Cardiovascular diseases

Withdrawal of nifedipine capsules: jeopardising the treatment of acute severe hypertension in pregnancy? Mark A Brown, Lesley M E McCowan, Robyn A North, Barry N Walters (for the Council of the Australasian Society for the Study of Hypertension in Pregnancy) Short-acting oral nifedipine has been withdrawn from the Australian market because of reports of its adverse effects after long-term treatment in non-pregnant patients with heart disease. This will have a major impact on the treatment of acutely hypertensive pregnant women, in whom the drug has proven to be safe, effective and easy to administer. Should pregnant women be forced to use less suitable agents, thus threatening their own and their babies' health? (MJA 1997; 166: 640-643) Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". Introduction - Antihypertensive medications in pregnancy - Adverse effects of nifedipine - Risk-benefit analysis of nifedipine in pregnancy - Withdrawal of nifedipine from the Australian market - Conclusions - Acknowledgement - References - Authors' details Make a comment - - ©MJA1997 Introduction Pre-eclampsia is the development of hypertension after 20 weeks' gestation in a woman with no known history of hypertension or renal disease, whose blood pressure was normal in the first half of the pregnancy and returns to normal after delivery.1 Despite advances in maternal and neonatal care, it remains an important cause of maternal morbidity (and sometimes mortality) and of fetal prematurity, growth retardation and perinatal death. The dangers of cerebral haemorrhage in pre-eclampsia and of convulsions (eclampsia) have led to the belief that severe hypertension (systolic blood pressure 170 mmHg and/or diastolic blood pressure 110 mmHg) should be treated promptly in pre-eclamptic women. However, the ability to treat acute hypertensive crises in pregnancy is about to be retarded considerably because of recommendations by the Australian Drug Evaluation Committee (ADEC) to withdraw short-acting nifedipine capsules,2 one of the most common drugs for treating acute severe hypertension in pregnancy, effective from 1 May 1997. Antihypertensive medications in pregnancy There are only a few options for the treatment of acute severe hypertension in pregnancy. Nifedipine (given orally or sublingually) and hydralazine (given intravenously or, sometimes, intramuscularly) are the most commonly used agents. They have both been endorsed for use for severe hypertension in pregnancy by the Australasian Society for the Study of Hypertension in Pregnancy (ASSHP) on the basis of clinical studies and extensive clinical experience by members of the ASSHP and other societies.1 Intravenous diazoxide was one of the earliest drugs to be used.3 It is effective but can cause sudden maternal hypotension, maternal hyperglycaemia and fetal hypoglycaemia, uterine atony and fetal distress. It is best given as incremental small-dose boluses to avoid a sudden drop in blood pressure. Intravenous labetalol has been used less widely but is at least as effective as intravenous diazoxide.3 Its safety in preterm infants has been questioned,4 with higher perinatal mortality than in subjects given hydralazine in one study. Intravenous glyceryl trinitrate is a potential candidate for treating severe hypertension in pregnancy.5 It has not yet been used widely and there is a risk that its predominant venodilator effect could reduce preload and compromise an already threatened cardiac output.6 Intravenous sodium nitroprusside is an excellent drug for acute severe hypertension, but its use in pregnancy is precluded by the risk of fetal cyanide toxicity.7 Adverse effects of nifedipine Unfortunately, some authors fail to discriminate between pregnant and non-pregnant subjects when providing recommendations about the continued use of nifedipine capsules. For example, Grossman et al. did a MEDLINE search of articles from 1966 to 1994 using the terms "side-effects" and "nifedipine" to document serious adverse effects with oral or sublingual nifedipine.8 They recommended that, given the seriousness of the reported adverse cardiac events and the lack of any clinical documentation attesting to a benefit, the use of nifedipine capsules for hypertensive emergencies and pseudoemergencies should be abandoned. Only one case of fetal distress was reported in this review9 (although we have noted three other cases), in a pregnant woman whose blood pressure fell from 150/115 mmHg to 90/55 mmHg, hardly a surprising event and one which could have occurred with any drug which lowered the blood pressure to this extent. A more disturbing report by Rehman et al. noted that 98% of hospitalised patients receiving nifedipine capsules failed to have a bedside evaluation and only half had had their blood pressure followed up within an hour of treatment.10 This is poor medical practice and a good reason to improve medical education, but not a reason to withdraw a drug from the market. Risk-benefit analysis of nifedipine in pregnancy Many small studies, comprising a total of about 150 pregnant women, have shown that nifedipine will acutely lower maternal blood pressure within 30 minutes of administration, without compromising the fetus.11-22 In studies involving approximately 200 pregnant women treated with nifedipine over a longer period, no adverse fetal effects were recorded.12,23-27 Three case reports (of four patients) have, at the same time, reported the potential risk of sudden hypotension following the use of nifedipine in severe pre-eclampsia, particularly when combined with magnesium sulfate (used parenterally as convulsion prophylaxis in pre-eclampsia).9,28,29 However, in a more recent prospective study, 10 women with severe pre-eclampsia already receiving intravenous magnesium sulfate were given between 10 mg and 40 mg nifedipine orally. Blood pressure was well controlled in each woman, none had significant hypotension and there was no fetal distress.30 Sudden hypotension has been reported with other antihypertensive drugs used to acutely lower blood pressure in pregnancy, including hydralazine.3,31 The risk of sudden hypotension with any form of acute antihypertensive therapy can be minimised by concomitant plasma volume expansion1,20,32 and avoidance of diuretics, as pre-eclampsia is a volume-contracted state compared with normal pregnancy.33 Several studies have found that nifedipine lowers maternal blood pressure without adversely affecting uteroplacental blood flow.13,14,17,23,34 Several studies have compared intravenous hydralazine with nifedipine in pre-eclampsia;12,19,20,35 all showed nifedipine to be of equal or greater efficacy and safety for both mother and fetus. Visser and Wallenburg observed similar maximum reductions in blood pressure during administration of each drug, but greater falls in pulmonary capillary wedge pressure as well as increased occurrence of fetal distress in women receiving hydralazine.20 In one randomised trial, there were fewer preterm infants and less acute fetal distress in the group of women given nifedipine than in the group of women given intravenous and then oral hydralazine.12 The most recent and largest studies showed that maternal and fetal outcomes were similar in pregnant women with severe hypertension (diastolic blood pressure > 120 mmHg) who received either sublingual nifedipine or intravenous hydralazine.36 The authors concluded that sublingual nifedipine may be advantageous "for use by midwives who work in rural areas where speed is essential in reducing acute hypertension . . ." Nifedipine also relaxes the myometrium, and therefore has a potentially important role in the treatment of preterm labour. In five separate randomised trials involving a total of 290 women, nifedipine was as effective as ritodrine for tocolysis and was associated with fewer serious maternal side effects.37-41 No adverse fetal effects were attributable to nifedipine in studies reporting on more than 350 women treated with the drug in preterm labour.42 Recent prospective data have provided further support for the safety of nifedipine, even when used in early pregnancy.43 Withdrawal of nifedipine from the Australian market The "position of comfort" -- that nifedipine can be used safely and easily in an emergency (before insertion of an intravenous cannula) -- has been lost. The plan to withdraw nifedipine capsules arose out of concern over the potential adverse effects (myocardial infarction, death) in non-pregnant patients with hypertension and ischaemic heart disease receiving long-term treatment with the drug.44-46 In New Zealand, the Ministry of Health has stated that nifedipine and some other calcium antagonists are contraindicated in pregnancy.47 There is no basis for this pronouncement in studies of nifedipine use in human pregnancy. As nifedipine was never officially listed in the Australian Register of Therapeutic Goods for use in pregnancy, clinicians cannot argue to retain the drug for the treatment of hypertension in pregnancy. The simple solution could be to accept defeat and rely on parenteral hydralazine. However, the most recent preparation of this drug is not marketed for intramuscular use (presumably because of its variable absorption), so that treatment must be delayed until an intravenous cannula is inserted. This delay adds to the dangers of severe hypertension for the pregnant woman. Moreover, it has been speculated that parenteral hydralazine will also be withdrawn shortly as it has been superseded by better drugs with fewer side-effects in non-pregnant patients. We now face the following situation: nifedipine capsules have been withdrawn from sale, and it is possible that intravenous hydralazine and diazoxide will also be withdrawn from the Australian market. Intravenous labetalol is not available in Australia, and magnesium sulfate, while known to have some blood pressure lowering effects, is not a sufficiently powerful antihypertensive agent for treatment of severe hypertension in pre-eclampsia. Therefore, intravenous sodium nitroprusside and glyceryl trinitrate will be the only agents left for the treatment of acute severe hypertension in pregnancy. The former can induce fetal cyanide toxicity, while the latter has been subject to far fewer studies in pregnancy than nifedipine, hydralazine or diazoxide -- and both drugs require highly skilled dose titration. Why do pregnant women now face the very real prospect that we will no longer be able to treat their severe hypertension as efficiently as before? In part, this relates to the bureaucratic nature of administering such matters -- if a drug has not been officially listed for an approved indication in the Australian Register of Therapeutic Goods (and nifedipine was never listed for use in pregnancy), then, despite widespread clinical use for that purpose, it can be withdrawn from the market by the pharmaceutical regulatory authorities. To be fair, this is probably the safest approach overall. At the same time, however, this situation highlights deficiencies in clinical and scientific interaction among clinicians, pharmaceutical companies and government agencies. The pharmaceutical company concerned has long known that nifedipine was being used for treating severe hypertension in pregnancy. They, of course, could not endorse such an action, but could have worked with clinicians to study the clinical outcomes in a proper manner, leading to an application for approval of a new indication. They chose not to do so. We clinicians are as much