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.

Aged, Alleles, Blood Pressure/genetics, DNA Transposable Elements/genetics, Epidemiologic Methods, Female, Genotype, Heart Failure, Congestive/*genetics, Humans, Hypertension/*genetics, Male, Middle Aged, Peptidyl-Dipeptidase A/*genetics, Polymerase Chain Reaction/methods, Polymorphism, Genetic, Research Support, Non-U.S. Gov't, Sequence Deletion,
European Heart Journal
Erasmus MC: University Medical Center Rotterdam

Schut, A.F.C, Bleumink, G.S, Stricker, B.H.Ch, Hofman, A, Witteman, J.C.M, Pols, H.A.P, … van Duijn, C.M. (2004). Angiotensin converting enzyme insertion/deletion polymorphism and the risk of heart failure in hypertensive subjects. European Heart Journal, 25(23), 2143–2148. doi:10.1016/j.ehj.2004.08.026