Triglycerides as Residual Risk for Atherosclerotic Cardiovascular Disease

rich in cholesterol relative to TGs.Thus, elevated serum TG levels reflect increased levels of TRLs and may serve as biomarkers of elevated levels of cholesterol in remnants and as causal factors for atherosclerosis and ASCVD.VLDL and VLDL remnants can penetrate the arterial S everal epidemiological studies have reported that elevated serum triglyceride (TG) levels are associated with the risk of coronary artery disease (CAD).1,2 Additionally, elevated serum TG levels appear to be associated with a residual risk of atherosclerotic cardiovascular disease (ASCVD), despite the use of low-density lipoprotein cholesterol (LDL-C)-lowering statin therapy.3,4 However, an independent association between serum TG levels and the risk of future CAD events remains controversial, because this association is attenuated after adjusting for other lipid profile parameters, such as LDL-C and high-density lipoprotein cholesterol (HDL-C).1,2 Recent genetic evidence and Mendelian randomization studies provide robust evidence of the role of serum TGs in the causal pathway for ASCVD, indicating a possible pathogenetic role of these lipids in atherosclerosis rather than merely serving as biomarkers of disease risk. 5,6Kajikawa et al have previously demonstrated endothelial dysfunction even in individuals with serum TG levels of 106-131 mg/dL.7 However, whether patients with highnormal serum TG levels (100-149 mg/dL) are at an increased risk of cardiovascular events remains unclear.Those authors evaluated the association between serum TG levels and future cardiovascular events in patients with CAD in a post-hoc analysis of the FMD-J (Flow-Mediated Vasodilatation-Japan) study A. 8 Their present study 9 in this issue of the Journal demonstrates that elevated serum TG levels are significantly associated with an increased risk of first major cardiovascular events (MACE).After adjusting for various confounders, serum TG levels >100 mg/dL were significantly associated with an increased risk of cardiovascular events compared with levels <100 mg/dL.They conclude that serum TG levels >100 mg/dL (even in those with high-normal serum TG levels) are independently associated with the incidence of MACE in patients with CAD treated with optimal medical therapy.However, serum TGs per se do not accumulate in atherosclerotic plaques and are unlikely to directly cause atherosclerosis.TGs are major components of TG-rich lipoproteins (TRLs), such as chylomicrons ( CMs), very low-density lipoproteins (VLDLs), and intermediatedensity lipoproteins (IDLs).The core TGs comprising CMs and VLDLs are catabolized rapidly in the circulating blood by lipoprotein lipase (LPL) on the blood vessel walls, producing CM remnants and VLDL remnants, which are Article p 1064