at fault here for not taking such an initiative when the company failed to do so. ADEC tried to balance these issues in its most recent consideration of the problem, but had no option other than to withdraw nifedipine capsules from sale. In New Zealand, nifedipine capsules are now available only in hospitals, which limits the access of rural practitioners to this drug. Perhaps this situation should force us to reconsider the speed at which we need to lower blood pressure in pre-eclampsia. Pregnancy outcomes are very good when severe hypertension is treated rapidly (over 20-30 minutes) and cerebral haemorrhage and eclampsia are now relatively rare. This does not mean there is necessarily a causal relationship between such treatment and the low rates of intracerebral haemorrhage and eclampsia. However, it would be difficult to prove a causal relationship because of the rarity of these complications as well as the ethical problems involved in randomising severly hypertensive pregnant women to a trial comparing rapid reductions in blood pressure (e.g., using nifedepine) with slower reductions (e.g., using oral clonidine or methyldopa). Conclusions The "best case" scenario is that withdrawal from sale of nifedipine capsules and intramuscular hydralazine will leave Australian clinicians with only intravenous diazoxide and intravenous hydralazine to fill an essential therapeutic niche (with intravenous labetalol still available in New Zealand). None of these drugs can be given urgently in hospitals without resident medical staff, and even in the larger tertiary hospitals resident medical staff can be delayed in other wards or operating theatres. Such delays could result in serious complications for the pregnant woman and her baby. The "worst case" scenario is that none of these drugs (nifedipine, labetalol, hydralazine or diazoxide) will be available for the treatment of acute severe hypertension in pregnancy. Pregnant women will then suffer from inadequate treatment or be exposed to the side effects of the remaining antihypertensive drugs, which are currently not recommended for use in pregnancy. Is all this enough to justify continued availability of short-acting nifedipine in pregnant women in Australia and New Zealand? Most clinicians would rapidly respond "yes" as they continue to practise medicine as both an art and a science. The "art" of using nifedipine successfully in pregnancy is well known to most of us, but, although the above review of the available literature shows that nifidepine capsules are as safe as any other drugs currently used to treat acute severe hypertension in pregnancy, we have failed to gather the science to a sufficient extent. We hope our patients will not suffer as a result of our combined shortfalls. Acknowledgement We thank Mrs Jodie Hendley for assistance in preparing this manuscript. References Brown MA, Buddle ML. Hypertension in pregnancy: maternal and fetal outcomes according to laboratory and clinical features. Med J Aust 1996; 165: 360-365. Australian Drug Evaluation Committee. Resolution No. 5857. Commonwealth of Australia Gazette No. GN 10, 25 October 1995. (See also Resolution No. 7129. 5-6 December 1996.) Michael CA. Intravenous labetalol and intravenous diazoxide in severe hypertension complicating pregnancy. Aust N Z J Obstet Gynaecol 1986; 26: 26-29. Visser W, Wallenburg HCS. Should labetalol be used in severe early onset preeclampsia patients? Protagonist and presentations. Proceedings of the 8th World Congress on Hypertension in Pregnancy; 1992 Nov 8-12; Buenos Aires, Argentina. Abstract 104: 290. Ramsay B, de Belder A, Campbell S, et al. A nitric oxide donor improves uterine artery diastolic blood flow in normal early pregnancy and in women at high risk of pre-eclampsia. Eur J Clin Invest 1994; 24: 76-78. Visser W, Wallenburg HCS. Central hemodynamic observations in untreated preeclamptic patients. Hypertension 1991; 17: 1072-1077. Baker A. Management of severe pregnancy induced hypertension, or gestosis, with sodium nitroprusside. Anaesth Intensive Care 1990; 18: 361-365. Grossman E, Messerli FH, Grodzicki T, Kowey P. Should a moratorium be placed on sublingual nifedipine capsules given for hypertensive emergencies and pseudo emergencies? JAMA 1996; 276: 1328-1331. Impey L. Severe hypotension and fetal distress following sublingual administration of nifedipine to a patient with severe pregnancy induced hypertension at 33 weeks. Br J Obstet Gynaecol 1993; 100: 959-961. Rehman F, Mansoor GA, White WB. Inappropriate physician habits in prescribing oral nifedipine capsules in hospitalised patients. Am J Hypertens 1996; 9: 1035-1039. Walters BNJ, Redman CWG. Treatment of severe pregnancy-associated hypertension with the calcium antagonist nifedipine. Br J Obstet Gynaecol 1984; 91: 330-336. Fenakel K, Fenakel G, Appelman Z, et al. Nifedipine in the treatment of severe preeclampsia. Obstet Gynecol 1991; 77: 331-337. Hanretty KP, Whittle MJ, Howie CA, Rubin PC. Effect of nifedipine on Doppler flow velocity waveforms in severe preeclampsia. BMJ 1989; 299: 1205-1206. Lindow SW, Davies N, Davey DA, Smith JA. The effect of sublingual nifedipine on uteroplacental blood flow in hypertensive pregnancy. Br J Obstet Gynaecol 1988; 95: 1276-1281. Duggan PM, McCowan LME, Stewart AW. Antihypertensive drug effects on placental flow velocity waveforms in pregnant women with severe hypertension. Aust N Z J Obstet Gynaecol 1992; 32: 335. Lurie S, Fenakel K, Friedman A. Effect of nifedipine on fetal heart rate in the treatment of severe pregnancy-induced hypertension. Am J Perinatal 1990; 7: 285-286. Pirhonen JP, Erkkola RU, Ekblad UU. Uterine and fetal flow velocity waveforms in hypertensive pregnancy: the effect of a single dose of nifedipine. Obstet Gynecol 1990; 76: 37-41. Puzey MS, Ackovic KL, Lindow SW, Gonin R. The effect of nifedipine on fetal umbilical artery Doppler waveforms in pregnancies complicated by hypertension. S Afr Med J 1991; 79: 192-194. Seabe SJ, Moodley J, Becker P. Nifedipine in acute hypertensive emergencies in pregnancy. S Afr Med J 1989; 76: 248-250. Visser W, Wallenburg HCS. A comparison between the haemodynamic effects of oral nifedipine and intravenous dihydralazine in patients with severe preeclampsia. J Hypertens 1995; 13: 791-795. Childress CH, Katz VL. Nifedipine and its indications in obstetrics and gynaecology. Obstet Gynecol 1994; 83: 616-624. Levin AC, Doering PL, Hatton RC. Use of nifedipine in the hypertensive diseases of pregnancy. Ann Pharmacother 1994; 28: 1371-1378. Moretti MM, Fairlie FM, Akl S, et al. The effect of nifedipine therapy on fetal and placental Doppler waveforms in pre-eclampsia remote from term. Am J Obstet Gynecol 1990; 163: 1844-1848. Constantine G, Beevers DG, Reynolds AL, Luesley DM. Nifedipine as a second line antihypertensive drug in pregnancy. Br J Obstet Gynaecol 1987; 94: 1136-1142. Greer IA, Walker JJ, Bjornsson S, Calder AA. Second line therapy with nifedipine in severe pregnancy induced hypertension. Clin Exp Hypertens Pregnancy 1989; B8: 277-292. Sibai BM, Barton JR, Akl S, et al. A randomized prospective comparison of nifedipine and bed rest versus bed rest alone in the management of preeclampsia remote from term. Am J Obstet Gynecol 1992; 167: 879-884. Jayawardana J, Lekamge N. A comparison of nifedipine with methyldopa in pregnancy induced hypertension. Ceylon Med J 1994; 39: 87-90. Hata T, Manabe A, Hata K, Kitao M. Changes in blood velocities of fetal circulation in association with fetal heart rate abnormalities: effect of sublingual administration of nifedipine. Am J Perinatal 1995; 12: 80-81. Waisman GD, Mayorga LM, Camera MI, et al. Magnesium plus nifedipine: potentiation of hypotensive effect in preeclampsia? Am J Obstet Gynecol 1988; 159: 308-309. Scardo JA, Vermillion ST, Hogg BB, Newman RB. Haemodynamic effects of oral nifedipine in pre-eclamptic hypertensive emergencies. Am J Obstet Gynecol 1996; 175: 336-340. Vink GJ, Moodley J, Philpott RH. Effect of dihydralazine on the fetus in the treatment of maternal hypertension. Obstet Gynecol 1980; 55: 519-522. Paterson-Brown S, Robson SC, Redfern N, et al. Hydralazine boluses for the treatment of severe hypertension in pre-eclampsia. Br J Obstet Gynaecol 1994; 101: 409-413. Brown MA, Gallery EDM. Volume homeostasis in normal pregnancy and pre-eclampsia. Baillieres Clin Obstet Gynaecol 1990; 8: 287-310. Hirose S, Yamada A, Kasugai M, et al. The effect of nifedipine and dipyridamole on the Doppler blood flow waveforms of umbilical and uterine arteries in hypertensive pregnant women. Asia-Oceania J Obstet Gynaecol 1992; 18: 187-193. Martins-Costa S, Ramos JG, Barros E, et al. Randomised, controlled trial of hydralazine versus nifedipine in pre-eclamptic women with acute hypertension. Clin Exp Hypertens Pregnancy 1992; B11: 25-44. Jegasothy R, Paranthaman S. Sublingual nifedipine compared with intravenous hydralazine in the acute treatment of severe hypertension in pregnancy: potential for use in rural practice. J Obstet Gynaecol Res 1996; 22: 21-24. Bracero LA, Leikin E, Kirshenbaum N, Tejani N. Comparison of nifedipine and ritodrine for the treatment of preterm labour. Am J Perinatol 1991; 8: 365-369. Meyer WR, Randall HW, Graves WL. Nifedipine versus ritodrine for suppressing preterm labor. J Reprod Med 1990; 35: 649-653. Ferguson JE, Dyson DC, Schutz T, Stevenson DK. A comparison of tocolysis with nifedipine or ritodrine: an analysis of efficacy and maternal, fetal and neonatal outcome. Am J Obstet Gynecol 1990; 163: 105-111. Kupferminc M, Lessing JB, Yaron Y, Peyser MR. Nifedipine versus ritodrine for suppression of preterm labor. Br J Obstet Gynaecol 1993; 100: 1090-1094. Read MD, Wellby DR. The use of a calcium antagonist (nifedipine) to suppress preterm labour. Br J Obstet Gynaecol 1986; 93: 933-937. Ray D, Dyson D. Calcium channel blockers. Clin Obstet Gynecol 1995; 38: 317-322. Magee LA, Schick B, Donnenfeld AE, et al. The safety of calcium channel blockers in human pregnancy: a prospective, multicenter cohort study. Am J Obstet Gynecol 1996; 174: 823-828. Psaty BM, Heckbert SR, Koepsell TD, et al. The risk of myocardial infarction associated with antihypertensive drug therapies. JAMA 1995; 275: 620-625. Buring JE, Glynn RJ, Hennekens CH. Calcium channel blockers and myocardial infarction. A hypothesis formulated but not yet tested. JAMA 1995; 274: 654-645. Horton R. Spinning the risks and benefits of calcium antagonists. Lancet 1995; 346: 586-587. New Zealand Ministry of Health. Managing high blood pressure in pregnancy. Prescriber Update 1994; 7: 2-10. (Received 26 Aug 1996, accepted 28 Jan 1997) Authors' details Departments of Medicine, Renal Medicine and Obstetrics, St George Hospital, Kogarah, NSW. Mark A Brown, FRACP, MD, Associate Professor of Medicine. Department of Obstetrics and Gynaecology, University of Auckland School of Medicine, National Women's Hospital, Auckland, NZ. Lesley M E McCowan, FRCOG, FRNZCOG, Senior Lecturer in Obstetrics and Gynaecology; Robyn A North, PhD, FRACP, Senior Lecturer in Obstetric Medicine. King Edward Memorial Hospital for Women, Perth, WA. Barry N Walters, FRACP, Physician in Obstetric Medicine. Council of the Australasian Society for the Study of Hypertension in Pregnancy, 145 Macquarie Street, Sydney, NSW 2000. No reprints will be available. Correspondence: Dr M A Brown, Departments of Medicine, Renal Medicine and Obstetrics, St George Hospital, Kogarah, NSW 2217. To top of article - ©MJA 1997 <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia. We appreciate your comments.

