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: 7587703
• 负责人: ADRIAN S. DOBS
• 金额: $ 14.73万
• 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 2010-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7587703
• 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; Condition; 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; Inflammatory; 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; Score; Serum; Severities; Sex Behavior; Sex Hormone-Binding Globulin; Staging; Testing; Testosterone; Thick; Universities; Vascular Diseases; Viral; Visceral; base; cardiovascular disorder risk; cardiovascular risk factor; cognitive function; cohort; cysteine rich protein; frailty; intima media; member; men; mortality; pre-clinical; 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心血管疾病 (CVD) 之间的关系及其 HIV 阳性男性和非法药物使用者 (IDU) 的危险因素。多项研究记录了这些人群中 CVD 的过早进展和加速进展。尽管这可能是潜在病毒机制、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该人群对动脉粥样硬化疾病和代谢异常的易感性增加。我们是最早报告艾滋病毒感染男性性腺功能减退症患病率增加的群体之一，最终发现这会导致生活质量差、去脂体重减少和内脏肥胖增加。几项基于人群的研究现已发现，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（导致葡萄糖不耐受、糖尿病）、炎症或更直接影响脉管系统而成为 CVD 的危险因素。 MACS 队列已经开展了一项子研究，记录约 1000 名男性的早期动脉粥样硬化情况，测量颈动脉内膜内侧厚度 (CIMT) 和冠状动脉钙 (CAC) 评分。我们的总体假设是，血清 T 水平较低的 HIV + 男性更有可能患有临床前 CVD。我们的具体目标是： #1：检查性激素与艾滋病毒感染者和注射吸毒者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：在调整疾病阶段、持续时间和 HIV 治疗成分的状态和标志物后，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，通过 CAC 和 CIMT 测量。 #2：测量性激素水平与可改变的心血管危险因素（炎症标志物、脂质、脂蛋白、糖尿病和血压）的患病率、水平和变化之间的关系，并调整疾病阶段和艾滋病毒成分的状态和标志物治疗）。假设#2：低血清 T 与可改变的 CVD 危险因素（炎症标志物、血脂、脂蛋白、糖尿病和血压）独立相关，并根据疾病阶段、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 MACS 博士合作使用最新的检测方法，测量 MACS 男性的总 T、性激素结合球蛋白 (SHBG)、雌二醇和黄体生成素 (LH)，这些男性已接受临床前动脉粥样硬化和代谢性疾病评估。巴辛，波士顿。此外，有了这些数据，我们就有了探索极有可能与性激素相关的其他研究途径的令人兴奋的可能性，例如。性行为、认知功能和虚弱。低睾酮水平可能是心血管疾病 (CVD) 及其危险因素（例如糖尿病）的危险因素。由于激素异常在 HIV 感染中很常见，因此我们打算测量 MACS 队列中一部分人的性激素，这些人已经接受了专门的测试来检测早期临床前 CVD。这将有助于更好地了解低性激素对代谢疾病的贡献和时间性质。