This Article Full Text Full Text (PDF) All Versions of this Article: 112/2/185    most recent CIRCULATIONAHA.104.496075v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ellervik, C. Articles by Nordestgaard, B. G. Search for Related Content PubMed PubMed Citation Articles by Ellervik, C. Articles by Nordestgaard, B. G. Related Collections Clinical genetics Chronic ischemic heart disease Epidemiology Related Article

(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

Related Article:

Issue Highlights
Circulation 2005 112: 147. [Extract] [Full Text]

This article has been cited by other articles:

				P. C. Adams, J. S. Pankow, J. C. Barton, R. T. Acton, C. Leiendecker-Foster, G. D. McLaren, M. Speechley, and J. H. Eckfeldt HFE C282Y Homozygosity Is Associated With Lower Total and Low-Density Lipoprotein Cholesterol: The Hemochromatosis and Iron Overload Screening Study Circ Cardiovasc Genet, February 1, 2009; 2(1): 34 - 37. [Abstract] [Full Text] [PDF]

				D. L. van der A, M. M. Rovers, D. E. Grobbee, J. J.M. Marx, J. Waalen, C. Ellervik, B. G. Nordestgaard, J. K. Olynyk, P. R. Mills, J. Shepherd, et al. Mutations in the HFE Gene and Cardiovascular Disease Risk: An Individual Patient Data Meta-Analysis of 53 880 Subjects Circ Cardiovasc Genet, October 1, 2008; 1(1): 43 - 50. [Abstract] [Full Text] [PDF]

				C. Ellervik, A. Tybjaerg-Hansen, M. Appleyard, H. Sillesen, G. Boysen, and B. G. Nordestgaard Hereditary hemochromatosis genotypes and risk of ischemic stroke Neurology, March 27, 2007; 68(13): 1025 - 1031. [Abstract] [Full Text] [PDF]

				F. B. Hu The Iron-Heart Hypothesis: Search for the Ironclad Evidence JAMA, February 14, 2007; 297(6): 639 - 641. [Full Text] [PDF]

				S. Goland, S. D. Malnick, C. Ellervik, B. G. Nordestgaard, A. Tybjaerg-Hansen, P. Grande, A. Tybjaerg-Hansen, M. Appleyard, and B. G. Nordestgaard Letter Regarding Article by Ellervik et al, "Hereditary Hemochromatosis and Risk of Ischemic Heart Disease: A Prospective Study and a Case-Control Study" * Response Circulation, January 3, 2006; 113(1): e10 - e10. [Full Text] [PDF]