Mark A Brown · Robyn A North · Barry N Walters

Salt intake, cardiovascular disease and public health We need to do more than take the salt shaker off the table MJA 1997; 166: 396 Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". - - ©MJA1997 The contribution of dietary salt intake to cardiovascular morbidity and mortality is a subject of ongoing discussion and controversy.1,2 What is unquestionable is that the average salt intake of most people in most nations exceeds physiological requirements (10-20 mmol/day) by a factor of between five and 30, and this relatively high intake contributes significantly to the average blood pressure of a population, and hence to the prevalence of hypertension.3 The relationship between blood pressure levels and morbidity and mortality from heart attack and stroke suggests that any reduction in levels of salt intake in a population would result in a corresponding reduction in cardiovascular morbidity and mortality. For example, it has been argued that a mean reduction in sodium intake of 50 mmol per day across the whole population in the United Kingdom would reduce coronary death rates there by 16% and stroke death rates by 22%, and create substantial monetary savings from the reduced prevalence of these and related diseases.4 there is unlikely to be much further progress in reducing Australians' salt intake unless more low-salt foods which are easily identifiable and affordable become available Such epidemiological observations have led national and international health authorities to set targets for reductions in population salt consumption.5,6 The Australian Government has set a target sodium intake of 100 mmol per day to be achieved by the year 2000. It is reasonable to ask whether this target (or any other for salt intake) is justified on public health grounds and whether it is achievable. For such a target to be appropriate requires that it be both safe and cost effective in reducing cardiovascular morbidity and mortality . Despite the consistent epidemiological data and experimental evidence, clinical trial data are limited. There are no randomised controlled trials of effects of varying sodium intake on cardiovascular outcome other than on blood pressure levels per se. However, there is experimental and limited clinical trial data suggesting that salt intake influences left ventricular mass independently of blood pressure,7 which is relevant in that left ventricular hypertrophy is itself a powerful predictor of cardiovascular morbidity and mortality. Is a target of 100 mmol/day realistic in countries like Australia? In this issue of the Journal Beard et al. have attempted to measure salt intake in an Australian population sample in the light of our national target for the year 2000. Using 24-hour urine collections to estimate sodium excretion, they found that only 6% of men and 36% of women had reached the year 2000 target. As only 52% of the eligible population were studied and as there was underepresentation of younger people and lower socioeconomic groups, these figures are likely to underestimate the true levels of sodium intake and to overestimate the extent to which the target was reached. Interestingly, among both men and women, and among both those who did and those who did not comply with the sodium intake target, most stated that they never or rarely added salt to food. This apparent anomaly may raise doubts about the reliability of the participants' reports, but is probably more readily explained by the poor reliability of a single 24-hour urine specimen for estimating usual sodium intake, and the high proportion of dietary salt hidden in food.8 The actual values for the percentage of the population complying with targets should perhaps be taken with "a pinch of salt", while the estimates of population average salt intake are in accord with other Australian data and those from countries (such as the United States) with similar dietary habits and are probably realistic. If the target of less than 100 mmol/day is desirable for most of the population why are we so far from achieving it, and is it realistic? As Beard et al. point out, at least 75% of salt in the British diet and those of other affluent societies comes from processed foods.8 Given the proportion of participants in the study by Beard et al. who claim not to add salt to food or in cooking, the figure may be higher in Australia. Bread is a major source of dietary salt, along with canned foods and preserves. Take-away foods are more likely to be salted, and the growing habit of eating out leaves the consumer with less control over salt intake. The smaller body mass, and hence lower total food consumption, of women compared with men may at least partly explain their lower salt intake -- perhaps the target for sodium intake for women should be lower than that for men. Beard et al. point out that there has been relatively little publicity about the national dietary target for salt and that, although some food manufacturers have taken initiatives to reduce salt use, shoppers receive relatively little advice or encouragement. The picture is perhaps not quite as bleak as it seems. The National Heart Foundation and State health departments have long been publicising the benefits of reducing salt intake as part of a more general healthy diet that includes eating more fresh fruit and vegetables and reducing saturated fat intake. These measures may have much greater value in cardiovascular health if adopted in combination with other lifestyle changes.9-11 However, there is unlikely to be much further progress in reducing Australians' salt intake unless more low-salt foods which are easily identifiable and affordable, as well as being economically viable for the food industry, become available. This will require more concerted efforts and cooperation between the food industry, government, consumers and food scientists. Novel approaches should be explored, such as the use of salt substitutes, which has resulted in long term blood pressure reduction in older patients with hypertension in Holland.12 Perhaps it is timely that the National Health and Medical Research Council consider a fresh approach to the problem that includes working with the food industry and food scientists to make it easier for consumers to reduce unnecessarily high and harmful levels of salt intake. A randomised controlled trial that showed that reducing salt intake decreased morbidity and mortality would undoubtedly dispel any lingering doubts on this issue and accelerate efforts. While purists might argue that such evidence should be as rigorously demanded of lifestyle changes as of new drugs or surgery, in the case of dietary salt we are in something of a "Catch-22" situation -- it is unlikely that an adequate trial could be mounted unless low salt foods were much more widely available than they are at present. However, a precedent for major public health initiatives in the absence of definitive clinical trial data has been set with the multitude of campaigns against cigarette smoking. The cumulative evidence for the benefits of moderating dietary salt intake is sufficient to justify more active public health initiatives now. Lawrie J Beilin Professor, Department of Medicine, University of Western Australia, Perth, WA Dyer AR, Stamler R, Elliot P, Stamler J. Dietary salt and blood pressure. Nature Med 1995; 1: 994-996. Wardener HL, Kaplan NM. On the assertion that a moderate restriction of sodium intake may have adverse health effects. Am J Hypertension 1993; 6: 810-814. Intersalt Cooperative Research Group. Intersalt: an international study of electrolyte excretion and blood pressure. Results of 24 hour urine sodium and potassium excretion. BMJ 1988; 297: 319-328. Law MR, Frost CD, Wald MJ. By how much does dietary salt lower blood pressure? III. Analysis of data from trials of salt reduction. BMJ 1991; 302: 819-823. National High Blood Pressure Education Program. National High Blood Pressure Education Program Working Group report on primary prevention of hypertension. Arch Intern Med 1993; 153: 186-208. Health Targets and Implementation (Health for All) Committee. Health for all Australians. Canberra: AGPS, 1988: 38. Langenfeld MRW, Schmeider RE. Salt and left ventricular hypertrophy: what are the links? J Hum Hypertens 1995; 9: 909-916. James WPT, Ralph A, Sanchez-Castillo CP. The dominance of salt in manufactured food in the sodium intake of affluent societies. Lancet 1987; 1: 426-429. Ascherio A, Rimm EB, Giovanucci EL, et al. A prospective study of nutritional factors and hypertension among US men. Circulation 1992; 86: 1475-1484. Beilin LJ. Non-pharmacological management of hypertension: optimal strategies for reducing cardiovascular risk. J Hypertens 1994; 12 Suppl 10: S71-S81. Jennings GL, Sudhir K. Initial therapy of primary hypertension. Med J Aust 1990; 152: 198-203. Geleeijnse JM, Witteman JCM, Bak AAA, et al. Reduction in blood pressure with a low sodium, high potassium, high magnesium salt in older subjects with mild to moderate hypertension. BMJ 1994; 309: 436-440. ©MJA 1997 <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia.

