Abstract Fund Year 2023 OAR Strategic Funds are requested to perform high-throughput proteomic measurements to investigate the protein signatures of cardiac dysfunction in MWCCS. Previously collected blood specimens in participants who completed baseline echocardiography in MACS Visits 67-71 (n=1195) and WIHS Visits 44-50 (n=1655) will be used to measure proteomics in order to permit discovery of protein markers. Genotypic data in MACS and WIHS will be leveraged to conduct Mendelian randomization analysis using protein quantitative trait loci, allowing causal inference and selection of protein targets for pharmacotherapy. This supplement will support HIV/AIDS research corresponding to the following NIH high-priority AIDS-designated topics: (1) HIV-associated comorbidities; (2) cross-cutting areas involving clinical translational research, cardiovascular disease, proteomics, multi-omics, and health disparities; and (3) training of the next generation of HIV investigators in omics and comorbidities research.