Heart-Rate Profile during Exercise as a Predictor of Sudden Death
Xavier Jouven, M.D., Ph.D., Jean-Philippe Empana, M.D., Peter J. Schwartz, M.D., Michel Desnos, M.D., Dominique Courbon, M.S.C., and Pierre Ducimetière, Ph.D.
Background Changes in heart rate during exercise and recoveryfrom exercise are mediated by the balance between sympatheticand vagal activity. Since alterations in the neural controlof cardiac function contribute to the risk of sudden death,we tested the hypothesis that among apparently healthy persons,sudden death is more likely to occur in the presence of abnormalheart-rate profiles during exercise and recovery.
Methods A total of 5713 asymptomatic working men (between theages of 42 and 53 years), none of whom had clinically detectablecardiovascular disease, underwent standardized graded exercisetesting between 1967 and 1972. We examined data on the subjects'resting heart rates, the increase in rate from the resting levelto the peak exercise level, and the decrease in rate from thepeak exercise level to the level one minute after the terminationof exercise.
Results During a 23-year follow-up period, 81 subjects diedsuddenly. The risk of sudden death from myocardial infarctionwas increased in subjects with a resting heart rate that wasmore than 75 beats per minute (relative risk, 3.92; 95 percentconfidence interval, 1.91 to 8.00); in subjects with an increasein heart rate during exercise that was less than 89 beats perminute (relative risk, 6.18; 95 percent confidence interval,2.37 to 16.11); and in subjects with a decrease in heart rateof less than 25 beats per minute after the termination of exercise(relative risk, 2.20; 95 percent confidence interval, 1.02 to4.74). After adjustment for potential confounding variables,these three factors remained strongly associated with an increasedrisk of sudden death, with a moderate but significantly increasedrisk of death from any cause but not of nonsudden death frommyocardial infarction.
Conclusions The heart-rate profile during exercise and recoveryis a predictor of sudden death.
Source Information
From the Service de Cardiologie, Faculté René Descartes, Université Paris-5, Hôpital Européen Georges Pompidou, Paris (X.J., M.D.); INSERM Avenir Unité 258, Epidémiologie Cardiovasculaire et Métabolique, Hôpital Paul Brousse, Villejuif, France (X.J., J.-P.E, D.C., P.D.); and the Department of Cardiology, University of Pavia and Istituto di Ricovera e Cura a Carattere Policlinico San Matteo, Pavia, Italy (P.J.S.).
Address reprint requests to Dr. Jouven at the Service de Cardiologie, Faculté René Descartes, Université Paris-5, Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75015 Paris, France, or at xavier.jouven{at}egp.aphp.fr.
Lahiri, M. K., Kannankeril, P. J., Goldberger, J. J.
(2008). Assessment of autonomic function in cardiovascular disease: physiological basis and prognostic implications.. J Am Coll Cardiol
51: 1725-1733
[Abstract][Full Text]
Hall, A S, Palmer, S
(2008). The heart rate hypothesis: ready to be tested. Heart
94: 561-565
[Abstract][Full Text]
Hughes, J. W., York, K. M., Li, Q., Freedland, K. E., Carney, R. M., Sheps, D. S.
(2008). Depressive Symptoms Predict Heart Rate Recovery After Exercise Treadmill Testing in Patients With Coronary Artery Disease: Results From the Psychophysiological Investigations of Myocardial Ischemia Study. Psychosom. Med.
70: 456-460
[Abstract][Full Text]
Palatini, P.
(2008). Exercise testing in asymptomatic subjects: from diagnostic test to prognostic tool?. Eur Heart J
0: ehn165v1-4
[Full Text]
Dewey, F. E., Kapoor, J. R., Williams, R. S., Lipinski, M. J., Ashley, E. A., Hadley, D., Myers, J., Froelicher, V. F.
