Female sex hormone-hormone receptor system as a coronary risk factor

为了验证雌激素-雌激素受体系统异常可能是新的冠心病危险因素的假设，进行了以下研究。由雌激素受体-α基因两个流行的多态组合确定的特定单倍型是冠状动脉造影证实的冠心病发病年龄的显著预测因素，并且这种关系独立于传统的冠状动脉危险因素(在日本循环学会第66届年度科学会议上发表)。另一个特定的雌激素受体-α基因单倍型与阿托伐他汀治疗后低密度脂蛋白胆固醇的降低和高密度脂蛋白胆固醇的升高显著相关，阿托伐他汀是动脉粥样硬化性冠状动脉疾病最可靠的治疗选择(提交)。用高敏感法测定雌二醇(E_2)和游离睾酮(FT)、…在236名经冠状动脉造影术定义为稳定性冠状动脉疾病的连续男性患者中，以及143名无疾病和年龄匹配的对照组中，有更多的研究。高敏E_2和FT水平在两组间反向略有差异，但均无统计学意义。然而，患者的FT与高敏E2的比率显著高于对照组，在调整了年龄和体重指数后，这种差异仍然显著。多元回归分析显示，年龄、糖尿病的关联性和冠状动脉粥样硬化的存在与FT/高敏感的E2比值显著且独立相关。接受检查的其他激素在患者和对照组之间没有显著差异。高敏的E_2测定显示，男性冠心病患者存在明显的FT/E_2失衡，但个体性激素水平在患者和对照组之间并无差异。(在新闻发布会上)更少

To examine the hypothesis that the abnormality in the estrogen-estrogen receptor system might be the novel coronary risk factor, following studies were performed.<Molecular genetic study>Specific haplotype determined by the combination of two prevalent polymorphisms in estrogen receptor-alpha gene was significant predictor of the onset age of angiographically-confirmed coronary heart disease, and this relation was independent from traditional coronary risk factors (presented at the 66^<th> Annual Scientific Session of Japanese Circulation Society).Another specific haplotype of estrogen receptor-alpha gene was significantly associated with the greater reduction of LDL cholesterol and the greater increase of HDL cholesterol after atorvastatin therapy, which was the most well-established therapeutic choice of atherosclerotic coronary artery disease (in submission).<Circulating sex hormone level>We determined levels of estradiol (E2) using high-sensitive method and free testosterone (FT), … More in 236 consecutive male patients with angiographically-defined stable coronary artery disease and in 143 disease-free and age-matched controls. The levels of high-sensitive E2 and FT in patients and controls differed slightly in opposing directions, but neither difference reached statistical significance. However, the ratio of FT to high-sensitive E2 in patients was significantly higher than in the controls, and this difference remained significant after adjustments for age and body mass index had been made. Multiple regression analysis revealed that age, the association of diabetes, and the presence of coronary atherosclerosis were significantly and independently associated with the values of the FT/high-sensitive E2 ratio. Other hormones examined did not differ significantly between the patients and the controls. High-sensitive E2 measurement demonstrated a significant imbalance of, FT to E2 in male patients with coronary artery disease, but individual sex hormone levels did not differ between the patients and the controls. (in press) Less