Migraine and subsequent risk of stroke in the Physicians' Health Study

J. E. Buring, P. Hebert, J. Romero, A. Kittross, N. Cook, J. Manson, R. Peto and C. Hennekens
Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.

OBJECTIVE: To evaluate, in a prospective design, whether migraine is an independent risk factor for subsequent stroke. DESIGN: Evaluated as part of the Physicians' Health Study, a randomized, double-blind, placebo-controlled trial of aspirin and beta-carotene in the primary prevention of cardiovascular disease and cancer begun in 1982. The aspirin component of the study was terminated in 1988, with average follow-up of 60.2 months. SETTING: Conducted by mail among male physicians throughout the United States. PARTICIPANTS: A total of 22,071 US male physicians aged 40 to 84 years in 1982 with no prior history of cancer or cardiovascular diseases who were enrolled in the Physicians' Health Study. INTERVENTIONS: Participants were randomized to receive 325 mg of aspirin or aspirin placebo every other day and to receive 50 mg of beta-carotene or placebo on alternate days. MAIN OUTCOME MEASURES: The primary outcomes of the Physicians' Health Study were cardiovascular disease and cancer. Because stroke was a main outcome, this provided the opportunity to evaluate the association between migraine headaches and stroke. RESULTS: Physicians reporting migraine (n = 1479) had significantly increased risks of subsequent total stroke and ischemic stroke compared with those not reporting migraine. After adjustment for age, aspirin and beta-carotene treatment assignment, and a number of cardiovascular risk factors, the relative risks were 1.84 (95% confidence interval, 1.06 to 3.20) for total stroke and 2.00 (95% confidence interval, 1.10 to 3.64) for ischemic stroke. There were too few hemorrhagic strokes in the study to evaluate this end point. No associations were seen between ordinary nonmigraine headache and subsequent stroke or between migraine and subsequent myocardial infarction or cardiovascular death. CONCLUSION: These data raise the possibility that vascular events associated with migraine may also have causative importance in stroke but require confirmation in other studies specifically designed to evaluate this question.