Pauline Anderson

July 03, 2014

LOS ANGELES — Women who suffer migraines are 1.52 times more likely to have cardiovascular disease than those without migraine, and they are also more likely to have a stroke or heart attack and to die of cardiovascular disease, new research shows.

"The results of this large, prospective study indicate a consistent link between migraine and cardiovascular disease," said Anke Winter, MD, a clinical epidemiologist and assistant professor, Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri. "Migraine should be considered a risk factor for increased risk of cardiovascular disease, including cardiovascular disease mortality in women."

Dr. Winter presented the new results here at the American Headache Society (AHS) 56th Annual Scientific Meeting.

Nurses Health Study

The study included participants in the Nurses' Health Study, an ongoing prospective cohort study of female registered nurses in the United States. The study was launched in 1989, when the nurses were between 25 and 42 years old.

Through self-administered questionnaires at baseline, researchers collected information on reproductive and lifestyle factors and medical history. They updated the information every 2 years. Response rates have been excellent: up to 90%.

In the baseline questionnaire in 1989, and in 2 subsequence questionnaires in 1991 and 1993, women were asked to report whether they had been diagnosed with migraine by a physician.

Every 2 years, women reported any incidence cardiovascular disease, with this self-report information being confirmed through medical record review by physicians. (The exception was the secondary outcome of angina/coronary revascularization procedure, for which there was no confirmation through medical records.)

The analysis included follow-up information until June 2011. The study included 115,541 women who were free of angina and any symptomatic cardiovascular disease at baseline.

The primary outcome measure was total cardiovascular disease, a combined endpoint of fatal and nonfatal stroke and myocardial infarction (MI). Secondary outcomes included MI, stroke (all subtypes), angina and coronary revascularization procedures (percutaneous transluminal coronary angioplasty or coronary artery bypass grafting surgery), and cardiovascular disease mortality.

Researchers adjusted for age, elevated cholesterol, diabetes, hypertension, body mass index, smoking, alcohol consumption, physical activity, menopause status, postmenopausal hormone use, oral contraceptive use, family history of MI, and aspirin use.

At baseline, migraine prevalence was 15.2% (17,531 women). An additional 3345 women reported newly diagnosed migraine on subsequent questionnaires, providing an overall migraine prevalence of 18%. The mean age was 35.1 years in the migraine group and 34.2 years in the no-migraine group

During the more than 20 years of follow-up, there were 1329 cardiovascular disease events (678 MIs and 651 strokes). There were also 203 angina/coronary revascularization procedures and 209 deaths resulting from cardiovascular disease.

Risk Profile

In general, women who reported a physician diagnosis of migraine had a more unfavorable cardiovascular disease risk profile. For example, they were more likely to have a body mass index of 30 kg/m2 or more (13.9% vs 10.9%), have a history of hypertension (8.9% vs 5.1%) and hypercholesterolemia (8.9% vs 5.1%), be current smokers (15.0% vs 13.2%), use postmenopausal hormones (6.1% vs 3.3%), and have family history of MI (17.5% vs 14.3%).

Women who reported migraine had a statistically significant multivariable adjusted risk of developing total cardiovascular disease (hazard ratio, 1.52; 95% confidence interval [CI], 1.36 - 1.71) compared with women with no migraine.

The researchers also consistently found that women were at increased risk of developing secondary cardiovascular disease outcomes: MI: HR, 1.42 (95% CI, 1.20 - 1.68); stroke: HR, 1.65 (95% CI, 1.40 - 1.95); angina/revascularization: HR, 1.75 (95% CI, 1.30 - 2.34); and cardiovascular disease mortality: HR, 1.43 (95% CI, 1.06 - 1.93).

Possible mechanisms linking migraine and cardiovascular disease have been debated in the literature, said Dr. Winter. These include endovascular function, increased thrombogenic susceptibility, increased prevalence of vascular risk factors, and shared genetic markers.

"Migraine could also be a systemic disorder which affects the vascular system," said Dr. Winter.

Future targeted research is needed to identify mechanisms that could explain the increased cardiovascular disease risk in patients at increased risk, as well as possible prevention strategies, said Dr. Winter.

The study had several limitations, one being that the physician diagnosis of migraine was self-reported, possibly leading to misclassifications. "However, our migraine prevalence is comparable to other population-based studies which applied [International Classification of Headache Disorders] diagnostic criteria," noted Dr. Winter.

Researchers had no information on migraine aura status. "That would have been interesting, particularly in the context of [cardiovascular disease]," Dr. Winter acknowledged.

It was also "unfortunate" that there was no information available on frequency or severity of migraines. "Every study has its trade-offs," said Dr. Winter.

Because of the observational nature of data, residual confounding was possible. In addition, as the study consisted predominantly of white nurses, it may not be generalizable to other populations

Not Very Useful

Asked to comment on this research, Peter Goadsby, MD, PhD, director, Headache Center, University of California, San Francisco, said the new information "is not very useful" in confirming a link between migraine and cardiovascular disease.

"It has been shown that migraine with aura carries a risk for stroke, while migraine without aura does not," said Dr. Goadsby. "Not being able to dissect the 2 apart here may simply lead to making all migraine sufferers concerned, when all the data generally points to migraine with aura for vascular issues."

In speculating what might be the most logical biological explanation for a possible link between migraine and cardiovascular disease, Dr. Goadsby said the association will likely ultimately be shown to be driven by migraine with aura.

The authors have disclosed no relevant financial relationships.

American Headache Society (AHS) 56th Annual Scientific Meeting. Presented Friday June 27, 2014.

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