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Exploring Genetic Link Between Migraines, Cardiovascular Trouble

Suspected variant is not a player, but two genotypes might be, study finds

TUESDAY, Feb. 17 (HealthDay News) -- In a finding that speaks to the complicated connection between having migraines with aura and an increased risk of cardiovascular trouble, Harvard researchers report that a gene variant that was suspected to be a link between the conditions is not but that two genotypes could well be.

"Migraine with aura, in women in particular, is associated with about a doubling of the risk of stroke and heart attack," said Dr. Richard Lipton, director of the Montefiore Headache Center in New York City.

Research has shown a strong relationship between migraines and an increased risk for stroke, heart attack and cardiovascular disease, especially in women and especially in those also experiencing auras, or visual disturbances, right before their migraine.

Researchers believe the association might be neurovascular and have been on the prowl for genes that might explain the link.

Their theory is bolstered by the fact that both migraines and cardiovascular disease can be treated effectively with ACE inhibitors, drugs that inhibit the angiotensin-converting enzyme, which is critical to cardiovascular health.

In the Harvard study, the investigators wanted to see if the ACE D/I gene variant somehow played a role in the heightened risk of stroke and heart attacks among women who have migraines, with or without aura. The study was funded by the National Institutes of Health and appears in the Feb. 17 issue of Neurology.

The research involved 25,000 white women who were part of the Women's Health Study, including 4,577 who had migraines currently or in the past. During about a dozen years of follow-up, 625 heart attacks or strokes were reported.

As it turned out, the researchers found no association between the ACE D/I variant and migraine, with or without aura. Nor was a linkage found between the variant and cardiovascular disease, ischemic stroke (involving restricted blood supply to the brain) or heart attack.

However, in an unexpected twist, women who reported migraine with aura and had the DD or DI genotype had a doubling of their risk for cardiovascular disease.

There appeared to be no heightened risk among those women with the II genotype, the study found.

"Their issue is that maybe an angiotensin-converting enzyme polymorphism … may account for some of the association between migraine and cardiovascular disease," Lipton said. "They ruled out one [polymorphism], but it's a single polymorphism in a gene and there could be a dozen that play in that gene, and if you looked at them all, you might see an effect."

And, the authors stated, the ACE DD/DI genotype could simply be a marker for a heightened risk of cardiovascular disease in people who have migraines with aura.

A limitation of the study, Lipton added, is that the authors did not distinguish between aura and other warning features of a migraine.

A second study -- from Italian researchers and appearing in the February issue of the Journal of the American College of Cardiology -- found that those suffering from severe migraines who underwent a procedure to close a small opening in the wall separating the right and left atria or chambers of the heart saw a significant lessening of the intense headaches.

More information

Visit the National Headache Foundation for more on migraines.

SOURCES: Richard Lipton, M.D., director, Montefiore Headache Center, and professor, neurology and epidemiology, Albert Einstein College of Medicine, New York City; February 2009, Neurology

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