Baseline, repeated-measure burden, and two-time-point patterns of the triglyceride-glucose index-visceral lipid ratio (TyG-VLR) and incident cardiovascular disease in cardiovascular-kidney-metabolic (CKM) syndrome stages 0-3: a longitudinal China Health and Retirement Longitudinal Study (CHARLS) analysis.

Background: Cardiovascular-kidney-metabolic (CKM) syndrome stages 0-3 define a population without overt clinical cardiovascular disease (CVD) but with accumulating metabolic, adiposity, lipid, and kidney-related risk. We evaluated whether baseline triglyceride-glucose-visceral lipid ratio (TyG-VLR), repeated-measure TyG-VLR burden, and two-time-point TyG-VLR patterns were associated with incident CVD and CVD subtypes in CHARLS.

Methods: Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS), with follow-up through the 2020 wave. CKM stages were operationalized using CHARLS-available measures of adiposity, prediabetes, diabetes, hypertension, dyslipidemia, chronic kidney disease, metabolic syndrome, predicted CVD risk, and clinical CVD status. TyG-VLR was calculated as TyG multiplied by the visceral lipid ratio (VLR; LDL-C × Chinese visceral adiposity index). Repeated-measure TyG-VLR burden was calculated as the average of Wave 1 and Wave 3 values multiplied by the interval between assessments before the landmark follow-up period. K-means clustering of standardized Wave 1 and Wave 3 TyG-VLR identified two-time-point patterns based on the available repeated measurements. Cox proportional hazards models, dose-response analyses, marker-specific comparisons, and prespecified sensitivity analyses were performed.

Results: The baseline analytic cohort included 7,132 participants with CKM stages 0-3 and 1,688 incident CVD events; the median follow-up for CVD was 9.00 years (IQR, 7.00-9.00). The repeated-measure/two-time-point cohort included 4,111 participants and 777 incident CVD events; the median landmark follow-up was 5.00 years (IQR, 4.92-5.00). Each 1-SD increase in baseline TyG-VLR was associated with incident CVD (HR 1.15, 95% CI 1.10-1.21), heart disease (HR 1.11, 95% CI 1.05-1.18), and stroke (HR 1.21, 95% CI 1.12-1.31). Repeated-measure TyG-VLR burden was associated with CVD (HR 1.21, 95% CI 1.12-1.30), and the highest two-time-point pattern group had greater CVD risk than the lowest group (HR 1.51, 95% CI 1.22-1.85). Restricted cubic spline and Kaplan-Meier analyses showed graded CVD risk patterns, whereas marker-specific comparisons showed that TyG-VLR performed broadly similarly to VLR, CVAI, and TyG-CVAI. Incremental discrimination beyond traditional factors and adapted CKM stage was modest. Associations remained consistent in inverse probability-weighted, multiple-imputation, alternative-formulation, and competing-risk analyses.

Conclusions: In middle-aged and older adults with adapted CKM syndrome stages 0-3, higher baseline TyG-VLR, repeated-measure TyG-VLR burden, and higher two-time-point TyG-VLR patterns were associated with incident CVD, particularly stroke. TyG-VLR may be interpreted as an epidemiological marker of combined metabolic, lipid, and adiposity burden, with potential value for population-level risk characterization pending further validation.