Serial Coronary Artery Calcium Progression and Risk of Major Adverse Cardiovascular Events in an Asian Cohort

Background/Objectives: The prognostic value of serial coronary artery calcium (CAC) progression remains uncertain in Asian populations and statin-treated patients. We evaluated the association between CAC progression and subsequent major adverse cardiovascular events (MACE) in a Taiwanese cohort. Methods: We retrospectively studied 1791 individuals undergoing two CAC-scoring cardiac CT scans at a tertiary center in Taiwan from 2006 to 2021, excluding those with MACE before the second scan. CAC progression was defined as an annualized Agatston score increase of ≥20 units/year. Time-to-event analyses used landmark Cox models beginning at the second scan, with inverse probability weighting (IPW), balance diagnostics, multivariable Cox regression, and multiple-imputation sensitivity analyses. Results: CAC progression occurred in 365 participants (20.4%). Progressors were older and had greater cardiometabolic risk and baseline CAC burden. In a landmark IPW analysis, CAC progression was associated with higher subsequent MACE risk (HR 2.02, 95% CI 1.49-2.74), with a graded association across annualized CAC change categories: HR 1.72 (95% CI 1.17-2.74) for 21-49 units/year and HR 2.86 (95% CI 2.29-3.57) for ≥50 units/year. The association remained consistent in multiple-imputation analysis (HR 1.90, 95% CI 1.36-2.66) and across major clinical subgroups. Discrimination for 10-year MACE was stronger among statin users than non-statin users (AUC 0.774 vs. 0.571), although statin-stratified analyses were exploratory. Conclusions: CAC progression was independently associated with subsequent MACE and showed a graded risk relationship. Serial CAC assessment may serve as a useful dynamic marker for refining longitudinal cardiovascular risk stratification, while prospective studies are needed to validate progression-guided management.