Abstract
BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome highlights the complex interplay between metabolic disturbances, kidney disease, and cardiovascular conditions. In this process, inflammation and insulin resistance play pivotal roles. The C-reactive protein-triglyceride-glucose index (CTI), a novel biomarker of insulin resistance and inflammation, remains unestablished for predicting cardiovascular disease (CVD) risk in CKM syndrome stages 0-3. METHODS: This study analyzed data from the China Health and Retirement Longitudinal Study. The outcome measure was self-reported CVD. The exposure measure, CTI, was calculated as: 0.412*Ln(C-reactive protein [mg/L]) + Ln[fasting triglycerides (mg/dL) * fasting glucose (mg/dL)/2]. Cumulative CTI was calculated as: (CTI 2012 + CTI 2015)/2 *Time (2015-2012). K-means clustering was used to categorize CTI fluctuations into four distinct clusters. Cox proportional hazards models were employed to examine the relationship between CTI and new-onset CVD risk in individuals across different CKM syndrome stages. The form of this relationship was further analyzed using restricted cubic splines. Additionally, the predictive ability was assessed using the receiver operating characteristic curve. RESULTS: This study included 5111 individuals with CKM syndrome stages 0-3, with a mean age of 61.78 ± 8.68 years, of which 45.7%(2337) were male. During the follow-up period, 555 new cases of CVD were observed (10.9%). Our findings demonstrated a significant positive linear relationship between CTI and the risk of CVD in individuals with CKM syndrome stages 0-3. In model 3, each 1.0-SD increase in cumulative CTI was associated with a 21% increase in CVD risk (adjusted hazard ratio, aHR = 1.21 [95% CI: 1.10-1.33]). Similarly, each 1.0-SD increase in baseline CTI was associated with an 18% increase in CVD risk (aHR = 1.18 [95% CI: 1.07-1.30]). Additionally, Receiver operating characteristic analysis revealed that cumulative CTI had a better predictive performance for CVD risk compared to the cumulative TyG index (AUC: 0.596 vs 0.560, DeLong test p < 0.05). CONCLUSIONS: Higher CTI levels in individuals with CKM syndrome stages 0-3 are significantly associated with increased CVD risk. Longitudinal monitoring of CTI changes over time can help early identification of high CVD risk in this population, and its predictive value is significantly superior to that of the TyG index.