The platelet Pl(A2) and angiotensin-converting enzyme (ACE) D allele polymorphisms and the risk of recurrent events after acute myocardial infarction

Chromosome 17q21-23 harbors genes for platelet glycoprotein Ilia and angiot ensin-converting enzyme (ACE), which are polymorphic for alleles pI(A2) and ACE "D." These alleles have been independently and often associated with i schemic coronary artery disease (CAD). We sought to determine if the pI(A2) and ACE D polymorphisms were risk factors for recurrent coronary events. I n the Cholesterol And Recurrent Events (CARE) trial, 4,159 men and women wi th documented myocardial infarction (MI) were randomized to receive either placebo or pravastatin, and were followed prospectively for 5 years. pI(A2) and ACE genotypes were determined in 767 patients: 385 cases who had exper ienced a recurrent primary event (death due to coronary disease or nonfatal MI), and 382 age- and gender-matched controls. In patients receiving place bo, the pI(A1,A2) genotype conferred a relative risk (RR) of 1.38 (confiden ce intervals [CI] 1.04 to 1.83; p = 0.028; adjusted RR = 1.32, Cl = 0.99 to 1.76; p = 0.058]) for the primary end point. Compared with the placebo gro up, pravastatin reduced the excess RR of coronary disease death and recurre nt MI in the pI(A1,A2) patient population by 31% (p = 0.06). The ACE D alle le appeared to have modestly additive effects on the pI(A1,A2) risk. Among the pI(A1,A2) patients, pravastatin had little effect on the risk of recurr ent events with the ACE II genotype, but reduced the adjusted RR from 1.42 (placebo) to 0.58 for ACE ID patients, and from 1.56 (placebo) to 0.83 for ACE DD. The pI(A1,A2) genotype was associated with an excess of recurrent c oronary events in patients after MI who did not receive pravastatin, and th e ACE D allele added to this risk. These data suggest that it would be impo rtant to perform a larger study to address the potential role of these geno types in therapeutic decision making. (C) 2001 by Excerpta Medica, Inc.