. Predictive value We used the results of the 458 children who returned for a full lipid profile to assess the positive predictive value of our screening method. The National Heart Foundation of Australia recommends a total cholesterol level of 4.5 mmol/L as the upper limit for children in this age range.13 With a level of over 4.5 mmol/L as the endpoint, Criterion 1 (elevated apo B only) had a positive predictive value of 84% (95% confidence interval [CI], 80%-88%), and with Criterion 2 (elevated apo B level and apo B : apo A-I ratio combined) the predictive value increased to 90% (95% CI, 85%-95%). However, Criterion 3 (elevated apo B : apo A-I ratio only) yielded only 66% (95% CI, 54%-77%), possibly reflecting children with low HDL cholesterol and normal total cholesterol levels. Raising the cut-off point did not substantially improve the positive predictive value of our screening method. When the cut-off point for apo B was increased from 0.550 g/L to 0.700 g/L, for example, the positive predictive value of Criterion 2, the most strongly predictive, only increased to 94% (95% CI, 91%-97%). ANOVA confirmed the association between high apo B levels from analysis of dried blood spot and an adverse lipid profile, and also that a combined high apo B level and apo B : apo A-I ratio was a stronger predictor. In this analysis, criteria established by high apo B, high apo B : apo A-I ratio and a combination of both were determinant categorical variables, and the total cholesterol and LDL cholesterol levels and total chol es terol to HDL cholesterol ratio were the continuous outcomes. Total (P < 0.0006) and LDL cholesterol (P < 0.0014) levels and the total cholesterol to HDL cholesterol ratio (P < 0.0006) were all significantly higher in Criterion 2 than in Criterion 1 or Criterion 3 (Table 2). Sex, age and ethnicity There was a highly significant difference in the apo B and apo B : apo A-I ratio levels between boys and girls (P < 0.00001 for each) (Figures 1 and 2), but no difference (P = 0.6) in apo A-I levels (data not shown). The girls had consistently higher apo B levels and apo B : apo A-I ratios over the age range studied (Figures 1 and 2). This resulted in a significant difference in the recall rate between girls and boys (chi-squared = 23.362; P < 0.00001). This sex difference was also reflected in the total cholesterol levels of children returning for further lipid tests (data not shown). As shown in Figures 1 and 2, there was a downward trend in apo B level and an upward one in apo B : apo A-I ratio in boys over the age range screened, while the opposite was observed in girls; but levels were relatively consistent in both between the ages of 6 and 10 years. Most of the 6951 children screened were white (71.1%); the remainder were of diverse ethnic origins (Table 1). The mixed-race group (8.3% of the total) included white/Asian (28.2%), white/Arabic (17.8%), white/South American (10.7%), and other combinations (56.7%). As age was a significant contributor to apo B concentrations, we compared the "age adjusted apo B levels" for both boys and girls to assess potential differences between major ethnic groups (Figure 3). Indian children had the highest apo B levels, followed by white children. Asian children had the lowest levels and these were significantly different from those of the Indian, white, mixed-race and South American children (P < 0.00001 for each). We did not include black, Australian Aboriginal or Pacific Islander ethnic groups in this analysis because of small numbers and highly skewed age distributions. In all ethnic groups, girls had higher levels than boys (Figure 3). Discussion We have established previously that apolipoprotein measurements provide a convenient and effective approach to the detection of dyslipidaemia,14 and that apo B levels in children are correlated with the occurrence of coronary events in their grandparents, which highlights the relevance of measurements in children to assessing risk of vascular disease in older family members.15 We have also established a clear-cut association between increased apo B levels and apo B : apo A-I ratios and body mass index in Australian children.16 Here, we extend these find ings by demonstrating the feasibility of screening of schoolchildren's capillary blood apolipoprotein levels as an approach to family-based primary coronary prevention. Although we do not have adequate data to determine the sensitivity or specificity of our screening method, the presence of both an elevated apo B level and raised apo B : apo A-I ratios had a positive predictive value of 90% for the detection of elevated total serum cholesterol level. Raising the apolipoprotein cut-off points only improved the predictive value to 94%. This method identified elevated apolipoprotein levels in 21.1% of our population, of whom 90% had elevated total cholesterol levels. Screening for apolipoprotein levels may be more relevant than screening for total cholesterol levels alone, as total cholesterol level does not show the interrelations between levels of the atherogenic LDL and the antiatherogenic HDL cholesterol.17 In a small number of children (0.48%) apo B levels were elevated without elevation of total cholesterol level.18 These families were also provided with dietary and lifestyle advice as this may also be associated with increased cardio vascular risk. Our findings clearly show highly significant differences between boys and girls at this age, with girls having higher apo B levels and apo B : apo A-I ratios than boys. We suspect this biological difference, which was evident before the onset of puberty in both boys and girls, to be hormonally based, although we have no data to support this. The vari ation in apolipoprotein levels within the age range studied could also be hormonally based. Whatever the mech anisms, these same age-related sex differences have been identified in several other studies in children.19,20 The consistency of these results clearly indicates a need to have different cut-off points in boys and girls for elevated apolipoprotein levels. Our results also define the age range (between 6 and 10 years) when levels are most stable and most appropriate for screening, findings which will be incorporated into future studies. There were uniform sex-related differences in apolipoprotein levels in each of the racial groups in