Association of cumulative exposure and dynamic trajectories of the C-reactive protein-triglyceride-glucose and its modified indices with cardiovascular disease in individuals with cardiovascular-kidney-metabolic syndrome stages 0–3: a longitudinal analysis based on CHARLS
Authors' conclusion
Incorporating obesity indicators, particularly CVAI, into the CTI framework significantly improves the reclassification of CVD risk in early to moderate CKM stages. However, the lack of significant discriminative (AUC) improvement necessitates a careful clinical trade-off between adopting complex composite metrics and maintaining screening feasibility.
Study context
- Population
- Individuals with Cardiovascular-Kidney-Metabolic (CKM) syndrome stages 0–3, CHARLS cohort
- Exposure
- CTI vs obesity-modified CTI indices for incident cardiovascular disease (CVD)
- Outcome
- Incident CVD
Methodological detailsCox proportional hazards, time-dependent Nearest Neighbor Estimation (NNE) AUC with bootstrap resampling, cNRI and IDI, Weighted Quantile Sum (WQS) regression and causal mediation analyses
- Cox proportional hazards
- Time-dependent NNE AUC with bootstrap resampling, cNRI and IDI
- WQS regression and causal mediation analyses
Main finding
As reported in the abstract
- Baseline and cumulative CTI-CVAI significantly improved risk reclassification, cNRI
- 0.093-0.126
- Baseline and cumulative CTI-CVAI significantly improved risk reclassification, IDI
- 0.024-0.026
- Reclassification improvement, P
- P < 0.001
Observational data: associations, not effects.
Further findings
Dose-response relationship
- Except for CTI-BMI, obesity-modified indices changed the dose-response from complex nonlinear to threshold linear
CKM stage stratification
- Stage-dependent effects: amplified relative risks in CKM 0-2; stronger reclassification increment in CKM 3
Mechanisms
- WQS: visceral adiposity was the dominant risk driver
- Physical frailty was a significant mediator
Original publication
Association of cumulative exposure and dynamic trajectories of the C-reactive protein-triglyceride-glucose and its modified indices with cardiovascular disease in individuals with cardiovascular-kidney-metabolic syndrome stages 0–3: a longitudinal analysis based on CHARLS. Cardiovasc Diabetol. Published 11 May 2026. doi:10.
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