Apolipoprotein E genotypes and response of plasma lipids and progression-regression of coronary atherosclerosis to lipid-lowering drug therapy.
OBJECTIVE
We sought to examine the association of apolipoprotein (apo) E genotypes 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 and CAD. However, the influence of apo E genotypes on the response of plasma lipids and CAD progression or regression to statin treatment in patients with mildly to moderately elevated cholesterol remains unknown.


METHODS
Apo E genotypes were determined by polymerase chain reaction and restriction mapping. Plasma lipids were measured at baseline and 12 weeks after therapy with fluvastatin or placebo in 320 subjects. In 287 subjects, quantitative coronary angiography was performed at baseline and after 2.5 years of treatment.


RESULTS
Subjects with the 3/3 genotype had greater reductions in total cholesterol (20.4% vs. 15.4%, p = 0.01) and low density lipoprotein (LDL) cholesterol (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 greater increase in high density lipoprotein cholesterol (19.1%) than did the subjects 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 baseline CAD severity and baseline lipids did not differ significantly among the genotypes, nor did CAD progression or clinical events.


CONCLUSIONS
Although subjects with the epsilon4 allele had less reduction in LDL cholesterol with fluvastatin, they had similar benefit in terms of CAD progression.
Ballantyne
C M
CM
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA. cmb@bcm.tmc.edu
Herd
J A
JA
Stein
E A
EA
Ferlic
L L
LL
Dunn
J K
JK
Gotto
A M
AM
Marian
A J
AJ
D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001057:Apolipoproteins E / Q000235:genetics*; D002784:Cholesterol / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D018450:Disease Progression; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use*; D005260:Female; D000077340:Fluvastatin; D005838:Genotype; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction
D000924:Anticholesteremic Agents; D001057:Apolipoproteins E; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D000077340:Fluvastatin; D002784:Cholesterol