REMNANT CHOLESTEROL IN ATHEROSCLEROTIC CARDIOVASCULAR DISEASE: CLINICAL AND THERAPEUTIC RELEVANCE

Rezumat

Background. Lowering low-density lipoprotein cholesterol (LDL-C) remains central to the prevention of atherosclerotic cardiovascular disease (ASCVD), yet clinically relevant residual risk persists in many patients despite attainment of recommended LDL-C goals. Remnant cholesterol (RC), which reflects the cholesterol carried by triglyceride-rich lipoproteins (TRLs) and their remnants, has therefore attracted interest as a complementary marker of lipid-related risk, particularly in hypertriglyceridemia and metabolic disease.

Methods. This narrative review synthesizes evidence from 40 publications identified through a comprehensive search of PubMed, Embase, Web of Science, and Scopus up to April 12, 2026. The search focused on peer-reviewed prospective studies, clinical trials, Mendelian randomization analyses, meta-analyses, and guidelines published in English between 2018 and 2026, alongside selected landmark studies required for clinical context. The review addresses RC metabolism and atherogenic mechanisms, methods of estimation, epidemiological and genetic associations with cardiovascular outcomes, and the implications of currently available and emerging lipid-lowering therapies.

Results. Remnant lipoproteins can be retained within the arterial wall and taken up by macrophages without obligatory prior oxidative modification, providing a biologically plausible link between RC and atherosclerosis. Prospective cohorts consistently associate higher RC with cardiovascular events, while Mendelian randomization studies support a causal contribution of remnant-related pathways. Repeated or cumulative RC exposure may add prognostic information in selected populations, including patients with metabolic dysfunction, chronic kidney disease (CKD), and metabolic dysfunction-associated steatotic liver disease (MASLD). Several lipid-lowering therapies reduce RC together with other apolipoprotein B (apoB)-containing lipoproteins; however, their cardiovascular benefit should not be interpreted as proof of an RC-specific treatment effect. High-dose icosapent ethyl has demonstrated outcome benefit in appropriately selected patients with elevated triglycerides.

Conclusions. RC is a clinically relevant complementary marker of residual lipid-related risk, especially in patients with hypertriglyceridemia and metabolic disorders. LDL-C remains the primary evidence-based therapeutic target. RC measurement may refine risk assessment in selected patients, but standardized thresholds and randomized outcome evidence for therapies directed specifically at RC are still needed before RC can be considered an independent routine treatment target.