Apolipoprotein A‐I (CSL112) and Cardiovascular Outcomes in Atherosclerotic Cardiovascular Disease: A Scoping Review

BACKGROUND: Apolipoprotein A-I (ApoA-I), the principal protein component of high-density lipoproteins (HDL), plays a pivotal role in cardiovascular physiology and has gained increasing attention in atherosclerotic cardiovascular disease (ASCVD). Its involvement extends beyond lipid transport to include anti-inflammatory and antioxidant mechanisms. OBJECTIVE: To comprehensively evaluate the role of ApoA-I in ASCVD, including its biological functions, clinical relevance as a biomarker, and potential as a therapeutic target. METHODS: A scoping review of the literature was conducted to examine current evidence on ApoA-I in cardiovascular health and disease. Studies assessing its role in reverse cholesterol transport (RCT), association with cardiovascular outcomes, and emerging therapeutic strategies were included. RESULTS: ApoA-I contributes significantly to reverse cholesterol transport and exhibits antioxidant and anti-inflammatory properties that protect against atherosclerosis. Elevated ApoA-I levels are consistently associated with reduced risk of major adverse cardiovascular events, supporting its utility as a biomarker for cardiovascular risk assessment. However, variability in HDL particle composition and the influence of confounding factors such as comorbidities and lifestyle limit its interpretability. Therapeutic approaches targeting ApoA-I, including infusion therapies and mimetic peptides, have shown mixed results in clinical trials, highlighting ongoing challenges. CONCLUSION: ApoA-I remains a promising biomarker and therapeutic target in ASCVD, though its clinical application is complicated by biological and methodological variability. Future research focusing on gene therapies, small molecule modulators, and ApoA-I mimetics may enhance its functional properties and clinical utility. Integrating ApoA-I into personalized treatment strategies could improve cardiovascular outcomes and reduce disease burden.