Abstract P186: HIV Status, Immune Cell Subsets and Type of Incident Heart Failure

Introduction: Immune dysfunction is a mechanism involved in atherosclerosis; atherosclerotic cardiac events contribute to heart failure (HF) risk. We investigated whether immune cell subtypes were associated with HF and HF types in people with and without HIV. Hypothesis: Six CD4+ and CD8+ T-cell subsets previously associated with atherosclerosis will be associated with increased HF with reduced ejection fraction (HFrEF) risk. Other lymphocyte subsets will be associated with increased HF with preserved ejection fraction (HFpEF) risk. Methods: We measured lymphocyte subsets (T-, B-, and natural killer cells) in the Veterans Aging Cohort Study (VACS) Biomarker Cohort. Primary analyses used Cox proportional hazards models to estimate hazard ratios of HFpEF or HFrEF per standard deviation increment in each of the 6 pro-atherosclerotic T-cell subsets. Secondary analyses used survival random forest analysis to rank the importance of a broader under-studied set of lymphocyte subsets in HF risk prediction and Cox models to estimate HF risk. Results: Among 2174 (66% PWH) participants without prevalent cardiovascular disease, 269 had incident HF (22% HFrEF, 47% HFpEF) over 8.8 years median follow-up time. Participants were predominantly male (>90%) and black (>66%). After adjusting for age, race/ethnicity, cytomegalovirus status, and HIV status, we did not detect associations the 6 T-cell subsets with HFrEF. We detected positive associations of CD4+CD28-, CD4+CD45RA+CD28-CD57+, TH1, TH17 cells with HFpEF. Survival random forest analysis revealed the relative importance of lymphocyte subsets for prediction of HF beyond those previously associated with atherosclerosis (Fig 1). Conclusion: Contrary to hypotheses, pro-atherosclerotic subsets of CD4+ and CD8+ T-cells were associated with HFpEF but not HFrEF. Other lymphocyte subsets previously-understudied for incident human cardiac outcomes were associated with HF incidence. Future work will examine whether these associations differ by HIV status.