Cardiovascular diseases

Clinical record An 88-year-old man presented to our emergency department with sudden loss of vision in his right eye. Past ocular history included amblyopia in his right eye and bilateral neovascular age-related macular degeneration (AMD). Previously recorded best corrected visual acuities were 6/120 and 6/18 in his right and left eye, respectively. The patient’s past medical history included acute myocardial infarction, atrial fibrillation, hypertension, hypercholesterolaemia and polymyalgia rheumatica. He had no history of diabetes, cerebrovascular accident or transient ischaemic attack. His medications included warfarin, aspirin, metoprolol, perindopril and simvastatin. His international normalised ratio (INR) had ranged between 1.3 and 2.3 over the preceding 12 months, with a target of 2.0. Visual acuity in the right eye was count fingers. Dilated slit lamp examination revealed a large submacular haemorrhage with associated vitreous haemorrhage (Figure A). An electrocardiogram showed atrial fibrillation with a heart rate of 72 beats/min. His blood pressure was 110/80 mmHg. His INR was 2.8. The eye was managed conservatively and, following resolution of the vitreous haemorrhage, vision remained at count fingers. Four months later, the patient reported sudden loss of vision in his left eye. Visual acuity was light perception, and dilated fundus examination revealed dense subretinal and associated vitreous haemorrhage (Figure B). The patient was still taking warfarin, and his INR at this time was 2.7. As this had been his better eye, he underwent pars plana vitrectomy and clearance of the vitreous haemorrhage. After surgery, his visual acuity was count fingers. After further discussion with the patient’s cardiologist, a decision was made to cease warfarin. A: Fundus photograph of the right eye at presentation, showing macular subretinal and intraretinal haemorrhage. The mild haziness of the photograph is indicative of vitreous haemorrhage. B: Fundus photograph of the left eye at the time of presentation of visual loss in this eye. Extensive subretinal haemorrhage is seen in the macula. Again, the haziness of the photograph is indicative of vitreous haemorrhage. This report highlights a potential interaction between a commonly used anticoagulant, warfarin, and an increasingly common ocular condition — AMD. The risk of AMD increases with age, with prevalence reaching 20% of people aged over 75 years in white populations.1 Neovascular (“wet”) AMD accounts for 10%–20% of cases,2 and for 80%–90% of patients who become legally blind from AMD.3 Peripheral vision is typically retained, and most patients are able to maintain a degree of functional independence. Development of large subretinal and vitreous haemorrhages in neovascular AMD is uncommon. Treatment options are limited and, even with surgical intervention, visual outcomes are in the range of light perception to counting fingers only, with significant loss of paracentral and peripheral vision.4 The functional effects are therefore profound. Previous studies have demonstrated an association between the use of anticoagulant medication, particularly warfarin, and large intraocular haemorrhages among patients with neovascular AMD.5,6 The largest of these, a retrospective case–control study comprising 100 patients, found that those with massive intraocular haemorrhage were 11.6 times more likely to be taking anticoagulant medication.6 Among these patients, INR ranged from 3.0 to 4.0. Patients with massive haemorrhage were twice as likely to be taking aspirin, although the significance of this finding is less certain, as the lower limit of the 95% confidence interval was less than 1. No patient was taking anticoagulants and aspirin concurrently.6 In our patient, the role of concurrent aspirin therapy is unclear, as there is no evidence in the literature to support or refute the hypothesis that concurrent antiplatelet therapy may have contributed to the development of haemorrhage. However, both instances of haemorrhage were noted to occur at times when his INR was high compared with those recorded over the previous 12 months. Our patient was taking aspirin at all times during this period. Although it is possible that intraocular haemorrhage may have occurred purely as a result of his underlying neovascular AMD, the temporal relationship between the development of the haemorrhages and the high INRs strengthens the case for the implication of warfarin therapy as a contributing factor. Application of the Naranjo probability scale7 indicates that this adverse drug event was probable (Naranjo score, + 5). The association between anticoagulant therapy and intraocular haemorrhage is of key importance for several reasons. Firstly, massive intraocular haemorrhage is an important diagnosis to consider in an anticoagulated patient who presents with loss of vision, and who has a background of neovascular AMD. Secondly, patients with neovascular AMD in one eye are at risk of developing neovascular AMD in the second eye,8 and therefore at risk of developing large intraocular haemorrhages in both eyes if long-term anticoagulation is continued. There are several clinical situations in which the indication for anticoagulation is relative. There are key roles for the ophthalmologist, cardiologist, and general practitioner to ensure that an appropriate risk–benefit evaluation is made before initiating anticoagulant therapy for patients with neovascular AMD. Patients taking anticoagulants who develop neovascular AMD, and in particular those with neovascular AMD who are taking anticoagulants and who develop intraocular haemorrhage in one eye, should have their therapy carefully re-evaluated. Importantly, awareness of the poor outcomes of intraocular haemorrhage in neovascular AMD, the role of anticoagulants as a risk factor, and effective communication between health professionals may help reduce the incidence of this devastating complication. Lessons from practice Patients with neovascular age-related macular degeneration (AMD) have a small but significant risk of intraocular haemorrhage, which may be increased in severity if patients are taking anticoagulant medication. The outcomes of intraocular haemorrhage are poor, with significant deterioration in paracentral and peripheral vision, and subsequent implications for ability to maintain functional independence. When considering anticoagulation therapy for patients with neovascular AMD, liaison between the general practitioner, cardiologist and ophthalmologist will ensure that an appropriate risk–benefit evaluation is made. If patients who take anticoagulant medication develop signs of neovascular AMD, it is essential that the ophthalmologist liaise with the GP and/or cardiologist to ensure that the need for anticoagulation, and the target international normalised ratio, are carefully reviewed.

Rajeev Chalasani MB BS · Salmaan Qureshi FRANZCO

The latest evidence for the essential elements of surgical prophylaxis protocols There is no question that antibiotic prophylaxis for cardiac surgery reduces surgical site infections.1 The successful implementation of prophylactic regimens, however, is often inconsistent or inadequate. The use of prophylaxis protocols or decision-support systems as either a single measure2 or as part of a patient care pathway3 has been demonstrated to improve adherence to prophylaxis, with a reduction in surgical site infections. In this issue of the Journal (page 141), a study by Haydon and colleagues4 shows that antibiotic prophylaxis protocol use in 45 Australian cardiac surgery units increased significantly between 2004 and 2008 (from 58% to 80%), but concordance with version 13 of the Australian Therapeutic guidelines: antibiotic5 was poor when both choice of agent and duration of administration were considered. In particular, there was an increased use of multidrug regimens, an increased use of vancomycin for routine prophylaxis, and a prolonged duration. The study did not examine surgical site infection rates. As prophylaxis protocols improve patient outcomes, and adherence to protocols in Australian cardiac surgery units seems to be high, it is timely to consider the optimum elements of such protocols in terms of timing of prophylaxis, duration of prophylaxis, and choice of agent. There have been a number of studies that show the relationship between timing of antibiotic administration and surgical site infections. An observational cohort study in a consecutive series of 3836 surgical procedures (vascular, trauma and abdominal) showed the optimal time for administration of β lactams was 30–60 minutes before incision.6 The risk-adjusted odds ratio of surgical site infections was 3.16 (95% CI, 1.4–7.0) if given 75–120 minutes before, 2.82 (95% CI, 1.5–5.3) for administration 15–29 minutes before, and 1.75 (95% CI, 0.9–3.4) if given in the last 14 minutes before incision. In a prospective study of 2048 patients given vancomycin prophylaxis for cardiac surgery (coronary artery bypass graft [CABG] or valve replacement), the optimum time for the start of a vancomycin infusion was shown to be 16–60 minutes before incision.7 The relative risk of infection was 7.8 (95% CI, 2.5–24.7) if started 0–15 minutes before incision and 2.2 (95% CI, 0.99–5.09) if started 61–120 minutes before. Duration of prophylaxis has been a controversial issue. The Society of Thoracic Surgeons practice guidelines8 recommend that prophylactic antibiotics be given for 48 hours or less, citing some evidence for effectiveness of single-dose or 24-hour regimens, but comment that additional studies are required to confirm the effectiveness of shorter courses. This has been addressed in a study on 838 patients undergoing CABG or valve replacement.9 Patients received cephazolin as either a single dose before incision or a prolonged regimen, with a dose before incision, then 8-hourly for 24 hours. There was a statistically significant difference in surgical site infections between the two groups (8.3% v 3.6%; P = 0.004). The choice of agent is mainly between a β lactam and vancomycin, although alternative choices are possible (eg, flucloxacillin plus gentamicin). The Society of Thoracic Surgeons practice guidelines10 recommend cephazolin for standard practice in populations that do not have a high incidence of methicillin-resistant Staphylococcus aureus (MRSA). Haydon et al’s study showed that routine vancomycin use for CABG surgical prophylaxis increased from 13% in 2004 to 44% in 2008, with similar increases seen for valve surgery — from 31% to 62% over the same period.4 Vancomycin prophylaxis for cardiac surgery is recommended in the current Therapeutic guidelines: antibiotic for institutions with a high prevalence of MRSA, for β lactam-allergic patients, or for procedures where there is a higher risk of infection with a coagulase-negative staphylococcus (eg, valve surgery, reoperations).5 Excessive vancomycin use is to be discouraged, as its activity is inferior to β lactam antibiotics for susceptible organisms and it will add selective pressure for hVISA (heteroresistant vancomycin-intermediate S. aureus), particularly if the duration of administration is prolonged. With the advent of rapid MRSA molecular detection tests, it is now possible to screen patients before surgery and use vancomycin selectively in those found to carry MRSA. An alternative is to use intranasal mupirocin routinely in the absence of a documented negative test for MRSA (and methicillin-sensitive S. aureus [MSSA]), as this agent has been shown to reduce both MSSA and MRSA surgical site infections.11 How do these recommendations relate to the Therapeutic guidelines: antibiotic? The current guidelines, version 13 (published in 2006),5 are concordant, except for the duration of therapy. It is very likely that this is the major issue that has resulted in the lack of adoption of the guidelines’ cardiac surgery prophylaxis regimens found by Haydon and colleagues. Version 14 of Therapeutic guidelines: antibiotic is currently in preparation and due to be published in 2010, and the recent studies described here have been noted by the writing committee. It is very likely that version 14 will recommend a 24-hour prophylaxis regimen and that the recommended antibiotic agents will remain unchanged. The purpose of any surgical prophylaxis protocol is to ensure adherence to the optimum choice of agent, timing of administration and duration of prophylaxis. With such adherence, surgical site infections will be minimised, thereby reducing morbidity and mortality for patients undergoing cardiac surgery.

