Cigarette smoking and stroke in a cohort of U.S. male physicians.

To examine the association between cigarette smoking and the risk for stroke in men. Prospective cohort study. Participants in the Physicians' Health Study, a randomized trial of aspirin and beta-carotene among U.S. male physicians. 22,071 men, 40 to 84 years of age at entry, free from self-reported myocardial infarction, stroke, and transient ischemic attack; followed for an average of 9.7 years; and classified as never-smokers, current smokers, and former smokers based on self-report. Incidence rates of total, ischemic, and hemorrhagic stroke. With never-smokers as the reference group (relative risk, 1.00), relative risks (adjusted for age and treatment assignment) for total nonfatal stroke (n = 312) were as follows: former smoking, 1.20 (95% CI, 0.94 to 1.53); currently smoking fewer than 20 cigarettes daily, 2.02 (CI, 1.23 to 3.31); and currently smoking 20 or more cigarettes daily, 2.52 (CI, 1.75 to 3.61) (P for trend, < 0.0001). For participants who had total fatal stroke (n = 28), the risk for stroke was not increased with smoking (P > 0.2). In proportional-hazards models that controlled simultaneously for other risk factors, these associations were not materially altered. Current but not former cigarette smoking was significantly associated with an increased risk for stroke in men. Smoking may account for a substantial amount of stroke-associated morbidity and mortality.