(2008). Ventricular Arrhythmias During Clinical Treadmill Testing and Prognosis. Arch Intern Med
168: 225-234
[Abstract][Full Text]
Sundaram, S., Carnethon, M., Polito, K., Kadish, A. H., Goldberger, J. J.
(2008). Autonomic effects on QT-RR interval dynamics after exercise. Am. J. Physiol. Heart Circ. Physiol.
294: H490-H497
[Abstract][Full Text]
De Ferrari, G. M., Sanzo, A., Bertoletti, A., Specchia, G., Vanoli, E., Schwartz, P. J.
(2007). Baroreflex Sensitivity Predicts Long-Term Cardiovascular Mortality After Myocardial Infarction Even in Patients With Preserved Left Ventricular Function. J Am Coll Cardiol
50: 2285-2290
[Abstract][Full Text]
Gu, H., Lin, M., Liu, J., Gozal, D., Scrogin, K. E., Wurster, R., Chapleau, M. W., Ma, X., Cheng, Z.
(2007). Selective impairment of central mediation of baroreflex in anesthetized young adult Fischer 344 rats after chronic intermittent hypoxia. Am. J. Physiol. Heart Circ. Physiol.
293: H2809-H2818
[Abstract][Full Text]
Nieminen, T., Lehtimaki, T., Viik, J., Lehtinen, R., Nikus, K., Koobi, T., Niemela, K., Turjanmaa, V., Kaiser, W., Huhtala, H., Verrier, R. L., Huikuri, H., Kahonen, M.
(2007). T-wave alternans predicts mortality in a population undergoing a clinically indicated exercise test. Eur Heart J
28: 2332-2337
[Abstract][Full Text]
London, B., Albert, C., Anderson, M. E., Giles, W. R., Van Wagoner, D. R., Balk, E., Billman, G. E., Chung, M., Lands, W., Leaf, A., McAnulty, J., Martens, J. R., Costello, R. B., Lathrop, D. A.
(2007). Omega-3 Fatty Acids and Cardiac Arrhythmias: Prior Studies and Recommendations for Future Research: A Report from the National Heart, Lung, and Blood Institute and Office of Dietary Supplements Omega-3 Fatty Acids and Their Role in Cardiac Arrhythmogenesis Workshop. Circulation
116: e320-e335
[Full Text]
Hjalmarson, A.
(2007). Heart rate: an independent risk factor in cardiovascular disease. Eur Heart J Suppl
9: F3-F7
[Abstract][Full Text]
Fox, K., Borer, J. S., Camm, A. J., Danchin, N., Ferrari, R., Lopez Sendon, J. L., Steg, P. G., Tardif, J.-C., Tavazzi, L., Tendera, M., for the Heart Rate Working Group,
(2007). Resting Heart Rate in Cardiovascular Disease. J Am Coll Cardiol
50: 823-830
[Abstract][Full Text]
Lin, M., Liu, R., Gozal, D., Wead, W. B., Chapleau, M. W., Wurster, R., Cheng, Z.
(2007). Chronic intermittent hypoxia impairs baroreflex control of heart rate but enhances heart rate responses to vagal efferent stimulation in anesthetized mice. Am. J. Physiol. Heart Circ. Physiol.
293: H997-H1006
[Abstract][Full Text]
Ingelsson, E., Larson, M. G., Vasan, R. S., O'Donnell, C. J., Yin, X., Hirschhorn, J. N., Newton-Cheh, C., Drake, J. A., Musone, S. L., Heard-Costa, N. L., Benjamin, E. J., Levy, D., Atwood, L. D., Wang, T. J., Kathiresan, S.
(2007). Heritability, Linkage, and Genetic Associations of Exercise Treadmill Test Responses. Circulation
115: 2917-2924
[Abstract][Full Text]
Tingley, W. G., Pawlikowska, L., Zaroff, J. G., Kim, T., Nguyen, T., Young, S. G., Vranizan, K., Kwok, P.-Y., Whooley, M. A., Conklin, B. R.
