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

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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.