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William Whang, MD, MS; JoAnn E. Manson, MD, DrPH; Frank B. Hu, MD, PhD; Claudia U. Chae, MD, MPH; Kathryn M. Rexrode, MD, MPH; Walter C. Willett, MD, DrPH; Meir J. Stampfer, MD, DrPH; Christine M. Albert, MD, MPH

JAMA. 2006;295:1399-1403.

Context  Exercise is associated with a lower risk of cardiovascular events but may transiently increase the risk of ventricular arrhythmias. Its short-term and long-term associations with risk of sudden cardiac death among women are unclear.

Objectives  To compare the risk of sudden cardiac death in women during moderate to vigorous exertion with the risk of sudden cardiac death during lighter or no exertion; and to assess the long-term association between moderate to vigorous exercise and sudden cardiac death.

Design, Setting, and Participants  Prospective, nested case-crossover study of 288 cases of sudden cardiac death within the Nurses' Health Study (1980-2004); and a prospective cohort analysis of 69 693 participants without prior cardiovascular disease followed up from 1986-2004.

Main Outcome Measure  Risk of sudden cardiac death associated with moderate to vigorous exertion.

Results  The absolute risk of sudden cardiac death associated with moderate to vigorous exertion was exceedingly low at 1 per 36.5 million hours of exertion. In case-crossover analyses, the risk of sudden cardiac death was transiently elevated during moderate to vigorous exertion (relative risk [RR], 2.38; 95% confidence interval [CI], 1.23-4.60; P = .01) compared with the risk during lesser or no exertion. Habitual moderate to vigorous exertion modified this transient risk (P = .005 for interaction) and the risk was no longer significantly elevated among those who exercised 2 or more hours per week. In the cohort analyses, an increasing amount of moderate to vigorous exercise was associated with a lower long-term risk of sudden cardiac death in age-adjusted and multivariable models that excluded biological intermediates (P = .006 for trend). This relationship was attenuated when biological intermediates were included (P = .06 for trend); however, the reduction in risk remained significant among women who exercised 4 or more hours per week (adjusted RR, 0.41; 95% CI, 0.20-0.83; P = .01) compared with women who did not exercise.

Conclusions  These prospective data suggest that sudden cardiac death during exertion is an extremely rare event in women. Regular exercise may significantly minimize this small transient risk and may lower the overall long-term risk of sudden cardiac death.

Author Affiliations: Cardiovascular Division, Massachusetts General Hospital, Boston (Drs Whang, Chae, and Albert); Channing Laboratory and the Department of Medicine, Harvard Medical School (Drs Manson, Hu, Willett, and Stampfer), Division of Preventive Medicine (Drs Manson, Chae, Rexrode, Stampfer, and Albert), and Center for Arrhythmia Prevention, Division of Preventive Medicine and Cardiovascular Division (Dr Albert), Brigham and Women's Hospital; and the Departments of Epidemiology (Drs Manson, Hu, Willett, and Stampfer) and Nutrition (Drs Willett and Stampfer), Harvard School of Public Health.

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