Boston, MA - Women who experience migraines with aura have an increased risk of cardiovascular events, a new study suggests [1]. But migraine without aura (the most common type) was not associated with increased risk.

The study, published in the July 19, 2006 issue of the Journal of the American Medical Association, was conducted by a group led by Dr Tobias Kurth (Brigham and Women's Hospital, Boston, MA). They note that migraine is a neurovascular disorder and that several studies have found associations between migraine, especially migraine with aura, and increased risk of ischemic stroke. They suggest that the vascular dysfunction of migraine may also extend to coronary arteries, and it is plausible that migraine, and especially migraine with aura, may be associated with other vascular events, not just ischemic stroke.

Kurth et al evaluated the association between migraine and subsequent risk of cardiovascular events in 27 840 US women aged 45 years or older who were participating in the Women's Health Study. All women were free of cardiovascular disease and angina at study entry (1992-1995), and information was available on self-reported migraine and aura status and lipid measurements.

At baseline, 5125 women (18.4%) reported a history of migraine; of the 3610 with active migraine (migraine in the prior year), 1434 (39.7%) had aura symptoms. During an average of 10 years of follow-up, 580 major cardiovascular events occurred.

Results showed that any history of migraine was associated with an increased risk of cardiovascular events. But this increased risk differed according to aura status. Compared with no migraine history, women who reported active migraine with aura had a significantly increased risk of subsequent major cardiovascular events, which remained after adjustment for a large number of cardiovascular risk factors. After adjustment for age, there were 18 additional major cardiovascular events attributable to migraine with aura per 10 000 women per year. In contrast, women who reported active migraine without aura did not have significantly increased risk for any ischemic vascular event.

Age- and multivariable-adjusted hazard ratios for cardiovascular events in women with active migraine compared with those with no migraine history

The researchers note that in the US, the one-year prevalence of migraine is approximately 18% in women and 6% in men; an estimated 28 million Americans have severe and disabling migraine.

They say that the biological links by which migraine may be associated with ischemic vascular events are likely to be complex and the precise mechanisms are currently unknown, but migraine has been associated with increases in prothrombotic or vasoactive factors. They also note that migraine with aura has been associated with a particular genotype linked to increased homocysteine levels. "Thus, a synergistic effect between the vascular and endothelial dysfunction of migraine and factors that increase the risk of thrombotic events can be envisioned."

But they also point out that migraine with aura has been associated with a more detrimental cardiovascular risk profile, including elevated cholesterol levels, higher blood pressure, and higher likelihood of hypertension. "Thus, it is possible that migraine with aura may be a characteristic that identifies women at increased risk of progressive atherosclerosis and subsequent vascular events."

In an accompanying editorial, Drs Richard Lipton and Marcelo Bigal, (Albert Einstein College of Medicine, New York, NY) note that while migraine with aura is well established as a risk factor for ischemic stroke, the relationship of migraine and ischemic cardiac disease has been less clear [2]. "But the study by Kurth and colleagues changes this landscape," they add.

They point out that most migraine patients have migraine without aura and therefore are not at increased risk of cardiovascular disease and can be reassured by the current data. But for patients with migraine with aura, clinicians should have heightened vigilance for modifiable cardiovascular risk factors, such as hypertension, hyperlipidemia, and smoking.

They call for further studies in men and in younger age groups of women and add that it will be important to determine whether migraine with aura is itself a modifiable risk factor for cardiovascular disease—that is, whether preventive medications for migraine or antiplatelet therapy might reduce the risk of cardiovascular disease in these individuals.