Subclinical Vascular Disease and Metabolic Abnormalities in MACS

MACS 中的亚临床血管疾病和代谢异常

• 批准号: 7691240
• 负责人: WENDY S POST
• 金额: $ 96.25万
• 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: 2008-09-25 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7691240
• 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; Immune; Immunologics; 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; abstracting; 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

DESCRIPTION (provided by applicant): 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. There is controversy regarding the degree to which HIV infection, highly active antiretroviral therapy (HAART), or immune suppression contribute to the risk of CVD. This study will use novel imaging technology to measure subclinical vascular and myocardial disease and examine mechanisms for increased risk in HIV- infected compared with HIV-seronegative men. Results can be used to target prevention strategies. (End of Abstract)

描述（由申请人提供）： 关于HIV感染和/或高效抗逆转录病毒治疗（HAART）对心血管疾病（CVD）风险的影响程度存在争议。多中心艾滋病队列研究（MACS）是一项独特的长期多中心观察性纵向队列研究，研究对象为美国四个大都市地区的男男性行为者（MSM），包括HIV感染者（HIV+）和HIV血清阴性（HIV-）男性。在MACS中，CVD事件的数量相对较低;因此，为了研究这个问题，我们进行了一项亚临床CVD研究，包括通过CT扫描测量冠状动脉钙（CAC）和通过超声测量颈动脉内膜中层厚度（IMT）和斑块。最初的横截面分析是模棱两可的。这些测试现在正在重复相同的人，以评估短期（3年）的纵向变化，这些参数的亚临床CVD。这些模棱两可的结果表明，进一步研究更敏感和更具体的成像方式，和/或更长的后续与HAART治疗的人，是必要的检查HIV感染和/或HAART和CVD之间的潜在关联，并确定与亚临床和最终临床CVD相关的因素。通过继续和扩展在MACS中开始的CVD研究，可以改善成像和延长随访时间。因此，本申请的具体目的是：1）确定HIV+和HIV-男性之间亚临床CVD的a）患病率和B）进展是否存在差异;和2）确定可能与HAART和/或HIV感染相关的代谢、炎症、免疫和拟人标志物是否与亚临床CVD的存在和/或进展相关，从而确定导致该人群亚临床CVD的潜在机制。为了实现这些目标，我们将在HIV+和HIV-男性中进行以下研究：（1）冠状动脉CT血管造影成像（CTA），这是一种可以显示钙化和非钙化动脉粥样硬化斑块的新技术，（2）炎症、免疫、代谢、和拟人参数与血液化验和CT成像和（3）CAC和颈动脉IMT的纵向变化，以MACS CVD子研究中获得的现有数据为基础。由于艾滋病与心肌功能障碍有关，我们将描述左心室收缩功能障碍的患病率和危险因素。MACS的一个重要优势是纳入了与HIV阳性男性具有相似人口统计学特征和HIV风险行为的HIV阳性男性对照组。这些男性患者采用相同的MACS方案进行纵向随访，从而可以与基础人群进行比较。随着接受HAART治疗的人数不断增加，进一步完善我们对任何潜在CVD风险的理解变得至关重要。拟议的研究将导致对HIV感染中的血管和心肌疾病以及导致亚临床CVD的潜在机制的更多了解，这些机制随后可用于在该人群中制定有效的CVD预防策略。 关于HIV感染、高效抗逆转录病毒治疗（HAART）或免疫抑制对CVD风险的影响程度存在争议。这项研究将使用新的成像技术来测量亚临床血管和心肌疾病，并研究与HIV血清阴性男性相比，HIV感染者风险增加的机制。研究结果可用于制定有针对性的预防战略。(End摘要）