Keryn J Christiansen MB BS, FRCPA

Objectives: To determine population lipid profiles, awareness of hyperlipidaemia and adherence to Australian lipid management guidelines.Design and setting: Population survey in rural south-eastern Australia, 2004–2006.Participants: Stratified random sample from the electoral roll. Data from 1274 participants (40%) aged 25–74 years were analysed.Main outcome measures: Population mean total, low-density lipoprotein and high-density lipoprotein cholesterol (TC, LDL-C and HDL-C) and triglyceride (TG) concentrations, prevalence of dyslipidaemia, and treatment according to 2001 and 2005 Australian guideline target levels.Results: Population-adjusted mean TC, TG, LDL-C and HDL-C concentrations were 5.38 mmol/L (95% CI, 5.30–5.45), 1.50 mmol/L (95% CI, 1.43–1.56), 3.23 mmol/L (95% CI, 3.16–3.30) and 1.46 mmol/L (95% CI, 1.44–1.49), respectively. Prevalence of hypercholesterolaemia (TC > 5.5 mmol/L or on treatment) was 48%. Lipid-lowering medication use was reported by 12%. Seventy-seven of 183 participants with established cardiovascular disease (CVD) or diabetes were untreated, and of the 106 treated, 59% reached the target LDL-C. Of those without CVD or diabetes already treated, 38% reached target LDL-C, and 397 participants at high absolute risk did not receive primary prevention. Ninety-five per cent of treated individuals with CVD or diabetes and 86% of others treated had cholesterol measured in the previous year. Sixty-nine per cent of individuals at low risk aged over 45 years had their cholesterol measured within the previous 5 years.Conclusions: A comprehensive national strategy for lowering mean population cholesterol is required, as is better implementation of absolute risk management guidelines — particularly in rural populations.

Edward D Janus MD, FRACP, PhD · Philip A Tideman MB BS, FRACP · James A Dunbar MD, FRCPE, FRACGP · Annamari Kilkkinen MSc, PhD · Stephen J Bunker PhD · Benjamin Philpot BSc, GradDip(ActuarialStud) · Rosy Tirimacco BSc · Kevin Mc Namara BSc, MSc · Sami Heistaro MD, PhD · Tiina Laatikainen MD, PhD

Objective: To evaluate national practice for antibiotic prophylaxis in cardiac surgery with respect to the use of protocols, agent selection and duration of administration.Design, setting and participants: Two point-prevalence surveys of intensive care units in 24 public and 27 private hospitals performing cardiac surgery in Australia, conducted in 2004 and 2008, using a structured telephone questionnaire of the attending senior intensive care clinician in each unit.Main outcome measures: Existence of a protocol in the unit for antibiotic prophylaxis, specific antibiotic agents used and their duration of administration.Results: Between 2004 and 2008, reported protocol use increased from 58% to 80% (P = 0.02), while concordance with version 13 of the Australian Therapeutic guidelines: antibiotic for both choice of agent and timing (duration of administration) remained around 10%. Use of multiple agents was common, as was continued antibiotic administration after completion of surgery. Over 4 years, the proportion of cardiac surgical units reporting vancomycin administration for routine valve surgery prophylaxis doubled to 62% (P < 0.001).Conclusion: Despite an increase in reported protocol use for antibiotic prophylaxis in cardiac surgery, concordance with national antibiotic guidelines remained low, with duration of antibiotic administration deviating most from recommendations. Prophylactic vancomycin use appears to have increased substantially in recent years. Clinical implementation of recommended perioperative cardiac surgical antibiotic prophylaxis may not occur until supported by evidence from either a large prospective randomised study or standardised national surveillance of cardiac surgical site infection rates.

Timothy P Haydon FRACP, FJFICM, FANZCA · Jeffrey J Presneill MB BS, MBiostat, PhD · Megan S Robertson FRACP, FJFICM, FANZCA

To the Editor: Congratulations on the 21 September 2009 issue of the Journal, highlighting preventive cardiology in Australia. I believe that the “working class man” of the well known Jimmy Barnes song has trouble affording preventive cardiology care in Australia. Assuming that he is currently employed, he will not be entitled to a Health Care Card and will be paying full price for care in general practice. There will be a gap of $20 to $60 between what he pays and the Medicare rebate per visit. He will have to pay about $30 per prescription. Assuming that he is taking antiplatelet agents, statins, and a blood pressure agent such as an angiotensin-converting enzyme inhibitor, he would be paying about $90 per month for medication. On an average income of $1200 per week1 ($800 after tax), and assuming that he visits his general practitioner monthly, preventive cardiology care might cost him about 4% of his disposable income. If our working class man is earning $900 weekly ($600 after tax), then preventive cardiology care would cost him 5% of his disposable income. Of course, the costs are similar for a wealthy man. However, the costs represent a far smaller percentage of his income than for the working class man. In this regard, the costs of preventive medicine are similar to the poll tax imposed in England in the 14th century. This regressive capitation tax was raised to pay for the imperial wars in France. However, the disproportionate burden it imposed on the serfs resulted in such anger that it led to the Peasants’ Revolt in 1381. Until medicine is funded more equitably, there will be a major disincentive to pursue preventive cardiology care for poorer people, who experience cardiovascular disease at an earlier age than their wealthier counterparts.2 The problem is not which model to use for absolute risk assessment,3 but the money to apply it.

V Michael Jelinek

Practical cardiology (+ CD ROM). 2nd ed. Tracey Baker, George Nikolic, Simon O’Connor. Sydney: Churchill Livingstone, 2008 (xxiii + 391 pp). ISBN 9780729538411. The first edition of Practical cardiology: an approach to the management of problems in cardiology, by Baker and O’Connor, appeared in 1999. This second edition includes a third author, George Nikolic. Baker is a Canberra general practitioner, while Nikolic and O’Connor are cardiologists at the Canberra Hospital. Larger than the first edition (391 pages versus 192), and including a supplementary CD of angiographic and echocardiographic video images, it is excellent value at $89.95. It is likely to be useful for GPs and their trainees, medical students and cardiac nurses, and could be read with profit by those training in general medicine or beginning advanced training in cardiology. The sections on case- or problem-based learning are practical, well done and worthwhile exercises for senior medical students and trainee physicians. There is a helpful chapter on clinical trials, although there is no mention of some of the important earlier studies (GISSI, ISIS, GUSTO, LATE, etc). There are useful sections on electrocardiography, arrhythmias, heart disease and non-cardiac surgery, coronary revascularisation, antiplatelet therapy, anticoagulants, heart disease in pregnancy and congenital heart disease. My primary concerns relate to the illustrations. Some of these have been reproduced poorly, so that, for example, the demonstration of rib notching in a chest radiograph of a patient with coarctation of the aorta is unconvincing, as are the illustrations of Kerley B lines and valve calcification. Some images of echocardiograms need more comprehensive labelling. The CD images are a worthwhile addition, but their value would also be enhanced by explanatory labels, diagrams or cartoons: intravascular or transoesophageal studies are unlikely to mean much to the uninitiated without such help. This book retains the attractive features of the first edition, in that it is concise, simple, authoritative and as up to date as we might expect of any publication when it deals with so rapidly changing a field as cardiology.

