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NEUROLOGY 2007;68:1025-1031
© 2007 American Academy of Neurology

Hereditary hemochromatosis genotypes and risk of ischemic stroke

C. Ellervik, MD, A. Tybjærg-Hansen, MD, DMSc, M. Appleyard, BMLT, H. Sillesen, MD, DMSc, G. Boysen, MD, DMSc and B. G. Nordestgaard, MD, DMSc

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

Address correspondence and reprint requests to Professor Børge G. Nordestgaard, Department of Clinical Biochemistry, Herlev University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark; e-mail: brno{at}heh.regionh.dk

Objective: We tested the hypothesis that the HFE genotypes H63D/H63D, H63D/wild type, C282Y/H63D, C282Y/C282Y, and C282Y/wild type are risk factors for symptomatic carotid atherosclerosis, ischemic cerebrovascular disease (ICVD), and ischemic stroke.

Methods: We performed an age- and gender-matched case-control study of 701 cases with symptomatic carotid atherosclerosis vs 2,777 controls, and a prospective study of 9,178 individuals from the Danish general population followed for 24 years, during which 504 developed ICVD, of whom 393 had ischemic stroke.

Results: Genotype was not consistently associated with symptomatic carotid atherosclerosis. The cumulative incidences of ICVD and ischemic stroke by age were increased for H63D/H63D vs wild type/wild type (log-rank: p = 0.003 and p < 0.001). H63D/H63D vs wild type/wild type had an age- and multifactorially adjusted hazard ratio of 2.0 (95% CI: 1.2 to 3.2; p = 0.007) and 2.1 (1.3 to 3.5; p = 0.004) for ICVD and of 2.4 (1.4 to 4.0; p = 0.001) and 2.8 (1.7 to 4.6; p < 0.001) for ischemic stroke; these remained significant after correction for multiple comparisons. Other hereditary hemochromatosis genotypes were not associated with ICVD or ischemic stroke.

Conclusions: Hereditary hemochromatosis H63D homozygosity predicts a two- to threefold risk of ICVD and ischemic stroke.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the March 27 issue to find the title link for this article.

The Danish Heart Foundation and Chief Physician Johan Boserup's and Lise Boserup's Fund supported the study.

Disclosure: The authors report no conflicts of interest.

Received May 31, 2006. Accepted in final form November 27, 2006.


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Neurology 2007 68: 972. [Full Text] [PDF]





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