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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.

关于艾滋病毒感染和/或高效抗逆转录病毒治疗的程度存在争议 (HAART)增加心血管疾病(CVD)的风险。多中心艾滋病队列研究(MACS) 是一项对男男性行为者进行的独一无二的长期多中心观察性纵向队列研究 (MSM)，包括HIV感染者(HIV+)和HIV血清阴性者(HIV-) 男人。在互委会，心血管事件的数量相对较少；因此，为了研究这个问题，我们有进行了一项亚临床CVD研究，包括CT扫描的冠状动脉钙化(CAC)和颈动脉内膜超声测量中膜厚度(IMT)和斑块。最初的横截面分析是模棱两可的。这些现在在同一批男性身上重复进行测试，以评估这些指标的短期(3年)纵向变化。亚临床脑血管病的相关参数。这些模棱两可的结果表明，进一步研究更敏感和有必要对接受HAART治疗的患者进行特定的成像方式和/或更长时间的随访。 HIV感染和/或HAART和CVD之间的潜在联系以及确定与亚临床和最终临床脑血管病。改进的成像和更长的随访时间都可以通过以下方式实现继续和延长在互委会开始的心血管疾病研究。因此，本申请的具体目的是 1)确定亚临床脑血管病的a)患病率和b)进展是否存在差异 HIV+和HIV男性之间的关系；以及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脑血管病的存在和/或进展，从而确定导致亚临床的潜在机制这一人群中的心血管疾病。为了达到这些目标，我们将获得以下关于艾滋病毒阳性和艾滋病毒男性的研究(1) 冠状动脉CT血管成像(CTA)--一种可显示钙化的新技术作为非钙化的动脉粥样硬化斑块，(2)炎症、免疫学、代谢和血液分析和CT成像的拟人化参数；(3)CAC和颈动脉IMT建立在MACS心血管疾病亚研究中获得的现有数据的基础上。因为HIV病毒疾病与心肌功能不全相关，我们将描述左心功能不全的患病率和危险因素心脏收缩功能不全。互委会的一个重要优势是纳入了艾滋病毒的控制组- 与HIV+男性具有相似人口统计和HIV危险行为的男性。这些人一直被跟踪纵向上使用相同的MACS协议，因此可以与潜在人口进行比较。作为接受HAART治疗的人数持续上升，需要进一步完善我们对任何潜在的心血管疾病风险变得至关重要。拟议的研究将导致对血管的更多了解 HIV感染中的心肌疾病和导致亚临床心血管疾病的潜在机制用于在这一人群中制定有效的心血管疾病预防战略。