Proteomics and the Role of HIV Infection in Cardiac Remodeling

Abstract

Cardiac remodeling, defined as structural and/or functional alterations of the heart, is an early and pivotal feature within the pathophysiologic spectrum of heart failure (HF). Improved detection of cardiac remodeling could aid in earlier HF intervention, more refined risk prediction, more precise characterization of clinical disease, and more effective mitigation of HF progression. This is true both in the general population and higher risk populations, such as persons living with HIV (PLWH). There is a large and growing burden of cardiovascular disease (CVD) among PLWH, and even in the context of effective, modern antiretroviral treatment, PLWH have a higher risk of HF relative to HIV-uninfected populations. Characterization of cardiac structural phenotypes among clinically relevant HIV patient populations is, however, both inconsistent and limited. In the first chapter, we analyzed data from the Multi-Ethnic Study of Atherosclerosis and report proteomic profiling of left ventricular structural phenotypes. Our results highlight the promise of more recently identified biomarker candidates for cardiac remodeling and HF. In the second chapter, we sought to externally validate previously identified cardiac remodeling biomarker candidates using data from the Veterans Aging Cohort Study, which has a high representation of PLWH. In the third chapter, we utilized data on over 19,000 veterans referred for echocardiography within Veterans Affairs healthcare system, the largest single provider of HIV care in the United States, to better characterize cardiac structure among PLWH. We found that HIV infection and measures of HIV disease severity were cross-sectionally associated with adverse cardiac structural phenotypes. Among a subsample of participants with proteomic profiling, we also observed associations between candidate biomarkers of cardiac remodeling and both HIV serostatus and measures of greater HIV disease severity. This dissertation ultimately leveraged data from unique and classical epidemiologic sources to advance research on candidate biomarkers of and the role of HIV infection in cardiac remodeling.