Serum Sex Hormone Levels and Subclinical Atherosclerosis

描述(由申请人提供)：在他们的一生中，男性比女性患冠心病的风险更高，然而，在更年期后，这种差异会减弱。这一观察结果表明，内源性性激素可能与冠心病风险有关。有证据表明，性激素对冠心病风险的影响可能部分是通过血脂水平或其他冠心病风险因素的变化来调节的。然而，其他证据支持循环激素水平与冠心病风险之间的独立关系。例如，我们最近报道，在年轻成年男性中，血清总睾酮浓度与亚临床冠状动脉钙化(CAC)之间存在显著的正相关，这与其他CHD危险因素无关。相反，我们发现女性的总睾酮浓度与颈动脉内中膜厚度(IMT)呈独立的负相关。总体而言，这些结果表明，与女性相比，激素环境对亚临床动脉粥样硬化的影响可能不同。拟议项目的总体目标是在多种族动脉粥样硬化研究(MESA)的3259名男性和2802名绝经后女性参与者中，检查血清性激素浓度与亚临床动脉粥样硬化的存在和进展的关系。亚临床动脉粥样硬化将同时使用CAC和颈动脉IMT来识别。进展将通过CAC在3.5年内的变化来确定。将评估在MESA基线检查中收集的储存血清样本中总(和游离)睾酮(T)、脱氢表雄酮(DHEA)、17β-雌二醇(E2)和性激素结合球蛋白(SHBG)的循环浓度。实验室结果将与在MESA收集的现有人口统计、人体测量、生活方式、冠心病风险因素和亚临床疾病数据合并。将使用横断面和前瞻性的统计分析方法来评估拟议的关联。MESA特别适合于弄清激素因素和冠心病风险因素对亚临床动脉粥样硬化的影响，因为可以获得高质量的数据、血清样本以及对大量多种族男性和女性的CAC和IMT测量。

DESCRIPTION (provided by applicant): Throughout their lifetime, men are at higher risk of coronary heart disease (CHD) than women, however, after menopause this difference is attenuated. This observation suggests that endogenous sex hormones could be associated with CHD risk. There is some evidence indicating that the effect of sex hormones on CHD risk could be mediated, in part, by alterations in lipid levels or other CHD risk factors. However, other evidence supports an independent relationship of circulating hormone levels with CHD risk. For example, we recently reported a significant positive association between serum total testosterone concentration and the presence of subclinical coronary artery calcium (CAC) in young adult men that was independent of other CHD risk factors. Conversely, we showed an independent inverse association between total testosterone concentration and carotid intimal-medial wall thickness (IMT) in women. Overall, these results suggest that the influence of the hormonal milieu on subclinical atherosclerosis may not be the same in men compared to that in women. The overall objective of the proposed project is to examine the associations of serum sex hormone concentrations with the presence and progression of subclinical atherosclerosis in 3,259 male and 2,802 postmenopausal female participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Subclinical atherosclerosis will be identified using both CAC and carotid IMT. Progression will be identified by the change in CAC over 3.5 years. Circulating concentrations of total (and free) testosterone (T), dehydroepiandrosterone (DHEA), 17 beta-estradiol (E2), and sex hormone binding globulin (SHBG) in stored serum samples collected at the MESA baseline exam will be assessed. Laboratory results will be merged with existing demographic, anthropometric, lifestyle, CHD risk factor, and subclinical disease data collected in MESA. Cross-sectional and prospective methods of statistical analysis will be used to assess the proposed associations. MESA is particularly well suited for disentangling the effects of hormonal factors and CHD risk factors on subclinical atherosclerosis because of the availability of high-quality data, serum samples, and CAC and IMT measurements in a large multi-ethnic population of men and women.