Lawrie J Beilin

The Hobart Salt Study 1995: few meet national sodium intake target Trevor C Beard, David R Woodward, Peter J Ball, Helen Hornsby, Richard J von Witt and Terence Dwyer MJA 1997; 166: 404 For editorial comment see Beilin Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". Abstract - Introduction - Methods - Statistical analysis - Results - Sodium and potassium excretion - Discretionary use of salt - Discussion - Public health implications - Conclusion - Acknowledgements - References - Authors' details - - ©MJA1997 Abstract Objective: To estimate 24-hour sodium and potassium excretion in an urban Australian population. Design and setting: Cross-sectional survey of an urban population in Hobart, Tasmania, in 1995. Participants: Systematic sample (87 men, 107 women) from the Commonwealth Electoral Roll of people aged 18-70 years on 30 June 1995 whose residential address was within 10 km of the Hobart General Post Office. Main outcome measure: Conformity with the national target for sodium intake for the year 2000 of ≤100 mmol/day. Results: The target was met by 6% of men and 36% of women. This difference between the sexes was significant ( P < 0.001), while differences between age groups and socioeconomic levels were not significant. Conclusion: Our findings confirm the low level of conformity with the national sodium target reported by the handful of Australian studies over the past decade. Given the major community costs associated with hypertension, our results highlight the need for effective and properly monitored action to reduce sodium intakes. MJA 1997; 166: 404-407 Introduction Many health problems are associated with the current sodium intake of people in Western societies.1 In 1988, an Australian target for a lower sodium intake was set for the express purpose of reducing the prevalence of hypertension.2 Although other factors, such as excess body weight, inadequate exercise, excess alcohol, low dietary potassium and "psychological influences", may contribute to hypertension,3 Australia's national target for sodium intake (≤100 mmol/day)2 is accepted internationally.4-6 Further, it is supported by the discovery that the usual human salt intake in Western diets induces hypertension in chimpanzees, and that this is reversed when they return to their natural diet.7 The effect of low dietary potassium on health has received less attention, but there is good evidence that potassium intake should at least equal sodium intake in molar units.8,9 Potassium predominates in unsalted foods because it is the major intracellular cation in the living tissues of both plants and animals. Thus, virtually all the natural foods available to mammals have a molar sodium to potassium ratio of less than 1.0. The human body must have evolved on this dietary ratio; its inversion is recent in phylogenetic terms, unnecessary and probably unsafe.8,9 Published data on current intakes of sodium and potassium among Australians are very few, and usually based on small samples10-12 We report electrolyte excretion data obtained from 194 Hobart residents for a behavioural study in 1995. Our estimates are based on 24-hour excretion of these electrolytes in the urine (widely accepted as the preferred method of assessment of intake).13,14 Methods People aged 18-70 years on 30 June 1995 and residing within 10 km of the Hobart General Post Office were selected from the Commonwealth Electoral Roll (revised to February 1995) as follows. Every 500th person on the roll was selected for contact or, if ineligible, replaced by the next eligible person. A letter inviting participation was mailed to each person, outlining the study (including the need to attend for interview and to provide a 24-hour urine sample) and enclosing a reply-paid envelope. Those failing to reply were sent a second letter two weeks later, followed, if necessary, by a telephone call within a further 10 days. Unpredictable variability in sodium excretion (a confounder in the behavioural study) was reduced by excluding volunteers with serious intercurrent illness, pregnancy, breast-feeding or use of potassium supplements, diuretics or other drugs likely to affect sodium excretion. We estimated socioeconomic status by the postcode of the participant's address, using the Index of Relative Socioeconomic Disadvantage (IRSD);15 data for specific postcodes were supplied by the Australian Bureau of Statistics. Suburbs whose postcodes had an IRSD ≤ 1000 (the national mean score) were classified as "lower socio economic status", and those with an IRSD ≥ 1000 as "higher socioeconomic status". Two subjects listed a GPO box address and were not assigned a socio economic status rating. At interview, we collected demographic and anthropometric data and a short medical history. Participants completed a food-frequency questionnaire and answered behavioural and cognitive questions, which will be reported elsewhere. Each participant received detailed verbal and written instructions on how to make a complete 24-hour collection of urine; all were asked to collect urine on weekdays, and women of reproductive age were asked to avoid collection during the premenstrual week, when sodium retention may occur.16 Participants collected urine in 2 L plastic containers containing 20 mL of 6 molar hydrochloric acid and returned them promptly. Urine volume was estimated by weighing. For 82 of the 194 samples the estimated volume was adjusted to 24 hours because of longer or shorter actual collection times; the maximum adjustment was 175 minutes over the 24 hours (12.2%), and only five adjustments exceeded 5%. The samples, identified only by code numbers, were diluted with neutral pH buffer and analysed for sodium and potassium by ion-selective electrodes on a Kodak Ektachem 750 XRC analyser (Johnson & Johnson Clinical Diagnostics, Rochester, NY, USA) and, for creatinine, by the Ektachem method also. Laboratory results were sent to those participants who requested them. A duplicate of every tenth sample was sent for analysis under a different code number for quality assurance. We calculated imprecision of laboratory measurements from the differences between results for duplicate samples using the formula published for the Intersalt study.17 The coefficients of variation for laboratory imprecision were 0.6% for sodium, 1.1% for potassium and 5.4% for creatinine. The protocol was approved by the University of Tasmania Committee on Ethical Aspects of Human Experimentation, and all subjects gave written informed consent. Statistical analysis We used SPSS18 to analyse the data; P< 0.05 was used as the criterion of statistical significance. Differences between sexes, age groups and socioeconomic status levels were assessed by t tests (for mean sodium and potassium excretion rates) and by chi-squared tests (for compliance with targets for sodium and sodium to potassium ratio). Results Of 619 individuals originally selected, 167 (27%) were uncontactable despite active follow-up, 80 (13%) were ineligible because they had moved out of the target area, 151 (24%) declined to take part, 18 (3%) were eliminated by our exclusion criteria (nine for medications, five for illness, and four for pregnancy or lactation), and nine participated incompletely. The remaining 194 (31% of the initial sample, or 52% of those known to be eligible) were interviewed and provided a 24-hour urine collection. Box 1 (below) compares sociodemographic characteristics for these 194 participants with those of the other 425 people originally selected. The two groups had a similar sex distribution, but participants were significantly older and had higher socioeconomic status. For participants, the sex ratio was similar in both age divisions (43% men in the 18-44 years group and 46% men in the 45-70 years group), and in both socioeconomic groups (47% and 44% men in the lower and higher socioeconomic status groups, respectively). While we do not have birthplace data for the non-participants, most participants were born in Australia (83%) or in the United Kingdom or Ireland (12%). Sodium and potassium excretion Twenty-four-hour sodium excretion was greater in men (range, 39-337 mmol) than in women (26-241 mmol), and the mean sodium intake (as reflected by this excretion rate) was 52 mmol higher in men than in women, a highly significant difference (P< 0.001). Only 6% of men, compared with 36% of women, met the Australian national target (≤ 100 mmol/day), represented by the vertical line in the Figure, and this difference was also significant at P< 0.001. Differences between age groups and socioeconomic status groups were not significant at the P< 0.05 level (Box 2, below). The mean potassium intake in men was 9 mmol higher than in women (P = 0.03), but differences between age groups and socioeconomic status groups were not significant (Box 2, above). Only 5% of men and 19% of women met the recommendation8,9 that the sodium to potassium ratio should not exceed 1.0 (diagonal line in the Figure); this sex difference was significant (P = 0.002). Differences were not statistically significant between younger and older participants (P = 0.33), and were on the margin of significance for socioeconomic status levels (P = 0.05). Discretionary use of salt Most of our 194 participants claimed that they never or rarely added salt at the table (51% of men and 73% of women), and that they never or rarely cooked with salt (54% of men and 61% of women). Compliers and non-compliers with the sodium target gave similar answers about the use of salt: 66% of compliers and 62% of non-compliers rarely or never added salt at the table, and 57% of compliers and 58% of non-compliers rarely or never cooked with salt. Discussion Despite our relatively low response rate, Box 1 shows that our participants had a similar sex ratio to that of a systematic sample from the Hobart electoral roll, and we found that sex differences in electrolyte excretion were significant. Although our sample was biased in terms of age and socioeconomic status, the effect of age and socioeconomic status on electrolyte excretion in the participants barely reached significance (Box 2), and hence these biases are unlikely to have influenced our findings. If the participants were unrepresentative in some other way -- more health-conscious, for example -- our data could underestimate sodium excretion and overestimate compliance with the sodium target. It is difficult to be certain of the completeness of 24-hour urine collections. Para-aminobenzoic acid has been used as a marker in overseas studies,19 but is not approved for use with healthy volunteers in Australia. Creatinine excretion is a customary indicator of completeness, but no standard cut-off points exist.19 As both undercollection and overcollection could have affected our results, we repeated the t-test analyses of Box 2 after excluding subjects whose creatinine outputs were in the lowest and highest 2.5% for men and women. For both sodium and potassium the changes in means and standard deviations were negligible, indicating no serious problem with outliers. Moreover, the range of excretion rates of each electrolyte in each sex remained unaltered. Accuracy and imprecision of assays are also important determinants of data quality. As reported in our Methods, duplicate assays indicated acceptable imprecision -- the laboratory is a participant in the Royal College of Pathologists of Australasia-Australian Association of Clinical Biochemists Quality Assurance Scheme and is accredited by the National Association of Testing Authorities. Few other Australian studies have been reported. In one, estimates based on food-frequency questionnaires were somewhat lower than ours,12 but urinary excretion is considered a more valid indicator of intakes.13,14 A Hobart study in 1989, with a similar protocol for sample selection and urine collection,10 found mean sodium and potassium excretion rates in men of 160 mmol/day and 77 mmol/day, respectively, compared with 124 mmol/day and 66 mmol/day in women. In Sydney, in 1992, Notowidjojo and Truswell11 found mean sodium and potassium excretion rates of 164 mmol/day and 74 mmol/day in men and 133 mmol/day and 66 mmol/day in women. These two studies support our conclusion that average intakes in Australia -- especially among men -- are substantially above the national target. Public health implications Meta-analysis by Law et al. indicates that a 50 mmol decrease in community sodium intake could reduce mortality from heart disease by 16% and from stroke by 22%.20 The annual cost to Australia of heart disease, stroke and hypertension was recently estimated at $1198 million, $666 million and $546 million, respectively.21 If a lower salt intake reduced prevalence as much as it reduced mortality, the saving from 16% less heart disease and 22% less stroke and hypertension would be $458 million annually, with added savings from reduced prevalence of other conditions.1 In the United Kingdom the complete elimination of table salt and cooking salt would reduce mean sodium intake by only about 15%.22 This figure might be even lower in Australia, as this and other studies show that most people already avoid adding salt to their food.23,24 The main source of dietary sodium -- at least 75% of the total -- is processed foods, and a major reduction depends on changing their composition.21 Government initiatives have been limited to recommending a lower salt content in processed foods,25 setting a national target for sodium intake of ≤100 mmol/day,2 and publishing the dietary guideline Choose low salt foods and use salt sparingly.26 Food manufacturers have made some commendable initiatives, but they depend on consumer demand, and little has been done to inform the public about the national target for sodium intake. Although some low-salt processed foods are available and labelled in accordance with the food regulations, shoppers receive little specific advice or encouragement to reduce their sodium intake by choosing them. Conclusion By setting a national sodium-intake target, Australian health authorities have accepted that excessive dietary sodium is an important health issue, with significant morbidity, mortality and economic costs. Our results