摘要BACKGROUND Despite effective control of low-density lipoprotein cholesterol,the residual risk of atherosclerotic cardiovascular dis-ease(ASCVD)remains substantial,underscoring the urgent need to identify novel targets to further reduce ASCVD risk.This study aim-ed to investigate the association between apolipoprotein C-III(APOC3)levels and ASCVD,and further explore the potential impact of AP-OC3 intervention for reducing ASCVD risk.METHODS We leveraged the 20-year longitudinal data from the Chinese Multi-provincial Cohort Study-Proteomics Project,obta-ined totaling 5308 APOC3 measurements from 2550 participants,with up to four repeated measurements per participant.The intensity model was employed to estimate the association between time-varying APOC3 and ASCVD,accounting for time-varying potential con-founders.The target trial emulation framework was used to emulate the effectiveness of various APOC3-targeted hypothetical interve-ntions on ASCVD risk,with a guideline-directed low-density lipoprotein cholesterol-lowering strategy serving as a positive control.RESULTS Of 2550 participants aged 57.5±7.9 years at baseline,and 56%of participants were females.The median level of APOC3 was 5554.8(interquartile range:3936.5-7913.8)Relative Fluorescence Units.The level of time-varying APOC3 level were associated with an inc-reased risk of incident ASCVD,and a stronger association was observed in populations with metabolic abnormalities.Furthermore,more intensive reductions in APOC3 produced progressively larger decreases in ASCVD risk,with a maximum estimated reduction of 9.3%ob-served at a 90%APOC3 reduction.CONCLUSIONS Our findings suggest that APOC3 may play an important role in ASCVD incidence and that targeting APOC3 may offer additional cardiovascular benefits beyond conventional lipid-lowering strategies.