Progression of Coronary Atherosclerosis in MACS

MACS 中冠状动脉粥样硬化的进展

• 批准号: 9047317
• 负责人: WENDY S POST
• 金额: $ 72.14万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-07 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9047317
• 关键词: Acquired Immunodeficiency Syndrome; Age; Aging; Arterial Fatty Streak; Atherosclerosis; Baltimore; Biological Markers; Blinded; Blood flow; Calcified; Cardiovascular Diseases; Characteristics; Chicago; Chronic; Cicatrix; Cohort Studies; Computer software; Coronary; Coronary Arteriosclerosis; Coronary artery; Coronary heart disease; Cross-Sectional Studies; Data; Databases; Disease; Event; Exposure to; Fatty acid glycerol esters; Functional disorder; Funding; General Population; HIV; HIV Infections; Health; Heart failure; Highly Active Antiretroviral Therapy; Image; Incidence; Individual; Interleukin-18; Knowledge; Lead; Left; Left Ventricular Ejection Fraction; Life Style; Measures; Methods; Myocardial; Myocardial perfusion; Myocardium; Observational Study; Outcome; Participant; Pathogenesis; Patients; Perfusion; Persons; Prevalence; Prevention strategy; Protocols documentation; Radiation; Recruitment Activity; Research Infrastructure; Rest; Risk; Rupture; Scanning; Serum; Thrombosis; Time; Ultrasonography; Ventricular; Visceral; Washington; Work; X-Ray Computed Tomography; acute coronary syndrome; aged; attenuation; base; calcification; cardiovascular disorder prevention; cohort; comparison group; coronary computed tomography angiography; coronary fibrosis; experience; follow-up; high risk; imaging modality; indexing; longitudinal design; men; men who have sex with men; novel marker; older men; primary outcome; study population; subcutaneous; sudden cardiac death

DESCRIPTION (provided by applicant): Observational studies suggest that HIV infection is associated with an increased incidence of cardiovascular disease (CVD) events, including coronary heart disease and sudden cardiac death (SCD), compared to the general population; however, the specific mechanisms leading to this increased risk are not well defined. The Multicenter AIDS Cohort Study (MACS) is an observational cohort study of men who have sex with men (MSM) that includes both HIV-infected (HIV+) and -uninfected (HIV-) participants. We have measured subclinical coronary atherosclerosis by coronary computed tomography angiography (CCTA) in 764 men in the MACS. We found a greater prevalence and extent of non-calcified coronary plaque among HIV+ than HIV- men. Older age was associated with a greater prevalence of non-calcified plaque in HIV+ men, but not HIV- individuals, in cross-sectional analyses of these 40-70-year old men. To clearly define the progression of coronary plaque in HIV+ treated people, a longitudinal CCTA study is needed. We propose a study to determine whether aging HAART-treated HIV+ men experience greater progression of non-calcified plaque volume than HIV- men. We will also identify plaques with specific features that characterize them as potentially vulnerable (i.e., plaques with low attenuation, outward remodeling, and spotty calcification) and put them at high risk for causing acute coronary syndromes. Emerging evidence suggests that HIV+ persons may be at increased risk for sudden cardiac death (SCD) and heart failure (HF) compared to the general population. We will evaluate left ventricular ejection fraction (EF) and myocardial perfusion abnormalities, since these are known to predispose to CVD events, including SCD and HF, and have not been well studied among HIV+ persons. Thus, this proposal will leverage an existing research infrastructure to achieve the following specific aims: Specific Aim 1: determine whether aging HIV+ men have a greater progression of non-calcified coronary atherosclerotic plaque than HIV- men over 4-6 years of follow-up. Secondary aims are to determine whether, compared to HIV- men, HIV+ men have a) a greater incidence of new non-calcified plaque and/or slower rates of transition from non-calcified to calcified plaque in individual coronary segments and b) a greater prevalence and incidence of high risk vulnerable plaques Specific Aim 2: determine whether HIV+ men are more likely than HIV- men to have myocardial abnormalities that could predispose them to SCD and HF. We will compare a) left ventricular EF and b) global myocardial perfusion index between HIV+ and HIV- men. Secondary aims include a comparison of the prevalences of left ventricular myocardial scar and resting perfusion abnormalities. The proposed studies will lead to a greater understanding of the pathogenesis and dynamics of CVD among HAART-treated HIV+ persons, knowledge which can then be used to develop effective CVD prevention strategies.

描述（由申请人提供）：观察性研究表明，与一般人群相比，HIV感染与心血管疾病（CVD）事件（包括冠心病和心源性猝死（SCD））的发生率增加相关;然而，导致这种风险增加的具体机制尚未明确。多中心艾滋病队列研究（MACS）是一项针对男男性行为者（MSM）的观察性队列研究，包括HIV感染者（HIV+）和未感染者（HIV-）。我们通过冠状动脉计算机断层扫描血管造影术（CCTA）测量了764名MACS男性的亚临床冠状动脉粥样硬化。我们发现HIV阳性者的非钙化性冠状动脉斑块的患病率和程度高于HIV阴性者。在对这些40-70岁男性的横断面分析中，年龄较大与艾滋病毒阳性男性非钙化斑块的患病率较高相关，但与艾滋病毒阴性男性无关。为了明确定义HIV+治疗人群中冠状动脉斑块的进展，需要进行纵向CCTA研究。我们提出了一项研究，以确定是否老化HAART治疗的HIV+男性经历更大的进展，非钙化斑块体积比HIV-男性。我们还将识别具有特定特征的斑块，这些特征将其表征为潜在的脆弱性（即，低衰减、向外重塑和点状钙化的斑块），并使它们处于引起急性冠状动脉综合征的高风险中。新出现的证据表明，与普通人群相比，HIV阳性者发生心脏性猝死（SCD）和心力衰竭（HF）的风险可能会增加。我们将评估左心室射血分数（EF）和心肌灌注异常，因为已知这些是CVD事件的易感因素，包括SCD和HF，并且尚未在HIV+人群中进行充分研究。因此，该提案将利用现有的研究基础设施来实现以下具体目标：具体目标1：确定在4-6年的随访中，老年HIV+男性的非钙化冠状动脉粥样硬化斑块的进展是否比HIV-男性更大。次要目的是确定与HIV-男性相比，HIV+男性是否a）新发非钙化斑块的发生率更高和/或个体冠状动脉段中非钙化斑块向钙化斑块转变的速率更慢，以及B）高危易损斑块的患病率和发生率更高。确定HIV阳性男性是否比HIV阴性男性更容易发生心肌异常，从而使他们易患SCD和HF。我们将比较HIV阳性和HIV阴性男性之间的a）左心室EF和B）总体心肌灌注指数。次要目的包括比较左心室心肌瘢痕和静息灌注异常的发生率。拟议的研究将导致更好地了解HAART治疗的HIV+人群中CVD的发病机制和动力学，这些知识可用于制定有效的CVD预防策略。