A novel biomarker to identify atherosclerotic cardiovascular disease in people with HIV and assessment of clinical and ECG features associated with incident sudden cardiac or undetermined death: Insights from the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE)

Abstract

The two manuscripts presented for this thesis have both analytical and thematic content links that are consistent with: 1. addressing important scientific questions in a historically underserved/under recognized high cardiovascular risk primary prevention population, and 2. Demonstrating the student’s facility with analysis and interpretation of clinical trial data using dieerent study designs for these secondary analyses. These analyses of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) also utilize the clinical trial expertise of the student’s mentors, one who is the study principal investigator (SG) and the other who was the study endpoint committee chairman (SW) who also serves in this capacity for many phase III cardiovascular clinical trials managed through the Harvard based academic research organization, the TIMI study group. The overarching theme is that people with HIV (PWH) are at increased risk of cardiovascular disease even in the present era of excellent viral suppression with antiviral therapy.(1) The first manuscript utilizes a cross-sectional design to evaluate the associations of “high-risk” coronary atherosclerosis imaged by CT coronary angiography (CTCA) in a REPRIEVE sub study with the cardiac specific circulating protein, cardiac troponin T (cTnT) measured by high-sensitive assay.(2, 3) We further sought to understand if this biomarker could augment discrimination between those participants with and without these plaque features.(3) Next utilizing a longitudinal study design we investigated clinical and ECG features associated with carefully adjudicated sudden cardiac and undetermined deaths highlighting the importance of meticulous adjudication to characterize the dieerences in the clinical phenotypes in participants with these outcomes.