Abstract
Obesity, insulin resistance (IR), and inflammation are key modifiable cardiovascular disease (CVD) risk factors. We investigated the synergistic effects of body fat percentage (BFP) and the C-reactive protein-triglyceride-glucose index (CTI) on CVD risk. This prospective cohort included 6303 CVD-free Chinese adults (≥ 45 years) from the CHARLS. BFP was calculated via the CUN-BAE equation; the CTI integrates CRP, triglycerides, and fasting glucose. Multivariate Cox regression was used to assess associations with incident CVD over 7 years. Mediation and receiver operating characteristic (ROC) analyses were used to evaluate pathways and predictive performance. Among 1124 incident CVD cases, concurrent high BFP (> 30.8%) and CTI (> 4.68) showed 1.48-fold higher CVD risk (95% CI 1.21-1.80) versus low-level groups. The combined BFP-CTI model improved prediction (AUC = 0.581; DeLong's P < 0.05) over individual indices. Mediation revealed bidirectional effects: CTI mediated 8.76% of BFP's CVD association, while BFP mediated 12.22% of CTI's effect (P < 0.001). Synergy was strongest in adults ≤ 60y (HR = 1.76, CI 1.25-2.48) and diabetics (HR = 3.52, CI 1.69-7.31). The combination of high BFP and high CTI was associated with a synergistic increase in CVD risk, with bidirectional mediation between adiposity and metabolic-inflammation pathways. Joint assessment enhances risk stratification, particularly in younger and diabetic populations.