Androgens and subclinical atherosclerosis in young women

描述（由申请人提供）：此修订后的申请代表了 年轻人冠状动脉风险发展的辅助研究 （CARDIA）研究，由NHLBI支持的大型队列研究。几项研究 已经证明了高雄激素血症的横断面相关性， 临床诊断的多囊卵巢综合征（PCOS）的生化特征， 冠状动脉危险因素和动脉粥样硬化。我们建议研究 血清雄激素，在生命早期测量，以及与 雄激素的合成、代谢和信号传导与早发性 来自社区的年轻成年女性的亚临床冠状动脉粥样硬化 此外，我们还将研究PCOS的临床特征是否 与年轻成年女性的亚临床冠状动脉粥样硬化相关， 在考虑了血清雄激素后CARDIA提供了一个独特的平台， 解决这些问题;拟议的辅助研究将增加 实验室和临床测量心脏需要检查这些 问题.在拟议研究的前瞻性部分，我们将审查 血清雄激素与遗传多态性和单倍型的关系 通过CT检测10个存在冠状动脉钙（CAC）的候选基因。 将使用储存的血清和DNA进行雄激素和基因分型测量 在CAC评估前5年和13年从1550名妇女中采集样本 年龄在33到45岁之间。在横截面组件中，我们将使用 在16年级拟定的辅助研究访视中收集的信息，以检查 PCOS的临床特征之间的关联，包括 经阴道超声检查发现多囊卵巢，月经 不规则，不孕症和多毛症，在15岁时存在CAC （n= 1200）。其次，我们将确定是否纵向变化， 肥胖、缺乏运动和胰岛素水平影响着 血清雄激素和候选基因中的遗传变异与 亚临床冠状动脉粥样硬化简而言之，拟议的研究涉及 潜在的重要和相对未探索的调查领域， 对女性心血管健康的影响

DESCRIPTION (provided by applicant): This revised application represents an ancillary study to the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a large cohort study supported by the NHLBI. Several studies have demonstrated cross-sectional associations of hyperandrogenism, the primary biochemical feature of clinically-diagnosed polycystic ovarian syndrome (PCOS), with coronary risk factors and atherosclerosis. We propose to examine whether serum androgens, measured earlier in life, and variation in genes related to androgen synthesis, metabolism, and signaling are associated with early-onset subclinical coronary atherosclerosis in young adult women from the community. Additionally, we will examine whether the clinical features of PCOS are associated with subclinical coronary atherosclerosis in young adult women, after taking into account serum androgens. CARDIA provides a unique platform to address these questions; and, the proposed ancillary study will add the laboratory and clinical measurements to CARDIA needed to examine these questions. In the prospective component of the proposed study, we will examine the associations of serum androgens and genetic polymorphisms and haplotypes in ten candidate genes with the presence of coronary artery calcium (CAC) by CT. Androgen and genotyping measures will be made using stored serum and DNA samples collected from 1550 women 5 and 13 years prior to the assessment of CAC at age 33 to 45 years. In the cross-sectional component, we will use information collected at a proposed ancillary study visit in Year 16 to examine the associations of the clinical features of PCOS, including the presence of polycystic ovaries detected using trans-vaginal ultrasound, menstrual irregularities, infertility, and hirsutism, with the presence of CAC at Year 15 (n= 1200). Secondarily, we will determine whether longitudinal changes in obesity, physical inactivity, and insulin levels influence the prospective associations of serum androgens and genetic variants in candidate genes with subclinical coronary atherosclerosis. In short, the proposed study addresses a potentially important and relatively unexplored area of investigation related to women's cardiovascular health.