Apolipoprotein E genotypes and response of plasma lipids and progression-regression of coronary atherosclerosis to lipid-lowering drug therapy

OBJECTIVES We sought to examine the association of apolipoprotein (apo) E g enotypes with baseline plasma lipid levels and severity of coronary artery disease (CAD), as well as the response to treatment with fluvastatin in the Lipoprotein and Coronary Atherosclerosis Study (LCAS). BACKGROUND Apo E genotypes have been associated with plasma lipid levels an d CAD. However, the influence of apo E genotypes on the response of plasma lipids and CAD progression or regression to statin treatment in patients wi th mildly to moderately elevated cholesterol remains unknown. METHODS Apo E genotypes were determined by polymerase chain reaction and re striction mapping. Plasma lipids were measured at baseline and 12 weeks aft er therapy with fluvastatin or placebo in 320 subjects. In 287 subjects, qu antitative coronary angiography was performed at baseline and after 2.5 yea rs of treatment. RESULTS Subjects with the 3/3 genotype had greater reductions in total chol esterol (20.4% vs. 15.4%, p = 0.01) and low density lipoprotein (LDL) chole sterol (28.8% vs. 22.7%, p = 0.03) than did the subjects with the 3/4 or 4/ 4 genotype. In contrast, subjects with the 2/3 genotype (n = 10) had a grea ter increase in high density lipoprotein cholesterol (19.1%) than did the s ubjects with the 3/3 genotype (4.3%, p = 0.002) and those with the 3/4 or 4 /4 genotype (7.0%, p = 0.02). Subjects with the. 3/4 or 4/4 genotype had an increased frequency of previous angioplasty, but other measures of baselin e CAD severity and baseline lipids did not differ significantly among the g enotypes, nor did CAD progression or clinical events. CONCLUSIONS Although subjects with the epsilon4 allele had less reduction i n LDL cholesterol with fluvastatin, they had similar benefit in terms of CA D progression. (C) 2000 by the American College of Cardiology.