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(Circulation. 2005;112:185-193.)
© 2005 American Heart Association, Inc.

Epidemiology

Hereditary Hemochromatosis and Risk of Ischemic Heart Disease

A Prospective Study and a Case-Control Study

Christina Ellervik, MD; Anne Tybjærg-Hansen, MD, DMSc; Peer Grande, MD, DMSc; Merete Appleyard; Børge G. Nordestgaard, MD, DMSc

From the Department of Clinical Biochemistry, Herlev University Hospital (C.E., B.G.N.), Department of Clinical Biochemistry (A.T.-H.), and Department of Cardiology (P.G.), Rigshospitalet, Copenhagen University Hospital, and The Copenhagen City Heart Study, Bispebjerg University Hospital (A.T.-H., M.A., B.G.N.), University of Copenhagen, Copenhagen, Denmark.

Correspondence to Børge G. Nordestgaard, MD, DMSc, Department of Clinical Biochemistry, Herlev University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark. E-mail brno{at}herlevhosp.kbhamt.dk

Received July 29, 2004; revision received March 11, 2005; accepted March 29, 2005.

Background— We tested the hypothesis that the hereditary hemochromatosis genotypes C282Y/C282Y, C282Y/H63D, or C282Y/wild-type are risk factors for ischemic heart disease (IHD) and myocardial infarction (MI).

Methods and Results— We performed a prospective study of 9178 individuals from the Danish general population followed up for 24 years, during which 1035 and 511 developed IHD and MI, respectively, and a case-control study of 2441 and 1113 IHD and MI cases versus 8080 controls. C282Y/C282Y, C282Y/H63D, and C282Y/wild-type versus wild-type/wild-type individuals were not associated with increased risk of IHD or MI in prospective studies, overall or stratified by gender. We had 90% power to detect a hazard ratio for IHD of 3.4 for C282Y/C282Y, 1.9 for C282Y/H63D, and 1.3 for C282Y/wild-type versus wild-type/wild-type. Furthermore, these genotypes were not associated with increased risk of IHD or MI in case-control studies, overall or stratified by gender. We had 90% power to detect an odds ratio for IHD of 3.6 for C282Y/C282Y, 1.8 for C282Y/H63D, and 1.3 for C282Y/wild-type versus wild-type/wild-type.

Conclusions— In these studies, hereditary hemochromatosis C282Y/C282Y, C282Y/H63D, and C282Y/wild-type genotypes were not associated with IHD or MI; however, the study lacked the power to exclude the possibility that C282Y/C282Y and C282Y/H63D individuals have a modestly increased risk of IHD or MI.

Key Words: cardiovascular diseases • prospective studies • case-control studies • hemochromatosis

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