Serum Sex Hormones and Cardiovascular Risk in the MACS

描述(由申请人提供)：我们的总体目标是了解性激素与心血管疾病(CVD)及其危险因素之间的关系，以及艾滋病毒阳性和非法药物使用者(IDU)的风险因素。几项研究记录了这些人群中过早和加速的CVD进展。虽然这可能是潜在的病毒机制、抗逆转录病毒药物治疗或IDU的结果，但我们试图记录其他机制来解释这一人群对动脉粥样硬化性疾病和代谢异常的易感性增加。我们是第一批报告感染艾滋病毒的男性性腺功能低下症患病率增加的小组之一，最终发现这会导致生活质量下降、瘦体重减少和内脏肥胖增加。几项基于人群的研究现在发现，低血清睾酮(T)与男性死亡率的增加有关。血清T降低可能是心血管疾病的危险因素，可能是内脏脂肪增加(导致糖耐量低减、糖尿病)、炎症或对血管系统更直接的影响。MACS队列已经有一个子研究来记录大约1000名男性的早期动脉粥样硬化，测量颈动脉内膜中层厚度(CIMT)和冠状动脉钙化(CAC)评分。我们的总体假设是，血清T水平低的HIV+男性更有可能患有临床前心血管疾病。我们的具体目标是：#1：通过调整经典的动脉粥样硬化危险因素，检验性激素与HIV感染者和静脉注射吸毒者动脉粥样硬化严重程度的关系。假设1：根据CAC和CIMT的测量，在调整了疾病阶段的状态和标志物以及HIV治疗的持续时间和成分后，低血清T与临床前动脉粥样硬化的存在和严重程度独立相关。#2：衡量性激素水平与可改变的心血管危险因素(炎症标志物、血脂、脂蛋白、糖尿病和血压)的患病率、水平和变化的关系，并调整疾病阶段的状态和标志物以及艾滋病毒治疗的组成部分)。假设2：低血清T与可修改的心血管危险因素(炎症标志物、脂类、脂蛋白、糖尿病和血压)独立相关，并与疾病阶段的状态和标志物以及HIV治疗的持续时间和成分进行调整。为了实现这些特定的目标，我们将与波士顿的巴辛博士合作，使用最新的分析方法，测量MACS中男性的总和游离T、SHBG、雌二醇和黄体生成素，他们已经接受了临床前动脉粥样硬化和代谢性疾病的评估。此外，有了这些数据，我们有可能探索其他很可能与性激素相关的研究途径，例如性行为、认知功能和脆弱。低睾酮水平可能是心血管疾病(CVD)及其危险因素(如糖尿病)的危险因素。由于荷尔蒙异常在HIV感染中很常见，我们打算测量Mac队列中接受专门测试以检测早期临床前心血管疾病的一部分人的性激素。这将有助于更好地理解低性激素在代谢性疾病中的作用和时间性质。

DESCRIPTION (provided by applicant): Our overall goal is to understand the relationship between sex hormones and cardiovascular disease (CVD) and its risk factors in men who are HIV+ and illicit drugs users (IDU). Several studies have documented premature and accelerated CVD progression in these populations. Although this may be a consequence of the underlying viral mechanisms, anti-retroviral drug therapy, or IDU, we seek to document other mechanisms to explain the increased susceptibility to atherosclerotic disease and metabolic abnormalities in this population. We were one of the first groups to report an increased prevalence of hypogonadism in the HIV-infected men, which was eventually found to result in poor quality of life, decreased lean body mass and increased visceral adiposity. Several population-based studies have now found that low serum testosterone (T) is associated with increased mortality in men. Low serum T may be a risk factor for CVD through increased visceral adiposity (leading to glucose intolerance, diabetes mellitus), inflammation or a more direct effect on the vasculature. The MACS cohort already has in place a substudy to document early atherosclerosis in about 1000 men, measuring carotid intima medial thickness (CIMT) and coronary calcium (CAC) scores. Our overall hypothesis is that HIV+ men with low serum T levels are more likely to have pre-clinical CVD. Our specific aims are: #1: To examine the associations of sex hormones with the severity of atherosclerosis in HIV-infected and IDU men with adjustment for classical atherosclerosis risk factors. Hypothesis #1: Low serum T is independently associated with the presence and severity of pre-clinical atherosclerosis, measured by CAC and CIMT, after adjustment for status and markers of disease stage and duration and components of HIV therapy. #2: To measure the association of sex hormone levels with prevalence, levels and changes in modifiable CV risk factors (inflammatory markers, lipids, lipoproteins, diabetes, and blood pressure), with adjustment for status and markers of disease stage and components of HIV therapy). Hypothesis #2: Low serum T is independently associated with modifiable CVD risk factors (inflammatory markers, lipids, lipoproteins, diabetes, and blood pressure), with adjustment for status and markers of disease stage and duration and components of HIV therapy. To accomplish these specific aims, we will measure total and free T, SHBG, estradiol and LH in men in the MACS, who have been evaluated for pre-clinical atherosclerotic and metabolic disease, using the most up to date assays in collaboration with Dr. Bhasin, Boston. In addition, with this data we have the exciting possibility to explore other avenues of research that are highly likely to be associated with sex hormones, e.g. sexual behaviors, cognitive function and frailty. Low testosterone levels may be a risk factor for cardiovascular disease (CVD) and its risk factors, such as diabetes. Since hormonal abnormalities are common in HIV-infection, we intend to measure sex hormones in a subset of the MACS cohort who have had specialized tests to detect early, pre- clinical CVD. This will lead to a better understanding of the contribution and temporal nature of low sex hormones to metabolic diseases.