our population, as well as very significant differences in levels between the various ethnic groups, as has also been found in previous studies.21,22 In our population, Indian and white children had the highest apo B and apo B : apo A-I ratios and Asian children had the lowest. It is well established that Chinese and Japanese populations have much lower cholesterol levels than whites and a correspondingly lower prevalence of coronary artery disease. Indian populations have a higher prevalence of cardiovascular disease.23 While these variations may relate to the genetic background of each ethnic group, diet and lifestyle undoubtedly make major contributions, and this is particularly evident in non-Western groups who have moved to live in a Western society. The higher prevalence of coronary disease in Indians living in the United Kingdom, for example, is well documented.24 Ethnic differences may become blurred with time if dietary habits become more uniform, and this has occurred among Asians emigrating to the United States and the United Kingdom; within a generation they acquired local lifestyles and a correspondingly higher prevalence of coronary artery disease than that in the communities they had left.25,26 In conclusion, our study demonstrates the feasibility of conducting a program of measuring apolipoprotein levels in capillary blood samples to assess lipid profiles in children to facilitate family-based coronary prevention. It documents wide acceptance by both schools and parents. Implicit in such a study is the potential for a multiplier effect in that, if a child has an elevated apolipoprotein level and therefore an adverse lipid profile, it is very likely that this will also be seen in at least one parent and other siblings.27 Our ongoing screening program requires the establishment of a concurrent intervention program to improve dietary and lifestyle habits of affected children and their parents. This is of more immediate relevance to affected parents as they are approaching the age of overt coronary disease. However, the program provides an ideal opportunity to establish healthy lifestyles in young children at a time of easy acceptance, and with the potential for preventing a disorder that may have its origins in childhood.28 References Heart and Stroke Facts. A report by the National Heart Foundation of Australia. Canberra: NHFA, 1996. Stary HC. Evolution and progression of atherosclerotic lesions in coronary arteries of children and young adults. Arteriosclerosis 1989; 9(1 Suppl): I19-I32. Tracy RE, Newman WP, Wattigney WA, Berenson GS. Risk factors and atherosclerosis in youth autopsy findings of the Bogalusa Heart Study. Am J Med Sci 1995; 310(Suppl 1): S37-S41. Berenson GS, Wattigney WA, Bao W, et al. Rationale to study the early natural history of heart disease: the Bogalusa Heart Study [review]. Am J Med Sci 1995; 310(Suppl 1): S22-S28. Sanchez-Bayle M, Gonzalez-Requjo A, Ruiz-Jarabo C, et al. Serum lipids and lipoproteins in Spanish children and adolescents: a 5 year follow-up. Acta Paediatr 1996; 85: 292-294. Bao W, Srinivassan SR, Berenson GS. Tracking of serum apolipoproteins A-I and B in children and young adults: the Bogalusa Heart Study. J Clin Epidemiol 1993; 46: 609-616. Wang XL, Dudman NP, Wilcken DE. Enzyme-linked immunosorbent assay of apolipoprotein B in blood spotted onto filter paper, suitable for neonatal screening. Clin Chem 1989; 35: 1000-1004. Wang XL, Dudman NP, Blades BL, Wilcken DE. Changes in the immunoreactivity of apo A-I during storage. Clin Chem 1989; 179: 285-293. Wang XL, Wilcken DE, Dudman NP. An indirect sandwich ELISA for Lp(a) in serum and dried blood spots. Clin Chim Acta 1992; 207: 73-86. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499-502. Norusis MJ. General factorial analysis of variance. SPSS for Windows Advanced Statistics, release 6.0. Chicago: SPSS Inc, 1993: 31-56. McNeil D. Statistical methods II: one-way analysis of variance. In: McNeil D, editor. Epidemiological research methods. New York: John Wiley & Sons, 1996: 66-71. National Diet and Heart Disease Advisory Committee, National Heart Foundation of Australia. Guide to plasma lipids for doctors. Curr Therap 1992; 10(Suppl 1): S1-S8. Wang XL, Wilcken DE, Dudman NP. Apolipoprotein A- I and B and the B/A-I ratio in the first year of life. Pediatr Res 1991; 30: 544-549. Wilcken DEL, Wang XL, Greenwood J, Lynch JF. Lipoprotein (a) and apolipoproteins B and A-I in children and coronary vascular events in their grandparents. J Pediatr 1993; 123: 519-526. Wilcken DE, Lynch JF, Marshall MD, et al. Relevance of body weight to apolipoprotein levels in Australian children. Med J Aust 1996; 164: 22-25. Taylor CJ, Olpin S, Rattenbury J, et al. Familial hyper cholesterolaemia: pilot study to identify children at risk. J Clin Pathol 1993; 46: 730-733. Grundy S. Small LDL. Atherogenic dyslipidaemia and the metabolic syndrome. Circulation 1997; 95: 1-4. Resnicow K, Morley-Kotchen J, Wynder E. Plasma cholesterol levels of 6585 children in the United States: results of the know your body screening in five states. Pediatrics 1989; 84: 969-976. Christensen B, Glueck C, Kwiterovich P, et al. Plasma cholesterol and triglyceride distributions in 13,665 children and adolescents: the Prevalence Study of the Lipid Research Clinics Program. Pediatr Res 1980; 14: 194-202. Zhang W, Evans AE, Cambien F, et al. Distribution of lipid variables in subjects in Belfast, Northern Ireland and Taiyuan, PR China. Atherosclerosis 1993; 102: 175-180. Freedman DS, Lee SL, Byers T, et al. Serum cholesterol levels in a multiracial sample of 7,439 preschool children from Arizona. Prev Med 1992; 21: 162-176. Enas EA, Mehta J. Malignant coronary artery disease in young Asian Indians: thoughts on pathogenesis, prevention, and therapy. Coronary Artery Disease in Asian Indians (CADI) Study [review]. Clin Cardiol 1995; 18: 131-135. Bhatnagar D, Anand IS, Durrington PN, et al. Coronary risk factors in people from the Indian subcontinent living in west London and their siblings in India. Lancet 1995; 345: 405-409. Egusa G, Murakami F, Ito C, et al. Westernized food habits and concentration of serum lipids in the Japanese. Atherosclerosis 1993; 100: 249-255. Robinson D, Kawamura T, Hinohara S, Sakamoto Y. Levels of cardiovascular risk factors in Japanese people living in the UK. J Cardiovasc Risk 1995; 2: 