J H Nicholas Bett

Many patients with heart failure do not have reduced left ventricular ejection fraction, and it is not yet clear whether their treatment should be the same as that of patients who do The syndrome of heart failure is one that is familiar to most clinicians. The cardinal symptoms of dyspnoea and fatigue when combined with signs of fluid retention — lung crackles, elevated jugular venous pressure and peripheral oedema — usually lead one to the diagnosis. Indeed, the Framingham criteria for diagnosis of heart failure are based largely on clinical findings that can be elicited at the bedside.1 When combined with what most of us have been taught in medical school, namely, that heart failure is usually caused by the loss of the pumping capacity of the left ventricle (eg, after myocardial infarction or due to cardiomyopathy), clinicians have become familiar with the concept that most cases of heart failure are associated with impaired left ventricular systolic function, shown by a reduction in the left ventricular ejection fraction (LVEF). As if to reinforce this mindset, major trials of new treatments for heart failure have historically focused on the group of patients with reduced LVEF. Applying echocardiography and other diagnostic imaging modalities to patients with heart failure has led to the realisation that many patients, as many as half in some series, do not have a reduced LVEF. Several terms have been used to describe this population, such as “diastolic heart failure’”, “heart failure with normal systolic function” and “heart failure with preserved systolic function”. All three terms are problematic. Diastolic dysfunction is common in patients with impaired LVEF2 and many patients with preserved LVEF have unequivocal evidence of systolic dysfunction.3 My personal preference is for the term “heart failure with preserved ejection fraction” (HFPEF), as it makes no assumptions about the pathophysiology of heart failure in affected patients. Even this descriptor is not without its problems, as different investigators appear to have differing opinions as to what should be considered a “preserved” LVEF. Investigators in different studies have drawn the line between preserved and reduced LVEF at 50%,4 45%,5,6 40%,7 or even 35%.8 Needless to say, this diagnostic confusion does nothing to help clinicians who are trying to care for these patients. Is it important to distinguish HFPEF from heart failure with reduced ejection fraction (HFREF)? Are they simply different ends of a continuous disease spectrum, or do they represent distinct entities with different causes and different natural histories? Given that they present with the same clinical syndrome, should they be treated the same way? These are important questions for which we currently lack answers. Multiple studies that have compared the demographics and natural history of HFPEF and HFREF have now been published,9 including the study by Wong and colleagues in this issue of the Journal.10 A reasonably consistent finding across these studies has been that, compared with patients with HFREF, patients with HFPEF were older, more likely to be female and more likely to have pre-existing hypertension and atrial fibrillation. Conversely, ischaemic heart disease was more common in those with HFREF. Comparison of the survival of patients with HFPEF versus HFREF has produced conflicting data. While some studies have suggested that those with HFPEF have better survival than those with HFREF, others, including Wong et al,10 have shown no difference in survival. A recently published meta-analysis of the natural history of HFPEF compared with HFREF collected data from 17 studies that included 24 501 patients.9 In that analysis, patients with HFPEF had a significantly better survival than those with HFREF, although it is noteworthy that over an average follow-up of 47 months, almost a third of those with HFPEF had died, indicating that the life expectancy of this group of patients is far below that of the healthy age-matched population. The poor survival of patients with HFPEF was also emphasised in the study by Wong et al,10 and in another recent publication from the Framingham investigators.6 An important observation made by Wong and colleagues is that comorbid conditions and psychosocial factors are important determinants of the outcome of patients with HFPEF.10 They found that anaemia, chronic obstructive pulmonary disease, cancer and dementia were all more common in patients with HFPEF compared with those with HFREF.10 A higher rate of comorbid conditions in patients with HFPEF has also been noted by other investigators.6 In addition, patients with HFPEF had fewer social supports, were more likely to live in nursing homes, and were more likely to require readmission to hospital — mainly for management of comorbid conditions rather than for heart failure. The prognosis and quality of life for patients with HFREF has been markedly improved by the implementation of evidence-based treatments including therapy with β-blockers and inhibitors of the renin–angiotensin–aldosterone system. On the other hand, no treatment has been proven to alter the natural history of HFPEF. Treatment remains empirical, and is aimed at controlling associated conditions such as hypertension and symptoms and signs of fluid retention. Thiazide diuretics, a class of drugs that has largely fallen out of favour for treating hypertension and HFREF, may yet prove to be the most effective drug class for preventing HFPEF. In a recent analysis of the very large ALLHAT trial of patients with hypertension and aged over 55 years,4 antihypertensive treatment with chlorthalidone was associated with a lower risk of developing HFPEF when compared with treatment with lisinopril, amlodipine or doxazosin. Therapeutic trials of other drug classes in HFPEF have been limited, and generally disappointing. Angiotensin-receptor blockers have been the most studied class of drugs, and have been shown in two large trials to have no impact on survival.5,7 β-Blockers appear more promising. In a prespecified analysis of the SENIORS study of the vasodilating β-blocker nebivolol in older patients with heart failure,8 the investigators reported similar benefits of nebivolol in patients with either HFPEF or HFREF; however, the definition of HFPEF in that study was an LVEF of greater than 35%. Clearly, more trials are needed. As our population continues to age, we are facing an impending epidemic of HFPEF together with other diseases associated with ageing. More effective blood pressure control of patients with systemic hypertension stands out as the most obvious preventive strategy, but it is clear that hypertension is only one of a number of antecedents to HFPEF. There is an urgent imperative to gain a better understanding of the pathogenesis of HFPEF in order to identify additional preventive and treatment approaches. This will be particularly challenging in a population exposed to multiple comorbid conditions, increasing physical frailty, and social isolation, as highlighted by Wong and colleagues.10 Optimal management of these patients will require a multidisciplinary approach with the general practitioner taking the central role.

Peter S MacDonald MB BS, FRACP, PhD

Objective: To determine whether heart failure with preserved systolic function (HFPSF) has different natural history from left ventricular systolic dysfunction (LVSD).Design and setting: A retrospective analysis of 10 years of data (for patients admitted between 1 July 1994 and 30 June 2004, and with a study census date of 30 June 2005) routinely collected as part of clinical practice in a large tertiary referral hospital.Main outcome measures: Sociodemographic characteristics, diagnostic features, comorbid conditions, pharmacotherapies, readmission rates and survival.Results: Of the 2961 patients admitted with chronic heart failure, 753 had echocardiograms available for this analysis. Of these, 189 (25%) had normal left ventricular size and systolic function. In comparison to patients with LVSD, those with HFPSF were more often female (62.4% v 38.5%; P = 0.001), had less social support, and were more likely to live in nursing homes (17.9% v 7.6%; P < 0.001), and had a greater prevalence of renal impairment (86.7% v 6.2%; P = 0.004), anaemia (34.3% v 6.3%; P = 0.013) and atrial fibrillation (51.3% v 47.1%; P = 0.008), but significantly less ischaemic heart disease (53.4% v 81.2%; P = 0.001). Patients with HFPSF were less likely to be prescribed an angiotensin-converting enzyme inhibitor (61.9% v 72.5%; P = 0.008); carvedilol was used more frequently in LVSD (1.5% v 8.8%; P < 0.001). Readmission rates were higher in the HFPSF group (median, 2 v 1.5 admissions; P = 0.032), particularly for malignancy (4.2% v 1.8%; P < 0.001) and anaemia (3.9% v 2.3%; P < 0.001). Both groups had the same poor survival rate (P = 0.912).Conclusions: Patients with HFPSF were predominantly older women with less social support and higher readmission rates for associated comorbid illnesses. We therefore propose that reduced survival in HFPSF may relate more to comorbid conditions than suboptimal cardiac management.

Dennis T Wong MB BS(Hons) · Robyn A Clark PhD, FRCNA · Benjamin K Dundon MB BS, FRACP · Andrew Philpott MB BS, FRACP · Payman Molaee MB BS, FRACP · Sepehr Shakib PhD, FRACP

To the Editor: We describe two liver transplant patients who presented with unexplained dyspnoea and were subsequently found to have unilateral right diaphragmatic palsy, an uncommon complication of orthotopic liver transplantation.1-3 Both transplant recipients were male. One, aged 64 years, had a liver transplant in 2005 for hepatitis C-related chronic liver disease. The other, aged 66 years, had a liver transplant in 2004 for end-stage alcoholic liver cirrhosis. Both patients had presented with exertional dyspnoea several weeks after transplantation. Both were reformed smokers with no prior respiratory symptoms or established respiratory or cardiac condition. Preoperative pulmonary function tests had been essentially normal in both patients (Box 1). Chest x-rays of both patients during the postoperative convalescence period showed unilateral elevation of the right hemidiaphragm compared with the immediate pre-transplant images. (Images for Patient 1 are shown in Box 2.) Fluoroscopic study (the “sniff test”) and a computed tomography scan of the chest confirmed the presence of right hemidiaphragmatic palsy in both patients. Follow-up chest x-rays and pulmonary function tests over 2 years showed no significant improvement. In both patients, the postoperative clinical course over these 2 years was characterised by recurrent hospital admissions with hypoxaemia and intercurrent respiratory tract infections, some requiring supplemental oxygen therapy, non-invasive positive pressure ventilation and invasive ventilation in the intensive care unit. Currently, one of these patients is well, apart from dyspnoea on moderate exertion. The other patient died from a cause unrelated to his diaphragmatic palsy. Unilateral diaphragmatic palsy following liver transplantation is thought to be related to traumatic crush injury to the right phrenic nerve from a clamp placed on the inferior vena cava (IVC) during surgery.1 The proximity of the phrenic nerve to the IVC renders it very vulnerable to this type of injury from side-to-side cross-clamping of the suprahepatic IVC.1,2 In 2008, we modified our technique to avoid cross-clamping of the IVC by performing cavocavostomy, a type of “piggyback” technique that involves “side-biting” (partial clamping) of the retrohepatic IVC away from the diaphragm.4 Unilateral diaphragmatic palsy can reduce exercise tolerance5 and may place additional mechanical stress on ventilation, which could exacerbate hypoxaemia if these patients develop intercurrent pulmonary infections. Reporting on a series of patients with phrenic nerve injury after liver transplantation, McAlister and colleagues1 found right hemidiaphragmatic palsy in 38% of patients after transplantation, but most of the patients recovered their diaphragmatic function within 9 months. In contrast, our patients did not show any signs of recovery for over 2 years, indicating that loss of diaphragmatic function after liver transplantation may be longstanding or permanent. 1 Comparison of pulmonary function tests before and after orthotopic liver transplantation* Patient 1 Patient 2 Pulmonary function test Before transplant After transplant Difference Before transplant After transplant Difference FEV1 (% of predicted) 2.72 L (80%) 1.73 L (51%) – 29% 2.78 L (85%) 1.40 L (47%) – 38% FVC (% of predicted) 3.79 L (87%) 2.41 L (56%) – 31% 3.83 L (92%) 2.17 L (57%) – 35% FEV1/FVC 0.72 0.72 0.73 0.65 TLC (% of predicted) 5.81 L (87%) 4.28 L (62%) – 25% 7.09 L (110%) 5.18 L (86%) – 24% FEV1 = forced expiratory volume in 1 second. FVC = forced vital capacity. TLC = total lung capacity. * Tests were performed while the patients were in a clinically stable condition. 2 Erect chest x-rays before and after orthotopic liver transplantation, Patient 1 A: In 2005, before liver transplant. B: In 2006, 6 months after liver transplant. Note marked elevation of the right hemidiaphragm and presence of bilateral calcified pleural plaques.

