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Triglyceride-Rich Lipoproteins and Remnant Cholesterol in Cardiovascular Disease
1Division of Endocrinology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea.
Insights
Elevated remnant cholesterol and triglyceride-rich lipoproteins (TRLs) contribute to atherosclerotic cardiovascular disease (ASCVD) risk, even with statin use. New therapies targeting TRLs show promise for managing this residual risk.
Area of Science:
- Cardiovascular Medicine
- Lipid Metabolism
- Atherosclerosis Research
Background:
- Statins effectively lower LDL-C but residual ASCVD risk persists.
- Triglycerides (TGs) and TG-rich lipoproteins (TRLs) are implicated in residual ASCVD risk.
- Remnant cholesterol, derived from TRLs, plays a significant role in atherogenesis.
Purpose of the Study:
- To review evidence linking elevated TRLs and remnant cholesterol to ASCVD.
- To explore the role of TRLs and remnant cholesterol as therapeutic targets.
- To discuss potential new therapies for managing residual ASCVD risk.
Main Methods:
- Review of preclinical studies, epidemiological data, and genetic research.
- Analysis of evidence supporting TRLs and remnant cholesterol as predictors of ASCVD.
- Examination of emerging therapeutic targets in TG metabolic pathways.
Main Results:
- Consistent evidence links TRLs and remnant cholesterol to ASCVD.
- These factors are emerging as prioritized therapeutic targets alongside LDL-C reduction.
- New therapies targeting angiopoietin-like protein 3 and apolipoprotein C-III show promise.
Conclusions:
- Elevated TRLs and remnant cholesterol represent a significant residual ASCVD risk.
- Further research is needed for routine clinical testing and treatment guidelines.
- Targeting TG metabolism offers a promising strategy to augment statin therapy.
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.
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