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Effect of Long-Term Hormone Replacement Therapy on Atherosclerosis Progression in Postmenopausal Women Relates to Functional Apolipoprotein E Genotype

Laboratory of Atherosclerosis Genetics (T.L., H.J., S.L., T.K.), Department of Clinical Chemistry, Centre for Laboratory Medicine, University Hospital of Tampere and Tampere University Medical School, Department of Clinical Chemistry (T.L.), Tampere; Departments of Diagnostic Radiology (P.D.) and Internal Medicine (S.L.), University Hospital of Tampere, Tampere; Department of Biochemistry (C.E.), National Public Health Institute, Helsinki; and Department of Obstetrics and Gynecology (R.P.) and Internal Medicine (S.L.), University Hospital of Tampere, and University of Tampere (R.P., P.D.), 33521 Tampere, Finland

Address all correspondence and requests for reprints to: Terho Lehtimäki, M.D., Ph.D., Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Center for Laboratory Medicine, University Hospital of Tampere, P.O. Box 2000, 33521 Tampere, Finland. E-mail: . terho.lehtimaki{at}uta.fi

Abstract

Apolipoprotein (apo)E gene 4 allele carrier status modulates the responses of lipoprotein metabolism to hormone-replacement therapy (HRT). We investigated the effect of long-term HRT on the progression of atherosclerosis in postmenopausal women with or without apoE 4 allele. One hundred forty-one nonsmoking postmenopausal women, 45–71 yr old, were divided into 3 groups based on the use of HRT. The HRT-EVP group (n = 61) used sequential estradiol valerate (EV) plus progestin (P), the HRT-EV group used EV alone (n = 40), and a control group had no HRT. Of these 141 women, 93 participated in a 5-yr follow-up study in 1998. In addition to serum lipid concentration and apoE genotype, the atherosclerosis severity score of the abdominal aorta and carotid arteries was determined by sonography. In apoE4-negative subjects, the progression of atherosclerosis severity score was significantly faster in control than in the HRT groups (genotype-by-time interaction P = 0.0026); whereas in apoE4-positive subjects, there were no significant differences in atherosclerosis severity score progression between the control and HRT groups. The effects of HRT on atherosclerosis progression in subjects with no apo 4-allele seems to be especially beneficial, compared with controls with same phenotype status but without HRT. These results may help us to understand, in more detail, the benefit and possible risk of HRT on atherosclerotic diseases.

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