H S Subhash · John W C Chen · Libby John · Jeffery J Bowden · Dimitar Sajkov · Peter Frith

Objectives: To compare the use of evidence-based pharmacological and invasive treatments and 12-month mortality rates between patients with and without diabetes who present with acute myocardial infarction (MI), and to explore the relationship between these treatments and late clinical outcomes.Design and setting: Prospective, nationwide multicentre registry: the Acute Coronary Syndrome Prospective Audit (ACACIA).Patients: Patients presenting to 24 metropolitan and 15 non-metropolitan hospitals with acute coronary syndrome (ACS) and a final discharge diagnosis of acute MI between November 2005 and July 2007.Main outcome measure: All-cause mortality at 12 months.Results: Nearly a quarter of 1744 patients with a final diagnosis of acute MI had a history of diabetes on presentation. Patients with diabetes were older, with a greater prevalence of comorbidities than non-diabetic patients, and were less likely to be treated at discharge with evidence-based medications (aspirin, clopidogrel, a statin and/or a β-blocker) or to receive early invasive procedures. After adjusting for baseline characteristics and therapeutic interventions, diabetes at presentation was independently associated with a higher mortality at 12 months after MI (hazard ratio, 1.79; 95% CI, 1.18–2.72; P = 0.007). Early invasive management and discharge prescription of guideline-recommended medications were associated with a significantly reduced hazard of mortality at 12 months.Conclusion: Patients with diabetes have a higher risk than non-diabetic patients of late mortality following an acute MI, yet receive fewer guideline-recommended medications and early invasive procedures. Increased application of proven pharmacotherapies and an early invasive management strategy in patients with diabetes presenting with ACS might improve their outcomes.Study protocol number (sanofi-aventis): PML-0051.

Joseph Hung FRACP, FACC, FCSANZ · David B Brieger PhD, FRACP, FCSANZ · John V Amerena FRACP, FACC, FCSANZ · Steven G Coverdale MB ChB, FRACP · James M Rankin MB BS, FRACP · Carolyn M Astley RN, BN(Hons) · Ashish Soman MB BS, MRCP(UK) · Derek P Chew MB BS, MPH, FRACP

Preventive cardiology: a practical manual. Catriona Jennings, Alison Mead, Jennifer Jones, et al. Oxford: Oxford Medical Press, 2009 (xvi + 218 pp). ISBN: 978 0 19 923630 5. While cardiovascular disease (CVD) remains the predominant cause of death in our society, books on the topic will continue to find interest in the market, particularly those on preventive cardiology. Relatively few books on prevention, however, are written for health professionals by health professionals. Preventive cardiology: a practical manual, by a group of seven authors, addresses cardiovascular risk management and lifestyle factor assessment and application, for the benefit of and use by health professionals. The authors include representatives of nursing, dietetics, physiotherapy, physical activity and cardiology, so Preventive cardiology provides a uniquely holistic overview. With this multidisciplinary approach, the authors deal with both the assessment of risk factors and the application of findings in the management of patients with cardiovascular risk factors. One of the strengths of this book is its fundamental family-oriented approach. In a clear and concise manner, the authors address the main issues of identifying and treating patients with CVD risk factors, and provide a guide for health professionals in their work of identifying, assessing, treating and managing patients/clients at high risk, and steering them and their families through appropriate programs. The book covers all the usual topics of diet, smoking cessation, risk assessment, physical activity, identification of asymptomatic patients, blood pressure, lipid and glucose management, compliance, and so on. More importantly, it aims to assist the health professional team in getting such vital information lucidly and comprehensively across to patients and their families in a way that is most likely to be of practical benefit. The book comes in a pocket-sized format for easy access, and can be regarded as a ready companion and consistent helper for the cardiovascular professional.

Ian R Hamilton-Craig

The relationship between drug dose and clinical outcome has not been established for many medications used to treat chronic disease. Evidence is emerging that chronic diseases can be treated effectively with low doses. Adverse drug reactions account for significant morbidity and mortality and are generally dose related. Optimal drug dose — the best balance of benefit and risk — varies between individuals and may change over time. When treating chronic disease it is important to establish and maintain the optimal dose for each patient by close clinical monitoring.

Simon B Dimmitt MB BS, BMedSc(Hons), FRACP · Hans G Stampfer MB BS, FRANZCP

To the Editor: A recent article in the Journal describes, again, barriers to implementation of cardiometabolic monitoring among patients prescribed antipsychotic drugs.1 The cardiac health of patients with psychosis is not routinely assessed at first presentation for mental health services, adverse side effects of antipsychotic drugs are not systematically monitored, and patients with treatable risk factors for heart disease are not identified.2 We propose a practical solution to the seemingly intractable problem of implementing guidelines for cardiometabolic monitoring — change the delivery system. We have employed a general nurse to conduct cardiometabolic monitoring in a pilot study at the Recovery And Prevention of Psychosis Service (RAPPS), a first-episode psychosis service in Melbourne. All 15 eligible patients had their height, weight, blood pressure, waist circumference, fasting total cholesterol, high- and low-density lipoprotein cholesterol, triglycerides and glucose assessed according to national guidelines3 within 1 month of entry to the service, in the hospital, as an outpatient, or in the patient’s home; 14/15 blood samples were taken while the patient was fasting. Very early monitoring (within 7 days of first exposure to antipsychotics) was not implemented for four patients because they were inpatients and judged by ward staff as too unwell to be approached by a general nurse. Future follow-ups will be conducted at 3, 6, 12 and 18 months. Abnormal findings are referred to the treating psychiatrist, who is responsible for ensuring the patient receives appropriate follow-up. A general nurse can implement clinical guidelines, but this initiative requires substantial planning and ongoing management. Systematic identification of all patients eligible for monitoring requires identification of all pathways into the relevant mental health service, so as to begin monitoring at, or very close to, the point of first exposure to antipsychotics; management tools to track patients over time; and a clinical pathway to track test results and ensure appropriate medical interventions occur when required. Failure to implement prescribed monitoring guidelines is important because individuals with schizophrenia have a 20% shorter life expectancy than individuals in the general community.4 Side effects of antipsychotic drugs may include dramatic weight gain and elevations in serum cholesterol and glucose levels, which exacerbate the risk for cardiovascular disease. Most early deaths among individuals with schizophrenia are due to cardiovascular disease.5 Failure to monitor cardiovascular health and the adverse side effects of antipsychotic drugs is an important, life-shortening, failure of care. A simple solution to a complex problem exists if an effective delivery system is used.

Debra L Foley · Katherine I Morley · Karyn E Carroll · John Moran · Patrick D McGorry · Brendan P Murphy

In reply: Foley and colleagues rightly point out that a way to improve the cardiometabolic health of patients with psychosis is to change the way that mental health services are delivered. Although barriers to monitoring exist at the level of the patient, the illness, and the service,1 by focusing too narrowly on the barriers presented by patients, a blaming culture can be perpetuated. If blame is to be attributed, it should be directed towards inflexible services with a medieval belief in separating mental and physical health care. A number of centres in Australia have started to innovate in service delivery, with structured physical health clinics running in parallel to, and integrated with, mental health clinical programs. Our own centre, the Concord Centre for Cardiometabolic Health in Psychosis (ccCHIP), has been developed to take the notion of integrated care a step further — to actually treat the cardiometabolic abnormalities present. Our model involves a multidisciplinary team comprising psychiatrists, endocrinologists, and dietitians. However, we believe the potential for broader multidisciplinary input exists, including nurses, pharmacists, psychologists, occupational therapists, social workers and the patient’s general practitioner. It is our philosophy that although detection is the first step to improving the parlous outcomes for our patients, without active intervention, these poor outcomes are unlikely to improve. Recently, we received funding from the New South Wales Department of Health to develop a more comprehensive plan for education and training, including the production of a manual, to help psychiatric services in NSW develop their own monitoring and intervention services, using ccCHIP as their resource base. This initiative points to the need for government involvement to support these initiatives. Finally, it is apposite that Foley and colleagues write from the perspective of an early psychosis service — we believe that early detection and intervention for psychosis should be for physical as well as mental health issues.2

