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）之间的关系及其在HIV+和非法吸毒者（IDU）的男性中的风险因素（IDU）。几项研究记录了这些人群中的过早和加速CVD的进展。尽管这可能是由于潜在的病毒机制，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，以解释该人群中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患病率增加的人之一，最终发现这会导致生活质量差，降低体重和内脏肥胖。现在，一些基于人群的研究发现，低血清睾丸激素（T）与男性死亡率的增加有关。低血清T可能是通过增加内脏肥胖（导致葡萄糖不耐症，糖尿病），炎症或对脉管系统更直接影响的CVD的危险因素。 MACS队列已经有了可以记录约1000名男性早期动脉粥样硬化的物质，测量了颈动脉内膜内侧厚度（CIMT）和冠状动脉钙（CAC）分数。我们的总体假设是，血清T水平较低的HIV+男性更有可能具有临床前CVD。我们的具体目的是：＃1：检查性激素与感染HIV感染和IDU男性的动脉粥样硬化的严重程度，并调整了经典动脉粥样硬化风险因素。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于CAC和CIMT测量，并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。 ＃2：衡量性激素水平与可修改的简历危险因素（炎症标志物，脂质，脂蛋白，糖尿病和血压）的患病率，水平和变化的关联，并调整了HIV疗法的疾病阶段和成分的状态和成分）。假设2：低血清T与可修改的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，并针对疾病阶段，持续时间以及HIV治疗的成分的状态和标记的调整调整。为了实现这些特定目标，我们将在MAC中衡量男性中的总和T，SHBG，雌二醇和LH，他们与波士顿Bhasin博士合作使用了最新的临床动脉粥样硬化和代谢性疾病。此外，借助这些数据，我们有令人兴奋的可能性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。低睾丸激素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，因此我们打算在MACS队列的一部分中测量具有专门测试以早期检测临床前CVD的性激素。这将使人们更好地理解低性激素对代谢疾病的贡献和时间性质。