Serum Sex Hormone Levels and Subclinical Atherosclerosis

描述（由申请人提供）：在其一生中，男性患冠心病（CHD）的风险高于女性，然而，绝经后这种差异减弱。这一观察结果表明，内源性性激素可能与冠心病的风险。有一些证据表明，性激素对冠心病风险的影响可能部分通过脂质水平或其他冠心病风险因素的改变来介导。然而，其他证据支持循环激素水平与CHD风险的独立关系。例如，我们最近报道了血清总睾酮浓度与年轻成年男性亚临床冠状动脉钙化（CAC）之间的显著正相关性，这与其他CHD风险因素无关。相反，我们发现女性的总睾酮浓度与颈动脉内膜-中层壁厚度（IMT）之间存在独立的负相关。总体而言，这些结果表明，激素环境对亚临床动脉粥样硬化的影响在男性中可能与女性不同。该项目的总体目标是在多种族动脉粥样硬化研究（梅萨）的3，259名男性和2，802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相关性。亚临床动脉粥样硬化将使用CAC和颈动脉IMT来识别。将通过CAC在3.5年内的变化确定进展。将评估梅萨基线检查时采集的储存血清样本中总（和游离）睾酮（T）、脱氢表雄酮（DHEA）、17 β-雌二醇（E2）和性激素结合球蛋白（SHBG）的循环浓度。实验室结果将与梅萨中收集的现有人口统计学、人体测量学、生活方式、CHD风险因素和亚临床疾病数据合并。将采用横断面和前瞻性统计分析方法来评估拟议的关联。梅萨特别适合于解开激素因素和CHD危险因素对亚临床动脉粥样硬化的影响，因为在大量多种族男性和女性人群中可以获得高质量的数据、血清样本以及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.