Timothy J R Lambert

We have a tool for absolute risk assessment — now we need a robust implementation program In March 2009, the National Vascular Disease Prevention Alliance (NVDPA), a consortium of Diabetes Australia, Kidney Health Australia, the National Heart Foundation of Australia, and the National Stroke Foundation, released evidence-based guidelines for assessing absolute cardiovascular risk.1 The guidelines are for use by health professionals who assess patients’ cardiovascular risk, primarily general practitioners. The risk charts that accompany the guidelines differ somewhat from the New Zealand risk charts,2 which are commonly used in Australia. Both the Australian and NZ charts are based on the Framingham Heart Study.3 The Australian cardiovascular risk charts are separated at the broader level into people with and without diabetes, rather than into men and women. In addition, systolic, but not diastolic, blood pressure is included because it is the stronger determinant of future events. The charts extend to upper cut-off points of 179 mmHg for systolic blood pressure and 7.5 mmol/L for total cholesterol level, respectively. The NVDPA guidelines also have an online risk calculator (http://www.cvdcheck.org.au). The new NVDPA guidelines and charts have the advantage of taking into account other drivers of practice in Australia, such as the Royal Australian College of General Practitioners’ Guidelines for preventive activities in general practice,4 and eligibility for Pharmaceutical Benefits Scheme subsidies for statins. Absolute risk assessment maximises the effectiveness of prediction of risk of future cardiovascular disease (CVD) events in people apparently free of such disease. This is because the underlying equations acknowledge fundamental epidemiological principles: risk depends on the range of independent risk factors and, for biomedical factors, risk typically increases in a log–linear manner above ideal levels (systolic blood pressure and total cholesterol level, 115 mmHg and 3.8 mmol/L, respectively).5 The present, somewhat arbitrary, definitions of hypertension and hypercholesterolaemia as ≥ 140/90 mmHg and ≥ 5.5 mmol/L, respectively, are fundamentally flawed, and most people who have CVD events have a clustering of risk factors with only modest abnormalities. If relative risk reduction with an intervention is relatively constant (the usual case), use of the intervention in those at higher absolute risk leads to greater absolute risk reduction and net benefit, thus also maximising cost-effectiveness. All absolute risk tools share some problems. As they are derived from large population studies, they are better at rank-ordering risk in subgroups and less precise in an individual. However, individual risk assessment may be refined (particularly in those initially assessed to be at intermediate risk) by measuring biomarkers or by imaging,6 and probably more so in the future, as more evidence becomes available. Other factors that might also be added to future algorithms include anthropometric measures (of these, waist circumference or waist : hip ratio appears more predictive than body mass index), a family history of premature atherosclerotic disease, and measures of socioeconomic deprivation.7 The NVDPA guidelines acknowledge that the Framingham risk equation may underestimate risk if these factors are present. The major determinant of CVD risk is increasing age, and it is also likely that equations specific for various age groups will become available. Particularly among younger people, this will improve identification of those with greater modifiable risk. Ideally, risk equations should be developed and validated in the local population. In Australia, algorithms for the general population have been developed from the Busselton8 and Dubbo9 studies. These are important contributions, although the relatively narrow endpoint (in Busselton) and the cohort age (in Dubbo) limit their application. How best can the NVDPA tools be used by practising clinicians? The first step is to identify high-risk groups. These include people with one or more of the following: prior CVD events, peripheral arterial disease, diabetes and age ≥ 60 years, chronic kidney disease, and familial hypercholesterolaemia. Such people should be treated accordingly and do not need absolute risk assessment. In all others, absolute risk assessments should commence at age 45 years, or 35 years for Aboriginal and Torres Strait Islander people, and be repeated at intervals reflecting the initial level of risk.1 An example of how to incorporate absolute cardiovascular risk assessment into management is given in the Box. What we now need is a robust implementation program. This makes economic sense. Recently, the National Health Service Health Check program was released in the United Kingdom.10 Everyone between 40 and 74 years, not already diagnosed with heart disease, stroke or kidney disease, will be invited, once every 5 years, to have their risk assessed using an absolute risk tool, and given support and advice to help them reduce or manage their risk. Analyses showed that this program would be very cost-effective compared with other accepted health interventions. The modelled cost-effectiveness ratio of this UK program is only £2480 per quality-adjusted life-year gained. Presently, in Australia, a Medicare item number supports a single health check for those aged 45–49 years. Although cost-effectiveness analyses are sensitive to the local health care system, the UK data strongly suggest that the current Medicare item number could be expanded, and other systems-based approaches implemented, to ensure that ongoing primary care risk assessments are supported, and that people at higher risk receive lifestyle and appropriate medical management. Implementation would be most likely to be effective if decision-support tools and recall mechanisms were used and incorporated into prescribing linked to electronic health records. Accompanying materials that appropriately communicate concepts of risk to patients would also be useful. The NVDPA is now developing a single CVD risk-management guide that will integrate the various specific risk-factor guides and make it easier to manage patients according to their absolute risk status. Absolute risk assessment does not replace the need to base all approaches to CVD prevention on lifestyle change. Studies have clearly shown the value of this, whether or not individuals are receiving blood-pressure or lipid-lowering therapies.11 However, absolute risk assessment leaves behind time-hallowed approaches based on individual risk factors, treated in silos, and often “dichotomised” to be regarded as “normal” or “abnormal”. It moves us forward to a more rational and effective paradigm for preventing our major health problem. How to incorporate absolute risk assessment into management using the Australian cardiovascular risk charts (the “People without diabetes” section of the charts is reproduced below) Example: Two women with similar risk profiles, but different ages Both women are smokers, without diabetes, with systolic blood pressure, 140 mmHg; total cholesterol : high-density lipoprotein cholesterol (TC : HDL) ratio, 7.2 mmol/L; and body mass index, 27 kg/m2. A is 46 years old and estimated to have a low risk (5%–9%) of developing cardiovascular disease (CVD) within 5 years. However, if she continues to smoke and to have a high TC : HDL ratio, she will place herself at high risk of prematurely developing CVD as she gets older. The chart can be used to demonstrate this to her. The priority intervention should be lifestyle advice, including smoking cessation, physical activity and healthy eating. B is 66 years old and estimated to be at high risk (20%–24%) of having a CVD event within 5 years. As a high priority, she should receive advice about smoking cessation and other lifestyle changes, as well as statin therapy. How to use the risk chart 1. Identify the chart relating to the person’s sex, diabetes status, smoking history and age. The charts should be used for all adults aged 45–74 years (and all Aboriginal and Torres Strait Islander adults aged 35 years or older) without known history of CVD or already known to be at high risk. 2. Within the chart, choose the cell nearest to the person’s age, systolic blood pressure (SBP) and total cholesterol (TC):HDL ratio. For example, the lower left cell contains all non-smokers without diabetes who are 35–44 years and have a TC:HDL ratio of less than 4.5 and a SBP of less than 130 mm Hg. 3. The colour of the cell that the person falls into provides their 5-year absolute cardiovascular risk level (see legend above for risk category). People who fall exactly on a threshold between cells are placed in the cell indicating higher risk. Charts are based on the NVDPA’s Guidelines for the assessment of absolute cardiovascular disease risk and adapted with permission from New Zealand Guidelines Group. New Zealand Cardiovascular Guidelines Handbook: A Summary Resource for Primary Care Practitioners. Second edition. Wellington, NZ: 2009. www.nzgg.org.nz. These charts are taken from Absolute cardiovascular disease risk assessment – quick reference guide for health professionals. © 2009 National Heart Foundation of Australia. Reproduced with permission. No further reproduction is allowed.

Andrew M Tonkin MD, FRACP, FCSANZ · Andrew N Boyden MPH, FRACGP · Stephen Colagiuri FRACP

A systematic, integrated national approach is needed to implement 2006 Australian guidelines for management of acute coronary syndromes (ACS). Clinical outcomes can be improved by closing the current gaps between evidence and practice. In 2007, the National Heart Foundation of Australia, the Cardiac Society of Australia and New Zealand, and the Australasian College for Emergency Medicine held a national forum to identify current gaps in ACS management and priority strategies to improve outcomes. Consensus recommendations were based on evidence and expert opinion. Prompt reperfusion for patients with ST-segment-elevation myocardial infarction should be ensured by establishing protocols for single-call activation of primary percutaneous coronary intervention, or, where unavailable, enabling health care workers to initiate thrombolysis. Accuracy of risk stratification of non-ST-segment-elevation ACS (NSTEACS) should be improved using clinical pathways that integrate ambulance, medical and nursing care. Rates of early invasive management for patients with high-risk NSTEACS should be increased using efficient systems for transfer to revascularisation facilities. All patients with an ACS should be referred to rehabilitation and secondary prevention programs, including alternative models of care where appropriate. Equal access to recommended care for all Australians with an ACS — including those in rural, remote and Aboriginal and Torres Strait Islander communities — should be achieved by improving workforce capacity in under-resourced regions and ensuring access to third-generation fibrinolytic agents, defibrillation, timely essential pathology tests and invasive revascularisation facilities. National standards for data collection and clinical outcomes should be established, and performance should be monitored.

on behalf of the National Heart Foundation ACS Implementation and Advocacy Working Group

