Abstract
OBJECTIVE: To investigate the association between 8 insulin resistance (IR) surrogate markers and incident atherosclerotic cardiovascular disease (ASCVD) in population with cardiovascular-kidney-metabolic syndrome (CKM) of stages 0-3, and to identify the surrogate marker with the best predictive performance. METHODS: A study was conducted on 20121 community residents classified as CKM stages 0-3 from the Chengdu cohort of the China Multi-Ethic Cohort. A Cox proportional hazards model was used to calculate hazard ratios (HRs) between each IR surrogate marker and incident ASCVD. Cubic spline regression was employed to explore the dose-response relationships between these markers and incident ASCVD. The relative relationships between different markers and incident ASCVD were examined through the ratio of HRs (RHRs). Time-dependent area under the receiver operating characteristic curve (TDAUC) and Uno's C-statistic were calculated to compare the predictive performance of each marker for incident ASCVD. Based on the PREVENT equation components and the 8 surrogate markers under analysis, random forest feature selection was used to determine the contribution of each marker to accurate prediction. RESULTS: During a follow-up period of 82741.93 person-years, 1447 incident cases of ASCVD were recorded, with an incidence density of 17.49 per 1000 person-years. Association analyses indicated that the triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL) and the TyG/(TG/HDL) index were not associated with incident ASCVD (P > 0.05). The TyG index combined with obesity measurement parameters emerged as a reliable predictor of ASCVD incidence. The most promising indicator, TyG index with waist-to-height ratio (TyG_WHtR), exhibited an inverted J-shaped association with incident ASCVD (P for nonlinearity = 0.045; TDAUC = 0.640; C = 0.634), while the TyG index with body mass index (TyG_BMI), waist circumference (TyG_WC), and waist-to-hip ratio (TyG_WHR) showed positive linear associations (all P for trend < 0.05), with relatively lower predictive performance (C = 0.564, 0.588, and 0.598, respectively). Although both the TyG index and the metabolic score for insulin resistance (METS-IR) were associated with increased ASCVD risk (TyG: Q2 vs. Q1, HR = 1.23 and Q4 vs. Q1, HR = 1.24; METS-IR: P for non-linearity = 0.045), they exhibited poor predictive performance for incident ASCVD. CONCLUSION: The TyG index combined with obesity measurement parameters is an ideal IR surrogate marker for predicting incident ASCVD in populations with stages 0-3 CKM. Monitoring these markers will facilitate the prevention and control of cardiovascular diseases in CKM populations.