Effect of Long-Term Hormone Replacement Therapy on Atherosclerosis Progression in Postmenopausal Women Relates to Functional Apolipoprotein E Genotype
Terho Lehtimäki,
Prasun Dastidar,
Hannu Jokela,
Timo Koivula,
Saara Lehtinen,
Christian Ehnholm and
Reijo Punnonen
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 modulatesthe responses of lipoprotein metabolism to hormone-replacementtherapy (HRT). We investigated the effect of long-term HRT onthe progression of atherosclerosis in postmenopausal women withor without apoE 4 allele. One hundred forty-one nonsmoking postmenopausalwomen, 4571 yr old, were divided into 3 groups basedon the use of HRT. The HRT-EVP group (n = 61) used sequentialestradiol valerate (EV) plus progestin (P), the HRT-EV groupused EV alone (n = 40), and a control group had no HRT. Of these141 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 andcarotid arteries was determined by sonography. In apoE4-negativesubjects, the progression of atherosclerosis severity scorewas significantly faster in control than in the HRT groups (genotype-by-timeinteraction P = 0.0026); whereas in apoE4-positive subjects,there were no significant differences in atherosclerosis severityscore progression between the control and HRT groups. The effectsof HRT on atherosclerosis progression in subjects with no apo4-allele seems to be especially beneficial, compared with controlswith same phenotype status but without HRT. These results mayhelp us to understand, in more detail, the benefit and possiblerisk of HRT on atherosclerotic diseases.
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