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Interrelationships among the ACE deletion/insertion (D/I) polymorphism (rs1799752), migraine, and cardiovascular disease (CVD) are biologically plausible but remain controversial.Association study among 25,000 white US women, participating in the Women's Health Study, with information on the ACE D/I polymorphism. Migraine and migraine aura status were self-reported. Incident CVD events were confirmed after medical record review. We used logistic regression to investigate the genotype-migraine association and proportional hazards models to evaluate the interrelationship among genotype, migraine, and incident CVD.At baseline, 4,577 (18.3%) women reported history of migraine; 39.5% of the 3,226 women with active migraine indicated aura. During 11.9 years of follow-up, 625 CVD events occurred. We did not find an association of the ACE D/I polymorphism with migraine or migraine aura status. There was a lack of association between the ACE D/I polymorphism and incident major CVD, ischemic stroke, and myocardial infarction. Migraine with aura doubled the risk for CVD, but only for carriers of the DD (multivariable-adjusted relative risk [RR] = 2.10; 95% CI = 1.22-3.59; p = 0.007) and DI genotype (multivariable-adjusted RR = 2.31; 95% CI = 1.52-3.51; p0.0001). The risk was not significant among carriers of the II genotype, a pattern we observed for myocardial infarction and ischemic stroke.Data from this large cohort of women do not suggest an association of the ACE deletion/insertion (D/I) polymorphism with migraine, migraine aura status, or cardiovascular disease (CVD). The increased risk for CVD among migraineurs with aura was only apparent for carriers of the DD/DI genotype. Due to limited number of outcome events, however, future studies are warranted to further investigate this association.

Interrelationships among the MTHFR 677CT polymorphism (rs1801133), migraine, and cardiovascular disease (CVD) are plausible but remain controversial.Association study among 25,001 white US women, participating in the Women's Health Study, with information on MTHFR 677CT polymorphism. Migraine and migraine aura status were self-reported. Incident CVD events were confirmed after medical record review. We used logistic regression to investigate the genotype-migraine association and proportional hazards models to evaluate the interrelationships of genotype and migraine on incident CVD.At baseline, 4,577 (18.3%) women reported history of migraine; 39.5% of the 3,226 women with active migraine indicated aura. During a mean of 11.9 years of follow-up, 625 CVD events occurred. Carriers of the TT genotype were less likely to have migraine with aura. The multivariable-adjusted relative risk (RR) in the recessive model was 0.79 (95% CI = 0.65-0.96; p = 0.02). The TT genotype did not increase the risk for CVD. In contrast, migraine with aura doubled the risk for CVD (multivariable-adjusted RR = 2.06; 95% CI = 1.53-2.78; p0.0001). Coexistence of migraine with aura and the TT genotype selectively raised this risk (RR = 3.66; 95% CI = 1.69-7.90; p = 0.001). This pattern was driven by a fourfold increased risk for ischemic stroke (multivariable-adjusted RR = 4.19; 95% CI = 1.38-12.74; p = 0.01) and was not apparent for myocardial infarction.Data from this large cohort of women suggest a modest protective effect of the MTHFR 677TT genotype on migraine with aura. The increased risk for cardiovascular disease among migraineurs with aura was magnified for TT genotype carriers, which was driven by a substantially increased risk of ischemic stroke.

Migraine has been associated with risk of cardiovascular disease (CVD). Data on the association between migraine frequency and CVD are sparse.Prospective cohort study of 27,798 US women agedor=45 years, who were free of CVD, and for whom we had information on lipids and migraine frequency. We categorized migraine frequency asmonthly, monthly, andor= weekly. Incident CVD was confirmed after medical record review.Of the 3,568 women with active migraine at baseline, 75.3% reported a migraine frequency ofmonthly, 19.7% monthly, and 5.0%or= weekly. During 11.9 years of follow-up, 706 CVD events occurred. Compared with women without migraine, the multivariable-adjusted hazard ratios (HRs) (95% confidence intervals) among active migraineurs for CVD were 1.55 (1.22-1.97), 0.65 (0.31-1.38), and 1.93 (0.86-4.33) for an attack frequency ofmonthly, monthly, andor= weekly, respectively. The association between migraine frequency and CVD was only apparent among migraineurs with aura. Among those, the multivariable-adjusted HRs for women with a migraine frequencymonthly ranged from 1.81 (1.30-2.50) for coronary revascularizations to 2.43 (1.58-3.74) for myocardial infarction. For women with active migraine with aura and migraine frequencies ofor= weekly, we only found significant increased risk of ischemic stroke (HR = 4.25 [1.36-13.29]).In our data, the association between migraine and cardiovascular disease varies by migraine frequency. Significant associations were only found among women with migraine with aura. Ischemic stroke was the only outcome associated with a high-attack frequency while a low-attack frequency was associated with any vascular event. Low number of outcome events should caution the interpretation.

The G1246A polymorphism in the gene of the hypocretin receptor 2 (HCRTR2) has been linked to the risk for cluster headache (CH). The authors examined this association in a large sample of 226 patients with CH and 266 controls from Germany. The genotype and allele distribution varied significantly between patients and controls. Homozygous carriers of the G-allele had a twofold increase in risk for CH (OR 1.97; 95% CI 1.32 to 2.92; p = 0.0007).