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AimsCardiac 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 resultsWe 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)).ConclusionOur findings suggest that the ACE I/D polymorphism may play a modifying role in the development of heart failure in hypertensive subjects.

Original publication




Journal article


European heart journal

Publication Date





2143 - 2148


Genetic Epidemiology Unit, Department of Epidemiology, Eramus Medical Centre Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.


Humans, Hypertension, Peptidyl-Dipeptidase A, DNA Transposable Elements, Epidemiologic Methods, Polymerase Chain Reaction, Sequence Deletion, Blood Pressure, Genotype, Polymorphism, Genetic, Alleles, Aged, Middle Aged, Female, Male, Heart Failure