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.

项目概要/摘要 HIV 感染者 (PWH) 的冠状动脉疾病 (CAD) 和不良事件风险较高，即使在感染后 控制传统的心血管（CV）危险因素。因此，改善心血管风险的需求尚未得到满足 PWH 之间的分层。 HIV 感染与全身免疫激活增加有关 炎症不属于传统心血管风险评估的一部分。重要的是，迄今为止，PWH 的工作已经 仅限于评估全身炎症生物标志物或利用血管的功能成像评估 比冠状动脉大的血管发炎。评估大型船舶阻碍了直接评估 促进冠状动脉斑块形成的局部冠状动脉炎症环境。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 直接包围冠状动脉的脂肪组织（PCAT）表明 PCAT 密度可能是 准确的非侵入性冠状动脉炎症指数。在拟议的研究中，我们将利用数据 从预防 HIV 血管事件的随机试验 (REPRIEVE) 中获得，我们在该试验中表明 无症状人群中易损斑块的比例很高，与关键的全身炎症标志物相关 接受 ART 治疗的 PWH 仅有低至中度的传统动脉粥样硬化性心血管疾病 (ASCVD) 风险。我们 首先将评估冠状动脉炎症与关键心脏 CT 和深度免疫表型分析的关系 参数，包括非钙化斑块体积，在 REPRIEVE 的机械亚研究中获得。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系列 评估 CTA 参数以评估冠状动脉炎症和斑块的自然史以及 他汀类药物治疗在 PWH 中的关键作用。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，以了解冠状动脉斑块的发展和斑块成分的变化 与其他心血管危险因素的关系，他汀类药物对冠状动脉炎症的影响与 斑块体积以及探索性分析中与 MACE 的关系。成功完成本研究将 告知冠状动脉炎症在冠状动脉斑块形成中的关键、独立作用 在 PWH 中，并首次确定冠状动脉炎症的减少是否有助于他汀类药物 对该人群中斑块参数的相关影响。来自本次资助的数据，利用关键的 ASCVD 因此，预防试验将为在感染者中制定更有针对性的心血管风险降低策略提供信息。