indicate the need for an active campaign to promote and monitor the nation's sodium target effectively. Acknowledgements This study was carried out with an educational grant from the National Heart Foundation of Australia, and financial assistance towards the purchase of computer equipment was received from Sizzler Restaurants and from Salt Skip Incorporated. We are indebted to Leigh Blizzard, statistician at the Menzies Centre, for statistical advice. References Antonios TFT, MacGregor GA. Deleterious effects of salt intake other than effects on blood pressure. Clin Exp Pharmacol Physiol 1995; 22: 180-184. Health Targets and Implementation (Health For All) Committee. Health for all Australians. Canberra: AGPS, 1988: 38. WHO/ISH Statement Committee. Prevention of hypertension and associated cardiovascular disease: a 1995 statement. Clin Exper Hypertension 1996; 18: 581-593. National Research Council. Committee on diet and health. Implications for reducing chronic disease risk. Washington DC: National Academy Press, 1989: 16-17. World Health Organization. Diet, nutrition, and the prevention of chronic diseases. WHO Technical Report No. 797. Geneva: WHO, 1990: 61. Committee on Medical Aspects of Food Policy. Nutritional aspects of cardiovascular disease. Department of Health and Social Security. Report on health and social subjects No. 46. London: HMSO, 1994: 138. Denton D, Weisinger R, Mundy NI, et al. The effect of increased salt intake on blood pressure of chimpanzees. Nature Med 1995; 1: 1009-1016. Truswell AS. Potassium. In: Truswell AS, Dreosti IE, English RM, et al., editors. Recommended nutrient intakes: Australian papers. Sydney: Australian Professional Publications, 1990: 191-198. Stamler J, Rose G, Stamler R, et al. Intersalt study findings: public health and medical care implications. Hypertension 1989; 14: 570-577. Beard TC, Eickhoff R, Mejglo ZA, et al. Population-based survey of human sodium and potassium excretion. Clin Exp Pharmacol Physiol 1992; 19: 327-330. Notowidjojo L, Truswell AS. Urinary sodium and potassium in a sample of healthy adults in Sydney, Australia. Asia Pacific J Clin Nutr 1993; 2: 25-33. Baghurst KI, Crawford D, Worsley A, et al. The Victorian nutrition survey: a profile of the energy, macronutrient and sodium intakes of the population. Community Health Studies 1988; 12: 42-54. Caggiula AW, Wing RR, Nowalk MP, et al. The measurement of sodium and potassium intake. Am J Clin Nutr 1985; 42: 391-398. Hunter D. Biochemical indicators of dietary intake. In: Willett W, editor. Nutritional epidemiology. New York: Oxford University Press, 1990: 143-216. Australian Bureau of Statistics. Socio-economic indexes for areas. Canberra: ABS, 1990. MacGregor GA, Markandu ND, Roulston JE, et al. Is idiopathic oedema idiopathic? Lancet 1979; 1: 397-400. Intersalt Cooperative Research Group. Intersalt: an international study of electrolyte excretion and blood pressure. Results for 24 hour urinary sodium and potassium excretion. BMJ 1988; 297: 319-328. SPSS for Windows, release 6.1 [computer program]. Chicago: SPSS Inc, 1994. Bingham SA, Cummings JH. The use of creatinine output as a check on the completeness of 24-hour urine collections. Hum Nutr Clin Nutr 1985; 39C: 343-353. Law MR, Frost CD, Wald MJ. By how much does dietary salt lower blood pressure? III. Analysis of data from trials of salt reduction. BMJ 1991; 302: 819-823. National Heart Foundation of Australia. Heart and stroke facts report. Canberra: The Foundation, 1995. James WPT, Ralph A, Sanchez-Castillo CP. The dominance of salt in manufactured food in the sodium intake of affluent societies. Lancet 1987; 1: 426-429. Bennett SA, Magnus P. Trends in cardiovascular risk factors in Australia. Med J Aust 1994; 161: 519-527. Thomson A, Rundle S, Singh BB, et al. Regional differences in cardiovascular risk factor prevalence in Tasmania: are they consistent with the increased cardiovascular mortality? Aust N Z J Med 1995; 25: 290-296. National Health and Medical Research Council. Report of the working party on sodium in the Australian diet. Canberra: AGPS, 1984: 4. National Health and Medical Research Council. Dietary guidelines for Australians. Canberra: AGPS, 1992: 70-83. (Received 24 Jun, accepted 4 Nov, 1996) Authors' details Menzies Centre for Population Health Research, University of Tasmania, Hobart, TAS. Trevor C Beard, OBE, MB BChir, MPH, Senior Research Fellow; Helen Hornsby, BA(Hons), Research Assistant; Terence Dwyer, MD, MPH, Director. Division of Biochemistry, University of Tasmania, Hobart, TAS. David R Woodward, PhD, Senior Lecturer. Department of Psychology, University of Tasmania, Hobart, TAS. Peter J Ball, BSc, MA, Senior Lecturer. Department of Clinical Chemistry, Royal Hobart Hospital, Hobart, TAS. Richard J von Witt, FRCPath, FRCPA, Director. Reprints: Dr T C Beard, Menzies Centre for Population Health Research, 17 Liverpool Street, Hobart, TAS 7000. ©MJA 1997 <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia.

Trevor C Beard · David R Woodward · Peter J Ball · Helen Hornsby · Terence Dwyer

Helping heart attack victims to save their own lives Reperfusion techniques can save both lives and heart muscle, but the key is prompt treatment MJA 1997; 166: 228 Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". - - ©MJA1997 The outlook for a person in the early hours after the onset of a myocardial infarction remains grim. Of the 40% who will die in the first month, a third will die in the first hour and up to a half in the first day.1 While some deaths are sudden and not amenable to treatment, the outcome in many cases can be improved by appropriate modern medical treatment, such as defibrillation and coronary reperfusion strategies, if administered early enough. publicise the symptoms of a possible heart attack, emphasise the importance of reporting them, and ensure that the message is aimed at all educational levels The risk of sudden cardiac death from ventricular fibrillation can be reduced by access to and use of a defibrillator. Coronary care ambulances with skilled paramedical staff have saved many lives since their introduction to Australia in the late 1960s.2 Increasingly, strategic placement of semi-automatic defibrillators -- for example, in large passenger aircraft and football stadiums -- is being considered, to further improve out-of-hospital survival. Once the patient reaches hospital, modern reperfusion strategies such as thrombo lysis and acute angioplasty can save lives, limit myocardial damage and reduce subsequent cardiac disability.3,4 Improved understanding of myocardial infarction from angiographic and postmortem studies has reaffirmed that most cases are indeed due to coronary thrombosis. The need to achieve coronary reperfusion as early as possible has long been recognised from pathophysiological studies and clinical trial experience.3,4 Since the mid 1980s, thrombolytic therapy has been studied in over 200 000 patients,3 and a recent overview has shown very clearly that streptokinase and recombinant tissue plasminogen activator (t-PA) are effective thrombolytic agents in acute myocardial infarction. Their appropriate use in patients with suspected myocardial infarction can save 20-30 lives per 1000 patients treated over the first 35 days,3 and there is the prospect of even better outcomes with new thrombolytic agents. More recently, reperfusion with acute coronary angioplasty has been shown to be equivalent to thrombolysis in most centres and to have superior outcomes in some centres, particularly those with a high level of expertise and readily available angioplasty services.4 The use of intracoronary stents adjunctive to angioplasty may improve even further the early outcome, with a reduced risk of late restenosis. The average loss of life per hour of delay of thrombolytic therapy is 1.6 lives per 1000 patients treated.3 The myocardial infarction triage and intervention trial in Seattle demonstrated even more accurately the importance of urgent treatment in the first hour.5 For patients surviving to hospital and being treated within 70 minutes of symptom onset, the 28-day mortality rate was 1.2% and only 5% of the left ventricular mass was infarcted; those treated later than 70 minutes had a mortality rate of 8.7% and 11% of myocardium was infarcted. These benefits were demonstrated with thrombolytic regimens now known to achieve early patency and restoration of normal coronary blood flow in less than half the patients treated. With the more aggressive reperfusion strategies now available the prospects are even brighter. The first hour after the onset of coronary thrombosis is indeed the "golden hour" of opportunity for preserving heart muscle and saving lives. These developments represent a quantum shift in what can be achieved in treating coronary thrombosis. Clinical management which allowed a passive acceptance of inevitable cardiac damage and high mortality rates is now out of date. The aim now is preservation of both life and myocardium by early restoration of coronary blood flow. From a mortality rate for hospitalised patients of 30% in the 1960s to 10%-15% after the introduction of coronary care units, a 28-day death rate of below 5% should now be achievable for coronary care patients after their first myocardial infarct.6,7 Given what can be achieved with early treatment, the reluctance of patients who suffer a heart attack to present to hospital is disappointing. Previous Australian studies8,9 have shown avoidable delays in presentation of up to several hours from the onset of symptoms. In this issue of the Journal Dracup and colleagues provide further evidence of this risk-taking behaviour -- they report an unusually long median delay of 6.4 hours, even longer than the approximately two-hour delay reported by Leitch et al.8 in a Sydney-based study in 1989 and the approximately 1.2-hour delay found by Bett et al.9 in a study of 22 centres in 1988-89. The difference is probably partly due to differences in the definition of time of onset. Dracup et al. report the duration from onset of the first symptoms until hospital presentation, whereas Leitch et al. reported the time of onset of the symptom which initiated action until hospital presentation8 (which does not take into account the duration of any preceding intermittent symptoms), and Bett et al. reported the time from onset of the symptom which initiated action to when "help was first sought"9 (as opposed to hospital presentation). Thus, the latter studies would be expected to give a shorter average interval than that reported by Dracup et al. It is noteworthy that Dracup et al. conducted their study before the May 1996 Heart Foundation Heart Week campaign, which emphasised how to recognise symptoms of heart attack, with posters and television commercials depicting squeezing chest pain as a python-like grip, and the need for early action by patients suffering symptoms of a heart attack. Dracup et al. found that the patients who recognised their symptoms as cardiac in origin had only one-third the response time of those who did not. It would be interesting to see if a follow-up study showed any effect of the 1996 campaign. Although the complex human response to chest pain is more likely to be instinctive rather than knowledge-based,9 Dracup and colleagues provide further useful insight into factors that cause delay. The independent predictors of delay were educational status (slower response times in less educated patients), a desire not to cause trouble, failure to recognise symptoms as being cardiac in origin, and an intermittent pattern of symptoms. The message for future public education campaigns is clear -- publicise the symptoms of a possible heart attack, emphasise the importance of reporting them (no-one ever died of embarrassment), and ensure that the message is aimed at all educational levels. The message for health professionals is especially clear -- a third of patients reported that they learnt about heart attack symptoms from a health professional. Doctors and nurses dealing with existing heart patients or those with substantial risk factors for myocardial infarction have many opportunities to educate patients about heart attack symptoms and to give clear instructions on how -- and why -- they should summon an ambulance and get to a hospital fast. Paul E Langton Cardiology Research Fellow, Sir Charles Gairdner Hospital, Perth, WA Peter L Thompson Clinical Professor, Department of Cardiovascular Medicine, Sir Charles Gairdner Hospital, Perth, WA Tunstall-Pedoe H, Kuulasmaa K, Amouzel P, et al. Myocardial infarction and coronary deaths in the World Health Organization MONICA project. Circulation 1994; 90: 563-612. O'Rourke MF. Acute myocardial infarction: prehospital coronary care. In: Thompson PL, editor. Coronary care manual. London: Churchill-Livingstone, 1997: 429-433. Fibrinolytic Therapy Trialists Collaborative Group. Fibrinolytic therapy -- indications in suspected acute myocardial infarction. Lancet 1994; 343: 311-322. Ryan TJ, Anderson JL, Autman EM, et al. ACC/AHA Guidelines for the management of patients with acute myocardial infarction: executive summary. Circulation 1996; 94: 2341-2350. Weaver WD, Cerqueria M, Hallstrom AP, et al. for the MITI project group. Prehospital-initiated v. hospital-initiated thrombolytic therapy. The myocardial infarction triage and intervention (MITI) trial. JAMA 1993; 270: 1211-1216. DeVreede JJM, Gorgels AP, Verstraaten GMP, et al. Did prognosis after myocardial infarction change during the past 30 years? J Am Coll Cardiol 1991; 18: 698-706. Jamrozik K, Broadhurst R, Parsons RW, et al. Ten year trends in medical management and case fatality in acute myocardial infarction [abstract]. J Am Coll Cardiol 1996; 27: 278A. Leitch JW, Birbara T, Freedman B, et al. Factors influencing the time from onset of chest pain to arrival at hospital. Med J Aust 1989; 150: 6-8. Bett N, Aroney G, Thompson PL. Impact of a national education campaign to reduce patient delay in possible heart attack. Aust N Z J Med 1993; 23: 157-161. Reprints: Dr P E Langton, Sir Charles Gairdner Hospital, Verdun Street, Nedlands, WA 6009. - - To top of article - ©MJA 1997 <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia.

