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.

项目摘要/摘要 艾滋病毒（PWH）的人即使在 控制传统的心血管（CV）风险因素。因此，需要改善简历风险的需求 PWH之间的分层。 HIV感染与全身免疫激活增加有关 炎症不是传统简历风险评估的一部分。重要的是，迄今为止在PWH的工作已经 限于评估系统性炎症生物标志物或利用血管的功能成像评估 大于冠状动脉的血管的炎症。评估大容器可防止直接评估 驱动冠状动脉斑块发展的当地冠状动脉炎症环境。尽管如此， 心脏计算机断层扫描（CT）的最新进展，专门评估了牙周围栏的密度 直接围绕冠状动脉的脂肪组织（PCAT），表明PCAT密度可能是 冠状动脉炎症的准确非侵入性指数。在拟议的研究中，我们将利用数据 从随机试验中获得的，以防止艾滋病毒（缓刑）中的血管事件 在无症状的关键系统性炎症标记中，易受伤害的斑块率很高 ART的PWH，只有低至中度的传统动脉粥样硬化心血管疾病（ASCVD）风险。我们 将首先评估冠状动脉炎症与关键心脏CT和深度免疫表型的关系 参数，包括在缓刑的机械性质量中获得的参数。我们将 进一步利用试验设计，涵盖了他汀类药物和序列的随机治疗试验 评估CTA参数以评估冠状动脉炎症和斑块的自然历史以及 他汀类药物治疗在PWH中的关键作用。具体而言，我们将分析冠状动脉炎症的独特关系， 以PCAT密度测量，以冠状斑块的发展和斑块组成的变化 与其他简历风险因素的关系，他汀类药物对冠状动脉炎症的影响 斑块量以及探索性分析中与MACE的关系。这项研究成功完成将 告知冠状动脉炎症在冠状牙菌斑发展中的关键，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。该赠款的数据，利用密钥ASCVD 因此，预防试验将为PWH中更具针对性的CV风险降低策略提供信息。