449-458. Shaukat N, de Bono DP, Jones DR. Like father like son? Sons of patients of European or Indian origin with coronary artery disease reflect their parents' risk factor patterns. Br Heart J 1995; 74: 318-323. Resnicow K, Cross D, Lacosse J, Nichols P. Evaluation of a school-site cardiovascular risk factor screening intervention. Prev Med 1993; 22: 838-856. (Received 15 Apr, accepted 15 Oct, 1997) Authors' details Department of Cardiovascular Medicine, Prince Henry and Prince of Wales Hospitals, Sydney; and Community Health Services and Programs, South Eastern Sydney Area Health Service, Royal South Sydney Hospital, Sydney, NSW. Judith F Lynch, HTech, Heart Health Education Program Co-ordinator; Michelle D Marshall, BSc, Scientific Officer; Xing L Wang, PhD, Research Fellow; David E L Wilcken , MD, FRACP, Visiting Professor of Medicine. Reprints will not be available from the authors. Correspondence: Professor D E L Wilcken, Department of Cardiovascular Medicine, Room 163, Clinical Sciences Building, Prince Henry Hospital, Little Bay, Sydney, NSW 2036. Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Judith F Lynch · Michelle D Marshall · Xing L Wang

Notable Case Ephedrine abuse causing acute myocardial infarction Jerome G L Cockings and Michael A Brown "On the street", the more expensive illegal psychostimulants, such as cocaine or amphetamine, may be mixed with or substituted for cheaper drugs such as ephedrine -- with added risk to the user. We report diffuse myocardial injury in a 25-year-old man who presented with pulmonary oedema after intravenously injecting himself with ephedrine, believing it to be amphetamine. MJA 1997; 167: 199-200 Introduction - Clinical record - Discussion - References - Authors' details - - Articles on similar material Introduction The abuse of psychostimulants, such as cocaine and amphetamines, is of concern in Australia -- they are among the most widely used of the illicit drugs after cannabis.1 Occupational use of stimulant drugs is also a problem -- there have been accidents involving heavy transport vehicles whose drivers had taken ephedrine.2 In addition, ephedrine may be taken by "recreational" drug abusers when it is mixed with or substituted for other illicit drugs such as amphetamines. Ephedrine has both cardiovascular and central nervous system effects, but, although the cardiovascular risks of major psychostimulants such as cocaine are well known,3 little has been reported for ephedrine. We report a patient who injected himself intravenously with ephedrine, sustaining diffuse myocardial injury which resolved with inotropic support and ventilation. Clinical record A 25-year-old man with a history of intravenous psychostimulant abuse presented to hospital with progressive dyspnoea two hours after injecting himself intravenously with a solution of a white powder he believed was amphetamine. He had no other medical history of note, was a non-smoker and had previously been well. There was no family history of sudden cardiac death. Serum lipid levels were not measured. On examination he was conscious but tachypnoeic and cyanosed. He was afebrile, tachycardic (pulse, 140 beats/min), normotensive (110/70 mmHg) and hypoxic (Pao2, 49 mmHg), with hypocapnia (Paco2, 33 mmHg), a mild alkalosis (pH, 7.45) and a pronounced leukocytosis (44 x 106 cells/L). He had a reduced cardiac output (2.2 L/min; normal range, 4.5-6.5 L/min), with a pulmonary artery occlusion pressure (an estimate of left atrial pressure) of 30 mmHg. There was bilateral "bat's wing" opacification on chest x-ray, consistent with a clinical diagnosis of pulmonary oedema. Within an hour of admission and treatment with diuretic and oxygen, further deterioration with cardiogenic shock necessitated intubation, ventilation and admission to an intensive care unit. Initially, the lungs were poorly compliant (49 mL/cmH2O; normal range, 70-100 mL/cmH2O) and the alveolar-arterial (A-a) O2 gradient was elevated (260 mmHg; normal range, < 50 mmHg when on 80% O2). He received continuous inotropic support with adrenaline, initially at 38 µg/min, which was steadily reduced over three days. By Day 3, his cardiac output was 5.5 L/min without inotropes. His respiratory function and gas exchange improved steadily and he was extubated on Day 5. Results of microbiological investigations (tracheal aspirate, blood culture and urine culture) were negative and antibiotics were not given. On admission, electrocardiograms revealed widespread ST-segment depression with T-wave inversion, consistent with subendocardial infarction and ischaemia. A posterior infarction could not be excluded. The peak serum creatine kinase (CK) level was 2360 U/L (normal range, 20-130 U/L) (CK-MB isozyme fraction, 6.1%; normally < 2%), with rises in serum levels of aspartate aminotransferase (to 222 U/L [normal range, < 45 U/L]) and lactate dehydrogenase (to 612 U/L [normal range, 110-230 U/L]). A technetium Tc 99m perfusion scan of the myocardium showed mild tracer uptake in the left myocardium and more intense uptake in the posterolateral wall, consistent with diffuse myocardial damage and an acute posterolateral infarction. Echocardiography soon after admission showed severe left ventricular dysfunction in all areas except the apex (which showed near-normal contractility), with a poor overall ejection fraction. There was mild mitral regurgitation with no vegetations. Right ventricular function was normal. On Day 6, mild to moderate impairment of left ventricular function was still present, maximum at the base, with mild ventricular dilatation. The patient continued to improve and was discharged from hospital nine days after admission. Laboratory analysis of the unused white powder identified only ephedrine. On review one month later the patient was symptom-free. The resting electrocardiogram showed non-specific ST-segment and T-wave changes. Exercise testing, carried out according to the Bruce protocol,4 was 13.5 min in duration and limited by fatigue. His peak heart rate was 192 beats/min, with no chest pain or ST-segment or T-wave changes. He attained an estimated oxygen consumption of 49 mL/kg per min (normal range, 50-70 mL/kg per min) and an aerobic capacity of 106% of the predicted value. At two months, echocardiography showed normal left ventricular function but persistent trivial mitral regurgitation with a minor prolapse