Abstract 4368444: Triglyceride in different ApoB-containing lipoproteins and risk of coronary artery disease: particle type matters

Abstract

Introduction: Plasma triglyceride (TG), mostly embedded in apoB-containing particle (apoB-P), has been proposed as a potential residual risk factor for atherosclerotic cardiovascular disease (ASCVD). However, the atherogenicity of TG in different types of ApoB-P, especially the causality, remains unclear given that the per-particle atherogenicity varies among different types of apoB-P. Research questions: To investigate the association TG content in various types of ApoB-P with the risk of coronary artery disease (CAD) in both observational and genetic study. Methods: Observational study was conducted in 169 301 UK Biobank participants with complete nuclear magnetic resonance lipoprotein profiling data and without a history of ASCVD, diabetes, or lipid-lowering therapy. Multivariate Cox proportional hazard regression was used to determine the association between TG levels in different apoB-P and risk of incident CAD. Genetic study was performed using individual-level data from 472 495 UK Biobank participants of European ancestry. One-sample mendelian randomization (MR) was performed with weighted polygenic scores as instrumental variables, which were calculated with genetic variants strongly associated with TG in various subfractions of ApoB-P. Results: In the observational study, very-low-density lipoprotein (VLDL) TG (adjusted hazard ratio [aHR] per one standard deviation [SD], 1.04; 95% CI, 1.02 - 1.06), intermediate-density lipoprotein (IDL) TG (aHR per one SD, 1.10; 95% CI, 1.08-1.12) and low-density lipoprotein (LDL) TG (aHR per one SD, 1.09; 95% CI, 1.07-1.11) were each individually associated with incident CAD. When subfractions of apoB-P were taken into account, the aHR were higher with TG in smaller size VLDL, ranging from 1.03 (95% CI, 1.01 - 1.05) for extra extra large VLDL TG to 1.08 (95% CI, 1.06 - 1.10) for extra small VLDL TG, whereas lower with TG in smaller size LDL, ranging from 1.06 (95% CI, 1.04 - 1.08) for small LDL TG to 1.10 (95% CI, 1.08 - 1.12) for large LDL TG. In one-sample MR, odds ratios (95% CI) per one SD higher genetically predicted VLDL TG, IDL TG, and LDL TG were 1.16 (1.12 - 1.21), 1.34 (1.29 - 1.39), and 1.37 (1.32 - 1.42) for CAD, respectively. Conclusions: The atherogenicity of both observed and genetically determined TG in apoB-P differs with regard to different particle size. The present observation reinforced the atherogenic mechanism of different apoB-P and shed light on critical target of TG-lowering strategy.