Triglyceride-Rich Lipoproteins and Remnant Cholesterol in Cardiovascular Disease

ABSTRACT

Despite the well-established benefits of statin treatments in lowering low-density lipoprotein cholesterol (LDL-C), a significant residual risk for atherosclerotic cardiovascular disease (ASCVD) remains. Triglycerides (TGs) have long been recognized as potential residual risk factors in this context, but recent studies now disclose the substantial role of TG-rich lipoproteins (TRLs) and cholesterol components of metabolized TRLs (commonly referred to as remnant cholesterol) in atherogenesis, not just TGs alone. Evidence derived through diverse sources, including preclinical studies of pathogenic mechanisms, epidemiologic investigations, and genetic research, has consistently supported the considerable contribution of TRLs and remnant cholesterol in predicting occurrences of ASCVD. As emerging biomarkers for predicting atherosclerosis, they have thus become prioritized therapeutic targets, meant to augment LDL-C lowering efforts in individuals at high risk of ASCVD. However, routine clinical testing for remnant cholesterol and TRLs is still in question, necessitating further research into appropriate treatment plans if levels are elevated. New therapies targeting proteins in TG metabolic pathways, particularly angiopoietin-like protein 3 and apolipoprotein C-III, have shown potential advantages in patients with mild-to-moderate hypertriglyceridemia by reducing blood levels of TGs and remnant cholesterol. The aim of this review is to summarize existing evidence linking elevated TRLs and remnant cholesterol with development of ASCVD and to explore additional guidance for clinical therapy.