For Both Sexes, Migraine and Heart Intertwined

BOSTON, April 24 -- Even though men are much less likely to suffer from migraine than are women, both genders have the same elevated heart disease risk, researchers here found.

In the Physicians' Health Study, men with migraine were 24% more likely to develop cardiovascular disease and 42% more likely to have a heart attack than those without migraine, reported Tobias Kurth, M.D., Sc.D., of Brigham and Women's Hospital here, and colleagues, in the April 23 issue of the Archives of Internal Medicine.

The findings meshed with those of the migraine-heart disease link for women already established by the Women's Health Study.

The Physicians' Health Study, designed to test aspirin and beta-carotene in the primary prevention of cardiovascular disease and cancer, included 20,084 men ages 40 to 84 without preexisting cardiovascular disease. Yearly questionnaires completed included cardiovascular disease events and migraine.

The 1,449 men (7.2%) who reported having migraine in the first five years of the study were classified as migraineurs, though no data was available on the presence of aura. Among them, 434 reported frequent migraine, defined as four or more events during that period.

Over the subsequent 15.7 years of follow-up, there were 2,236 first occurrences of major cardiovascular disease events-- nonfatal ischemic stroke, nonfatal myocardial infarction, or death from ischemic cardiovascular disease There were 2,257 coronary revascularizations, and 2,625 angina cases reported.

For men with migraine versus those without migraine, the multivariate adjusted findings were:

• Significantly elevated risk of the primary endpoint, major cardiovascular disease events (hazard ratio 1.24, 95% confidence interval 1.06 to 1.46, P=0.008).
• Significantly elevated risk of myocardial infarction (HR 1.42, 95% CI 1.15 to 1.77, P

For women with any history of migraine versus none, there was a multivariable-adjusted hazard ratio of 1.42 for major cardiovascular disease events, 1.41 for myocardial infarction, and 1.22 for ischemic stroke.

However, women with migraine had significantly increased risk of coronary revascularization, angina, and cardiovascular death whereas the same was not true for men in the Physicians' Health Study.

These differences and the lack of a link between cardiovascular risk and migraine in an earlier analysis of the Physicians' Health Study may be explained by the lower prevalence of migraine among men, the researchers said. The prevalence of migraine among women in the United States is 18% compared with 6% among men.

For both sexes, several complex mechanisms are likely at work. One may be progressive atherosclerosis, though "the increased risk of vascular events remained after controlling for major cardiovascular risk factors in the present data and other studies," Dr. Kurth and colleagues wrote.

The authors pointed out that as an observational study, the presence of unknown confounders could not be eliminated. In addition several other limitations of the study were noted:

• "We had no information about the use of migraine specific drugs (ie, triptans and ergot alkaloids), which owing to their vasoconstrictive ability may be associated with increased risk of ischemic vascular events."

• "The Physicians' Health Study was composed of middle-aged and mostly white physicians; thus, generalizability may be limited."

Other researchers reported conflicts of interest from the National Institutes of Health, BASF, DSMPharmaceuticals, Wyeth Pharmaceuticals, McNeil Consumer Products, Pliva, Bayer, Merck, Nutraquest, GlaxoSmithKline, Pfizer, Roche Molecular Systems, Lilly Pharmaceutical, the German Research Foundation, Allergan, Almirall, AstraZeneca, Janssen-Cilag, Berlin Chemie, Boehringer Ingelheim, Bristol-Meyers Squibb, Grnenthal, 3M Medica, MSD, Novartis, Johnson & Johnson, Pierre Fabre, Schaper & Brmmer, Sanofi-Aventis, Weber & Weber, DowCorning Corporation, the Natural Source Vitamin E Association, and Procter & Gamble.