Remnant Cholesterol and Residual Risk of Atherosclerotic Cardiovascular Disease

Remnant cholesterol (RC) is increasingly recognized as a key target in the treatment of atherosclerotic cardiovascular disease (ASCVD), addressing much of the residual risk that persists despite standard therapies. However, integrating RC into clinical practice remains challenging. Key issues, such as the development of accessible RC measurement methods, the identification of safe and effective medications, the determination of optimal target levels, and the creation of RC-based risk stratification strategies, require further investigation. This article explores the complex role of RC in ASCVD development, including its definition, metabolic pathways, and its association with both the overall risk and residual risk of ASCVD in primary and secondary prevention. It also examines the effect of current lipid-lowering therapies on RC levels and their influence on cardiovascular outcomes. Recent research has highlighted promising advancements in therapies aimed at lowering RC, which show potential for reducing major adverse cardiovascular events (MACEs). Inhibitors such as angiopoietin-like protein 3 (ANGPTL3), apolipoprotein C-III (apoCIII), and proprotein convertase subtilisin/kexin type 9 (PCSK9) have demonstrated their ability to modulate RC and reduce MACEs by targeting specific proteins involved in RC synthesis and metabolism. There is a pressing need for larger randomized controlled trials to clarify the role of RC in relevant patient populations. The development of targeted RC-lowering therapies holds the promise of significantly reducing the high rates of morbidity and mortality associated with ASCVD.