Paul E Langton · Peter L Thompson

Australian patients' delay in response to heart attack symptoms Kathleen Dracup, Sharon M McKinley and Debra K Moser MJA 1997; 166: 233 For comment see Langton and Thompson Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". Abstract - Introduction - Methods - Statistical analyses - Results - Associations with delay time - Discussion - Acknowledgements - References - Authors' details - - ©MJA1997 Abstract Objectives: To examine delay in seeking treatment among patients with an evolving acute myocardial infarction (MI), and to identify factors which contributed to this delay. Design: Patient interview combined with medical record review. Participants and setting: 317 patients with confirmed diagnosis of acute MI interviewed within 72 hours of admission to three hospitals. Main outcome measures: Delay from onset of symptoms to arrival at hospital, and cognitive, emotional, sociodemographic and clinical factors which contributed to increased prehospital delay. Results: Median prehospital delay was 6.4 hours; 41% of patients delayed less than four hours, while 28% delayed less than two hours. Prehospital delay was increased in patients with fewer years of education (P = 0.001), lower income (P = 0.003) and transportation to the hospital by private car rather than ambulance (P = 0.02). Delay time was increased by several cognitive and emotional processes (P < 0.001), such as waiting to see if symptoms would go away, being too embarrassed to ask for assistance, and not recognising the importance of symptoms. Delay time was increased with heartburn, breathlessness or intermittent symptoms and decreased with sweating and dizziness (P < 0.05). Independent predictors of increased prehospital time (P < 0.01) were fewer than 10 years of education, not wanting to trouble anyone, failing to recognise the symptoms of delay, and the intermittent nature of symptoms. Conclusion: Over 50% of acute MI patients delay seeking treatment by six hours or more. Many factors related to cognitive and social processes that contribute to this delay may be remediable with appropriate patient and community education. MJA 1997; 166: 233-236 Introduction Every year in Australia approximately 22 000 people suffer a heart attack and approximately half of these die. Most of these deaths occur out of hospital.1 The high mortality associated with acute myocardial infarction (MI) is dismaying, given that major large-scale clinical trials have shown that thrombolytic therapy can significantly reduce mortality from MI.2 With this therapy, the shorter the interval between the onset of symptoms and when the drug is given, the better the outcome.2 If therapy is started within three hours of symptoms, mortality is reduced by 23%;3 this becomes 45% if started within one hour of symptoms.3 Similarly, the earlier the treatment, the better the resulting cardiac function and the lower the incidence of morbidity after MI.4 Prehospital delay is known to be a substantial problem. Median delay times ranging from just under two hours5 to six-and-a-half hours have been reported.6 Overall, approximately 25%-50% of MI patients delay seeking medical care for cardiac symptoms for more than six hours.7,8 In other countries, the factors associated with increased prehospital delay are being older; being female; having a clinical history of hypertension, diabetes, angina or congestive heart failure; having low emotional or somatic awareness; consultation with a spouse or other relative; consultation with a doctor; and self-treatment. Decreased prehospital delay occurs when there is haemodynamic instability, large infarct size, sudden onset of severe chest pain, recognition of symptoms as heart-related and consultation with a non-relative.8,9 We do not know if the characteristics that contribute to delay in seeking treatment for acute MI symptoms are similar for Australian patients. Such information is important for designing appropriate patient and community education programs. Therefore our aims were, firstly, to describe prehospital delay time in Australian patients experiencing symptoms of evolving acute MI and, secondly, to identify the cognitive, emotional, sociodemographic and clinical factors which contribute to this delay. Methods We gained appropriate institutional ethics committee review and approval for the study from the study hospitals and the University of Technology, Sydney. Eligible patients admitted to three hospitals between 1 March and 31 July 1995 were invited to participate in the study and gave written informed consent. Patients were eligible if they were able to read and write English, lived independently, were free from malignancy or other complicating illness, alert and orientated, were within 24 and 72 hours of hospital admission, and had a diagnosis of acute MI, determined by:Chest pain lasting longer than 20 minutes; Serial electrocardiographic evidence of acute MI (i.e., appearance of new Q waves in at least two leads of a 12-lead standard electrocardiogram); and Elevations in serum creatine kinase-MB consistent with evolving MI. Only patients with Q-wave MI were studied. Patients were excluded if they were being mechanically ventilated. The hospitals were two metropolitan university-affiliated city teaching hospitals and a district hospital, chosen because their geographical catchment areas were relatively small, so transportation time would not add significantly to the time between symptom onset and arrival at the hospital. We reviewed medical records to obtain sociodemographic and clinical data. We assessed information about the cognitive, emotional and social processes surrounding the decision to seek treatment using the Response to symptoms questionnaire, designed to obtain information about patient delay and factors contributing to delay in six domains: (1) context in which MI symptoms appeared; (2) antecedents of symptoms; (3) affective response to symptoms; (4) behavioural response to symptoms; (5) cognitive response to symptoms; and (6) the response of others to patient symptoms.10 Based on growing evidence that cognitive, symptom-appraisal and social factors may be more important determinants of delay than knowledge about appropriate re sponse to symptoms,10 we modified the instrument to further assess cognitive, symptom-appraisal and social factors surrounding a patient's decision to seek care for acute MI symptoms. The resulting instrument assesses factors surrounding the onset of acute MI symptoms, the response of others to symptoms, and the patient's response to symptoms. We established the time from symptom onset to hospital admission by reviewing the medical record for the time stated in the admission record by the admitting physician and the time of admission to the hospital. Also, each patient was asked about the time of first symptoms. If symptoms had come and gone, patients were carefully interviewed to determine the nature of those symptoms and the exact time that cardiac symptoms began. Where the patient's account differed from the time recorded by the admitting doctor, cardiac enzymes and serial electrocardiograms were reviewed to identify the most likely time of symptom onset. The value that most closely matched the expected clinical course reflected in the tests was chosen. Patients were asked if they wanted to complete the questionnaire themselves or if they wanted the researcher to read the questions; 96% chose the latter. Statistical analyses Independent t tests or analysis of variance (with post-hoc t tests adjusted for multiple comparisons) were used to assess the impact of sociodemographic, clinical, cognitive and social factors. Delay time was markedly skewed, so we used square root transformations to obtain a normal distribution, and all analyses were performed on transformed values. Multiple logistic regression and χ2 tests were used to determine odds ratios for delays of more than two hours among several sociodemographic, clinical, social and cognitive variables. Variables that were significantly different (P < 0.05) on delay time were entered into the forward stepwise logistic regression. Criteria for entry and removal of variables were based on the likelihood ratio test, with enter and remove limits set at P < 0.05 and P > > 0.05. Results Of 321 eligible patients approached, 317 agreed to participate in the study; four declined, giving fatigue as a reason. Patients were predominantly older (mean, 63 years; standard deviation, 12 years), male, married and white. There was diversity in years of formal education and socioeconomic status. Most patients experienced their symptoms at home and most went to hospital by ambulance (Box 1). Many patients were at greater than average risk for suffering an acute MI, with previous medical histories of angina pectoris (43%), MI (28%), hypertension (53%) and/or diabetes mellitus (19%). Most MIs were inferior (46%) or anterior (32%). Median prehospital delay time was 6.4 hours (interquartile range, 1.9-19.9 h; mean, 17.3 h). Only 14% of patients arrived within one hour of the onset of symptoms, 28.5% within two hours and 41% within four hours. However, 54% arrived at the hospital more than six hours after first experiencing cardiac symptoms. One hundred and fifty-three patients (48%) received thrombolytic therapy; 29 within one hour of the onset of symptoms. Associations with delay time Sociodemographic factors: Box 1 shows that there were differences in delay time according to education, annual income and use of ambulance. There was no significant association with sex, age, ethnicity, the location where symptoms occurred or whether or not a spouse was present when they occurred. Symptoms and pain: We examined breathlessness, fatigue, weakness, vague chest discomfort, chest pain, neck pain, arm numbness, pain between shoulder blades, back pain, nausea, feeling that something was wrong, dia phoresis, feeling clammy, heartburn, and dizziness. Delay time was less if patients were dia phoretic (P = 0.001) or experienced dizziness (P = 0.03) and increased if they were breathless (P = 0.03) or experienced heartburn (P = 0.03). The remaining symptoms made no difference to delay times. If symptoms were intermittent, patients took longer to seek treatment (P = 0.0001), while those who believed their symptoms to be cardiac in nature delayed for shorter times (P = 0.001). However, 60% originally attributed their symptoms to another cause (e.g., muscle pain, fatigue, indigestion). Patients who appraised their pain as very serious delayed a shorter time than patients who appraised their pain as not serious (P = 0.001). However, patients who rated their initial chest pain as severe had similar delay times to patients who rated their pain as mild (P = 0.644). Knowledge