Effect of hormone replacement therapy on plasma lipoproteins and apolipoproteins, endothelial function and myocardial perfusion in postmenopausal women with estrogen receptor-α IVS1-397C/C genotype and established coronary artery disease
Effect of hormone replacement therapy on plasma lipoproteins and apolipoproteins, endothelial function and myocardial perfusion in postmenopausal women with estrogen receptor-α IVS1-397C/C genotype and established coronary artery disease
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DOI：
10.1159/000092598
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发表时间：
2006-01-01
期刊：
影响因子：
1.9
通讯作者：
Ersek, Birsen
中科院分区：
文献类型：
--
作者：
Emre, Ayse;Sahin, Sinan;Ersek, Birsen
雌激素受体-α（ER-α）IVS 1 -397 C/C基因型和确诊冠心病的绝经后妇女激素替代（HRT）治疗对血浆脂蛋白和载脂蛋白、内皮功能和心肌灌注的影响背景/目标：已经研究了各种ER-α多态性与临床表型之间的关联，包括脂质水平和冠状动脉粥样硬化。我们研究了48名绝经后妇女，以确定ER-α IVS 1 -397多态性对HRT治疗反应的影响。方法：采用随机、双盲、安慰剂对照、交叉设计。根据ER α IVS 1 -397多态性将患者分为两组：CC基因型（n = 9）; CT或TT基因型（n = 39）。HRT连续给予4周，治疗期之间有4周的洗脱期。在每个治疗期结束时进行肱动脉多普勒和TI-201血管造影。结果如下：HRT使总胆固醇、LDL-c和Apo-B水平较基线值降低（所有p < 0.05），CC和CT/TT基因型患者的降低程度相似。HRT使雌二醇、HDL-c和Apo A-1水平相对于基线值升高，但CC患者的升高程度更大（ANOVA分别为p = 0.04、0.05和0.04）。HRT增加前臂峰值血流量，肱动脉直径在两组反应性充血和内皮依赖性舒张，但在CC患者更大程度上（P = 0.03，0.03和0.04的方差分析，分别）。CC患者的压力和休息评分总和也更明显降低（分别为p = 0.04和0.05）。雌激素水平的增加与内皮依赖性舒张功能的改善密切相关（r = 0.66，p < 0.01），而内皮依赖性舒张功能的改善又与CC基因型组的总应激（r =-0.62，p < 0.01）和静息评分（r =-0.52，p < 0.05）呈负相关。结论：这些数据表明，改善内皮依赖性舒张和减少灌注异常增加雌二醇水平与HRT的绝经后妇女冠状动脉疾病可能不同的基因型，效果更突出的ER-α IVS 1 -397 CC基因型的患者。版权所有（c）2006 S. Karger AG，巴塞尔。
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. Background/ Aims: Associations between various ER-a polymorphisms and clinical phenotypes have been studied, including lipid levels and coronary atherosclerosis. We studied 48 postmenopausal women to determine the effect of ER-a 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 TI-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. Conclusion: 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. Copyright (c) 2006 S. Karger AG, Basel.