Slight Increased Risk of Premature Myocardial Infarction and Hemorrhagic Stroke Observed in Women With Migraine

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In a large-scale, nationwide cohort, the impact of migraine on risk of premature myocardial infarction was slightly greater for women and may potentially only exist for women.

Cecilia Fuglsang, a PhD student in the Department of Clinical Epidemiology at Aarhus University

Cecilia Fuglsang

A recently published study using Danish medical registries showed identified an increased risk of ischemic stroke in persons with migraine compared with the general population that was similar for men and women. For premature myocardial infarction (MI) and hemorrhagic stroke, findings indicated an increased risk associated with migraine only among women.1

Conducted from 1996 to 2018, the analysis featured 179,680 women with migraine and 40,757 men with migraine who were matched on sex, index year, and birth year 1:5 to a random sample of the general population who did not use migraine-specific medications. At the conclusion of the analysis, the risk difference (RD) of premature MI for those with migraine vs those without was 0.3% (95% CI, 0.2-0.4; P <.001) for women and 0.3% (95% CI, –0.1 to 0.6; P = .061) for men, with adjusted HRs of 1.22 (95% CI, 1.14-1.31; P <.001) and 1.07 (95% CI, 0.97-1.17; P <.001) for the respective sexes.

Led by Cecilia Fuglsang, a PhD student in the Department of Clinical Epidemiology at Aarhus University, the aim of the study was to examine the impact of migraine on the risk of premature (age ≤60 years) MI and ischemic/hemorrhagic stroke among men and women. All men and women aged 18 to 60 years with at least 2 redeemed prescriptions for migraine medication were included in 1 of the 2 sex-specific migraine cohorts. Compared with migraine-free individuals of the same sex, a larger proportion of patients with migraine had redeemed prescriptions for beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin II antagonists, diuretics, platelet inhibitors, and nonsteroidal antidepressants.

After following the cohorts for a median of 8.8 years (IQR, 4.3-4.4), findings showed a RD of 0.5% (95% CI, 0.1-0.8; P <.001) and 0.3% (95% CI, 0.2-0.4) for men and women, respectively, for the outcome of premature ischemic stroke. For premature hemorrhagic stroke as the outcome, the RD was –0.1% (95% CI, –0.3 to 0.0%; P = .176) for men and 0.1% (95% CI, 0.0-0.2; P = .011) for women.

"The reason for the association between migraine and cardiovascular disease remains unclear, although several explanations have been suggested," Fuglsang at al wrote.1 "The cortical spreading depressions associated with migraine with aura could dispose to ischemia of the brain. Migraine also has been associated with increased prevalence of patent foramen ovale and increased levels of von Willebrand factor, which might contribute to increased risk of ischemic stroke. A possible association between migraine and coronary vasospasms has been suggested, leading to the theory that migraine may be a generalized disorder affecting vascular tone both of the brain and the coronary arteries."

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When comparing migraine vs nonmigraine, the adjusted HR for premature ischemic stroke was 1.23 (95% CI, 1.10-1.38; P <.001) for men and 1.21 (95% CI, 1.13-1.30; P <.001) for women. Women continued to show slightly greater risk for premature hemorrhagic stroke, as indicated by adjusted HRs of 1.13 (95% CI, 1.02-1.24; P = .014) vs adjusted HRs of 0.85 (95% CI, 0.69-1.05; P = .131) for men.

The study was limited by the potential for misclassification of migraine. In addition, investigators noted that the cohorts would presumably represent a broader spectrum of individuals with migraine compared with those with a hospital diagnosis who were captured in the DNPR. The prescription data used also did not allow to differentiate patients with and without aura.

Nielsen et al conducted sensitivity analyses that defined migraine by International Classification Diagnostic codes rather than by redeemed medications. Among 25,274 women with migraine and 7397 men with migraine, findings on the outcome of MI or ischemic stroke yielded similar results to the main analysis, albeit that the impact of migraine appeared greater for both women and men. For premature hemorrhagic stroke, the RD comparing migraine vs no migraine was –0.1% (95% CI, –0.6 to 0.4%; P = .403) for men and 0.3% (95% CI, 0.0-0.7; P = .011) for women, resulting in adjusted HRs of 1.16 (95% CI, 0.73-1.83; P = .534) and 1.40 (95% CI, 1.07-1.84; P =.015), respectively.

REFERENCE
1. Fuglsang CH, Pedersen L, Schmidt M, Vandenbroucke JP, Botker HE, Sorensen HT. Migraine and risk of premature myocardial infarction and stroke among men and women: a Danish population-based cohort study. Published online June 13, 2023. doi:10.1371/journal.pmed.1004238
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