Abstract Body (Do not enter title and authors here): BACKGROUND: Higher total cholesterol (TC) and LDL-C levels may improve outcomes in heart failure (HF) patients. Elevated remnant cholesterol (RC) is a novel potential atherosclerosis risk factor, but its role in HF is underexplored.

AIM: To investigate classical (TC, LDL-C, triglycerides (TG), and HDL-C) and novel (RC) lipid parameters (LP) as risk determinants for CV events in HF patients across the LVEF spectrum.

METHODS: We pooled participant-level data from the PARADIGM-HF (LVEF ≤40%) and PARAGON-HF (LVEF ≥45%) trials to assess the association of LP with CV outcomes. RC was calculated as TC minus the sum of HDL-C and LDL-C. Lipid levels were classified per the National Lipid Association and RC by quartiles. The associations with time to first HF hospitalization and myocardial infarction (MI) were evaluated by adjusted Cox proportional hazards models stratified by trial. Restricted cubic splines accounted for potentially non-linear relationships.

RESULTS: Of 12,819 participants with available lipid data, 1,967 (15.3%) experienced HF hospitalization and 442 (3.4%) had an MI. Over a median follow-up of 2.6 years, various LP were not consistently or significantly associated with risk of HF hospitalization, while higher RC and TC were linked to increased risk of MI (Table 1). When evaluating LP continuously, there was a significant non-linear association between RC and risk of HF hospitalization, with a nadir in risk at ~ 20-30 mg/dL (Figure 1). In contrast, higher levels of RC, LDL-C, and TC were linearly and significantly associated with risk of MI. None of the results were modified by LVEF.

CONCLUSION: In a global HF population, higher RC levels were consistently associated with increased risk of MI, while the relationship between RC and the more frequent endpoint of HF hospitalization appeared to be more complex and inconsistent. These data might explain why previous interventional lipid lowering trials have not modified disease course in HF.