Identifying Risk Factors for Subclinical Myocardial Disease in HIV Infection
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DESCRIPTION (provided by applicant): HIV-infected (HIV+) adults are at increased risk for heart failure (HF) and sudden cardiac death (SCD) due to direct cardiotoxicity from HIV, highly active antiretroviral therapy (HAART) use, immune activation and inflammation, a high prevalence of traditional cardiovascular disease (CVD) risk factors and coronary artery disease (CAD), and substance use (including illicit drug and alcohol use). Myocardial fibrosis, assessed by cardiac MRI (CMR) or novel serum biomarkers, is strongly associated with CVD outcomes in HIV- cohorts. Other novel biomarkers of inflammation, cardiac injury and neurohormonal activation also predict outcome in HIV- cohorts and if applied to HIV+ cohorts, in combination with myocardial fibrosis measures, could provide etiologic explanations for the reported increases in HF and SCD. Only small studies of HIV+ adults have been done and suggest an increased prevalence of subclinical myocardial disease by CMR and elevated biomarkers of fibrosis and inflammation compared to HIV- individuals. None have examined etiologic relationships and small sample sizes limited assessment of mediators and confounding factors. We propose a study that will include both men and women with diverse modes of HIV acquisition and risk behaviors drawn from three long-standing, longitudinal cohort studies of demographically similar HIV+ and HIV- persons: men who have sex with men (MSM) in the Multicenter AIDS Cohort Study (MACS); women with and without intravenous drug use (IDU) in the Women's Interagency HIV Study (WIHS); and men and women with past and current IDU in the AIDS Linked to the Intravenous Experience (ALIVE) study. Each study has detailed data on risk factors for CVD. We will perform CMR to characterize subclinical myocardial disease burden and measure serum biomarkers of fibrosis, inflammation, injury and neurohormonal activation to determine if: (1) HIV+ individuals have greater myocardial disease burden than HIV- individuals, after controlling for age, sex and traditional CVD risk factors; (2) substance us and its characteristics are associated with myocardial disease burden and if greater substance use affects the association between HIV infection and myocardial disease burden; and (3) among the MACS participants who have undergone coronary CT angiography, CAD burden is associated with myocardial disease and its anatomic distribution, and whether this association differs by HIV serostatus. Overall, this study aims to investigate mechanisms that increase the risk for SCD and HF in HIV+ persons, by controlling for and identifying important confounding and modifying factors and by focusing on subclinical myocardial disease.
