Improvement of myocardial blood flow by lipid-lowering therapy with pravastatin is modulated by apolipoprotein E genotype.

Objective. Apolipoprotein E (apoE) polymorphism affects the risk of advanced coronary artery disease, but its role in early atherosclerosis remains unknown. We used positron emission tomography (PET) to study whether coronary reactivity or its response to pravastatin is related to the apoE genotype. Material and methods. Samples from 44 mildly hypercholesterolaemic men (aged 35 +/- 4 years) of an earlier trial were re-analysed according to apoE genotype. Subjects were randomized to receive either 40 mg/day pravastatin or placebo for 6 months. To assess coronary reactivity, myocardial blood flow was measured by PET at rest and during adenosine infusion. PET studies and lipid analyses were done at baseline and after 6 months of therapy. Results. There were no differences between apoE epsilon 3/3 and epsilon 4/3 genotypes in basal or adenosine-stimulated flow or in coronary flow reserve (CFR) at baseline. There was a significant apoE genotype-by-treatment group interaction regarding the change in adenosine-stimulated flow (ANCOVA; p=0.018) and CFR (p=0.020) at the end of the study. In the pravastatin group, the adenosine-stimulated flow increased by 32.5% in subjects with epsilon 3/3 (n=9), but decreased non-significantly (-14.4%) in subjects with epsilon 4/3 (n=9) (p=0.0009). The corresponding changes in CFR were +17.8% for epsilon 3/3 and (-11.9% for epsilon 4/3 (p=0.05). There were no significant changes from the baseline values in placebo recipients. After pravastatin treatment, both genotype groups showed a similar decrease in serum total and low-density lipoprotein cholesterol (p < 0.0001 for both). Conclusions. Coronary function improves by 6 months of pravastatin in subjects with the apoE epsilon 3/3 genotype, but not in those with the epsilon 4/3.