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Effect of Long-Term Hormone Replacement Therapy on Atherosclerosis Progression in Postmenopausal Women Relates to Myeloperoxidase Promoter Polymorphism

Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Center for Laboratory Medicine, University Hospital of Tampere (R.M., H.J., M.S., T.L.), and Department of Clinical Chemistry, Tampere University Medical School (T.L.); Departments of Diagnostic Radiology (P.D.) and Obstetrics and Gynecology (R.P.), University Hospital of Tampere, and University of Tampere (R.P., P.D.), 33521 Tampere, Finland

Address all correspondence and requests for reprints to: Dr. Riikka Mäkelä, 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: riikka.makela{at}uta.fi.

Myeloperoxidase (MPO) is an oxidative enzyme present in phagocytes and atherosclerotic lesions. The MPO gene has a promoter polymorphism -463G/A, which leads to high (GG) and low expression (AG, AA) genotypes. We investigated the effect of long-term hormone replacement therapy (HRT) on the progression of atherosclerosis in a 5-yr follow-up study of postmenopausal women with different MPO genotypes. Eighty-seven nonsmoking postmenopausal women, aged 45–71 yr, were divided into three groups based on the use of HRT. The HRT-EVP group (n = 25) used sequential estradiol valerate plus progestin, the HRT-EV group used estradiol valerate alone (n = 32), and the control group (n = 30) used no HRT. The atherosclerosis severity score (ASC) for abdominal aorta and carotid arteries was determined by ultrasonography, and the MPO genotype was analyzed. In subjects with the GG genotype, the progression of ASC was significantly faster in the control group than in the HRT group (genotype by time interaction, P = 0.042), whereas in A allele carriers there were no significant differences in ASC progression between control and HRT. The effects of HRT on atherosclerosis progression in subjects with the GG genotype seem to be especially beneficial compared with controls with the same genotype but without HRT. These results may help us understand in greater detail the benefit and possible risk of HRT in atherosclerotic diseases.

This work was supported by grants from the Finnish Foundation of Cardiovascular Research (Helsinki, Finland), the Elli and Elvi Oksanen Fund of the Pirkanmaa Fund under the auspices of the Finnish Cultural Foundation, the Emil Aaltonen Foundation, the Juho Vainio Foundation, the Research Foundation of Orion Corp., and the Medical Research Fund of Tampere University Hospital (Tampere, Finland).

Abbreviations: ANCA, Antineutrophil cytoplasmic antibodies; ANCOVA, analysis of covariance; ASC, atherosclerosis severity score; BMI, body mass index; CAD, coronary artery disease; EV, estradiol valerate; HRT, hormone replacement therapy; MPO, myeloperoxidase; NAP, number of plaques; P, progestin; RANOVA, ANOVA for repeated measures.

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