Mentored Scientist Award

HIV-infected individuals on otherwise effective therapy have a higher than expected risk of cardiovascular disease (CVD). MicroRNAs (miRNAs) have emerged as potential, promising biomarkers that can not only provide incremental value over current risk prediction models for CVD but can also shed light on the molecular mechanisms underlying HIV-associated CVD. We will determine the association between circulating and endothelial miRNAs with myocardial infarction (MI) and impaired endothelial function in HIV-infected individuals using flow-mediated vasodilation of the brachial artery (FMD), which is a physiologic assessment of endothelial function and a strong predictor of future CVD events. Objective: Aim 1: We will use specimens from the Center for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) cohort, a multicenter clinic-based cohort of 27,000 HIV-infected individuals with detailed clinic data, adjudicated CV events, and archived biologic specimens, to determine the association between circulating miRNAs and MI. Aim 2: To correlate endothelial and circulating microRNA expression with FMD. Design/Duration: In Aim 1, we will perform a nested case-control study of the CNICS cohort over the next year comparing circulating microRNA expression in HIV-infected individuals with and without subsequent adjudicated MI within 6 months. For Aim 2, we will perform a cross-sectional study over the next year of treated and suppressed HIV-infected individuals from a well-characterized local HIV cohort to correlate endothelial and circulating miRNA expression with CVD risk, as measured by FMD. Statistical Analysis: We will use descriptive statistics and Wilcoxon rank sum test to compare miRNA levels between cases and controls and between high FMDs and low FMDs group. We will use multivariable conditional logistic regression to analyze the association of circulating microRNAs with presence of MI, before and after adjusting for traditional CVD risk factors and HIV-related features. We will adjust final p-values by using Holm multiple testing adjustment method.