A 49-year-old man presented with verapamil toxicity complicated by hypotension and a junctional rhythm, in the context of deliberate self-poisoning with multiple drugs. The patient’s hypotension normalised following the early use of high-dose insulin euglycaemic therapy (HIET), without the need for additional vasopressors; it recurred when HIET was prematurely stopped, and again stabilised when HIET was recommenced. Consideration should be given to the early use of HIET in treating severe calcium channel blocker toxicity, rather than as a last resort after other therapies have failed. (MJA 2009; 191: 350-352) Clinical recordA 49-year-old man presented to a peripheral hospital emergency department 1–1.5 h after deliberately ingesting multiple medications: verapamil (unknown amount), controlled-release morphine sulfate (20 × 30 mg), diazepam (50 × 5 mg) and tramadol (15 × 200 mg). He was a smoker with a history of depression, ethanol misuse, chronic back pain, hypertension and a previous instance of deliberate self-poisoning with multiple drugs. At initial assessment, the patient’s vital signs were: temperature, 36.8°C; pulse, 84 beats/min; respiratory rate, 19 breaths/min; blood pressure (BP), 115/80 mmHg; oxygen saturation, 95% on room air; and Glasgow Coma Scale score, 14/15. He was drowsy, disorientated to time, and had 2 mm pupils that were equal and reactive. He had ataxia, dysarthria and was generally weak. His breath ethanol concentration was 0.172 mg%. Thirty minutes later, the patient was hypotensive (BP, 85/45 mmHg; pulse, 72 beats/min). He was treated with oxygen, 2 L intravenous (IV) 0.9% saline, a naloxone IV infusion (400 μg/h), and 10 mL IV 10% calcium gluconate. He was transferred to a tertiary referral centre and, on arrival (at 2.25 h after initial presentation), his BP was 85/45 mmHg, pulse was 64 beats/min, and an electrocardiogram (ECG) showed a junctional rhythm. Rapid sequence intubation (with propofol 40 mg + 20 mg IV and suxamethonium 100 mg IV) was performed for airway protection and ongoing management of haemodynamic instability, while metaraminol IV boluses (total, 0.7 mg) were administered. Activated charcoal (50 g) was given, and sedation was maintained with a propofol infusion. The patient remained hypotensive (BP, 75/45 mmHg; pulse, 56 beats/min) after intubation, so high-dose insulin euglycaemic therapy (HIET) was commenced at 3.5 hours after presentation. He was given dextrose (50 mL 50% glucose) and a 30 IU short-acting insulin IV bolus (~ 0.5 IU/kg), followed by a further bolus of 50 mL 50% glucose and a short-acting insulin IV infusion (30 IU/h) (Box 1). His BP improved to 110/70 mmHg at 4 hours, with a pulse of 82 beats/min and sinus rhythm on ECG, and he remained stable during transfer to the intensive care unit (ICU). The insulin infusion was abruptly stopped 5.5 hours after presentation, on arrival in the ICU. The patient’s hypotension subsequently recurred (systolic BP, 70 mmHg; pulse, 75 beats/min), prompting administration of 500 mL IV Gelofusine (a colloidal plasma volume substitute; B. Braun, Sydney, NSW) and commencement of an adrenaline IV infusion (20 μg/min). The insulin infusion (30 IU/h) was restarted at 8.5 hours, and his BP again stabilised (Box 1). The propofol IV infusion was gradually increased from 50 mg/h to 150 mg/h between 5.5 hours and 11.5 hours after presentation, and a noradrenaline IV infusion was commenced at 9.5 hours to maintain normotension. At 15.5 hours, pulmonary artery catheter measurements showed a high cardiac index (5.1 L/min/m2; reference range [RR], 2.5–4.0 L/min/m2) and a low systemic vascular resistance index (1047 dynes·s/cm5/m2; RR, 1900–2400 dynes·s/cm5/m2); the patient’s pulse was 85 beats/min and BP was 140/60 mmHg. HIET was continued and the patient remained haemodynamically stable. Adrenaline and noradrenaline were weaned off (at 17.5 hours and 23.5 hours, respectively), despite the propofol infusion rate being increased to 500 mg/h at 18.5 hours. Once sedation was withdrawn, the patient was extubated at 26.5 hours. Insulin was weaned over 5 h and discontinued at 30.5 hours; dextrose was stopped 1 h later. The patient was transferred to the observation ward and discharged well later that day, after psychiatric clearance. During treatment with HIET, the patient’s blood glucose levels were checked hourly and ranged from 6.6 mmol/L to 13.2 mmol/L (RR, 3.5–5.5 mmol/L). He received about 25 g/h of dextrose (mostly as 50% dextrose infusions). Potassium and magnesium levels were also serially monitored; the minimum potassium level was 2.7 mmol/L (RR, 3.5–5.0 mmol/L) at 8.75 hours, and the magnesium level troughed at 0.5 mmol/L (RR, 0.75–1.05 mmol/L) at 15 hours. These were corrected with a total of 200 mmol of potassium chloride and 20 mmol magnesium chloride. DiscussionHIET is an increasingly accepted therapy for calcium channel blocker (CCB) toxicity, but reports of its use are limited and it remains controversial. Indeed, the scarcity of severe CCB poisoning cases means that a randomised controlled trial of HIET may not be feasible.1 Treating clinicians who seek advice from clinical toxicologists are often hesitant about the high doses required and the potential for adverse effects. Such hesitancy is potentially harmful, as a hypotensive patient with a CCB overdose who otherwise appears well is at risk of abrupt lethal cardiovascular collapse.1 HIET is traditionally recommended after other therapies have failed.2,3 This case report aims to raise awareness of HIET for the treatment of CCB toxicity and supports its early use, rather than as a last resort.4 Verapamil binds the alpha-1 subunit of L-type calcium channels, preventing the intracellular influx of calcium.5 These channels are functionally important in cardiac myocytes, vascular smooth muscle cells, and islet beta cells.5 Verapamil’s cardiac toxicity results from excessive negative inotropy, negative chronotropy and negative dromotropy, characterised by myocardial depression, sinus bradycardia, and atrioventricular node blockade.4 Vascular smooth muscle tone is impaired, resulting in decreased afterload, systemic hypotension, and coronary vasodilation.5 Less well known are the metabolic effects of CCBs such as verapamil. Under the stress of the drug-induced shock state, the cardiac myocytes shift from using free fatty acids, their favoured “resting state” energy substrate, to carbohydrates.3,4 CCB toxicity also impairs the uptake of glucose and free fatty acids by cardiac myocytes3,4 and inhibits calcium-dependent mitochondrial activity required for glucose catabolism.3,4 Furthermore, insulin release is dependent on calcium influx into islet beta cells through L-type calcium channels.3,4 Thus, CCB toxicity can cause hypoinsulinaemia,3,4 which, in conjunction with CCB-induced insulin resistance, may lead to hyperglycaemia and a ketoacidotic state.6 Atropine, calcium boluses and infusions, glucagon, inotropes, vasopressors, and cardiac pacing have all been advocated for managing CCB toxicity, despite questionable efficacy.3,4,7-9 For instance, the evidence for glucagon is limited to small, non-blinded animal studies where no survival benefit or improvement in mean arterial pressure was shown, although heart rate improved in some cases.7 Rarely, heroic measures such as extracorporeal circulatory support and intra-aortic balloon counterpulsation have been successfully employed.5,10 HIET was first used to treat verapamil toxicity in humans in 1993, with a favourable outcome.6 Since then, in addition to animal studies, there have been nearly 70 cases reporting the beneficial use of HIET in humans, with an overall survival rate of 85%.8 However, to our knowledge, use of HIET in humans before the administration of glucagon or vasopressors has only been reported once.6 There have been some reports of HIET failure in treating CCB toxicity, although the dosing of insulin was low or uncertain, or it was used late.6,8 Early use of HIET may be more effective than HIET rescue therapy, as CCB-induced insulin resistance is greatest in the first 24 hours2 and the maximal haemodynamic benefit of HIET may not occur immediately.6 HIET may allow the heart to overcome metabolic starvation in CCB toxicity, which compounds the direct CCB impairment of myocardial contractility.3,4 Insulin increases glucose and lactate uptake by myocardial cells and improves function without increased oxygen demand.11,12 It also induces pyruvate dehydrogenase, hastening myocardial lactate oxidation, and helps clear the cytosol of glycolytic byproducts that impair calcium handling and cause diastolic dysfunction.3 Insulin promotes excitation–contraction coupling and contractility because enhanced glycolysis promotes increased sarcoplasmic reticulum-associated calcium ATPase activity and increased cytoplasmic calcium concentrations, and promotes calcium entrance into mitochondria and sarcolemma.3 HIET may be best used adjunctively with other measures such as catecholamines, for two reasons. First, insulin-mediated inotropy is not catecholamine-mediated, and is not affected by β blockers.3 Second, although insulin appears to improve myocardial contractility, it has no chronotropic effect and may cause vasodilation.3,8 HIET is safe, and adverse events are predictable, uncommon, and easily managed.2,8 The maximum safe dose of insulin is unknown, but loading doses of 0.5–1.0 IU/kg followed by infusions of 0.1–2.5 IU/kg/h are typically used.8 Interestingly, neither the inadvertent administration of a 1000 IU insulin loading dose for verapamil toxicity13 nor treatment of toxic cardiogenic shock for 2 days with a 6 IU/kg/h insulin infusion had any adverse effects.14 Adverse effects of HIET include hypoglycaemia, hypokalaemia, hypomagnesaemia, and hypophosphataemia.2,6,8 Although these are rarely clinically significant, they necessitate careful monitoring. Hypoglycaemia (blood glucose < 3.3 mmol/L) occurred in 16% of 55 published cases,8 and no cases of hypoglycaemia within 24 hours of CCB overdose were noted in Greene and colleagues’ series of seven cases.2 Greene et al also reported a mean dextrose requirement of 0.05 g/kg/h (range, 0–0.17 g/kg/h), although the mean blood glucose level exceeded the euglycaemic range.2 Some cases of severe CCB toxicity in patients presenting with hyperglycaemia do not require any additional glucose administration despite high-dose insulin therapy,15 and hypoglycaemia may be more likely in milder cases without marked hypotension.8 In addition, hypokalaemia (potassium < 3.5 mmol/L) was noted in only two patients in Greene et al’s small series, with a minimum potassium level of 2.8 mmol/L.2 Excessive correction of hypokalaemia should be avoided, because it reflects the intracellular shift of potassium from the extracellular compartment due to the action of insulin, rather than a potassium-depleted state.4 Interestingly, hypokalaemia in HIET may augment myocardial contractility by enhancing calcium entry during systole, and increased intracellular potassium may have a membrane-stabilising effect in excitable cells.4,6 In conclusion, we advocate consideration of the early use of HIET (as detailed in Box 2) for the prevention and treatment of life-threatening complications from potentially lethal CCB overdoses. HIET is safe, inexpensive and freely available, and suitable for use even in remote settings before transfer to a referral centre. 1 Early changes in the patient’s systolic blood pressure (SBP) and heart rate, relative to treatment with high-dose insulin and adrenaline infusions Following administration of a 0.5 IU/kg short-acting insulin bolus 3.5 hours after presentation, a short-acting insulin intravenous infusion (0.5 IU/kg/h) was commenced (black line), and the patient’s blood pressure improved. The infusion was abruptly discontinued 2 hours later and the patient again became hypotensive. This resolved following commencement of an adrenaline infusion (20 μg/min) (grey arrow), and the insulin infusion (0.5 IU/kg/h) was restarted 8.5 hours after presentation (black arrow). 2 Recommended high-dose insulin euglycaemic therapy protocol,3,4,9 based on the clinical experience of the Western Australian Toxicology Service, published case reports, reviews and animal studies Commence therapy with: Glucose 25 g (50 mL of 50% solution) IV bolus, unless marked hyperglycaemia (blood glucose > 22 mmol/L) is present Short-acting insulin 1 IU/kg bolus to maximally saturate insulin receptors Continue therapy with: Short-acting insulin infusion starting at 0.5 IU/kg/h and titrated every 30 min to a maximum of 5 IU/kg/h* Dextrose 25 g/h IV infusion titrated to maintain euglycaemia (blood glucose, 5.5–14 mmol/L); central venous access may be required to allow use of concentrated solutions (eg, 50% dextrose) and limit excess volume administration Monitor: Glucose — every 20 min for first hour, then every 1 h Potassium — replace only if < 2.5 mmol/L and there is a source of potassium loss Therapeutic end points: Improvement in myocardial ejection fraction (> 50%); increased BP (systolic BP > 90 mmHg in adults) Adequate heart rate (> 60 beats/min) Resolution of acidaemia; euglycaemia; adequate urine output (1–2 mL/kg/h) Reversal of cardiac conduction abnormalities (QRS interval < 120 ms) Improved mentation Therapy is weaned after the withdrawal of other vasopressors, as cardiotoxicity resolves. Dextrose may be required after cessation of insulin. IV = intravenous. BP = blood pressure. * The maximum safe and effective rate of infusion is unknown but may be even higher than 5 IU/kg/h. In animal studies, insulin infusions as high as 10 IU/kg/h have been safely used.11

Christopher P Nickson MB ChB, DTMH, GCertClinTox · Mark Little FACEM, DTMH, MPHTM