of coronary heart disease: There were no differences in the average time to arrival at hospital related to previous myocardial infarction, previous cardiac surgery, diabetes mellitus, hypertension or angina. Forty per cent of patients reported that their source of information about MI symptoms was television or reading; 27% received their information from a friend; 23% from a doctor; and 10% from a nurse. Sixteen per cent of patients knew about thrombolysis therapy for acute MI and these, on average, came to the hos pital earlier than patients who did not know about this treatment (P = 0.001). Cognitive and psychological factors: Box 2 (below) shows significant associations between patients' responses and delays in seeking medical treatment. Independent predictors of delay: We tested factors that were significant on univariate analyses in a multiple regression model. The five independent predictors of delay are shown in Box 3. Discussion In 317 patients admitted to hospital for evolving acute MI, we found that median prehospital delay was 6.4 hours. Almost 60% of patients delayed more than four hours, while more than 70% delayed longer than two hours. These times are substantially longer than those recorded in most studies from other countries,4-6,8,11 as well as those documented in previous Australian studies.12,13 The disparity between this and previous Australian studies is un doubtedly related to a difference in the definitions used to characterise prehospital delay. In the first Australian study, time from symptom onset to the first attempt to get help was reported.12 In the second, the definition of total delay time was the period from the onset of chest pain to arrival at hospital; where there were multiple episodes of chest pain, the time from the last episode of pain was used.13 Both variations in definitions would shorten reported delay time relative to the definition we used. It is unlikely that longer transportation times to the hospital contributed to longer delay times in our study because of the geographic situation of the participating hospitals and the high rate of ambulance use. Moreover, all studies on this topic have found that home-to-hospital time, as well as in-hospital time, play a minor role in the delay that occurs before definitive treatment.8,14,15 We included only those patients who survived to hospital admission and who met our inclusion criteria, and hence our patients were clearly not representative of all patients with acute MI. Unfortunately, approximately 30% of such patients die of sudden cardiac death before reaching the hospital,1 and we excluded patients because they were unable to respond to questions within the designated 72 hours of hospital admission (e.g., because they required mechanical ventilation or had compromised mental status). In the past, most researchers have focused on identifying patients who are more likely to delay a decision to come to the hospital because of various sociodemographic and clinical characteristics. In our study, the most important factor predicting delay was years of formal education, a characteristic that health professionals cannot alter. However, it may be linked with other characteristics (e.g., income, age, coping styles or other underlying cognitive mechanisms affecting delay), some of which may be amenable to change. Many of our patients had difficulty identifying their symptoms as cardiac in nature, initially thinking they were gastrointestinal, musculoskeletal, or fatigue. Many patients knew the classic signs of acute MI but did not know the diversity of its presentation, notably its often intermittent nature. Patients should be told that the symptoms may come on gradually or may not be constant, as many believe that MI is accompanied by sudden, crushing chest pain and unconsciousness. As in other studies,5,12,16,17 experience of a previous MI did not result in patients coming to the hospital sooner. Thus, the public, particularly patients at high risk for a future MI, need to be informed that the manifestations of an evolving MI may vary, even within the same individual, and should be clear about the actions to take if and when symptoms occur. In most studies in the United States, less than half of MI patients arrive by ambulance,18 whereas in our study most patients in all three hospitals used this means of transportation. Ambulance is preferable to other types of transportation because of the early treatment available and because delay times are usually reduced.18 From the accounts of patients in this study, doctors and nurses played minimal roles in providing information about the symptoms of MI, compared with knowledge gained from television, reading and friends. Counselling strategies tested in other clinical populations support the assumption that individuals who are prepared for certain signs and symptoms will delay less in seeking care than individuals who have no such preparation.19-21 They also suggest that health professionals should take a more proactive and intensive approach to educating patients about the nature of MI signs and symptoms and the steps to take to receive early treatment. These data also indicate the opportunity for professional organisations to enhance the knowledge and beliefs of patients by community educational programs via television, radio and newspapers. Very few patients knew about thrombolysis and its effectiveness in treating acute MI, but those who did presented sooner than those who did not. Based on these findings, health care professionals should emphasise the rationale for early treatment to patients at high risk for future MI, and public campaigns should advertise the benefit of seeking early treatment. Patients need to know that their decision to seek immediate treatment has important future rewards as this may override whatever trepidation they experience in acknowledging that they might be having a heart attack. In summary, almost all the significant predictors of delay we identified related to social and cognitive processes that might be amenable to change. Health care professionals should recognise the reluctance of patients to recognise MI symptoms as cardiac and provide them with the necessary guidance, so that they will seek care as soon as possible. The availability of newer forms of treatment, particularly thrombolytic therapy, provides a compelling reason for physicians and nurses to encourage patients and their families to seek care early to preserve ischaemic myocardium and reduce infarct size in the face of an evolving MI. Acknowledgements Funding for this study was provided by a Fulbright Foundation Senior Scholars grant and from the L W Hassenplug Chair funds. We thank the following nurses who assisted with data collection: Patricia Cameron, Marie Droulers, Cameron Goodear, Jennifer Kidd, Jacqueline Padley, Rebecca Scammell and Jennifer Williams. References Heart and stroke facts. Canberra: National Heart Foundation of Australia, 1995. Fibrinolytic Therapy Trialists' (FTT) Collaborative Group. Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Lancet 1994; 343: 311-322. Gruppo Italiano per lo Studio della Stretochinasi nell'Infarto Miocardico (GISSI). Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986; 1: 397-401. Simoons ML, Serruys PW, Brand MVD, et al. Early thrombolysis in acute myocardial infarction: Limitation of infarct size and improved survival. J Am Coll Cardiol 1986; 7: 717-721. Maynard C, Althouse R, Olsufka M, et al. Early versus late hospital arrival for acute myocardial infarction in the western Washington thrombolytic therapy trials. Am J Cardiol 1989; 63: 1296-1300. Cooper RS, Simmons B, Castaner A, et al. Survival rates and prehospital delay during myocardial infarction among black persons. Am J Cardiol 1986; 57: 208-211. Dracup K, Moser D. Treatment seeking behavior among those with symptoms and signs of acute myocardial infarction. Heart Lung 1991; 20: 570-575. GISSI-Avoidable Delay Study Group. Epidemiology of avoidable delay in the care of patients with acute myocardial infarction in Italy. Arch Intern Med 1995; 155: 1481-1488. Dracup K, Moser D, Eisenberg M, et al. Causes of delay in seeking treatment for symptoms of acute myocardial infarction. Soc Sci Med 1995; 40: 379-392. Burnett RE, Blumenthal JA, Mark DB, et al. Distinguishing between early and late responders to symptoms of acute myocardial infarction. Am J Cardiol 1995; 75: 1019-1022. Schwarz B, Schoberberger R, Rieder A, Dunze M. Factors delaying treatment of acute myocardial infarction. Eur Heart J 1994; 15: 1595-1598. Bett N, Aroney G, Thompson P. Impact of a national educational program to reduce patient delay in possible heart attack. Aust N Z J Med 1993; 23: 157-161. Leitch JW, Birbara T, Freedman B, et al. Factors influencing the time from onset of chest pain to arrival at the hospital. Med J Aust 1989; 150; 6-8. Schroeder JS, Lamb IH, Hu M. The pre-hospital course of patients with chest pain: analysis of the prodromal, symptomatic, decision-making, transportation and emergency room periods. Am J Med 1978; 64: 742-748. Schmidt SB, Borsch MA. The prehospital phase of acute myocardial infarction in the era of thrombolysis. Am J Cardiol 1990; 65: 1411-1415. Turi ZG, Stone PH, Muller JE, et al. Implications for acute intervention related to time of hospital arrival in acute myocardial infarction. Am J Cardiol 1986; 58: 203-209. Weilgosz ATJ, Nolan RP, Earp JA, Biro E. Reasons for patients' delay in response to symptoms of acute myocardial infarction. Can Med Assoc J 1988; 139: 853-857. Meischke H, Ho MT, Eisenberg MS, et al. Reasons patients with chest pain delay or do not call 911. Ann Emerg Med 1995; 25: 193-197. Bandura A. Self-efficacy; toward a unifying theory of behavior change. Psychol Bull 1977; 84: 191-198. Bailey WC, Richards JM Jr, Brooks CM, et al. A randomized trial to improve self-management practices of adults with asthma. Arch Intern Med 1990; 150: 1664-1667. Avis NE, Smith DW, McKinlay JB. Accuracy of perceptions of heart attack risks: what influences perceptions and can they be changed? Am J Public Health 1989; 17: 1608-1611. (Received 28 Mar, accepted 20 Nov, 1996) Authors' details University of California, Los Angeles, CA, USA. Kathleen Dracup, RN, DNSc, L W Hassenplug Professor of Nursing. University of Technology, Sydney, and Royal North Shore Hospital, Sydney, NSW. Sharon M McKinley, RN, PhD, Professor of Critical Care Nursing. College of Nursing, Ohio State University, Columbus, OH, USA. Debra K Moser, RN, DNSc, Assistant Professor. Reprints: Professor S M McKinley, Level 6, Royal North Shore Hospital, St Leonards, NSW 2065. E-mail: smckinle AT doh.health.nsw.gov.au - - To top of article - ©MJA 1997 <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia.