of the anterior leaflet. The patient was counselled about the health risks (such as the risk of bacterial endocarditis) of continuing to inject illegally obtained drugs. Discussion Our patient presented with diffuse myocardial injury consistent with sympathomimetic abuse -- the agent was identified as ephedrine. He recovered adequately after intensive treatment. The stimulatory central nervous system effects of ephedrine -- increased arousal, restlessness and insomnia -- have been recognised for many years. Preparations of the herb ephedra were used in ancient Chinese medicines, and ephedrine, the active alkaloid, was identified in the late 19th century.5 Ephedrine is a direct agonist of both alpha and beta sympathetic receptors and an indirect adrenoreceptor agonist, causing release of noradrenaline from presynaptic sympathetic nerve terminals. Its cardiovascular effects include tachycardia, increased inotropy, arterial vasoconstriction and hypertension,6 and these are the effects for which it is used therapeutically. Amphetamine and pseudoephedrine have similar actions, although amphetamine has more pronounced central nervous system effects.7 Ephedrine is widely available, but despite the potential for abuse that this creates there are few reports of its cardiovascular risks. Bruno et al. described two cases of intracranial haemorrhage and one of a thalamic infarct following excessive ephedrine ingestion,6 highlighting the potential dangers of non-prescribed self-administration of this drug. Chronic cardiomyopathy was documented after long-term ingestion of ephedrine in a cough mixture.8 Myocardial injury occurred after ephedrine given therapeutically for hypotension during labour,9 and coronary artery spasm leading to myocardial injury has been described with pseudoephedrine ingestion.10 The mechanism of the myocardial injury caused by ephedrine overdose is probably similar to that caused by cocaine -- intense diffuse vasoconstriction of both the coronary and the systemic arterial systems, decreasing myocardial perfusion, increasing afterload, and increasing myocardial oxygen utilisation.3 Although severe hypertension would be expected with ephedrine overdose, and may have been present in our patient soon after the injection of ephedrine, on presentation he had severe acute left ventricular failure with a consequent fall in contractility and blood pressure. This necessitated inotropic support rather than the use of vasodilators. Various other factors may have contributed to the myocardial injury in our patient. There may have been contaminants in the syringe, and the injection of insoluble particulate matter may have caused vascular occlusion. This could have been compounded by catecholamine-enhanced platelet aggregation induced by ephedrine. Further, although no other agents were identified in the remaining unused powder, the original injection may have included another myotoxin. Pre-existing coronary artery disease was unlikely in an otherwise healthy young non-smoker. A coronary angiogram was not performed. Although the leukocytosis was pronounced, this was consistent with the severe physiological stress. Nevertheless, in the absence of any other antecedent events or prior myocardial disease, this case report strongly suggests that the acute myocardial infarction was precipitated by the self-injection of ephedrine. "On the street", small quantities of a cheaper drug such as ephedrine may be mixed with stimulants such as amphetamine. This case illustrates the risks associated with the total substitution of ephedrine and the subsequent injection of what is likely to have been a high dose of this drug. References Australian Social Issues Research 1991. Report on the national campaign against drug abuse. Sydney: Social Issues Household Survey 1985-1991. Canberra: AGPS, 1991. Staysafe Committee of NSW 1992. Staysafe 19: Alcohol and other drugs on NSW roads 1. The problem and countermeasures. Sydney: NSW Parliament, 1992. Goldfrank LR, Hoffman RS. The cardiovascular effects of cocaine. Ann Emerg Med 1991; 20: 165-175. Bruce RA. Exercise testing of patients with coronary artery disease. Principles and normal standards for evaluation. Ann Clin Res 1971; 3: 323-332. Kalix P. The pharmacology of psychoactive alkaloids from Ephedra and Catha. J Enthnopharmacol 1991; 32: 201-208. Bruno A, Nolte KB, Chapin J. Stroke associated with ephedrine use. Neurology 1993; 43: 1313-1316. Gawin FH, Ellinwood EH. Cocaine and other stimulants: actions, abuse and treatment. N Engl J Med 1988; 318: 1173-1182. To LB, Sangster JF, Rampling D, Cammens I. Ephedrine-induced cardiomyopathy. Med J Aust 1980; 2: 35-36. Menegakis NE, Amstey MS. Case report of myocardial infarction in labour. Am J Obstet Gynecol 1991; 165: 1383-1384. Weiner I, Tilkian AG, Palazzolo M. Coronary artery spasm and myocardial infarction in a patient with normal coronary arteries: temporal relationship to pseudo-ephedrine ingestion. Cathet Cardiovasc Diagn 1990; 20: 51-53. (Received 27 Feb, accepted 12 June 1997) Authors' details Royal Adelaide Hospital, Adelaide, SA. Jerome G L Cockings, FFICANZCA, FANZCA, Senior Registrar in Intensive Care; Michael Brown, MD, FRACP, Consultant Cardiologist. Reprints will not be available from the authors. Correspondence: Dr J G L Cockings, Consultant Intensivist, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Brisbane, QLD 4102. E-mail: J. Cockings@mailbox.uq.edu.au Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Michael A Brown

