It’s been well recognized that LDL cholesterol reduction, particularly with statin therapy, is of great benefit for the prevention of atherosclerotic cardiovascular disease (ASCVD). However, there is still a significant “residual risk” regarding ASCVD prevention for those whose LDL levels have reached an ideal goal. This residual risk may of course include many other well known risk factors, such as smoking, hypertension, diabetes, inflammatory diseases, even air pollution, …and so forth. Some risk factors are still an issue of debate, among them, triglyceride (TG)-rich lipoproteins (TGRLPs) and low HDL levels have recently drawn lots of attention.
　　Recommendations for the management of hypertriglyceridemia from well-known professional organizations or associations have fluctuated over the past three decades. Guidelines have varied from a need to reduce TG levels to no advice on treatments. Epidemiological studies suggest that TGRLPs characterized by high TG and remnant cholesterol are strong predictors of ASCVD and all-cause mortality. For individuals in the general population with nonfasting TG of 580 mg/dl versus those with levels of 70 mg/dl, the risks are 5.1-fold for myocardial infarction, 3.2-fold for stroke, and 2.2-fold for all-cause mortality. However, epidemiological studies which are excellent in demonstration of the association between biomarkers and ASCVD, fail to reveal causal relationship, leading to an impression that low HDL cholesterol levels have long been deemed as a “cause” of ASCVD. Recent genetic evidence using the Mendelian randomization design suggests that TGRLPs are causally associated with ASCVD and all-cause mortality, but HDL is not. For TGRLPs, the strongest evidence revolves around lipoprotein lipase and its endogenous facilitator (APOA5) and inhibitory protein (APOC3, ANGPTL4).
　　Taken together, these genetic results suggest that pharmacological lowering of TGRLPs would reduce risk for ASCVD, but this remains to be confirmed through randomized controlled trials.