To the Editor: The ASPREE (ASPirin in Reducing Events in the Elderly) study may provide useful data on the benefits and risks of aspirin therapy in patients aged ≥ 70 years, as described by Woods and colleagues.1 However, the decision to allow general practitioner co-investigators to “help decide whether the patient is a suitable candidate for the placebo-controlled trial” introduces a source of selection bias that may limit the generalisability of the results. Without pre-specified objective selection criteria, it is likely that primary-prevention patients assessed by GP co-investigators as being at high vascular risk will be excluded because the GPs believe they should be taking antiplatelet agents. Similarly, those at low risk may be thought inappropriate participants because the risks of random allocation to this therapy might outweigh the perceived benefits, as has been shown in previous meta-analyses.2,3 ASPREE may end up with a disproportionate number of intermediate-risk patients. In the case of diabetes, a recent observational study from our group highlighted patients with diabetes and retinopathy and those taking a sulfonylurea as being at increased risk of complicated peptic ulcer disease.4 By contrast, we did not find that aspirin use, positive serological results for Helicobacter pylori, or the interaction of these two factors predicted complicated peptic ulcer disease. If GP co-investigators were aware of these findings, they might also influence the screening and recruitment of patients with diabetes to ASPREE. According to the trial registration details (ISRCTN83772183), patients with diabetes were eligible for recruitment to ASPREE from late February 2009, even though the trial started 6 years ago.5 Given this delayed eligibility, the fact that a substantial proportion of patients with diabetes older than 70 years will already have vascular disease, and the expected total sample size of 19 000,1 the trial might include fewer than 1000 patients with diabetes and thus have insufficient statistical power to assess the risks and benefits of aspirin for primary prevention in this important subgroup. We question why subjective assessment forms part of patient selection for a potentially important study such as ASPREE, and also what steps the investigators are taking to determine whether the sample they recruit is representative. In addition, details of planned statistical analyses involving diabetic participants in this non-superiority trial would be reassuring.

Timothy M E Davis · Brett A Sillars · Wendy A Davis

In reply: Recruitment to clinical trials through general practice is representative of the population, as a high proportion of all Australians regularly attend their general practitioners.1 GP co-investigators are appropriate to decide whether their patients are suitable for the ASPREE (ASPirin in Reducing Events in the Elderly) study because their assessment includes objective inclusion and exclusion criteria that must be satisfied before enrolment in the study (clinical trial registration number ISRCTN83772183),2 as well as patient-specific potential risks with using aspirin, and known medical factors likely to influence patient survival during the trial. These include the risk of complicated peptic ulcer disease in patients with diabetes treated with a sulfonylurea.3 GP co-investigators support participation in ASPREE by eligible patients because of aspirin’s therapeutic equipoise for primary prevention in older patients4 and in those with diabetes.5 Because of age alone, ASPREE participants will be at least at intermediate risk of cardiovascular disease and also at increased risk of bleeding. Determining the aspirin balance underpins the importance of collecting more data in older people, who have been under-represented in previous primary prevention trials. ASPREE is a superiority trial with pre-specified subgroup analyses, including for the subgroup with diabetes.2 The study is powered to address the primary question reliably in the total cohort rather than subgroups. To date, fewer than 500 participants have been randomly allocated, with recruitment slowed subject to National Institutes of Health funding deliberations. Recruitment will be reinvigorated in late 2009, and will continue to include people with diabetes.

Robyn L Woods · Mark R Nelson · Andrew M Tonkin · Christopher M Reid

How you can use the evidence to improve your patients’ outcomes The most recent edition of Heart Foundation guidelines for the management of hypertension is an evidence-based and practical guide for doctors.1 It is self-evident that clinical guidelines need to be used by doctors if they are to improve population health outcomes. Despite publication of multiple editions of the hypertension guidelines, blood pressure (BP) control in Australia is less than ideal.2 The reasons for this are varied, and include health system, doctor and patient factors.3 Here, I outline simple but effective strategies for addressing some of the doctor factors associated with lack of BP control (Box), based on the Heart Foundation guidelines and supplemented by research conducted in Australian general practice. These strategies should help protect patients from stroke, myocardial infarction and other major organ damage, and are all practical in the general practice setting. Although they will not lead to universal control (because other factors are at play), they should help protect against therapeutic inertia and doctors’ doubts about their own self-efficacy — issues that may adversely affect patient health. Get blood pressure measurements from a variety of sources. When doctors measure BP, the measurements they record may differ from the true values, because of measurement error, “white coat effect”, poor technique, single measurements, observer error, and data misinterpretation.4 These problems can be addressed, to some degree, in a variety of ways. One approach is to have someone else, or something else, record BP for adult patients. In clinical practice, BP should be measured repeatedly (and preferably by a nurse) — three times, 5 minutes apart, and the last two measurements averaged. The process can be automated with some oscillometric devices, which further reduces bias.4 Away from the practice, the patient can record their BP on a validated,5 regularly serviced machine that they have been taught to use, or they can have their BP recorded by an ambulatory BP monitor. The latter are superior predictors of hard clinical endpoints compared with clinical measurements.6 Specific advice about technique for patients (as well as clinicians) is covered in the chapter of the Heart Foundation guidelines entitled “Measuring blood pressure”.1 Repeated measurements help reduce measurement error and variability, but they need to be interpreted logically. Suitable home BP monitoring can be achieved by asking the patient to measure BP in the morning and evening, to do so twice on each occasion (2 minutes apart after sitting quietly for 5 minutes), and to record the second measurement in a spreadsheet or diary for use at their next appointment. Interpreting the data can be as simple as highlighting elevated measurements, calculating the percentage of elevated systolic and diastolic measurements, or averaging the measurements. The goal is all or nearly all measurements (or average BP) at or below target levels. When interpreting the data, remember that cut-points are lower for recordings made away from the practice; for example, 135/85 mmHg is the cut-point for BP measured away from the practice in patients with uncomplicated hypertension. Act on absolute risk. In cases where repeated measurements of elevated BP are recorded in at-risk individuals, general practitioners may still not initiate or intensify BP management. Barriers to initiation or adjustment of drug therapy include: clinical uncertainty about underlying true BP and distrust of the technology used to measure BP; distrust of the evidence underpinning the recommendations for management of hypertension; a perceived increased rate of adverse events associated with drug therapy among older patients; perceived patient attitudes towards drug therapy or the need for it; a lack of internal motivation on the part of the practitioner; and health system issues such as lack of time in consultations. The decision to initiate treatment of elevated BP should not be based on BP alone (unless it is very high). An absolute cardiovascular disease risk score should be used, such as the recently released Australian cardiovascular risk charts, that now include risk for Aboriginal and Torres Strait Islander peoples.7,8 This is a more holistic approach than use of a single risk factor — it integrates all risk factors and thus more accurately identifies at-risk individuals. In primary prevention, population risk calculators are required as doctors cannot reliably estimate absolute risk.9 Patients with mildly elevated BP, who are at low absolute risk, do not require drug therapy but still need action on lifestyle factors that affect BP (eg, alcohol intake, diet, overweight/obesity, and physical inactivity). Don’t neglect behavioural factors. GPs recognise that behavioural factors underlie elevated BP and mitigate against effective BP control, but may feel that they have limited influence on their patients’ lifestyle. However, brief advice from a GP is the most cost-effective intervention for smoking cessation.10 Also, walking is a simple, free, all-year activity that GPs can recommend. For overweight patients, caloric restriction can be recommended and, for all patients, recommendations that can be considered include moderation of alcohol intake (do not recommend alcohol to non-drinkers), restriction of salt intake (by reading and interpreting processed food labels), and consumption of fruit and vegetables (two serves of fruit and five serves of vegetables per day). Advice should be supplemented with appropriate referrals (eg, to a dietitian). Accept that most patients will need more than one drug. Most patients will need more than one drug to control their BP.11 This is exacerbated by the need to manage the clustering of risk factors and multiple morbidity, which is common among patients, and especially older patients, with high blood pressure. These factors drive a high evidence-based pill count, which should be distinguished from unnecessary polypharmacy. Thus, the need for two or more drugs to effectively manage hypertension should be communicated to patients from the outset. Follow the guideline recommendations for combinations of drugs. Ways to deal with the necessary polypharmacy in managing high BP in at-risk individuals include: minimising side effects by starting with low doses (especially in older patients and patients with renal impairment), using low-dose combinations, discontinuing ineffective drugs, avoiding agents contraindicated for other conditions that are present, and monitoring for adverse outcomes such as renal impairment; minimising cost by using fixed-dose combinations, generics, agents with a larger number of daily doses dispensed, and drugs listed on the Pharmaceutical Benefits Scheme (avoiding “brand premiums”); increasing adherence by using combination therapies (especially those that allow within-combination dose adjustments); and reducing polypharmacy across morbidities by choosing antihypertensive agents that are indicated for other diseases that are present. Treat to goal. Once treatment of high BP has been moved to an absolute risk basis, the goals are logically reduced to lower levels for those individuals who are at high absolute risk. For example, the guidelines recommend lower BP targets for increasing levels of proteinuria in patients with chronic kidney disease.1 These patients will require greater individual risk factor reduction to reach low risk than patients who are at intermediate risk. This means more drugs, higher doses, higher costs, and greater difficulty in reaching therapeutic targets. In cases where the goal is not being reached, assessing for adherence to drug therapy is important — especially during the initiation of drug therapy. Participants in the Second Australian National Blood Pressure Study who answered yes to the question “Did you ever forget to take your medication?” were significantly more likely to experience a cardiovascular event or death than those who answered no.12 Strategies for dealing with necessary polypharmacy will also help reach the goals of target BP and adherence to drug therapy. The five ways together. Combining these strategies will help to improve BP control via an evidence-based chain of action: obtaining BP measurements systematically, in and away from the general practice setting; stratifying patients according to absolute risk, and acting on risk; considering behavioural measures for all patients; and utilising drugs (usually two or more) for patients who are at high risk, to reach recommended, targeted goals. Simple evidence-based strategies for managing high blood pressure in general practice Get blood pressure measurements from a variety of sources Act on absolute risk Don’t neglect behavioural factors Accept that most patients will need more than one drug Treat to goal

