Interactions between angiotensin-I converting enzyme insertion/deletion polymorphism and response of plasma lipids and coronary atherosclerosis to treatment with fluvastatin: the lipoprotein and coronary atherosclerosis study

Abstract

Objectives: Our objectives were to determine whether angiotensin-1 converting enzyme (ACE) insertion/deletion (I/D) polymorphism was associated with the severity of coronary artery disease (CAD) and its progression/regression in response to fluvastatin therapy in the Lipoprotein and Coronary Atherosclerosis Study (LCAS) population.

Background: Genetic factors are involved in susceptibility to CAD. Angiotensin-1 converting enzyme I/D polymorphism, which accounts for half of the variance of plasma and tissue levels of ACE, has been implicated in susceptibility to CAD and myocardial infarction (MI).

Methods: Angiotensin-1 converting enzyme genotypes were determined by polymerase chain reaction (PCR). Fasting plasma lipids were measured and quantitative coronary angiograms were obtained at baseline and 2.5 years following randomization to fluvastatin or placebo.

Results: Ninety-one subjects had DD, 198 ID and 75 II genotypes. The mean blood pressure, minimum lumen diameter (MLD), number of coronary lesions and total occlusions were not significantly different at baseline or follow-up among the genotypes. There was a significant genotype-by-treatment interaction for total cholesterol (p = 0.018), low-density lipoprotein cholesterol (LDL-C) (p = 0.005) and apolipoprotein (apo) B (p = 0.045). In response to fluvastatin therapy, subjects with DD, compared with those with ID and II genotypes, had a greater reduction in total cholesterol (19% vs. 15% vs. 13%), LDL-C (31% vs. 25% vs. 21%) and apo B (23% vs. 15% vs. 12%). Definite progression was less (14%) and regression was more common (24%) in DD as compared with those with ID (32% and 17%) and II (33% and 3%) genotypes (p = 0.023). Changes in the mean MLD and lesion-specific MLD also followed the same trend.

Conclusions: Angiotensin-1 converting enzyme I/D polymorphism is associated with the response of plasma lipids and coronary atherosclerosis to treatment with fluvastatin. Subjects with DD genotype had a greater reduction in LDL-C, a higher rate of regression and a lower rate of progression of CAD.