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From the Division of Preventive Medicine (M.S., R.Y.L.Z., J.E.B., T.K.), Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School; Department of Epidemiology (J.E.B., T.K.), Harvard School of Public Health; and Department of Ambulatory Care and Prevention (J.E.B.), Harvard Medical School, Boston, MA; and INSERM Unit 708, Neuroepidemiology (T.K.) and University Pierre et Marie Curie (T.K.), Paris, France.
Address correspondence and reprint requests to Dr. Markus Schürks, Division of Preventive Medicine, Brigham and Women’s Hospital, 900 Commonwealth Avenue East, 3rd Fl, Boston, MA 02215-1204 mschuerks{at}rics.bwh.harvard.edu
Background: Interrelationships among the ACE deletion/insertion (D/I) polymorphism (rs1799752), migraine, and cardiovascular disease (CVD) are biologically plausible but remain controversial.
Methods: 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.
Results: 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; p < 0.0001). The risk was not significant among carriers of the II genotype, a pattern we observed for myocardial infarction and ischemic stroke.
Conclusions: 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.
Abbreviations: ACE = angiotensin-converting enzyme; CI = confidence interval; CVD = cardiovascular disease; D/I = deletion/insertion; HRs = hazard ratios; IHS = International Headache Society; MI = myocardial infarction; OR = odds ratio; WHS = Women’s Health Study.
Supplemental data at www.neurology.org
*These authors contributed equally.
The Women’s Health Study is supported by grants from the National Heart, Lung, and Blood Institute (HL-43851 and HL-080467) and the National Cancer Institute (CA-47988). The research for this work was supported by grants from the Donald W. Reynolds Foundation, the Leducq Foundation, and the Doris Duke Charitable Foundation. F. Hoffmann La-Roche and Roche Molecular Systems, Inc., also supported the genotype determination financially and with in-kind contribution of reagents and consumables. Dr. Schürks was supported by a grant from the Deutsche Forschungsgemeinschaft (SCHU 1553/2-1). The funding agencies played no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
Disclosure: Author disclosures are provided at the end of the article.
Received May 29, 2008. Accepted in final form November 19, 2008.
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