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Julie E. Buring, ScD; Patricia Hebert, PhD; Jorge Romero, MD; Ann Kittross; Nancy, ScD; JoAnn Manson, MD; Richard Peto, FRS; Charles Hennekens, MD

Arch Neurol. 1995;52(2):129-134.

Abstract
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 betacarotene 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.

Author Affiliations
From the Divisions of Preventive Medicine (Drs Buring, Hebert, Cook, Manson, and Hennekens and Ms Kittross) and Neurology (Dr Romero), Department of Medicine, and the Department of Ambulatory Care and Prevention (Drs Buring, Cook, and Hennekens), Brigham and Women's Hospital, Harvard Medical School, Boston, Mass; and the Clinical Trial Service Unit and Nuffield Department of Clinical Medicine, University of Oxford (England) (Mr Peto).

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