This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Heikkinen, A.-M. Articles by Saarikoski, S. Search for Related Content PubMed PubMed Citation Articles by Heikkinen, A.-M. Articles by Saarikoski, S. Related Collections Risk Factors Genetics of cardiovascular disease Lipid and lipoprotein metabolism

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:402-407.)
© 1999 American Heart Association, Inc.

Original Contributions

Is the Response of Serum Lipids and Lipoproteins to Postmenopausal Hormone Replacement Therapy Modified by ApoE Genotype?

Anna-Mari Heikkinen; Leo Niskanen; Markku Ryynänen; Marja H. Komulainen; Marjo T. Tuppurainen; Markku Parviainen; Seppo Saarikoski

From the Departments of Obstetrics and Gynecology (A.-M.H., M.H.K., M.T.T., S.S.), Medicine (L.N.), Clinical Genetics (M.R.), and Clinical Chemistry (M.P.), University Hospital of Kuopio, Finland.

Correspondence to Dr. A.-M. Heikkinen, Department of Obstetrics and Gynecology, Kuopio University Hospital, PO Box 1777, FIN-70211 Kuopio, Finland. E-mail anna-mari.heikkinen{at}pp.inet.fi

Abstract—Postmenopausal hormone replacement therapy (HRT) has favorable effects on the serum lipid profile, and it also decreases the risk of cardiovascular diseases. The apolipoprotein E genotype has influence on serum levels of lipids and lipoproteins; apoE allele 4 (apoE4) is associated with high total and LDL cholesterol levels. Genotype also influences the lipid responses 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 concentrations 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 postmenopausal women were randomized into 2 treatment groups: an HRT group (n=116), which received a sequential combination of 2 mg estradiol valerate (E₂Val) from day 1 to 21 and 1 mg cyproterone acetate (CPA) from day 12 to 21 (Climen), and a placebo group (n=116), which received 500 mg/d calcium lactate. Serum concentrations of total, LDL, and HDL cholesterol and triglycerides 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, serum total cholesterol and LDL cholesterol concentrations decreased in the HRT group in apoE4-negative women (8.1% and 17.1%, respectively; P<0.001) but did not change in the HRT group in apoE4-positive women or in the placebo group. Serum HDL cholesterol concentrations decreased in the placebo group (apoE4-negative, 3.9%, P=0.015; apoE4-positive, 8.1%, P=0.004) but did not change significantly in the HRT group. Serum triglyceride levels tended to increase in both study groups and genotypes (15.1% to 36.2%, P<0.038 to 0.001), but no differences were observed between the study groups or genotypes, respectively. Our finding was that in postmenopausal Finnish women LDL cholesterol levels in apoE4-negative subjects respond more favorably to HRT than those in apoE4-positive subjects. This finding has potential importance in postmenopausal women with hypercholesterolemia, if confirmed in other studies.

Key Words: ApoE genotype • postmenopausal hormone replacement therapy • LDL cholesterol • prospective study

This article has been cited by other articles:

				I. Lambrinoudaki, G. Kaparos, D. Papadimitriou, T. N Sergentanis, M. Creatsa, A. Alexandrou, E. Logothetis, G. Christodoulakos, and E Kouskouni Methylenetetrahydrofolate reductase C677T polymorphism is associated with central adiposity and increased androgenicity in healthy postmenopausal women Eur. J. Endocrinol., September 1, 2008; 159(3): 233 - 241. [Abstract] [Full Text] [PDF]

				D. S. Christidis, E. N. Liberopoulos, A. I. Kakafika, G. A. Miltiadous, M. Cariolou, E. S. Ganotakis, D. P. Mikhailidis, and M. S. Elisaf The effect of apolipoprotein e polymorphism on the response to lipid-lowering treatment with atorvastatin or fenofibrate. Journal of Cardiovascular Pharmacology and Therapeutics, September 1, 2006; 11(3): 211 - 221. [Abstract] [PDF]

				C. Atkinson, W. Oosthuizen, S. Scollen, A. Loktionov, N. E. Day, and S. A. Bingham Modest Protective Effects of Isoflavones from a Red Clover-Derived Dietary Supplement on Cardiovascular Disease Risk Factors in Perimenopausal Women, and Evidence of an Interaction with ApoE Genotype in 49-65 Year-Old Women J. Nutr., July 1, 2004; 134(7): 1759 - 1764. [Abstract] [Full Text]

				T. Lehtimaki, P. Dastidar, H. Jokela, T. Koivula, S. Lehtinen, C. Ehnholm, and R. Punnonen Effect of Long-Term Hormone Replacement Therapy on Atherosclerosis Progression in Postmenopausal Women Relates to Functional Apolipoprotein E Genotype J. Clin. Endocrinol. Metab., September 1, 2002; 87(9): 4147 - 4153. [Abstract] [Full Text] [PDF]

				J. M. HAGBERG, K. R. WILUND, and R. E. FERRELL APO E gene and gene-environment effects on plasma lipoprotein-lipid levels Physiol Genomics, December 18, 2000; 4(2): 101 - 108. [Abstract] [Full Text] [PDF]

				A. Karjalainen, J. Heikkinen, M. J. Savolainen, A.-C. Backstrom, and Y. A. Kesaniemi Mechanisms Regulating LDL Metabolism in Subjects on Peroral and Transdermal Estrogen Replacement Therapy Arterioscler. Thromb. Vasc. Biol., April 1, 2000; 20(4): 1101 - 1106. [Abstract] [Full Text] [PDF]