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Heart-Rate Profile during Exercise as a Predictor of Sudden Death
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     To the Editor: The study by Jouven and colleagues (May 12 issue)1 advances our understanding of the factors involved in the precipitation of sudden death. However, the authors' assertion that exercise-induced changes in heart rate "may have clinical implications in terms of the early identification of high-risk subjects" is untenable given the very low incidence of sudden death in their studied population. Only 1.4 percent of the 5713 healthy middle-aged men died suddenly during the 23-year follow-up. On the basis of the criterion the investigators found most discriminating — subnormal exercise-induced increase in heart rate — 500 men would have to undergo exercise testing in order for 100 men to be classified as belonging to the "high-risk" quintile. During the subsequent 23 years, only 2 of these 100 men would actually die suddenly. Thus, while the risk in this quintile is slightly increased, it is certainly not high, nor is it sufficient to justify stigmatization or the institution of nonvalidated primary prevention.

    Mayer M. Bassan, M.D.

    Clallit Health Services

    94110 Jerusalem, Israel

    References

    Jouven X, Empana J-P, Schwartz PJ, Desnos M, Courbon D, Ducimetière P. Heart-rate profile during exercise as a predictor of sudden death. N Engl J Med 2005;352:1951-1958.

    To the Editor: The article by Jouven et al. about heart rates during exercise and their relation to sudden death conclusively extends the known risk of poor heart-rate variability in patients with cardiac conditions to middle-aged men without a known history of cardiac disease. In doing so, the authors provide a new target for primary prevention of life-altering cardiac events — one that is thought to be independent from coronary lesions.1 Just as the patients who have had a myocardial infarction have benefitted from exercise strategies that focus on the autonomic nervous system,2 so might asymptomatic age-appropriate patients benefit. In fact, exercise has been shown to increase autonomic responses in several asymptomatic groups, including people with diabetes,3 sedentary postmenopausal women,4 and healthy young women.5 Further studies should be undertaken to see whether asymptomatic patients have decreased mortality after engaging in exercise training that targets the autonomic nervous system. In the meantime, physicians should revisit cases in which there were "negative" results on exercise stress tests for signs of poor heart-rate variability. In addition, the "normal" resting heart rate of 75 to 99 beats per minute —which apparently confers an almost fourfold relative risk of sudden death — should be questioned.

    Ian G. Harnik, M.D.

    Mount Sinai Hospital

    New York, NY 10029

    ian.harnik@mssm.edu

    References

    Vivekananthan D, Blackstone EH, Pothier CE, Lauer MS. Heart rate recovery after exercise is a predictor of mortality, independent of the angiographic severity of coronary disease. J Am Coll Cardiol 2003;42:831-838.

    La Rovere MT, Bersano C, Gnemmi M, Specchia G, Schwartz PJ. Exercise-induced increase in baroreflex sensitivity predicts improved prognosis after myocardial infarction. Circulation 2002;106:945-949.

    Loimaala A, Huikuri HV, Koobi T, Rinne M, Nenonen A, Vuori I. Exercise training improves baroreflex sensitivity in type 2 diabetes. Diabetes 2003;52:1837-1842.

    Jurca R, Church TS, Morss GM, Jordan AN, Earnest CP. Eight weeks of moderate-intensity exercise training increases heart rate variability in sedentary postmenopausal women. Am Heart J 2004;147:e21-e21.

    Goldsmith R, Dardik I, Bloomfield DM, et al. Implementation of a novel cyclic exercise protocol in healthy women. Am J Med Sports 2002;4:135-41, 151.

    The authors reply: Dr. Bassan addresses the classic difference between relative and absolute risk. This long-term, prospective study was conducted in a highly selected population of asymptomatic working men; subjects with any cardiac abnormalities at rest or during exercise testing were excluded from the analysis. As is generally the case in studies of risk factors, absolute risk is artificially low. Conversely, populations of patients with cardiac failure or with a history of myocardial infarction have a much higher absolute risk of sudden death (but also numerous confounding factors, including beta-blocker therapy, that challenge the interpretation of the heart-rate profile). Moreover, the strict criteria that were applied for coding sudden death in the current study were responsible for a decrease in sensitivity. Taken together, these points explain why, in the current study, sudden death failed to account for 5 to 10 percent of total mortality, as it is usually reported.1 Consequently, any attempt to assess the incidence of sudden death in our study, which was clearly not designed for this purpose, should be regarded with caution.

    The assumption made by Dr. Bassan that regular sports activity is a nonvalidated primary-prevention measure is highly debatable. As pointed out in the article, our findings do not address this issue. However, fundamental experimental work by Schwartz et al.2 and Hull et al.3 clearly indicates that exercise training is associated with a decrease in sudden death risk, in part through the restoration of autonomic control. In addition, and as stated by Dr. Harnik, the benefit of exercise strategies that target the autonomic nervous system has been observed in high-risk populations. In asymptomatic subjects, regular physical activity has also been associated with an increase in heart-rate variability.4 Meanwhile, further studies are required to see whether asymptomatic patients show decreased rates of sudden death after exercise training.

    Xavier Jouven, M.D., Ph.D.

    H?pital Européen Georges Pompidou

    75015 Paris, France

    Jean Philippe Empana, M.D., Ph.D.

    Pierre Ducimetière, Ph.D.

    H?pital Paul Brousse

    94807 Villejuif, France

    References

    Zipes DP, Wellens HJ. Sudden cardiac death. Circulation 1998;98:2334-2351.

    Schwartz PJ, Vanoli E, Stramba-Badiale M, De Ferrari GM, Billman GE, Foreman RD. Autonomic mechanisms and sudden death: new insights from analysis of baroreceptor reflexes in conscious dogs with and without a myocardial infarction. Circulation 1988;78:969-979.

    Hull SS Jr, Vanoli E, Adamson PB, Verrier RL, Foreman RD, Schwartz PJ. Exercise training confers anticipatory protection from sudden death during acute myocardial ischemia. Circulation 1994;89:548-552.

    Rennie KL, Hemingway H, Kumari M, Brunner E, Malik M, Marmot M. Effects of moderate and vigorous physical activity on heart rate variability in a British study of civil servants. Am J Epidemiol 2003;158:135-143.