Reducing the burden of chronic heart failure It's time to adopt new management strategies MJA 1997; 167: 61-62 Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". - ©MJA1997 Chronic heart failure (CHF) is a major public health problem.1 The disease is associated with poor prognosis2 and markedly reduced quality of life. Unlike other cardiovascular conditions, it is increasing in incidence and prevalence.1,3 Its management imposes a substantial burden on the health care system, accounting for 1%-2% of total health care costs in industrialised nations.4 About 70% of these costs are related to hospitalisation. Most epidemiological data on heart failure have come from the United States and Europe. In Australia, carefully conducted studies of the incidence, prevalence and hospitalisation rates of CHF have been sadly lacking. Thus, the report by Blyth et al. in this issue of the Journal5 is welcome as it provides us with local data on the impact of CHF in the hospital setting. Their findings confirm the massive burden that heart failure imposes on the patient and the health care system. What can we do to contain or even reverse this situation? Despite therapeutic advances, CHF remains a disease with unacceptably high mortality rates, poor quality of life and massive socioeconomic cost. The current approach to managing heart failure comprises non-pharmacological interventions (sodium restriction, alcohol abstention, exercise), drug therapies and, in selected patients, surgery. Surgery has a limited role: if objective evidence exists of reversible ischaemia and/or hibernating myocardium, coronary artery bypass grafting should be considered. Several new surgical approaches may also be useful as long-term therapy in some patients, including cardiomyoplasty, ventriculectomy and insertion of a left ventricular assist device. Transplantation is an extremely effective therapy, but limited by donor organ availability, and the age and comorbidities of many patients with CHF. Drug therapies have a substantial impact on disease outcomes. Angiotensin-converting enzyme (ACE) inhibitors relieve symptoms, improve quality of life and prolong survival.6,7 Digoxin has no overall effect on mortality,8 but may be of symptomatic benefit in patients receiving ACE inhibitor therapy.9 However, mortality remains high even in CHF patients receiving the best available drug therapy. In the CONSENSUS study of patients with severe heart failure, 12-month mortality was almost 50% despite patients receiving diuretics, digoxin and high doses of ACE inhibitors.7 New drugs are continually being evaluated in CHF. Many provide short-term symptomatic benefit, but at the expense of long-term increases in mortality: these include non-digitalis inotropic agents (milrinone, xamoterol, ibopamine, vesnarinone) and direct-acting vasodilator drugs (flosequinan).10 New drugs that appear to offer symptomatic benefit without adverse mortality outcomes include b -adrenoceptor-blocking agents (specifically, carvedilol) and angiotensin II receptor antagonists (specifically, losartan). Recent studies have suggested prolonged survival in chronic heart failure with both agents.11-12 Despite these therapeutic advances, CHF remains a disease with unacceptably high mortality rates, poor quality of life and massive socioeconomic cost. Effective new management strategies are urgently required. In most patients heart failure is a complex disorder requiring an integrated treatment strategy. Physicians, general practitioners, nurse practitioners, nutritionists, physiotherapists and psychologists need to be drawn together to maximise thera peutic benefits to the patient. One approach has been to establish multidisciplinary clinics where patients have access to dedicated physicians, dietary expertise, literature about the disease, behaviour modification interventions and exercise programs. Patients are encouraged to become active participants in managing their disease. They are asked to weigh themselves regularly, monitor dietary sodium intake, watch closely for signs of fluid accumulation or changing symptoms and to interact frequently by telephone with members of the multidisciplinary team. The nurse practitioner regularly checks on patient status and addresses specific enquiries. This approach brings together the skills of multiple health care providers in an environment of frequent and regular appraisal of the patient. Outcomes from pilot studies of this approach have included reduced dietary salt intake, improved compliance with drug therapies, improved patient well-being, and reduced hospitalisations.13,14 In one study, emergency department visits were reduced by 67% and hospitalisations by 87%.14 This was found to be highly cost-effective. Heart failure remains a major clinical challenge for health care professionals in the 1990s. It is no longer sufficient to manage the hospitalised patient well; the real goal of treatment is to address the health of people with heart failure in the community so that they do not require hospital admission. Henry Krum Associate Professor of Medicine, Clinical Pharmacology Unit Department of Epidemiology and Preventive Medicine, and Department of Medicine Monash University, Alfred Hospital, Melbourne, VIC Garg R, Packer M, Pitt B, Yusuf S. Heart failure in the 1990s: evolution of a major public health problem in cardiovascular medicine. J Am Coll Cardiol 1993; 22 (4 Suppl A): 3A-5A. Franciosa JA, Wilen M, Ziesche S, et al. Survival in men with severe left ventricular failure due to either coronary heart disease or idiopathic dilated cardiomyopathy. Am J Cardiol 1983; 51: 831-836. Schocken DD, Arrieta MI, Leaverton PE. Prevalence in mortality rate of congestive heart failure in the United States. J Am Coll Cardiol 1992; 20: 301-306. McMurray J, Hart W. The economic impact of heart failure on the UK National Health Service . Eur Heart J 1993; 14 Suppl: 133. Blyth FM, Lazarus R, Ross D, et al. Burden and outcomes of hospitalisation for congestive heart failure. Med J Aust 1997: 167; 67-70. SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991; 325: 293-302. CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med 1987; 316: 1429-1435. The Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 1997; 336: 525-533. Packer M, Gheorgiade M, Young JB, et al. Withdrawal of digoxin from patients with chronic heart failure treated with angiotensin converting enzyme inhibitors. N Engl J Med 1993; 329: 1-7. Niebauer J, Coats AJS. Treating chronic heart failure: time to take stock. Lancet 1997; 349: 966-967. Packer M, Bristow MR, Cohn JN, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. N Engl J Med 1996; 334: 1349-1355. Pitt B, Segal R, Martinez FA, et al. Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE). Lancet 1997; 349: 747-752. Rich MW, Beckham V, Wittenberg C, et al. A multidisciplinary intervention to prevent the readmission of elderly patients with congestive heart failure. N Engl J Med 1995; 333: 1190-1195. West JA, Miller NH, Parker KM, et al. A comprehensive management system for heart failure improves clinical outcomes and reduces medical resource utilization. Am J Cardiol 1997; 79: 58-63. ©MJA 1997 <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia.

