Effect of hormone replacement therapy on plasma lipoproteins and apolipoproteins, endothelial function and myocardial perfusion in postmenopausal women with estrogen receptor-alpha IVS1-397 C/C genotype and established coronary artery disease.
Effect of hormone replacement (HRT) therapy on plasma lipoproteins and apolipoproteins, endothelial function and myocardial perfusion in postmenopausal women with estrogen receptor-alpha (ER-alpha) IVS1-397 C/C genotype and established coronary artery disease.


OBJECTIVE
Associations between various ER-alpha polymorphisms and clinical phenotypes have been studied, including lipid levels and coronary atherosclerosis. We studied 48 postmenopausal women to determine the effect of ER-alpha IVS1-397 polymorphism on the response to treatment with HRT.


METHODS
The study had a randomized, double-blind, placebo-controlled and crossover design. Patients were divided into two groups according to ER-alpha IVS1-397 polymorphism: CC genotype (n = 9); CT or TT genotype (n = 39). HRT was given continuously for 4 weeks, with 4-week washout periods between the treatment periods. Brachial artery Doppler and Tl-201 scintigraphy were performed at the end of each treatment period.


RESULTS
HRT lowered total cholesterol, LDL-c and Apo-B levels from baseline values (all p < 0.05) and to a similar degree in CC and CT/TT genotype patients. HRT increased estradiol, HDL-c and Apo A-1 levels relative to baseline values, but to a greater degree in CC patients (p = 0.04, 0.05 and 0.04 by ANOVA, respectively). HRT increased peak forearm blood flow, brachial artery diameter during reactive hyperemia and endothelium-dependent dilation in both groups, but to a greater degree in CC patients (p = 0.03, 0.03 and 0.04 by ANOVA, respectively). Summed stress and rest scores were also more markedly reduced in CC patients (p = 0.04 and 0.05, respectively). The increase in estradiol levels was strongly correlated with the improvement in endothelium-dependent dilation (r = 0.66, p < 0.01), which in turn showed negative correlation with summed stress (r = -0.62, p < 0.01) and rest scores (r = -0.52, p < 0.05) in the CC genotype group.


CONCLUSIONS
These data suggest that the improvement in endothelium-dependent dilation and the reduction in perfusion abnormalities by increasing estradiol levels with HRT in postmenopausal women with coronary artery disease may differ with respect to different genotypes, the effect being more prominent in those patients with ER-alpha IVS1-397 CC genotype.
Emre
Ayse
A
Department of Cardiology, Siyami Ersek Thoracic and Cardiovascular Surgery Center, Istanbul, Turkey. aysesay@superonline.com
Sahin
Sinan
S
Erzik
Can
C
Nurkalem
Zekeriya
Z
Oz
Dilaver
D
Cirakoglu
Beyazit
B
Yesilcimen
Kemal
K
Ersek
Birsen
B
D001053:Apolipoproteins / Q000097:blood*; D001916:Brachial Artery / Q000502:physiology; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics / Q000503:physiopathology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects*; D004958:Estradiol / Q000097:blood; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D005838:Genotype; D020249:Hormone Replacement Therapy; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017698:Postmenopause / Q000097:blood / Q000187:drug effects* / Q000502:physiology; D011374:Progesterone / Q000097:blood; D014664:Vasodilation / Q000187:drug effects
D001053:Apolipoproteins; D047628:Estrogen Receptor alpha; D008074:Lipoproteins; D011374:Progesterone; D004958:Estradiol