Do Triglyceride-Rich Lipoproteins Equal Low-Density Lipoproteins in Risk of ASCVD?

Abstract

Recent large clinical trials have failed to show that triglyceride-rich lipoprotein-lowering therapies decrease the risk of atherosclerotic cardiovascular disease (ASCVD). In this review, we reconcile these findings with evidence showing that elevated levels of triglyceride-rich lipoproteins and the cholesterol they contain, remnant cholesterol, cause ASCVD alongside low-density lipoprotein (LDL) cholesterol. Results from observational epidemiology, genetic epidemiology, and randomized controlled trials indicate that lowering of remnant cholesterol and LDL cholesterol decrease ASCVD risk by a similar magnitude per 1 mmol/L (39 mg/dL) lower non-high-density lipoprotein cholesterol (remnant cholesterol+LDL cholesterol). Indeed, recent guidelines for ASCVD prevention recommend the use of non-high-density lipoprotein cholesterol instead of LDL cholesterol. Current consensus is moving towards recognizing remnant cholesterol and LDL cholesterols as equals per 1 mmol/L (39 mg/dL) higher levels in the risk assessment of ASCVD; hence, triglyceride-rich lipoprotein-lowering therapies should also lower levels of non-HDL cholesterol to reduce ASCVD risk.