(Circulation. 1999;100:1268-1273.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Heterozygosity for a Hereditary Hemochromatosis Gene Is Associated With Cardiovascular Death in Women
From the Julius Center for Patient Oriented Research, Utrecht University Medical School (M.R., Y.T.v.d.S.), and the Departments of Internal Medicine (M.R., B.d.V., J.J.M.M., J.D.B.) and Hematology (M.R., M.J.T., P.G.d.G., J.J.S.), University Hospital Utrecht, The Netherlands.
Correspondence to Yvonne T. van der Schouw, PhD, Julius Center for Patient Oriented Research, Utrecht University Medical School, Room D01.335, PO Box 85500, 3508 GA Utrecht, The Netherlands. E-mail Y.T.VanDerSchouw{at}jc.azu.nl
Background—The genetic background of hereditary hemochromatosis (HH) is homozygosity for a cysteine-to-tyrosine transition at position 282 in the HFE gene. Heterozygosity for HH is associated with moderately increased iron levels and could be a risk factor for cardiovascular death.
Methods and Results—We studied the relation between HH heterozygosity and cardiovascular death in a cohort study among 12 239 women 51 to 69 years of age residing in Utrecht, the Netherlands. Women were followed for 16 to 18 years (182 976 follow-up years). The allele prevalence of the HH gene in the reference group was 4.0 (95% CI 2.9 to 5.4). The mortality rate ratios for HH heterozygotes compared with wild types was 1.5 (95% CI 0.9 to 2.5) for myocardial infarction (n=242), 2.4 (95% CI 1.3 to 3.5) for cerebrovascular disease (n=118), and 1.6 (95% CI 1.1 to 2.4) for total cardiovascular disease (n=530). The population-attributable risks of HH heterozygosity for myocardial infarction and cerebrovascular and total cardiovascular death were 3.3%, 8.8%, and 4.0%, respectively. In addition, we found evidence for effect modification by hypertension and smoking.
Conclusions—We found important evidence that inherited variation in iron metabolism is involved in cardiovascular death in postmenopausal women, especially in women already carrying classic risk factors.
Key Words: atherosclerosis • genes • genetics • cardiovascular diseases • cerebrovascular disorders
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