PHILADELPHIA — Migraine with or without aura was associated with a significant increase in the risk of cardiovascular disease, including stroke and heart attack, in a population-based study that included more than 6,000 U.S. adults with migraine.
In another study that also was presented at the International Headache Congress, migraine with aura was associated with an increased risk of cardiovascular death in a large cohort of adults in Iceland.
One of the authors of the U.S. study, Dr. Marcelo E. Bigal, noted that many studies have hinted at an association between migraine with aura and cardiovascular events. But the study that he performed with his colleague, Dr. Richard Lipton, was the first to examine the association in a large national sample in which migraine, with and without aura, was diagnosed using accepted criteria.
Dr. Bigal of Merck Research Laboratories, Whitehouse Station, N.J., and Dr. Lipton of Albert Einstein College of Medicine, New York, used data from the American Migraine Prevalence and Progression Study. It was the largest migraine study ever conducted, based on a sample of 162,576 Americans aged 12 years and older.
The cardiovascular substudy included data on 6,102 adults with migraine and 5,243 controls. Migraineurs were significantly more likely than controls to have diabetes (13% vs. 9%, respectively), hypertension (33% vs. 26%), and hypercholesterolemia (33% vs. 26%). Framingham risk scores also were significantly higher for migraine overall and for migraine with and without aura (mean 11) than for controls (mean 9).
Myocardial infarction occurred in 2% of controls and 4% of migraineurs, which yielded an unadjusted odds ratio of 2.2. Stroke occurred in 1.2% of the controls and 2% of the migraineurs—a significant 60% increased risk. Rates of stroke were higher in those who had migraine with aura (4%) than without aura (1%).
The findings remained significant after adjustment for gender, age, disability, triptan use, diabetes, smoking, hypertension, and high cholesterol. Overall, migraineurs were twice as likely as controls to have had a heart attack and were 50% more likely to have had a stroke. Migraineurs with aura were three times more likely than controls to have had either of those outcomes. Migraineurs without aura were twice as likely as controls to have had a heart attack, but they had no increased risk of stroke.
The findings may help physicians “to properly identify individuals at particularly high risk, as well as to plan treatment that targets not only migraine, but the complications potentially associated with it,” Dr. Bigal said at the meeting, sponsored by the International Headache Society and the American Headache Society.
In the Iceland study, men and women who had a history of migraine with aura were significantly more likely to die from cardiovascular disease than were those without such a history. Women with nonmigraine headache also were significantly more likely to die from cardiovascular disease than were women without headache, but that hazard ratio was smaller, Dr. Larus S. Gudmundsson reported in a poster.
Dr. Gudmundsson of the University of Iceland, Reykjavik, and his colleagues used data from the Reykjavik Study, a population-based cohort of adults followed from middle age, representing 474,360 person-years of observation. The cohort comprised 18,882 adults who were a mean of 53 years old at baseline. Baseline interviews took place between 1967 and 1991.
The researchers divided the cohort into four categories: those without a headache once or more per month, those with nonmigraine headache, those with migraine without aura, and those with migraine and aura (visual, sensory, or both). Individuals with nonaura headache symptoms, including nausea, unilateral location, and photophobia, were categorized as having “migraine without aura.”
After entering the study, the subjects were followed for up to 40 years (mean follow-up 26 years). Statistics on those who died during that time were obtained from the Icelandic government and hospital records. Cox regression analysis was used to control for age, body mass index, smoking, blood pressure, hypertension medication, oral contraceptive use, diabetes, and lipid levels.
Both men and women with migraine and aura were at a significantly increased risk for all-cause mortality, compared with adults without headache (20%). The hazard ratio for cardiovascular death was 1.38 among men with migraine and aura and 1.18 among women with migraine and aura. Adults who had migraine without aura did not have an increased risk of cardiovascular death, compared with those without headache.
Women with nonmigraine headaches were at a slightly—yet still statistically significant—elevated risk of cardiovascular mortality, compared with women without headache (HR 1.14). Men with nonmigraine headache did not have a significant increase in this risk.
The authors noted that the increased risk of death was not as great as risks conferred by other common factors. “The risk is relatively low when compared with conventional risk factors such as hypertension, high cholesterol, and smoking,” they said.
Dr. Bigal is an employee of Merck Research Laboratories. Dr. Lipton has received research grants and honoraria from Merck and serves on its advisory board. Conflict of interest disclosures were not available for Dr. Gudmundsson.
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