Henry Krum

Burden and outcomes of hospitalisation for congestive heart failure Fiona M Blyth, Ross Lazarus, David Ross, Michael Price, Gary Cheuk and Stephen R Leeder For editorial comment see Krum Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - ©MJA1997 Abstract Objective: To describe the hospital burden and health outcomes associated with admission for congestive heart failure (CHF). Design and setting: Descriptive follow-up study in a tertiary-level metropolitan teaching hospital. Patients: Acute adult inpatients with a clinical diagnosis of CHF for more than 24 hours admitted to Westmead Hospital, Sydney, during the four months from September 1993 to January 1994. At baseline, 122 patients were assessed; 88 patients were assessed at four-month follow-up. Interventions: Usual clinical care. Main outcome measures: Length of stay; hospital bed-days; readmissions; mortality; health related quality of life (SF-36); patient knowledge. Results: The average age of subjects was 73.4 years. Many were using informal domiciliary care before admission. Mean length of stay for the baseline admission was 13.8 days, accounting for 7.6% of hospital separations and 1683 hospital bed-days, or 4.2% of bed-days for all inpatients aged 65 years and over. Fifteen patients were readmitted for CHF during the following four months, with a total of 26 CHF-related admissions. Twenty-one patients (17.2%) died during the course of the study. Quality of life at baseline was poor compared with population normative data, with a slight improvement among survivors at four-month follow-up. Patient knowledge of CHF was poor in a subsample survey ( n = 24). Conclusions: CHF represents a significant burden to patients (through morbidity and mortality), their carers (through provision of daily care), and hospitals (through multiple admissions for acute decompensation). It is difficult to monitor the hospital burden of CHF using routine data sources. MJA 1997; 167: 67-70 Introduction Congestive heart failure (CHF) has been estimated to affect 3%-5% of those aged over 65 years, and 10% of those over 75 years.1 It is the fastest growing cardiovascular disorder in the United States,2 the only one increasing in incidence and prevalence,3 and the leading cause of hospital admission and readmission in Americans aged over 65 years.4 In 1990, CHF cost the US economy $US8 billion, and accounted for five million hospital bed-days.5,6 In Scotland, CHF hospital discharge rates have risen in a decade to be almost equal to those for myocardial infarction.7 In the United Kingdom, the National Health Service spends £360 million per year in diagnosis and management, on a par with spending on stroke or asthma. Most of this expenditure is on hospital admissions.8 As there is little information available on the outcomes of current hospital management of CHF patients,9,10 we describe the health outcomes of a cohort of patients hospitalised with CHF, and the impact of their hospitalisation on a health service. Methods All acute adult patients admitted to Westmead Hospital during four months (September 1993 to January 1994) with a clinical diagnosis of CHF, or who developed CHF of more than 24 hours' duration during an admission, were eligible for inclusion in the study. The diagnosis of CHF was made by medical staff on clinical grounds. Additional eligibility criteria were fluency in English and absence of significant cognitive impairment. Two cardiology-trained research nurses implemented an active daily case-finding strategy to overcome the difficulties encountered in identifying CHF patients from existing record systems. Diagnostic codes are generally not added to the patient's medical record until some time after discharge. Patients were identified by review of the computerised admissions log, medical record chart audit in the relevant ward areas, and consultation with medical staff. Potential subjects were assessed for their general condition and fluency in English and, if appropriate, screened for cognitive impairment by means of the Mini-Mental State examination.11 Informed consent was then sought. If patients were unable to participate fully, consent was sought to review their medical record and follow them up four months later to ascertain vital status. Baseline data were collected by interview, medical record review and self-administered questionnaires. Data were collected on demographic characteristics, domiciliary arrangements, current and past medical history, clinical severity of heart failure (according to the New York Heart Association [NYHA] criteria for grading functional incapacity of patients with cardiac disease), investigations, drug treatment, hospital resource use, formal and informal use of domiciliary care, and health-related quality of life (HRQOL) before admission (measured with the SF-36 [Medical Outcomes Study 36 Item Short Form Health Survey]).12 Patient knowledge about CHF was assessed by a short questionnaire in a subset of 24 consecutive patients. Four months after baseline admission, subjects were contacted by telephone to arrange follow-up by questionnaire. Data were sought on health status, HRQOL, current treatment, and domiciliary arrangements. The hospital's computer system was searched for any readmissions during the follow-up period. All analysis was performed using SAS version 6.08 for Windows.13 Two-sample t tests were used to assess the statistical significance of differences between groups, with adjustments made for multiple comparisons. SF-36 data were scored and subscales were calculated with the recommended scoring algorithm.12 Westmead Hospital Human Research Ethics Committee approved the study, and informed consent was obtained from all participating patients. Results There was no "gold standard" available for checking the accuracy and completeness of study case ascertainment methods. However, a list was assembled of all separations from Westmead Hospital during the study recruitment period with a principal diagnosis