1. Tiukinhoy, Susan MD, MS

Article Content

Jouven X, Empana JP, Schwartz PJ, Desnos M, Courbon D, Ducimetiere P


N Engl J Med. 2005;352(19):1951-1958.



Changes in heart rate during exercise and exercise recovery are mediated by a balance between sympathetic and parasympathetic activities. Alterations in the neural control of cardiac function contribute to the risk of sudden death.



To test the hypothesis that among apparently healthy persons, sudden cardiac death is more likely to occur in the presence of abnormal heart rate profiles during exercise and exercise recovery.



Between 1967 and 1972, 5713 asymptomatic middle-aged men (age range 42-53 years) from the Paris Prospective Study I, with no known cardiovascular disease, underwent a standardized graded bicycle exercise stress test. Data on resting heart rate, peak heart rates achieved, and heart rate recovery were collected, and subgrouped into quintiles. Mortality rates were collected until January 1, 1994. The Cox-proportional hazards model was used to estimate the relative risk of death among quintiles of the heart rate variables.



During the mean follow-up of 23 years, there were 400 cardiac deaths, of which 81 were sudden cardiac deaths. One hundred twenty-nine deaths were classified as nonsudden death from a myocardial infarction (MI). The mean interval between the initial clinical examination and the event of death was 12 +/- 5 years for sudden cardiac death, and 17 +/- 6 years for nonsudden MI-related death. The risk of sudden cardiac death increased progressively with an increase in resting heart rate (P for trend <.001). There was a significant association between heart rate reserve (peak exercise heart rate minus resting heart rate) and mortality. Heart rate recoveries at 1, 2, 3, and 4 minutes were associated with all cause mortality and sudden cardiac death, but were not associated with nonsudden MI-related death. The risk of sudden cardiac death was higher among subjects with a resting heart rate of >75 bpm (RR = 3.92; 95% CI = 1.91-8.00), those whose heart rate reserve was <89 bpm (RR = 6.18; 95% CI = 2.37-16.11), and in those whose 1-minute heart rate recovery was <25 bpm (RR = 2.2; 95% CI = 1.02-4.74). Despite adjustment for potential confounding variables, these 3 factors remained strongly associated with an increased risk of sudden cardiac death. Among these 3 heart rate markers, the strongest predictor of sudden cardiac death was a low heart rate reserve.



This study, obtained from a large cohort of apparently healthy persons, indicate that heart rate profiles during exercise and exercise recovery are strong predictors of sudden cardiac death. These data support the concept that alterations in autonomic balance may precede manifestations of cardiovascular disease. The association between altered heart rate responses during exercise and sudden cardiac death, but not nonsudden MI-related death, suggest that this risk may be mediated by an increased susceptibility to cardiac arrhythmias. Heart rate profiles may be useful for the early identification of persons at high risk for sudden cardiac death.



The bicycle exercise stress test protocol used in this study was designed to achieve the maximum predicted heart rate as rapidly as possible, and was not designed to be symptom-limited. Hence, findings may not be readily applicable to clinical practice wherein symptom-limited treadmill testing is more commonly used. Furthermore, this study enrolled only men. Nevertheless, this study does add to the growing literature supporting the utility of heart rate profiles for risk stratification for cardiac mortality. The incorporation of exercise variables such as exercise capacity and heart rate profiles into our evaluation of a patient's cardiac risk is long overdue. Whether exercise intervention among apparently healthy persons identified to be at high risk for sudden cardiac death using these heart rate parameters results in a reduction of this risk, however, is not known.