Is the response of serum lipids and lipoproteins to postmenopausal hormonereplacement therapy modified by ApoE genotype?

Postmenopausal hormone replacement therapy (HRT) has favorable effects on t he serum lipid profile. and it also decreases the risk of cardiovascular di seases. The apolipoprotein E genotype has influence on serum levels of lipi ds and lipoproteins; apoE allele epsilon 4 (apoE4) is associated with high total and LDL cholesterol levels. Genotype also influences the lipid respon ses to treatment with diet and statins, but the effect of HRT in different apoE genotypes is unknown. We studied the effects of HRT on the concentrati ons of serum lipids in apoE4-positive early postmenopausal women (genotypes 3/4 and 4/4) compared with apoE4-negative women (genotypes 2/3 and 3/3) in a population-based, prospective 5-year study. In all, 232 early postmenopa usal women were randomized into 2 treatment soups: an HRT group (n = 116), which received a sequential combination of 2 mg estradiol valerate (E(2)Val ) from day 1 to 21 and I mg cyproterone acetate (CPA) from day 12 to 21 (Cl imen), and a placebo group (n = 116), which received 500 mg/d calcium lacta te. Serum concentrations of total, LDL, and HDL cholesterol and triglycerid es were measured at baseline and after 2 and 5 years of treatment, A total of 154 women completed the final analysis. During the follow-up period, ser um total cholesterol and LDL cholesterol concentrations decreased in the HR T group in apoE4-negative women (8.1% and 17.1%, respectively; P < 0.001) b ut did not change in the HRT group in apoE4-positive women or in the placeb o group. Serum HDL cholesterol concentrations decreased in the placebo grou p (apoE4-negative, 3.9%, P = 0.015; apoE4-positive, 8.1%, P = 0.004) but di d not change significantly in the HRT group. Serum triglyceride levels tend ed to increase in both study groups and genotypes (15.1% to 36.2%, P < 0.03 8 to 0.001), but no differences were observed between the study groups or g enotypes, respectively. Our finding was that in postmenopausal Finnish wome n LDL cholesterol levels in apoE4-negative subjects respond more favorably to HRT than those in apoE4-positive subjects, This finding has potential im portance in postmenopausal women with hypercholesterolemia, if confirmed in other studies.