migraine and heart disease in women

Analysis of the Nurses' Health Study found a significant increase in cardiovascular disease in those with migraine (see cad and migraine in women bmj2016 in dropbox, or http://dx.doi.org/10.1136/bmj.i2610 ). details:

--115 541 women aged 25-42 years at baseline and free of angina and cardiovascular disease were followed from the prospective Nurses' Health Study II (from 1989-2011)
--mean age 35; BMI <25 in 68%, 25-30 in 19%; history hypertension 6%, hypercholesterolemia 12%, smoking 14%; no alcohol in 38%, up to 15 g/d in 58%; oral contraceptives in 12%.
--17 531 (15.2%) women reported a physician’s diagnosis of migraine (though no data on presence of aura, migraine frequency, or migraine meds)
--women with migraine were more likely to have hypertension, hypercholesterolemia, family history of MI, BMI>30 or be current smoker
--Results:
    --1329 major cardiovascular disease events occurred, and 223 women died from cardiovascular disease
    --adjusting for potential confounding factors (age, cholesterol, diabetes, hypertension, BMI, smoking, alcohol, physical activity, postmenopausal estrogens, menopausal status, oral contraceptives, aspirin/acetaminophen/NSAID use, and family history MI), migraine was associated with an increased risk for:
            --major cardiovascular disease (hazard ratio1.50, 95% confidence interval 1.33 to 1.69)
            --myocardial infarction (HR 1.39, 1.18 to 1.64)
            --stroke (HR 1.62, 1.37 to 1.92)
            --angina/coronary revascularization procedures (HR 1.73, 1.29 to 2.32)
            --cardiovascular disease mortality (HR 1.37, 1.02 to 1.83)
            ​--associations were similar across subgroups of women, including by age (<50/≥50), smoking status (current/past/never), hypertension (yes/no), postmenopausal hormone therapy (current/not current), and oral contraceptive use (current/not current)

Commentary:
--several studies have found that migraine (specifically migraine with aura) is associated with increased risk of stroke
--the Women's Health Initiative found similar increase in cardiovascular disease (about the same +/- 50% increase as above), but only in those reporting migraine with aura
--several other studies from different countries (Taiwan, Iceland, as well as the American Migraine Prevalence and Prevention Study) have found similar results
--how to explain the association?? unclear. ?increased thrombogenic susceptibility, shared genetic markers, endothelial dysfunction, or inflammation (all have been shown in both migraine and cardiovascular disease). and a recent small study found that the combination of a statin and vitamin D, perhaps through their anti-inflammatory or endothelial effects, decreased the frequency of migraines (for analysis of this study, see prior blog: http://gmodestmedblogs.blogspot.com/2016/01/migraine-prophylaxis-with.html 

--so, it probably makes sense to include migraine (perhaps more so if aura present) in the overall gestalt of cardiovascular risk factors – ie, it would be an added reason to strongly encourage lifestyle changes (smoking, appropriate weight, increasing fruits/veges in diet, exercise) in general, and it might sway me to use statins in those otherwise on the borderline for medical therapy
​ 

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