Kathleen Dracup · Sharon M McKinley · Debra K Moser

Clinical Practice Clinical exercise stress testing -- Safety and performance guidelines* The Cardiac Society of Australia and New Zealand Clinical exercise testing has wide application in medicine, including the assessment of functional capacity, ventilatory function, gas exchange, muscle function, and endocrine and metabolic function, and as a test for claudication in peripheral vascular disease. The major use of exercise testing, however, is as a stress test in patients with known or suspected coronary artery disease. This article outlines the minimum safety and performance guidelines for exercise stress testing with electrocardiography, although many of the safety guidelines are common to other types of exercise tests, particularly exercise stress scintigraphy and echocardiography. MJA 1996; 164: 282-284 Introduction - Exercise equipment - Electrocardiograph (ECG) - Blood pressure measurement - Documentation - Postexercise period - Resuscitation equipment - Personnel - References - Authors' details - - Articles on similar material Introduction Clinical exercise stress testing with exercise electrocardiography is usually performed in patients with known or suspected coronary artery disease (see Box 1). It is thus not without risk: one in 10 000 people will die, and two to three in 10 000 will have a major morbid event such as myocardial infarction, a major arrhythmia requiring resuscitation, severe hypotension, severe heart failure or unstable angina pectoris. (The complication rates may be higher in some laboratories because of the mix of referred patients.) Those who perform exercise stress testing must thus be able to recognise and exclude patients at high risk, and have the clinical skills and equipment to recognise and deal effectively with complications. They should also obtain informed consent from the patient before performing the test. Exercise equipment Energy expenditure is best quantified by measurement of oxygen consumption (Vo2), expressed in METS, during exercise. A MET unit is the energy expenditure at rest, equivalent to an oxygen uptake of approximately 3.5 mL O2 per kilogram bodyweight per minute. This is the most precise measurement of metabolic load, and therefore cardiovascular load, and can vary considerably between individuals with differing exercise efficiency working at the same treadmill or cycle ergometer setting. Vo2 is not usually measured directly; energy expenditure in METS can be estimated from nomograms1 which assume that energy expenditure can be quantified as watts (cycle ergometer) or as speed and grade (treadmill). Treadmills must be motorised and calibrated, and should be capable of providing measured increases in speed and gradient. The treadmill speed can be easily checked by measuring the visible length of belt, multiplying by two, and multiplying this by manually counted belt revolutions/ minute to give km/hour. Treadmill inclination can be checked by a protractor. Cycle ergometers must be able to vary the external workload and quantify it in watts. Preference is for electrical or mechanical braking, although wind-braking is probably adequate. Thumb-screw braking is not adequate as the load cannot be quantified and is not reproducible. Simple step devices (including "Masters two-step"), or any other form of non-quantified and unmonitored exercise, are not adequate for clinical exercise stress testing. Equipment should be serviced on a regular basis to ensure performance within specifications. Electrocardiograph (ECG) Use 12-lead ECG equipment, recording on a 3-channel device with adequate low frequency and phase response. Devices which record only one or three ECG leads, even if these are bipolar chest leads, are not adequate. If the device provides computer-averaged complexes, raw ECG traces should also be inspected at each stage of exercise, or at least every three minutes, to avoid incorrect interpretation resulting from noise or artefact. Electrodes must be firmly fixed to the patient's skin with adhesive or continuous suction, and have good contact with the ECG lead, to prevent movement artefact in the ECG trace. Use an alcohol solution to remove oil from the patient's skin and abrade the horny layer of the epidermis with fine sandpaper or a disposable abrasive device. Record a standard supine ECG (with limb leads on the limbs) for each patient, and an additional supine ECG with the limb electrodes on the torso if this is where they will be placed during exercise. Monitor the ECG continuously during the exercise period and for five minutes after the cessation of exercise on a video display of two or three leads, preferably selected to be semiorthogonal (i.e., an inferior lead, V5, and V1 or V2). Monitoring a single lead is suboptimal for detecting arrhythmias and ischaemic patterns during exercise. Monitoring devices should have a memory loop capable of providing hard copy or storing rhythm traces on request by the operator. Record further ECGs with the patient upright; during each stage of exercise (or at least every three minutes); at peak exercise; immediately upon cessation of exercise; and at least twice during the post- exercise period. Blood pressure measurement Measure blood pressure before, during (ideally every minute but at least every three minutes, coinciding with each stage of exercise) and after exercise (at least two measurements). If possible, a measurement should be made at peak exercise. Additional measurements may be required depending on clinical circumstances. Documentation Document the resting and peak heart rate and blood pressure, and any abnormalities of these or the ECG. The peak rate-pressure product (heart rate x systolic blood pressure) should be calculated as this provides the best estimate of myocardial load. Question the patient about symptoms such as angina, anginal equivalents, shortness of breath, presyncope and claudication during and after exercise. Identify the major symptom which limits exercise and record its intensity, at least descriptively, but ideally with a quantitative measure such as the Borg scale2 (see Box 2). Also record the duration of exercise and the maximum workload achieved. Postexercise period Patients should be observed for at least 10 minutes after cessation of exercise. Continue ECG monitoring for at least five minutes, or longer if clinically indicated. The duration of ECG monitoring may be abbreviated to three minutes in special circumstances, such as thallium scintigraphy, when imaging must commence as soon as possible after exercise. In such cases, the patient should be closely observed for the first 10 minutes after exercise. Resuscitation equipment Exercise stress test laboratories must be adequately equipped to provide advanced life support in the event of a cardiac arrest (see Box 3). The exercise room must be sufficiently large to allow the patient to be removed from the treadmill or cycle and be placed on the ground for resuscitation if complications occur. All resuscitation equipment must be easily accessible and maintained and tested on a regular basis. Personnel Two people (at least one of whom is a registered medical practitioner, see Box 4) should be present in the exercise room at all times during exercise stress testing and the immediate postexercise period. Both should be trained in cardiopulmonary resuscitation and in the recognition of the major arrhythmias and ischaemic patterns on the ECG. No regular specific courses are currently available in exercise stress testing. The assistant for exercise stress testing should be a professional person with training in an area related to health (e.g., ECG technician, graduate of a course approved by the Australian Association for Exercise and Sports Sciences, coronary care-trained nurse, physiotherapist, occupational therapist). He or she must be able to perform cardiopulmonary resuscitation, obtain a high quality ECG trace, and recognise the major arrhythmic and ischaemic ECG and clinical manifestations likely to occur during exercise stress testing. He or she should also have observed exercise stress tests under the supervision of a cardiologist and performed tests under supervision of an experienced assistant. A retraining program in cardiopulmonary resuscitation should be undertaken every two years. References The Committee on Exercise, American Heart Association. Exercise testing and training of apparently healthy individuals: a handbook for physicians. Dallas, TX: American Heart Association, 1972: 13. Noble BJ, Borg GAV, Jacobs I, et al. A category-ratio perceived exertion scale: relationship to blood and muscle lactates and heart rate. Med Sci Sports Exerc 1983; 15: 523-528. * Adapted from a Cardiac Society guideline document, copies of which are available from Professor Freedman. Authors' details 145 Macquarie Street, Sydney, NSW 2000. The Cardiac Society of Australia and New Zealand. No reprints will be available. Correspondence: Professor Ben Freedman, Honorary Secretary. ©MJA 1998 Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/> © 1998 Medical Journal of Australia. 1: Indications for exercise stress testing* As a diagnostic test in patients with suspected coronary artery disease (e.g., men with symptoms that are atypical for myocardial ischaemia, patients with symptoms consistent with recurrent exercise-induced cardiac arrhythmias). To assist in identifying patients with documented coronary artery disease who are at high risk (e.g., due to advanced disease and/or left ventricular dysfunction). To evaluate patients after coronary artery bypass surgery or angioplasty. To quantify a patient's functional capacity, prognosis or response to therapies, and to follow the natural course of disease at appropriate intervals (e.g., after uncomplicated myocardial infarction, in selected patients with congenital heart disease). General contraindications Unstable angina prior to a period of stabilisation Untreated life-threatening arrhythmias Uncompensated severe congestive heart failure Advanced atrioventricular heart block Acute myocarditis Critical aortic stenosis * Adapted from: Guidelines for exercise testing. A report of the American College of Cardiology/American Heart Association Task Force on Assessment of Cardiovascular Procedures (Subcommittee on Exercise Testing). J Am Coll Cardiol 1986; 8: 725-738. Back to text 2: Borg scale2 for ratings of perceived exertion 0Nothing at all0.5 Very, very weak1 Very weak2 Weak3 Moderate4 Somewhat strong5 Strong67 Very strong8910 Very, very strong(maximal)Back to text 3: Essential resuscitation equipment Defibrillator with electrogel or electrode pads Suction (motor driven or gas cylinder [Venturi] device with appropriate plastic or metal suckers) Airway plus self-inflating ventilation bag Oxygen and appropriate masks Drugs, intravenous cannulas and giving sets, including atropine, lignocaine, adrenaline, and sotalol or amiodarone for intravenous use, a β2-agonist inhaler (e.g., salbutamol), and short-acting nitrates (e.g., sublingual glyceryl trinitrate or isosorbide dinitrate, or glyceryl trinitrate spray) Alarm to summon nearby personnel and a telephone to call an intensive care ambulance in the event of an emergency Back to text 4: Medical practitioners supervising exercise stress tests should be able to: Evaluate indications for exercise stress testing and recognise contraindications. Interpret all the major abnormalities that can be detected on 12-lead electrocardiography, particularly those associated with ischaemic heart disease; those likely to preclude interpretation of the exercise ECG; those which might indicate deferral of the exercise test; and the tachy- and bradyarrhythmias that may occur during exercise. Differentiate ischaemic from non-ischaemic symptoms during exercise. Perform basic and advanced life support with skill in an emergency situation, and show evidence of continuing competence by, for example, attending retraining courses at two-yearly intervals. Demonstate previous experience in exercise stress testing supervised by a cardiologist, including determination of the most appropriate protocol for individual patients. Back to text

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