(2007). Gene-trapped mouse embryonic stem cell-derived cardiac myocytes and human genetics implicate AKAP10 in heart rhythm regulation. Proc. Natl. Acad. Sci. USA
104: 8461-8466
[Abstract][Full Text]
Leeper, N. J., Dewey, F. E., Ashley, E. A., Sandri, M., Tan, S. Y., Hadley, D., Myers, J., Froelicher, V.
(2007). Prognostic Value of Heart Rate Increase at Onset of Exercise Testing. Circulation
115: 468-474
[Abstract][Full Text]
Genovesi, S., Zaccaria, D., Rossi, E., Valsecchi, M. G., Stella, A., Stramba-Badiale, M.
(2007). Effects of exercise training on heart rate and QT interval in healthy young individuals: are there gender differences?. Europace
9: 55-60
[Abstract][Full Text]
Billman, G. E., Kukielka, M.
(2007). Effect of endurance exercise training on heart rate onset and heart rate recovery responses to submaximal exercise in animals susceptible to ventricular fibrillation. J. Appl. Physiol.
102: 231-240
[Abstract][Full Text]
Legramante, J. M., Iellamo, F., Massaro, M., Sacco, S., Galante, A.
(2007). Effects of residential exercise training on heart rate recovery in coronary artery patients. Am. J. Physiol. Heart Circ. Physiol.
292: H510-H515
[Abstract][Full Text]
Kligfield, P., Lauer, M. S.
(2006). Exercise Electrocardiogram Testing: Beyond the ST Segment. Circulation
114: 2070-2082
[Full Text]
Diller, G.-P., Dimopoulos, K., Okonko, D., Uebing, A., Broberg, C. S., Babu-Narayan, S., Bayne, S., Poole-Wilson, P. A., Sutton, R., Francis, D. P., Gatzoulis, M. A.
(2006). Heart Rate Response During Exercise Predicts Survival in Adults With Congenital Heart Disease. J Am Coll Cardiol
48: 1250-1256
[Abstract][Full Text]
Developed in Collaboration With the European Heart, , Zipes, D. P., Camm, A. J., Borggrefe, M., Buxton, A. E., Chaitman, B., Fromer, M., Gregoratos, G., Klein, G., Moss, A. J., Myerburg, R. J., Priori, S. G., Quinones, M. A., Roden, D. M., Silka, M. J., Tracy, C., Smith, S. C. Jr, Jacobs, A. K., Adams, C. D., Antman, E. M., Anderson, J. L., Hunt, S. A., Halperin, J. L., Nishimura, R., Ornato, J. P., Page, R. L., Riegel, B., Priori, S. G., Blanc, J.-J., Budaj, A., Camm, A. J., Dean, V., Deckers, J. W., Despres, C., Dickstein, K., Lekakis, J., McGregor, K., Metra, M., Morais, J., Osterspey, A., Tamargo, J. L., Zamorano, J. L.
(2006). ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death). J Am Coll Cardiol
48: e247-e346
[Full Text]
Writing Committee Members, , Zipes, D. P., Camm, A. J., Borggrefe, M., Buxton, A. E., Chaitman, B., Fromer, M., Gregoratos, G., Klein, G., Moss, A. J., Myerburg, R. J., Priori, S. G., Quinones, M. A., Roden, D. M., Silka, M. J., Tracy, C., ESC Committee for Practice Guidelines, , Priori, S. G., Blanc, J.-J., Budaj, A., Camm, A. J., Dean, V., Deckers, J. W., Despres, C., Dickstein, K., Lekakis, J., McGregor, K., Metra, M., Morais, J., Osterspey, A., Tamargo, J. L., Zamorano, J. L., ACC/AHA Task Force Members, , Smith, S. C. Jr, Jacobs, A. K., Adams, C. D., Antman, E. M., Anderson, J. L., Hunt, S. A., Halperin, J. L., Nishimura, R., Ornato, J. P., Page, R. L., Riegel, B.
