Stroke Risk in Women with Migraine

Women with increased cardiovascular (CV) risk who have a history of migraine headaches have over twice the long-term risk of stroke compared to similar women without migraines, according to results from the Women’s Ischemia Evaluation (WISE) study published in the American Journal of Medicine.¹

“Among women presenting with signs and symptoms of ischemia, those reporting a history of migraine headache are at increased risk of cardiovascular events at long-term follow-up. This is mainly driven by a two-fold higher risk of stroke among those with migraine,” wrote first author Cecil Rambarat, MD, of the University of Florida (Gainsville, FL), and colleagues.

“These results suggest that particular attention should be placed on higher risk women reporting a history of migraine headache for optimization of future cardiovascular risk by intensive secondary prevention,” they added.

Migraine headache may affect up to 14% of the US population. Women are at higher risk than men, with the highest prevalence among women aged 18 to 44, according to background information in the article.

Studies that have evaluated the association between migraine and CV outcomes have shown inconsistent results. Past studies have suggested that a link between migraine and CV events, if it exists, may be time-dependent, with short-term studies failing to find such a link and long-term studies suggesting a link exists.

Earlier results from the WISE study did not support an association between migraine and CV outcomes at 4.4 years of follow-up.² The current study reports long-term follow-up results.

The study included 936 women (mean age 58 years) who presented with symptoms of myocardial ischemia at four centers in the US. Researchers collected data on demographics, medical, psychosocial and migraine history, and cardiac risk factors using questionnaires. Participants also provided a blood sample and underwent coronary angiography. Follow-up on cardiovascular outcomes occurred via phone interview.

The analysis included data on migraine for 917 women, data on all-cause mortality for 936 women (median follow-up 9.5 years), and data on non-fatal CV events in 888 women (median follow-up 6.5 years). 

Results were adjusted for age, race, BMI, diabetes, hypertension, dyslipidemia, smoking, family history of coronary artery disease (CAD), CAD severity, and aspirin use.

Key Results:

• Migraine: reported by 24.4% (n=224)

• 83% increased risk of CV events with migraine vs without (adjusted HR 1.83, 1.22-2.75)

• Two-fold increase in stroke risk with migraine vs without (adjusted HR 2.33, 1.16-4.68)

• Similar all-cause mortality between the two groups (adjusted HR 1.11, 0.72-1.71)

• Women with migraine also had increased risk of myocardial infarction, heart failure hospitalization, and CV death, though the results were not significant

The authors noted that the results regarding stroke agree with research over the past four decades suggesting a history of migraine doubles the risk of ischemic stroke, in particular.

Though the mechanism underlying the association between migraine and stroke is poorly understood, they wrote that dysfunction of vascular endothelium may be involved. Other explanations include increased inflammation related to the release of pro-thrombotic and vasoactive factors, patent foramen ovale, or a genetic tendency toward vascular events.

Participants self-reported their migraine history, which may have limited the study. Also, the study lacked data on the presence or lack of aura, migraine duration, and type of stroke. Because the women in this study presented with signs of myocardial ischemia and were already at increased CV risk, the results may not apply to the general population.

 Take-home Points

• Past studies have suggested that a link between migraine and CV events may be time-dependent, with short-term studies failing to find such a link and long-term studies suggesting it exists.

• Short-term results from the WISE study failed to find a link between migraine and CV outcomes in women.

• Long-term results from the WISE study found 83% increased risk of CV outcomes in women with migraine, compared to those without.

• These results were driven mostly by a two-fold increase in stroke risk in women with migraine, vs those without.

• Women at higher CV risk who also have a history of migraine may need increased focus on secondary prevention of CV events.

The study was sponsored by the National Heart, Lung and Blood Institute.

References:

1. Rambarat CA, et al. Migraine headache and long term cardiovascular outcomes: an extended follow-up of the Women's Ischemia Syndrome Evaluation. Am J Med. 2017 Jan 18.

2. Ahmed B, et al for the WISE Study Group. Migraines, angiographic coronary artery disease and cardiovascular outcomes in women. Am J Med. 2002;119(8):670-675.