Pericoronary adipose tissue density a novel CT-derived marker of local inflammation and coronary artery disease in people living with HIV

冠状动脉周围脂肪组织密度是 HIV 感染者局部炎症和冠状动脉疾病的新型 CT 衍生标志物

• 批准号: 10762536
• 负责人: Borek Foldyna
• 金额: $ 43.04万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10762536
• 关键词: Acceleration; Address; Adipose tissue; Arterial Fatty Streak; Atherosclerosis; Biological Markers; Blood Vessels; Cardiac; Cardiovascular system; Characteristics; Coronary; Coronary Arteriosclerosis; Coronary artery; Data; Development; Distal; Etiology; Event; Fatty acid glycerol esters; Functional Imaging; General Population; Grant; HIV; HIV Infections; Immune; Inflammation; Inflammatory; Investments; Measurement; Measures; Mediating; Mediation; Natural History; Participant; Pathogenesis; Patients; Persons; Phenotype; Placebos; Population; Prevalence; Prevention trial; Randomized; Risk Assessment; Risk Factors; Risk Reduction; Role; Site; Time; Work; X-Ray Computed Tomography; adverse event risk; arm; atherogenesis; cardiovascular disorder prevention; cardiovascular disorder risk; cardiovascular risk factor; cohort; coronary plaque; cytokine; density; disorder risk; fluorodeoxyglucose positron emission tomography; histological studies; immune activation; improved; indexing; inflammatory marker; inflammatory milieu; novel; prevent; randomized trial; risk stratification; treatment trial; trial design; uptake; vascular inflammation

PROJECT SUMMARY/ABSTRACT People with HIV (PWH) have a heightened coronary artery disease (CAD) and adverse event risk even after controlling for traditional cardiovascular (CV) risk factors. Hence, there is an unmet need for improved CV risk stratification among PWH. HIV infection is associated with increased systemic immune activation and inflammation that is not part of the traditional CV risk assessment. Importantly, work to date in PWH has been limited to evaluating systemic inflammatory biomarkers or utilizing functional imaging assessments of vascular inflammation at vessels larger than the coronary arteries. Assessing large vessels prevents direct assessment of the local coronary inflammatory milieu that drives the development of coronary plaques. Nevertheless, recent advances in cardiac computed tomography (CT), specifically assessing the density of peri-coronary adipose tissue (PCAT) that directly surrounds the coronary arteries, suggest that PCAT density may be an accurate non-invasive index of coronary artery inflammation. In the proposed study, we will leverage data obtained from the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE), in which we have shown high rates of vulnerable plaque, in association with key systemic inflammatory markers, among asymptomatic PWH on ART, with only low to moderate traditional atherosclerotic cardiovascular disease (ASCVD) risk. We will first assess the relationship of coronary inflammation to critical cardiac CT and deep immune phenotyping parameters, including noncalcified plaque volume, obtained in the mechanistic substudy of REPRIEVE. We will further leverage the trial design, encompassing a randomized treatment trial of statin therapy and serial assessments of CTA parameters to assess the natural history of coronary inflammation and plaque and the key effects of statin therapy in PWH. Specifically, we will analyze the unique relation of coronary inflammation, measured as PCAT density, to coronary plaque development and changes in plaque composition in relationship to other CV risk factors, the effects of statins on coronary inflammation in relation to changes in plaque volume, and the relationship to MACE in exploratory analyses. Successful completion of this study will inform the field of the critical, independent role of coronary inflammation in the development of coronary plaque in PWH and determine for the first time whether a reduction in coronary inflammation contributes to statin- related effects on plaque parameters in this population. Data from this grant, leveraging a key ASCVD prevention trial, will thus inform the development of more targeted CV risk reduction strategies among PWH.

项目总结/摘要 HIV感染者（PWH）即使在治疗后也有较高的冠状动脉疾病（CAD）和不良事件风险。 控制传统的心血管（CV）风险因素。因此，改善CV风险的需求尚未得到满足 威尔斯亲王医院分层。HIV感染与增加的全身免疫激活有关， 炎症不是传统CV风险评估的一部分。重要的是，到目前为止，威尔斯亲王医院的工作 仅限于评价全身炎症生物标志物或利用血管功能成像评估 比冠状动脉大的血管的炎症。评估大型船舶妨碍直接评估 局部冠状动脉炎症环境的影响，导致冠状动脉斑块的发展。然而，尽管如此， 心脏计算机断层扫描（CT）的最新进展，特别是评估冠状动脉周围的密度 直接围绕冠状动脉的脂肪组织（PCAT），表明PCAT密度可能是一个 准确的冠状动脉炎症无创指数。在拟议的研究中，我们将利用数据 从随机试验中获得，以防止艾滋病毒血管事件（REPRIEVE），其中我们已经表明， 在无症状人群中，易损斑块的发生率较高，与关键的全身炎症标志物相关 接受ART的PWH，仅具有低至中度传统动脉粥样硬化性心血管疾病（ASCVD）风险。我们 将首先评估冠状动脉炎症与关键心脏CT和深层免疫表型的关系 REPRIEVE机制子研究中获得的参数，包括非钙化斑块体积。我们将 进一步利用试验设计，包括他汀类药物治疗的随机治疗试验和 评估CTA参数，以评估冠状动脉炎症和斑块的自然史， 他汀类药物治疗PWH的关键作用。具体来说，我们将分析冠状动脉炎症的独特关系， 测量为PCAT密度，冠状动脉斑块的发展和斑块组成的变化， 与其他CV风险因素的关系，他汀类药物对冠状动脉炎症的影响与 探索性分析中的斑块体积以及与MACE的关系。成功完成本研究将 告知该领域冠状动脉炎症在冠状动脉斑块发展中的关键、独立作用 并首次确定冠状动脉炎症的减少是否有助于他汀类药物- 对该人群斑块参数的相关影响。来自该补助金的数据，利用关键的ASCVD 因此，预防试验将为威尔斯亲王医院制定更有针对性的降低心血管风险策略提供信息。