code for CHF (ICD-9 codes 428.0, 428.1, 428.9). These were then cross-checked against a list of study subjects. This list identified seven patients who were not identified by study case-finding methods. These were considered "missed" potential cases, but represented a small proportion of this group (4.3%). During the study recruitment period, 154 patients met the required clinical criteria and 122 (79%) consented to participate. Participation and follow-up are detailed in Box 1. Sample characteristics: Women made up 54.9% of the study participants. The mean age was 73.4 years (range, 24-97 years); women were older on average than men (76.8 compared with 69.4 years; P = 0.0001). Most patients had a history of established CHF; 35.2% were undergoing their first hospital admission for CHF. Only 1.8% of patients were NYHA grade I on baseline admission, 12.3% grade II, 64.4% grade III, and 17.5% grade IV (4% lacked data for NYHA classification). Thirty-eight patients had their ejection fraction measured at the baseline admission, with a mean value of 35% (range, 9%-74%). Ischaemic heart disease (58.2%) and hypertension (39.3%) were major aetiological factors in CHF. The cohort was cared for by cardiologists (n = 74; 60.7%), and geriatricians (n = 48; 39.3%). Admission diagnoses are shown in Box 2 (below). When admission diagnoses were compared with ICD-9 codings on the medical record, 39 (86.6%) of the 45 with heart-failure-specific admission diagnoses and 30 (78.9%) of the 38 with suggestive diagnoses had a CHF-related ICD-9 code (428, 428.0, 428.1, 428.9) in one of the first six ICD-9 coding positions. Preadmission characteristics: Data were available for 99 subjects: 88 lived in private accommodation, 50 reported needing regular help from family or friends with general housekeeping, and 23 reported needing help with supervision of medication. Length of stay: The study participants accounted for 7.6% of hospital separations (excluding day-only patients). The mean length of stay during the baseline admission was 13.8 days (SD = 12.1). Length of stay had a markedly skewed distribution (median, 10 days; range, 2-66 days). Overall, the sample accounted for 1683 bed-days during baseline admissions and 10.6% of hospital bed-days associated with the geriatricians and cardiologists who participated in the study. Of those patients aged 65 years and over admitted during the same period, the CHF cohort accounted for 4.2% of bed-days. Readmissions: During the follow-up period, there were 73 readmissions to Westmead Hospital from the study cohort, 26 due to a further episode of CHF in 15 patients. A total of 171 bed-days were used for CHF-related readmissions by the 14 patients for whom data were available. Deaths: Twenty-one patients died during the study (17.2%). Changes in domicile: Eight patients (8.1%) were discharged to a higher level of domiciliary care, suggesting a decline in independence and increased use of health and/or community services. Quality of life: Data on HRQOL before admission were obtained from 84 of the 85 subjects at baseline (Box 3). Mean SF-36 subscale scores for these subjects were generally low, particularly for subscales with physical health components. For each subscale there was a wide range of scores, indicating substantial variability in health-related quality of life before admission. Compared with Australian normative SF-36 data for men and women aged 65 years and over,14 the study cohort reported significantly lower mean HRQOL for all subscales. Follow-up SF-36 data were obtained for 58 subjects (Box 4). Patients with missing follow-up data had either died before follow-up (n = 15) or were too unwell to fill in the form (n = 6). In that sense, the SF-36 results at follow-up represent the "survivor" population within the study cohort. Mean follow-up subscale scores in survivors were somewhat higher compared with their baseline scores. The smallest improvements were in the subscales related to physical health. Improvements in the Social Function, Vitality and Mental Health subscales were statistically significant. Patient knowledge: The 24 patients who completed the questionnaire were similar to the CHF cohort in age, sex, length of stay, and type of treating specialist. Nineteen had been admitted to hospital previously for CHF. Only 11 knew that they had been diagnosed as having heart failure. Although 16 agreed that patients with heart failure would need to take medication permanently, six thought that CHF was unlikely to recur. Nineteen agreed that shortness of breath and 15 agreed that ankle swelling were important symptoms, but only four recognised that rapidly increasing weight was important. Discussion CHF has a significant impact on hospital services. The study cohort contributed significantly to adult bed-days attributable to participating clinicians. A substantial proportion (12.3%) of the cohort was readmitted with CHF within four months of their baseline admission, suggesting an annual readmission rate of around 36%. This compares with an annual readmission rate of nearly 20% in the SOLVD (Studies of Left Ventricular Dysfunction) registry study cohort, who were younger.10 CHF admissions show seasonal variations, with a winter peak that is probably associated with chest infection. Therefore, the impact of CHF on acute hospital services may be even greater at that time of year. The 48 subjects (39.3%) who were admitted under the care of geriatricians were, by hospital admission policy, those aged over 65 with serious comorbidity and/or likely to represent a placement problem after discharge. Many required substantial help with tasks essential for independent living, and most of this help was provided informally. This was clearly a group that would require increased resources with deteriorating health. HRQOL was generally poor in the study participants compared with normative data,14 probably reflecting the combined effects of disease severity and comorbidity. There was limited improvement