Abstract 14092: Remnant Cholesterol as a Causal Risk Factor for Ischemic Heart Disease

Abstract

Objective. We tested the hypothesis that elevated nonfasting remnant cholesterol is a causal risk factor for ischemic heart disease independent of reduced HDL cholesterol.

Background. Elevated remnant cholesterol associates with elevated levels of triglyceride-rich lipoproteins and with reduced high-density lipoprotein(HDL) cholesterol, and all associate with ischemic heart disease.

Methods. We genotyped 73,513 individuals from Copenhagen, of which 11,984 had ischemic heart disease diagnosed between 1976 and 2010. We selected 15 genetic variants affecting either 1) nonfasting remnant cholesterol alone, 2) nonfasting remnant cholesterol and HDL cholesterol combined, 3) HDL cholesterol alone, or 4) low-density lipoprotein(LDL) cholesterol alone as a positive control. The variants were used in a Mendelian randomization design.

Results. The causal odds ratio for a 1mmol/L(39mg/dL) genetic increase of nonfasting remnant cholesterol was 2.8(1.9-4.2), with a corresponding observational hazard ratio of 1.4(1.3-1.5). For nonfasting remnant cholesterol to HDL cholesterol ratio, corresponding values were 2.9(1.9-4.6) causal and 1.2(1.2-1.3) observational for a 1unit increase. However, for HDL cholesterol corresponding values were 0.7(0.4-1.4) causal and 1.6(1.5-1.7) observational for a 1mmol/L(39mg/dL) decrease. Finally, for LDL cholesterol corresponding values were 1.5(1.3-1.6) causal and 1.2(1.2-1.2) observational for a 1mmol/L(39mg/dL) increase.

Conclusions. Nonfasting remnant cholesterol increases of 1mmol/L(39mg/dL) associate with a 2.8-fold causal risk of ischemic heart disease, independent of reduced HDL cholesterol. This implies that elevated cholesterol content of triglyceride-rich lipoprotein particles cause ischemic heart disease.