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European Heart Journal 2004 25(23):2143-2148; doi:10.1016/j.ehj.2004.08.026
Copyright © 2004 by the European Society of Cardiology.
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Clinical research

Angiotensin converting enzyme insertion/deletion polymorphism and the risk of heart failure in hypertensive subjects

Anna F.C. Schuta,b, Gysèle S. Bleuminka, Bruno H.Ch. Strickera, Albert Hofmana, Jacqueline C.M. Wittemana, Huibert A.P. Polsa,b, Jaap W. Deckersa,c, Jaap Deinumd and Cornelia M. van Duijna,*

a Genetic Epidemiology Unit, Departments of Epidemiology & Biostatistics, Eramus Medical Centre Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands
b Department of Internal Medicine, Erasmus Medical Centre Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands
c Department of Cardiology, Erasmus Medical Centre Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands
d Department of Internal Medicine, University Medical Centre Radboud Nijmegen, The Netherlands

Received January 26, 2003; revised August 26, 2003; accepted August 3, 2004 * Corresponding author. Tel.: +31 104 087 394; fax: +31 104 089 406 (E-mail: c.vanduijn{at}erasmusmc.nl).

AIMS: Cardiac angiotensin-I converting enzyme (ACE) activity is influenced by the ACE I/D polymorphism. Evidence suggests that the DD-genotype may be a risk factor for cardiac hypertrophy and heart failure, especially in hypertensive subjects. We assessed the relation between the ACE I/D polymorphism and the risk of incident heart failure in normotensive and hypertensive subjects.

METHODS AND RESULTS: We investigated 4264 normotensive and 2174 hypertensive participants of the Rotterdam Study, a population based prospective cohort study. All subjects were available for follow-up from 1990 until 2000. Incidence rates (IR) of heart failure in normotensive subjects were the same over all genotype strata (10 per 1000 person-years). In hypertensive subjects, the IR increased with the number of D-alleles present (II: IR=13, ID: IR=18 and DD: IR=20 per 1000 person-years). Hypertensive subjects carrying the II-genotype did not have an increased risk of heart failure compared to normotensive II subjects. However, hypertensive subjects carrying one or two copies of the D-allele did have a significantly increased risk of heart failure (ID: RR: 1.4 (1.1–1.9) and DD: RR: 1.5 (1.2–2.1)).

CONCLUSION: Our findings suggest that the ACE I/D polymorphism may play a modifying role in the development of heart failure in hypertensive subjects.


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