Migraine and Stroke Risk in Postmenopausal Women in the Women's Health Initiative

BACKGROUND AND OBJECTIVES: Migraine is a known risk factor for stroke in women of reproductive age, although its relationship with stroke among postmenopausal women remains unclear. We assessed the association between migraine history and incident stroke in a sample of postmenopausal women. METHODS: We included women enrolled in the Women's Health Initiative, a large US longitudinal cohort study of postmenopausal women, and excluded those with previous stroke or those with missing data on key variables. The primary exposure was self-reported, physician-diagnosed migraine at baseline, and the primary outcome was incident stroke (total, ischemic, or hemorrhagic). Multivariable Cox proportional hazards models were used to test the cause-specific hazard ratios (HRs) between migraine history and total, ischemic (overall and by subtype), and hemorrhagic stroke, sequentially adjusted for age, traditional cardiovascular risk factors, and female-specific risk factors (age at menopause, age at menarche, menstrual irregularity, presence of vasomotor symptoms, parity, breastfeeding, and use of menopausal hormone therapy). We then quantified the association between a history of migraine and total stroke by age at baseline (in 5-year age groups) using multivariable models. Data on the presence of aura and migraine frequency were not available. RESULTS: Participants (N = 130,277) had a median age of 63 years (interquartile range IQR 57-69). A total of 5,743 incident stroke events occurred over a median follow-up period of 19.9 years (IQR 9.1-25). In multivariable models, there was no significant association between migraine history and total stroke (HR 1.07, 95% CI 0.99-1.17), but there was a significant association between migraine history and ischemic stroke (HR 1.12, 95% CI 1.02-1.23). In planned secondary analysis of ischemic subtypes, the associations were most pronounced in the cardioembolic (HR 1.17, 95% CI 0.98-1.39) and undetermined (HR 1.14, 95% CI 0.98-1.33) categories. Migraine was not associated with hemorrhagic stroke (HR 0.85, 95% CI 0.67-1.09). Risk did not differ significantly by age group. DISCUSSION: Over 20 years of follow-up, postmenopausal women with a history of migraine had a higher risk of ischemic stroke, but not total or hemorrhagic stroke. Along with other factors, a history of migraine should be considered a risk marker when assessing ischemic stroke risk after menopause.