Serum Sex Hormones and Cardiovascular Risk in the MACS

MACS 中的血清性激素和心血管风险

• 批准号: 7686101
• 负责人: ADRIAN S. DOBS
• 金额: $ 14.08万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2010-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7686101
• 关键词: Acquired Immunodeficiency Syndrome; Anti-Retroviral Agents; Atherosclerosis; Biological Assay; Biological Markers; Blood Pressure; Boston; C-reactive protein; CD4 Lymphocyte Count; Calcium; Cardiovascular Diseases; Cardiovascular system; Chronic; Clinical; Clinical Markers; Cohort Studies; Collaborations; Coronary; Coronary artery; Data; Diabetes Mellitus; Disease; Disease Marker; Disease Progression; Doctor of Medicine; Drug user; Estradiol; Event; Glucose Intolerance; Goals; Gonadal Hormones; Gonadal Steroid Hormones; HIV; HIV Infections; HIV therapy; Highly Active Antiretroviral Therapy; Hormonal; Hypogonadism; Illicit Drugs; Inflammation; Lead; Lipids; Lipoproteins; Malignant Neoplasms; Measures; Medial; Metabolic Diseases; Metabolic Pathway; Methodology; Modeling; Nature; Obesity; Outcome; Participant; Pharmacotherapy; Population; Predisposition; Prevalence; Quality of life; RNA; Reporting; Research; Risk Factors; Serum; Severities; Sex Behavior; Sex Hormone-Binding Globulin; Staging; Testing; Testosterone; Thick; Universities; Vascular Diseases; Viral; Visceral; cardiovascular disorder risk; cardiovascular risk factor; cognitive function; cohort; frailty; inflammatory marker; intima media; member; men; mortality; population based; pre-clinical; premature; prospective; wasting

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.

描述（由申请人提供）：我们的总体目标是了解性激素与男性HIV+和非法药物使用者（IDU）心血管疾病（CVD）及其危险因素之间的关系。一些研究已经证实了这些人群中心血管疾病的过早和加速进展。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疾病和代谢异常的易感性增加。我们是第一批报告艾滋病毒感染男性性腺功能减退患病率增加的群体之一，最终发现这导致生活质量差，瘦体重下降和内脏肥胖增加。几项基于人群的研究发现，低血清睾酮(T)与男性死亡率增加有关。低血清T可能通过增加内脏脂肪（导致葡萄糖耐受不良、糖尿病）、炎症或对脉管系统更直接的影响而成为CVD的危险因素。MACS队列已经进行了一项亚研究，记录了大约1000名男性的早期动脉粥样硬化，测量了颈动脉内膜中层厚度（CIMT）和冠状动脉钙（CAC）评分。我们的总体假设是，血清T水平低的HIV阳性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：检查性激素与hiv感染和IDU男性动脉粥样硬化严重程度的关系，并调整经典动脉粥样硬化危险因素。假设1：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，通过CAC和CIMT测量，在调整疾病阶段和持续时间的状态和标志物以及HIV治疗成分后。#2：测量性激素水平与患病率、可改变的CV危险因素（炎症标志物、脂质、脂蛋白、糖尿病和血压）的水平和变化之间的关系，并调整疾病阶段和HIV治疗成分的状态和标志物。假设2：低血清T与可改变的CVD危险因素（炎症标志物、脂质、脂蛋白、糖尿病和血压）独立相关，并与疾病分期、持续时间和HIV治疗成分的状态和标志物进行调整。为了实现这些具体目标，我们将与波士顿Bhasin博士合作，使用最新的检测方法，测量MACS男性的总T和游离T、SHBG、雌二醇和LH，这些男性已被评估为临床前动脉粥样硬化和代谢疾病。此外，有了这些数据，我们有可能探索其他极有可能与性激素相关的研究途径，例如性行为、认知功能和脆弱性。低睾酮水平可能是心血管疾病（CVD）及其危险因素（如糖尿病）的一个危险因素。由于激素异常在hiv感染中很常见，我们打算在MACS队列的一个子集中测量性激素，这些患者已经进行了专门的测试来检测早期临床前CVD。这将有助于更好地理解性激素水平低对代谢性疾病的贡献和时间性质。