Abstract 10438: Genetically Determined Levels of Apolipoprotein B and Low-Density Lipoprotein Are Not Associated With Increased Mortality in Heart Failure

Abstract

Introduction: Increased levels of low-density lipoprotein cholesterol (LDL-C) and its constituent apolipoprotein B (ApoB) are associated with atherosclerotic coronary disease, a risk factor for heart failure (HF). However, among patients with established HF, increased LDL-C has been associated with a lower risk of death. The potential causality of this association is unclear. Hypothesis: This study investigated the relationship between ApoB/LDL-C and adverse outcomes in participants with HF. Methods: We measured ApoB levels using the SomaScan assay among participants in the Penn Heart Failure Study (PHFS, n=1268). We performed one-sample Mendelian Randomization (MR) for ApoB and two-sample MR for ApoB and LDL-C. Results: Measured ApoB levels were inversely associated with the risk of death (Fig 1A) or death and heart failure hospital admission (DHFA; Fig 1B). One-sample MR revealed no significant association between genetically determined ApoB and the risk of death (HR 0.497, [95% CI, 0.20-1.2], p=0.125) or DHFA (HR 0.653, [95% CI, 0.35-1.2], p=0.182). Two-sample MR analyses were also consistent with a non-significant association between ApoB (Fig 2) or LDL-C (Fig 3) and risk of death or DHFA. Conclusions: ApoB is associated with the risk of death or DHFA in established HF. However, MR does not support a causal link between ApoB/LDL-C and the risk of adverse outcomes in this population.