Joint association of high-sensitivity C-reactive protein–triglyceride glucose index and coronary artery calcification with adverse outcomes in patients with coronary artery disease: a large-scale cohort study

BACKGROUND: The high-sensitivity C-reactive protein triglyceride glucose index (CTI) integrates metabolic dysregulation and systemic inflammation, whereas moderate-to-severe coronary artery calcification (MSCAC) reflects anatomic atherosclerotic burden. Whether CTI prognostic value varies by MSCAC status and whether these measures interact clinically remains unclear. METHODS: This prospective cohort study included 22 218 patients with angiography‑confirmed coronary artery disease (CAD) enrolled from January 2017 to December 2018, categorized by CTI median (≤9.08 vs. >9.08) and MSCAC presence. CTI was calculated as Ln(fasting glucose [mg/dl] × triglycerides [mg/dl])/2 + Ln(hs‑CRP [mg/L]) × 0.412. The primary endpoint was cardiovascular events; the secondary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). Restricted cubic spline, Kaplan-Meier, and Cox regression analyses were applied. RESULTS: Each 1-unit CTI increase was associated with 15% higher cardiovascular event risk [hazard ratio: 1.15, 95% confidence interval (CI): 1.02-1.29] and 9% higher MACCE risk (hazard ratio: 1.09, 95% CI: 1.03-1.15). MSCAC independently conferred a 32% higher risk of cardiovascular events (hazard ratio: 1.32, 95% CI: 1.05-1.67) and 23% higher MACCE risk (hazard ratio: 1.23, 95% CI: 1.10-1.38). Patients with both elevated CTI and MSCAC had 66% increased cardiovascular event risk (hazard ratio: 1.66, 95% CI: 1.20-2.30) and 38% increased MACCE risk (hazard ratio: 1.38, 95% CI: 1.18-1.62) versus neither. No statistically significant additive or multiplicative interaction was detected. CONCLUSION: In patients with CAD, elevated CTI and MSCAC independently portend adverse outcomes, and their coexistence identifies a particularly high‑risk phenotype. These findings support the complementary value of metabolic‑inflammatory and anatomic measures in risk stratification.