Can Headaches Put the Heart at Risk? Yes, for Patients with Migraine with Aura

Abstracts & Commentary

By Dara G. Jamieson, MD, Associate Professor, Clinical Neurology, Weill Medical College, Cornell University. Dr. Jamieson is a consultant for Boehringer Ingelheim and Merck, and is on the speaker's bureau for Boehringer Ingelheim, Merck, Ortho-McNeil, and Pfizer.

Synopsis: Active migraine with aura increases risk of myocardial infarction, coronary revascularization, and angina, as well as ischemic stroke. Active migraine without aura and non-migraine headaches are not associated with increased vascular risk.

Sources: Kurth T, et al. Migraine and Risk of Cardiovascular Disease in Women. JAMA. 2006;296:283-291. Erratum in: JAMA. 2006;296:332-333, 654; Lipton RB, Bigal ME. Migraine and Cardiovascular Disease. JAMA. 2006;296:332-333.

About one in 3 adults have some form of cardiovascular or cerebrovascular disease, and over 28 million Americans have severe and disabling migraine headaches. These common diseases are linked by more than just coincidental overlap. Migraine with aura is associated with an increased risk of ischemic stroke. The relationship between migraine and cardiovascular disease, however, is less well understood. In this report, data from the Women's Heart Study (WHS) was analyzed for correlation between migraine of different types and vascular events.

The WHS was a randomized, placebo controlled trial designed to test the benefits and risks of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease (CVD) in healthy women. Health care professionals older than 45 years at entry into the study (1992-1994) were randomized to treatment and were followed by questionnaire till the end of March 2004. The primary outcome measurement of this prospective cohort study of women participating in the WHS was the combined endpoint of major CVD (first non-fatal ischemic stroke, first non-fatal myocardial infarct, or death due to ischemic CVD). Of 27,840 women initially free of cardiovascular disease or angina, 18% reported any history of migraine. From the 3610 women with active migraine, 39.7% reported migraine with aura. As compared to women without any migraine history, these women with aura had higher cholesterol and were less likely to drink any alcohol or exercise. They were more likely to use or have used oral contraception or hormone replacement therapy, but they also were less likely to smoke. The women with a prior history of migraine were older (mean age 55.5 years) and had more vascular risk factors than women with active migraine (mean age 53.2 years, with aura; 52.6 years, without aura).

During a mean of 10 years of follow-up there were 251 ischemic strokes, 249 myocardial infarctions, and 130 ischemic CVD deaths in the total cohort. The age and multivariable-adjusted associations between migraine status and vascular events were calculated. Compared with women with no migraine history, women who reported either an active or a prior history of migraine were at increased risk of ischemic events, except for ischemic stroke. The most striking risk was for women with active migraine with aura. After adjusting for age, there were 18 additional major CVD events attributable to migraine with aura per 10,000 women per year. As compared with women with no migraine history, the hazard ratios (HRs) were 2.15 (95% confidence interval, 1.58-2.92; P <.001) for major CVD, 1.91 (95% CI, 1.17-3.10; P =.01) for ischemic stroke, and 2.08 (95% confidence interval, 1.30-3.31; P = .002) for myocardial infarction. Women with migraine with aura also had an increased risk of myocardial revascularization, angina, and CVD death. Increased risk was noted after approximately 6 years of follow-up. Women with active migraine without aura did not have any significantly increased risk of any CVD event or angina compared with women without any migraine history. Women who reported prior migraine had significantly increased risk of coronary revascularization and angina. The highest association between active migraine with aura and ischemic stroke was in women younger than age 50 and women with total cholesterol < 200 mg/dL. In contrast, the association between active migraine with aura and myocardial infarction was not modified by age or cholesterol level. The association between migraine with aura and major CVD, ischemic stroke, and myocardial infarction was not statistically significantly modified by vascular risk factors. No significant association was found between non-migraine headaches and any CVD events.

Commentary

This study confirms that women with migraine with aura have a greater risk of cardiovascular, as well as cerebrovascular disease. Increased vascular risk remained even after controlling for the increase in risk factors seen in women with migraine with aura. The precise mechanisms to explain the link are currently unknown. Increases in prothrombotic and vasoactive factors are associated with migraine, but other migraine associations, including congenital heart disease, do not correlate with coronary artery disease. The authors of the accompanying editorial (Lipton, et al.) point out that the observations need to be evaluated in men and younger women with migraine. They suggest study of the role of migraine preventative medications or antiplatelet therapy in reducing vascular risk.

Since migraine without aura is far more common than migraine with aura, the majority of migraine patients are not at increased vascular risk. However women who have migraine with aura have increased risk of vascular events, including coronary heart disease and stroke, and should be screened for risk factors. This risk should be considered when counseling patients and selecting drugs for both acute and preventative treatment of migraine headaches.