Glycemic control impacts plaque progression in premature coronary artery disease: A longitudinal CCTA analysis.

BACKGROUND: Premature coronary artery disease (PCAD) is an escalating public health issue. While diabetes mellitus (DM) is a known risk factor, the specific impact of glycemic control (GC) on those younger patients remains poorly defined. AIMS: To investigate the impact of GC on plaque progression and major adverse cardiovascular events (MACE) in PCAD using serial coronary computed tomography angiography (CCTA). METHODS: This cohort study enrolled PCAD patients with serial CCTA between 2019 and 2024. Poor GC was defined as HbA1c ≥ 7%. Plaque progression was defined as annualized change in total percent atheroma volume (ΔPAV) >0%. MACE included cardiac death, myocardial infarction, and unplanned revascularization. Causal mediation analysis was performed. RESULTS: We retrospectively enrolled 225 PCAD patients (age 40.5 ± 3.6 years) with serial CCTA (mean interval: 2.0 years). After multivariable adjustment, poor GC independently predicted plaque progression (OR 2.81, 95%CI 1.21-6.55, p = 0.017) and 3-year MACE (HR 3.08, 95%CI 1.11-8.50, p = 0.030). Notably, patients with good GC showed comparable annualized ΔPAV to non-DM patients (p = 0.434), while poor GC was associated with global acceleration across all plaque subtypes. Mediation analysis revealed that plaque progression mediated 19.6% of the effect of poor GC on MACE (p = 0.044). CONCLUSIONS: In PCAD patients, poor GC was linked to accelerated plaque progression and a higher 3-year risk of MACE, with 19.6% of this association mediated by plaque progression. These findings underscore the necessity of strict glycemic management and the value of serial CCTA-based monitoring for personalized risk stratification in this population.