Subclinical Vascular Disease and Metabolic Abnormalities in MACS

MACS 中的亚临床血管疾病和代谢异常

基本信息

批准号：
8300148
负责人：
WENDY S POST
金额：
$ 95.3万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-25 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8300148
关键词：
Abdomen Acquired Immunodeficiency Syndrome Address Angiography Area Arterial Fatty Streak Atherosclerosis Biological Assay Biological Markers Blood Blood Tests Blood Vessels Blood specimen CD4 Lymphocyte Count Calcified Calcium Cardiomyopathies Cardiovascular Diseases Carotid Artery Plaques Cells Chest Clinical Cohort Studies Control Groups Coronary artery Cross-Sectional Studies Data Disease Event Fatty acid glycerol esters Fibrinolysis Functional disorder General Population HIV HIV Infections Hepatic Highly Active Antiretroviral Therapy Hormones Image Imaging technology Immunologics Immunosuppression Individual Inflammatory Lead Left Lipoatrophy Liver diseases Measures Metabolic Myocardial dysfunction Obesity Obstruction Participant Pericardial body location Population Prevalence Prevention strategy Protocols documentation Risk Risk Behaviors Risk Factors Stenosis Testing Thick Thigh structure Thrombophilia Ultrasonography Vascular Diseases Ventricular Visceral X-Ray Computed Tomography adipokines bone turnover cardiovascular disorder prevention cardiovascular disorder risk cytokine demographics follow-up imaging modality improved intima media men men who have sex with men metropolitan new technology non-alcoholic fatty liver novel subcutaneous

项目摘要

There is controversy regarding the degree to which HIV infection and/or highly active antiretroviral therapy (HAART) contribute to the risk for cardiovascular disease (CVD). The Multicenter AIDS Cohort Study (MACS) is a unique long-standing multi-center observational longitudinal cohort study of men who have sex with men (MSM) in four U.S. metropolitan areas, and includes both HIV-infected (HIV+) and HIV-seronegative (HIV-) men. In the MACS, the number of CVD events is relatively low; therefore, to study this question, we have conducted a subclinical CVD study including coronary artery calcium (CAC) by CT scanning and carotid intima media thickness (IMT) and plaque by ultrasound. The initial cross sectional analyses are equivocal. These tests are now being repeated in the same men to evaluate short-term (3-year) longitudinal changes in these parameters of subclinical CVD. These equivocal results suggest that further study with more sensitive and specific imaging modalities, and/or longer follow-up of people treated with HAART, are necessary to examine potential associations between HIV infection and/or HAART and CVD and to identify factors associated with subclinical and ultimately clinical CVD. Both improved imaging and longer follow-up can be accomplished by continuing and extending the CVD studies begun in the MACS. Therefore, the specific aims of this application are: 1) to determine whether there is a difference in the a) prevalence and b) progression of subclinical CVD between HIV+ and HIV- men; and 2) to determine whether metabolic, inflammatory, immunologic and anthropomorphic markers potentially associated with HAART and/or HIV infection are associated with presence and/or progression of subclinical CVD, thus identifying potential mechanisms leading to subclinical CVD in this population. To address these aims, we will obtain the following studies in HIV+ and HIV- men (1) CT angiographic imaging of the coronary arteries (CTA), a novel technology that can visualize calcified as well as non-calcified atherosclerotic plaque, (2) measures of inflammatory, immunologic, metabolic, and anthropomorphic parameters with blood assays and CT imaging and (3) longitudinal changes in CAC and carotid IMT to build on the existing data that have been obtained in the MACS CVD substudy. Since HIV disease is associated with myocardial dysfunction we will characterize the prevalence and risk factors for left ventricular systolic dysfunction. An important strength of the MACS is the inclusion of a control group of HIV- men of similar demographics and HIV risk behaviors as HIV+ men. These men have been followed longitudinally with the same MACS protocol, thus allowing a comparison to the underlying population. As the number of people treated with HAART continues to rise, the need to further refine our understanding of any potential CVD risks becomes critical. The proposed studies will lead to an increased understanding of vascular and myocardial disease in HIV infection and potential mechanisms leading to subclinical CVD which can later be used to develop effective CVD prevention strategies in this population.

关于 HIV 感染和/或高效抗逆转录病毒治疗的程度存在争议（HAART）会增加心血管疾病（CVD）的风险。多中心艾滋病队列研究 (MACS) 是一项针对男男性行为者的独特的长期多中心观察性纵向队列研究 (MSM) 在美国四个大都市地区，包括 HIV 感染者 (HIV+) 和 HIV 血清阴性 (HIV-) 男人。在MACS中，CVD事件的数量相对较少；因此，为了研究这个问题，我们有进行了亚临床 CVD 研究，包括 CT 扫描和颈动脉内膜的冠状动脉钙 (CAC) 超声检查中层厚度 (IMT) 和斑块。最初的横截面分析是模棱两可的。这些现在正在同一男性身上重复进行测试，以评估这些方面的短期（3年）纵向变化亚临床CVD的参数。这些模棱两可的结果表明，进一步的研究需要更加敏感和需要特定的成像方式和/或对接受 HAART 治疗的患者进行更长时间的随访来检查 HIV 感染和/或 HAART 与 CVD 之间的潜在关联，并确定与亚临床和最终临床CVD。改进的成像和更长的随访时间可以通过继续并扩展 MACS 中开始的 CVD 研究。因此，本申请的具体目标是： 1) 确定亚临床 CVD 的 a) 患病率和 b) 进展是否存在差异 HIV+ 和 HIV- 男性之间； 2) 确定代谢、炎症、免疫和可能与 HAART 和/或 HIV 感染相关的拟人化标记与亚临床 CVD 的存在和/或进展，从而确定导致亚临床 CVD 的潜在机制该人群的CVD。为了实现这些目标，我们将获得以下针对 HIV+ 和 HIV- 男性的研究 (1) 冠状动脉 CT 血管造影 (CTA) 是一种可以显示钙化情况的新技术作为非钙化动脉粥样硬化斑块，(2) 炎症、免疫、代谢和血液分析和 CT 成像的拟人化参数以及 (3) CAC 和的纵向变化颈动脉 IMT 以 MACS CVD 子研究中获得的现有数据为基础。自从艾滋病毒疾病与心肌功能障碍有关，我们将描述左心室心肌病的患病率和危险因素心室收缩功能障碍。 MACS 的一个重要优势是纳入了 HIV 对照组人口统计数据和艾滋病毒风险行为与艾滋病毒阳性男性相似的男性。这些人已被跟踪纵向使用相同的 MACS 协议，从而可以与基础人群进行比较。作为接受HAART治疗的人数持续增加，需要进一步完善我们对任何治疗的理解潜在的CVD风险变得至关重要。拟议的研究将加深对血管的了解 HIV 感染中的心肌病和导致亚临床 CVD 的潜在机制用于针对该人群制定有效的 CVD 预防策略。