(2006). ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: A report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death) Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Europace
8: 746-837
[Full Text]
Kizilbash, M. A., Carnethon, M. R., Chan, C., Jacobs, D. R., Sidney, S., Liu, K.
(2006). The temporal relationship between heart rate recovery immediately after exercise and the metabolic syndrome: the CARDIA study. Eur Heart J
27: 1592-1596
[Abstract][Full Text]
Billman, G. E.
(2006). Heart rate response to onset of exercise: evidence for enhanced cardiac sympathetic activity in animals susceptible to ventricular fibrillation. Am. J. Physiol. Heart Circ. Physiol.
291: H429-H435
[Abstract][Full Text]
Hautala, A. J., Rankinen, T., Kiviniemi, A. M., Makikallio, T. H., Huikuri, H. V., Bouchard, C., Tulppo, M. P.
(2006). Heart rate recovery after maximal exercise is associated with acetylcholine receptor M2 (CHRM2) gene polymorphism. Am. J. Physiol. Heart Circ. Physiol.
291: H459-H466
[Abstract][Full Text]
Goldberger, J. J., Le, F. K., Lahiri, M., Kannankeril, P. J., Ng, J., Kadish, A. H.
(2006). Assessment of parasympathetic reactivation after exercise. Am. J. Physiol. Heart Circ. Physiol.
290: H2446-H2452
[Abstract][Full Text]
Jankowska, E. A., Ponikowski, P., Piepoli, M. F., Banasiak, W., Anker, S. D., Poole-Wilson, P. A.
(2006). Autonomic imbalance and immune activation in chronic heart failure - Pathophysiological links. Cardiovasc Res
70: 434-445
[Abstract][Full Text]
Jae, S. Y., Fernhall, B., Heffernan, K. S., Kang, M., Lee, M.-K., Choi, Y.-H., Park, W. H.
(2006). Chronotropic response to exercise testing is associated with carotid atherosclerosis in healthy middle-aged men. Eur Heart J
27: 954-959
[Abstract][Full Text]
De Sutter, J., Van de Veire, N., Elegeert, I.
(2006). Chronotropic incompetence: are the carotid arteries to blame?. Eur Heart J
27: 897-898
[Full Text]
Stecker, E. C., Vickers, C., Waltz, J., Socoteanu, C., John, B. T., Mariani, R., McAnulty, J. H., Gunson, K., Jui, J., Chugh, S. S.
(2006). Population-Based Analysis of Sudden Cardiac Death With and Without Left Ventricular Systolic Dysfunction: Two-Year Findings from the Oregon Sudden Unexpected Death Study. J Am Coll Cardiol
47: 1161-1166
[Abstract][Full Text]
Savonen, K. P., Lakka, T. A., Laukkanen, J. A., Halonen, P. M., Rauramaa, T. H., Salonen, J. T., Rauramaa, R.
(2006). Heart rate response during exercise test and cardiovascular mortality in middle-aged men. Eur Heart J
27: 582-588
[Abstract][Full Text]
Falcone, C., Buzzi, M. P., Klersy, C., Schwartz, P. J.
(2005). Rapid Heart Rate Increase at Onset of Exercise Predicts Adverse Cardiac Events in Patients With Coronary Artery Disease. Circulation
112: 1959-1964
[Abstract][Full Text]
Gehi, A., Haas, D., Fuster, V.
(2005). Primary Prophylaxis With the Implantable Cardioverter-Defibrillator: The Need for Improved Risk Stratification. JAMA
294: 958-960
[Full Text]
Bassan, M. M., Harnik, I. G., Jouven, X., Empana, J. P., Ducimetiere, P.
(2005). Heart-Rate Profile during Exercise as a Predictor of Sudden Death. NEJM
353: 734-735
[Full Text]
Malik, I.
(2005). JournalScan. Heart
91: 1118-1120
[Full Text]