between baseline and follow-up, particularly in the subscales related to physical health, perhaps indicating that at baseline the lower limits of some SF-36 subscales did not adequately reflect the subjects' condition (i.e., a "floor" effect was operating). The mean changes in scores over time were small, but underlying this was great variability between individuals. At the time of this study there were few educational resources for CHF patients. This is surprising, as CHF is a chronic condition with acute exacerbations that may be ameliorated by early recognition and intervention, and which requires compliance with medication. Some CHF patients may avoid hospital admission by timely intervention prompted by self-monitoring of signs and symptoms. Seventy-six subjects (62.3%) had a recorded history of acute deterioration lasting for more than 24 hours, suggesting a possible opportunity for early recognition and intervention. The patient knowledge survey was limited, but it demonstrated an apparent lack of understanding of key features of CHF. Recent acute illness could have contributed to this. That almost a quarter of the cohort required daily help with taking medications has implications for the targeting of educational interventions. For elderly patients experiencing readmissions for CHF, the risk of dying in the near future and the palliative nature of treatment are additional issues which may need to be explored. This study was constrained, for practical reasons, by reliance on a clinical diagnosis of CHF. In a larger study with more resources, verification of diagnosis and more detailed examination of diagnostic coding practices would be desirable, and would allow identification of subgroups of particular clinical interest. Diagnostic coding practices in routine record keeping do not facilitate monitoring of the public health impact of CHF. A hospital admission for CHF may be assigned a principal ICD-9 code which reflects the underlying cause of CHF, and secondary ICD-9 codes are sometimes used to identify a past medical history of CHF rather than a feature of the current admission. In this study, poor health represented a further barrier to study participation and monitoring outcomes. Most losses to follow-up resulted from death or worsening health. During the study 21 subjects (17.2%) died. This represents a poor survival rate, worse than for many malignancies of adulthood. Cause of death was not ascertained, but in the SOLVD registry cohort10 most deaths were due to progressive CHF. In addition, sudden death occurs in CHF patients at five times the rate in the general population of the same age.15 Chronic CHF represents a significant burden to patients (through morbidity and mortality), their carers (through provision of daily care), and the hospital system (through multiple admissions for acute decompensation). Acknowledgements We acknowledge the contribution of Moira Hewitt, RN, and Jeanette Bunn, RN, to the Westmead CHF Outcomes study, and study coinvestigator Dr Julia Lowe from the Newcastle Heart Failure Group. This study was funded by the NSW Health Department's Health Outcomes Program. References Failure to treat heart failure [editorial]. Lancet 1992; 330: 278-279. Mortality from congestive heart failure --United States, 1980-1990. MMWR Morb Mortal Wkly Rep 1994; 43: 77-81. Yamani M, Massie BM. Congestive heart failure: insights from epidemiology, implications for treatment. Mayo Clin Proc 1993; 68: 1214-1218. Gooding J, Jette AM. Hospital readmissions among the elderly. J Am Geriatr Soc 1985; 33: 595-601. National Centre for Health Statistics, Graves EJ. National Hospital Discharge Survey: Annual Summary, 1990. Vital Health Stat [13] 1992; 112: 28. Munoz E, Chalfin D, Birnbaum E, et al. Hospital costs, resource characteristics, and the dynamics of death for patients with a primary diagnosis of congestive heart failure. N Y State J Med 1989; 89: 60-63. McMurray J. Trends in hospitalisation for heart failure in Scotland 1980-1990. Eur Heart J 1993; 14: 1158-1162. McMurray J, Hart W. The economic impact of hearfailure on the U K National Health Service. Eur Heart J 1993; 14 Suppl: 133. Parameshwar J, Poole-Wilson PA, Sutton GC. Heart failure in a district hospital. J R Coll Physicians Lond 1992; 26: 139-142. Bourassa MG, Gurne O, Bangdiwala SI, et al. for the SOLVD investigators. Natural history and patterns of current practice in heart failure. J Am Coll Cardiol 1993; 22 Suppl A: 14A-19A. Folstein MF, Folstein SE, McHugh PR. "Mini-Mental State": a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12: 189-198. Ware JE, Snow KK, Kosinski M, Gandek B. SF-36 health survey: manual and interpretation guide. Boston: The Health Institute, New England Medical Centre, 1993 . SAS for the Microsoft Windows Environment, Version 6. Cary, NC: SAS Institute Inc, 1993. Stevenson CE. SF-36: Interim norms for Australian data. Canberra: Australian Institute of Health and Welfare, 1996. Kannel WB, Ho K, Thom T. Changing epidemiologic features of cardiac failure. Br Heart J 1994; 72 Suppl: S3-S9. (Received 8 Oct 1996, accepted 10 Apr 1997) Authors' details Westmead Hospital, Sydney, NSW. Fiona M Blyth, FAFPHM, Registrar, Department of Public Health and Community Medicine. Ross Lazarus, FAFPHM, Senior Lecturer in Epidemiology, Department of Public Health and Community Medicine, University of Sydney at Westmead Hospital. David Ross, FRACP, Head, Department of Cardiology. Michael Price, FRACP, Head, Geriatric Medicine Unit. Gary Cheuk, FRACP, Registrar, Geriatric Medicine Unit. Stephen R Leeder, FRACP, PhD, FAFPHM, Professor of Public Health and Community Medicine, University of Sydney at Westmead Hospital. Reprints will not be available from the author. Correspondence: Dr F M Blyth, Department of Public Health and Community Medicine, Westmead Hospital, Westmead, NSW 2145. ©MJA 1997 <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia.

Fiona M Blyth · Ross Lazarus · David Ross · Michael Price · Gary Cheuk · Stephen R Leeder