Association Between C‐Reactive Protein–Triglyceride Glucose Index and All‐Cause and Cardiovascular Mortality Across Cardiovascular–Kidney–Metabolic Syndrome Stages 0–4

Abstract

Objective Advanced cardiovascular–kidney–metabolic (CKM) syndrome corresponds to an elevated risk of mortality. The C‐reactive protein–triglyceride glucose index (CTI) reflects both insulin resistance and inflammation, processes that are crucial to CKM progression. However, it remains uncertain whether CTI is linked to mortality risk and how this relationship may vary across different CKM progression stages. Methods A total of 8314 participants were drawn from American adults. Participants were then grouped by advanced CKM stages. CTI was calculated as 0.412 × Ln (CRP [mg/L]) + Ln (TG [mg/dl] × FBG [mg/dl])/2. The endpoints focused on all‐cause and cardiovascular mortality. Associations of CTI with advanced CKM stages and mortality were examined using logistic and Cox regression models, respectively. Results The highest CTI quartile (Q4) exhibited a markedly greater prevalence of advanced CKM stages relative to Q1 (p < 0.001). During a median follow‐up of 152 months, 1606 participants died, including 475 cardiovascular deaths. Each SD increase in CTI was associated with a 35% higher risk of all‐cause mortality (95% CI: 1.24–1.48) and a 40% higher risk of cardiovascular mortality (95% CI: 1.20–1.62). Similarly, compared with Q1, participants in Q4 of CTI had higher risks of all‐cause mortality (HR = 1.82, 95% CI: 1.46–2.27) and cardiovascular mortality (HR = 2.29, 95% CI: 1.56–3.34), with homogeneous associations across different CKM stages (interaction p > 0.05). Conclusion Higher CTI levels were accompanied by a greater prevalence of advanced CKM stages and were associated with increased risks of all‐cause and cardiovascular mortality across CKM stages. CTI may provide complementary information for mortality‐risk assessment although further validation is needed.