Article

...establishing an association between cardiovascular risk factors and migraine could ultimately explain the relationship between migraine with aura and subsequent cardiovascular disease events...

The latest results from the Women's Health Study (WHS) suggest that women aged ≥ 45 years who experience migraines accompanied by transient neurologic symptoms (known as the "migraine aura") are at increased risk of major cardiovascular disease events, including myocardial infarction (MI), ischemic stroke, and death due to ischemic cardiovascular disease.^[1] This migraine study also found that women who experience migraine without aura (the most common form of migraine) were not at significantly increased risk for any cardiovascular event.

In the United States, the 1-year prevalence of migraine is approximately 18% in women and 6% in men, and an estimated 28 million Americans have severe and disabling migraines. Migraine, especially migraine with aura, has previously been associated with increased risk of stroke and with an unfavorable cardiovascular profile, but no firm association between migraine and coronary events has been established.

Design and Results

Tobias Kurth, MD, ScD, of Brigham and Women's Hospital and the Harvard School of Public Health (Boston, Massachusetts) and colleagues in Boston and Germany analyzed data from 27,840 WHS participants. All women enrolled in the main WHS were aged ≥ 45 years, with no history of cardiovascular disease, cancer, or other major disease at study entry (1992-1995). The women in the migraine study were also free of angina and provided self-reported information on migraine and aura status and on lipid levels.

At baseline, 5125 women (18.4%) reported a history of migraine, of whom 3610 had active migraine (migraine during the prior year) and 1434 (39.7%) reported migraine with aura symptoms. Compared with women with no migraine, women with active migraine with aura at baseline had a more unfavorable cholesterol profile and were less likely to smoke, consume alcohol, or exercise, but more likely to be using postmenopausal hormones or to have used oral contraceptives and to report a family history of MI before age 60 years.

During an average of 10 years of follow-up, there were 580 first major cardiovascular disease events, 251 ischemic strokes, 249 MIs, and 130 deaths due to ischemic cardiovascular disease, along with 514 coronary revascularizations and 408 cases of angina.

Women who reported active migraine without aura did not have significantly increased risks for any cardiovascular disease event or angina compared with women with no history of migraine. However, compared with no migraine history, women who reported active migraine with aura had risks significantly increased by:

The association between active migraine with aura and ischemic stroke, but not major cardiovascular disease, was significantly modified by age and total cholesterol levels.

Conclusions

The authors concluded that "Since migraine without aura is far more common than migraine with aura, our data demonstrate no increased risk of cardiovascular disease for the majority of migraine patients. Future research should focus on a better understanding of the relationship between migraine, aura status, and cardiovascular events." They note that "the biological links by which migraine may be associated with ischemic vascular events are likely to be complex," and they envisage "a synergistic effect between the vascular and endothelial dysfunction of migraine and factors that increase the risk of thrombotic events."

Commentary

In an editorial written to accompany the study by Kurth and colleagues,^[2] Richard B. Lipton, MD, and Marcelo E. Bigal, MD, PhD, of Albert Einstein College of Medicine and the Montefiore Headache Center (Bronx, New York), respectively, suggest that establishing an association between cardiovascular risk factors and migraine could ultimately explain the relationship between migraine with aura and subsequent cardiovascular disease events. They suggest that genetic polymorphisms may predispose to both cardiovascular risk factors and migraine with aura. "A polymorphism in the methyltetrahydrofolate reductase gene (C677T) is associated with a moderately increased homocysteine level, which, in turn, is associated with risk of cardiovascular disease." The same polymorphism has been shown to be overexpressed in migraine with aura but not migraine without aura, the authors note.^[3]

Ultimately, however, it will be important to determine whether migraine with aura is itself a modifiable risk factor for cardiovascular disease. Future studies should investigate the possibility that preventive medications for migraine or antiplatelet therapy might reduce the risk of cardiovascular disease in patients with migraine with aura. In the meantime, the conclusion appears to be that for patients with migraine with aura, clinicians should have heightened vigilance for modifiable cardiovascular risk factors, such as hypertension, hyperlipidemia, and smoking.

The Women's Health Study was supported by grants from the Donald W. Reynolds Foundation, Las Vegas, Nevada, and from the National Institutes of Health.