INSERTION DELETION POLYMORPHISM IN THE ANGIOTENSIN-CONVERTING ENZYME GENE AND RISK OF AND PROGNOSIS AFTER MYOCARDIAL-INFARCTION/

Objectives. We sought to prospectively investigate whether genetic var iation at the angiotensin converting enzyme gene locus defined by an i nsertion (I)/deletion (D) polymorphism influences the risk of myocardi al infarction or prognosis after infarction, or both. Background. It h as been suggested that the deletion allele of the angiotensin-converti ng enzyme gene, and specifically the DD genotype, may increase the ris k of myocardial infarction, although previous studies have produced co nflicting reports. No studies have yet examined the effect of I/D poly morphism on survival after infarction. Methods. Angiotensin converting enzyme genotypes in 684 patients with myocardial infarction recruited at the time of the acute event through coronary care units in two cen ters were compared with those of 537 control subjects recruited from t he base populations. All patients were followed up to assess the impac t of the angiotensin-converting enzyme genotype on prognosis. Results. We found no difference (p = 0.89) in the genotype distribution betwee n patients and control subjects (patients DD 31%, ID 47%, II 22%; cont rol subjects DD 30%, ID 48%, IT 22%). The odds ratio for myocardial in farction for DD compared with II/ID genotype adjusted for age, gender and center was 1.16 (95% confidence interval [CI] 0.82 to 1.65, p = 0. 44). The study had 90% power to detect a 1.5-fold increase in risk of myocardial infarction associated with the DD genotype. For one center, data were available for other risk factors (hypertension, diabetes, a ngina, previous myocardial infarction, smoking, body mass index, total and high density lipoprotein cholesterol) in both patients and contro l subjects. In a stepwise logistic regression analysis the odds ratio for DD versus ID/II genotypes remained nonsignificant (1.44, 95% CI 0. 84 to 2.46, p = 0.20) for these subjects. Over a median follow-up peri od of 15 months (range 3 to 22), 155 patients (22.7%) died. There was no difference in mortality between subjects with the DD genotype and t hose with ID/II genotypes. (21.8% vs. 23.1%, p = 0.25). Likewise, ther e was no difference in the distribution of survival times in the two g roups (p = 0.62). The study had 70% power to detect a 1.5-fold increas e in mortality during follow-up associated with the DD genotype. Concl usions. We conclude that in the groups studied, genetic variation at t he angiotensin converting enzyme gene locus defined by I/D polymorphis m does not significantly influence either the risk of or the short- to medium-term prognosis after myocardial infarction.