Mark R Nelson MB BS(Hons), FRACGP, PhD

To the Editor: We concur wholeheartedly with Gill and colleagues1 in support of recognising obesity as a public health issue, and we dispute claims that the current problem of obesity is being exaggerated. Gill and colleagues point out that obesity trends have climbed over decades, and state that 6%–8% of Australian school children are affected.1 While this is a substantial burden of over a quarter of a million children, we also consider that restricting definitions of obese to arbitrary cutoff points may underestimate the problem, given that the entire distribution of childhood weight is increasing, not just the extreme group classified as obese. Adiposity is related to cardiovascular outcomes such as myocardial infarction and stroke in a (curvi)linear fashion. Defining obesity by arbitrary cutoff points is vulnerable to differences between sexes, ethnicity and age, and limits our understanding of obesity-related diseases. It is well known that cardiovascular risk factors cluster, particularly the adiposity-driven components of the so-called metabolic syndrome. In the Western Australian Pregnancy Cohort (Raine) Study, we have used cluster analysis to identify a group of children at risk of future cardiovascular disease with features of the metabolic syndrome.2 The differences in characteristics are shown in the Box. The “high risk” and “low risk” cluster groups differ widely in terms of not only body mass index, the most widely used measure of obesity, but also waist circumference (a measure of central adiposity), insulin resistance, blood pressure, and levels of triglycerides, high-density lipoprotein cholesterol, total cholesterol (data not shown) and low-density lipoprotein cholesterol (data not shown). Not only the conventionally used 95% confidence intervals, but also the 99% confidence intervals do not overlap for any of these intermediate cardiovascular risk factors. We found that 29% of children were in the high-risk cluster at the age of 14 years2 and a similar analysis suggested that even at age 8 years, 25% of children were at increased risk of future obesity, cardiovascular disease and diabetes.3 C-reactive protein (CRP) level is known to be associated with future cardiovascular diseases in adults,4 and with an adverse metabolic profile in children.5 The “high risk” children had significantly higher CRP levels at the age of 14 years than their low-risk counterparts. Certainly, the magnitude of this problem, affecting up to a third of our youth, needs to be addressed by government and health-planning bodies. We suggest our approach of cluster analysis will help identify earlier those children at substantially increased risk of cardiovascular and other adiposity-related disorders in Australia. Features of the cluster groups with respect to components of the metabolic syndrome, showing 99% CIs* BMI = body mass index. HOMA = homeostatic model assessment (for quantifying insulin resistance). SBP = systolic blood pressure. HDL = high-density lipoprotein cholesterol. * From Huang et al.2 Reprinted with permission from the American Diabetes Association.

Rae-Chi Huang · Fiona J Stanley · Lawrence J Beilin

To the Editor: There is a substantial volume of evidence from a range of national and state-based surveys illustrating increases in the rates of obesity and overweight among Australian children over the past two decades,1 concurring with trends observed in most developed countries.2 The recent article by Gill and colleagues highlighted questions that have been raised publicly regarding the extent and impact of levels of obesity and overweight among Australian children, including whether trends have been exaggerated.1 To examine these issues using the latest data available, we present data from the three most recent national surveys in which weight and height of Australian children were measured: the Australian Health and Fitness Survey (1985),3 the National Nutrition Survey (1995),4 and the Australian National Children’s Nutrition and Physical Activity Survey (2007).5 We examined overweight and obesity levels among young Australians from comparable age groups at three time points over more than 20 years, using the same internationally accepted definitions of childhood overweight and obesity. For 1985 and 1995 data, we used the figures reported by Magarey et al in 2001,6 which compared results from the 1985 and 1995 surveys using new standard international definitions to classify overweight and obesity among Australian children and adolescents.7 We calculated body mass index for the 2007 Australian National Children’s Nutrition and Physical Activity Survey using the raw data file obtained through the Australian Social Science Data Archive,8 categorising children as overweight or obese based on the same international definitions used by Magarey et al.6 We based our calculations on the age group common to each of the three surveys: 7–15-year-olds. As shown in the Box, the prevalence of overweight and obesity in boys aged 7–15 years has risen from 11.0% (95% CI, 10.99%–11.01%) in 1985 to 20.0% (95% CI, 19.97%–20.03%) in 1995 and 23.7% (95% CI, 23.68%–23.72%) in 2007. In 7–15-year-old girls, the prevalence of overweight and obesity has increased from 12.2% (95% CI, 12.19%–12.21%) in 1985 to 21.5% (95% CI, 21.47%–21.53%) in 1995 and 25.8% (95% CI, 25.78%–25.82%) in 2007. While data from additional time points are required to map national trends more comprehensively, our analysis clearly indicates an upward trend in overweight and obesity levels in both boys and girls aged 7–15 years between 1985, 1995 and 2007. This trend is cause for alarm, given the widely recognised body of evidence on the significant short-term and long-term consequences of childhood obesity.9 Prevalence of overweight and obesity in Australian children aged 7–15 years, 1985–2007 * Data weighted for age, sex and region with the weighting variable in the raw data file obtained from the Australian Social Science Data Archive.8

Lyn M Roberts · Tessa R Letcher · Alexandra A Gason · Tim Lobstein

To the Editor: Davis and colleagues stated that the Framingham and United Kingdom Prospective Diabetes Study (UKPDS) cardiovascular risk equations are not suitable for predicting risk in an Australian population with type 2 diabetes.1 If confirmed, this would be extremely disappointing. However, before accepting this conclusion the following important considerations should be noted. Davis noted that the Fremantle Diabetes Study (FDS) patient group differed significantly from the UKPDS baseline group (eg, 38% of the FDS patients were aged outside the validated age range of the risk engine [25–65 years] and were assessed by non-validated extrapolation). Similarly, it cannot be assumed that the FDS group is representative of patients in general practice and hospital diabetes clinics around Australia. Moreover, it would be interesting to know how well the engine performs in FDS patients in the age group in which it was validated (ie, patients diagnosed with diabetes at age 25–65 years). It is likely that the low rate of cardiovascular events in the FDS (4.8% with at least one myocardial infarction, and 2.9% with at least one stroke)1 affects the accuracy of the results obtained with the UKPDS risk engine. The Framingham risk score has already been found to vary considerably in accuracy between populations, with predicted-to-observed ratios ranging from underprediction of 0.43 to overprediction of 2.87.2 Further, the UKPDS risk engine recently overestimated the risk of cardiovascular disease events in a UK general practice population.3 In purely pragmatic terms, most patients with type 2 diabetes aged over 50 years are at “high risk” for cardiovascular events (cardiovascular risk of more than 20% over 10 years),4 and the UKPDS risk engine is unlikely to influence prescribing practice significantly. However, we have found the engine to be a useful educational tool for explaining risk to patients. Even if the UKPDS risk engine is not optimally calibrated, the FDS analysis revealed that the coronary heart disease risk equation had modest discrimination (area under the receiver operating characteristic curve [AUC], 0.68), and the stroke risk equation had good discrimination (AUC ≥ 0.86),1 identifying those at highest risk. We believe that, rather than being irrelevant in Australians, the UKPDS risk engine continues to identify those at highest risk for cardiovascular events, operates well within its validated age group, and provides a motivational tool for encouraging changes in patient behaviour. Until a large dataset is pooled from various Australian studies, we believe the UKPDS risk engine should not be discarded.

Roland W McCallum · John R Burgess · Timothy M Greenaway

In reply: We thank McCallum and colleagues for their comments. In relation to their specific points: The Fremantle Diabetes Study (FDS) cohort is representative and drawn from a typical Australian urban centre.1 The 488 cardiovascular disease-free FDS participants with type 2 diabetes who were aged 25–65 years at both diagnosis and study entry had 22 coronary heart disease (CHD) events compared with 72 predicted, with a similar area under the receiver operating characteristic curve (AUC) to that for all 791 patients who were included in the analysis2 (0.66 v 0.68). Calibration indicated significant discrepancies between predicted and actual outcomes (P ≤ 0.02), and positive predictive values were low (≤ 3.5%). Therefore, restricting our patient sample to a “UKPDS” cohort did not alter our conclusions. We agree that the low observed CHD event rate in the FDS compared with that predicted by the UKPDS risk engine undermines its validity in Australians with type 2 diabetes. There was a similarly low CHD event rate in the FIELD study, which included many Australasians.3 Contemporary diabetes care clearly differs from that during the Framingham Study and UKPDS. Although the study cited by McCallum and colleagues, in a UK general practice population, is not strictly comparable to our study, it also found that the UKPDS cardiovascular disease risk engine performed only moderately (AUC, 0.72).4 Accurate risk prediction should be a basis for cost-effective care. We have developed an FDS risk calculator which should improve clinical management for Australians with diabetes.5

Wendy A Davis · Stephen Colagiuri · Timothy M E Davis

Implementing existing knowledge about cardiac rehabilitation (CR) and heart failure management could markedly reduce mortality after acute coronary syndromes and revascularisation therapy. Contemporary CR and secondary prevention programs are cost-effective, safe and beneficial for patients of all ages, leading to improved survival, fewer revascularisation procedures and reduced rehospitalisation. Despite the proven benefits attributed to these secondary prevention interventions, they are not well attended by patients. Modern programs must be flexible, culturally safe, multifaceted and integrated with the patient’s primary health care provider to achieve optimal and sustainable benefits for most patients.

Tom G Briffa PhD · Leigh Kinsman RN, MSc · Andrew J Maiorana MSc, PhD · Robert Zecchin RN, MN · Julie Redfern BSc, BAppSc(Physio)(Hons), PhD · Patricia M Davidson RN, PhD · Glenn Paull RN, CCUCert, BN(Hons) · Amanda Nagle PhD · A Robert Denniss FRACP, FAHA, FCSANZ