Association of novel triglyceride-glucose-related indices with incident stroke in early-stage cardiovascular-kidney-metabolic syndrome

Abstract

Background: Emerging triglyceride-glucose (TyG)-related indices, such as the TyG-related body roundness index (TyG-BRI), a body shape index (TyG-ABSI), weight-adjusted waist index (TyG-WWI), and Chinese visceral adiposity index (TyG-CVAI), have gained attention as promising predictors of diverse cardiometabolic conditions. Nevertheless, their prospective associations with stroke onset remain insufficiently characterized, especially in individuals affected by cardiovascular-kidney-metabolic (CKM) syndrome.

Methods: This prospective cohort study included 7,503 middle-aged and older adults with CKM syndrome stages 0-3 (see Methods: Definition of CKM Stages 0 to 4) from the China Health and Retirement Longitudinal Study (CHARLS). Cox proportional hazards models were used to evaluate the associations between TyG-related indices and incident stroke, with potential non-linear relationships examined via restricted cubic splines (RCS). Discriminative performance was compared using receiver operating characteristic (ROC) curves. Mediation analysis was conducted to assess whether systolic blood pressure (SBP) mediated the associations. Subgroup and sensitivity analyses were also performed to verify robustness.

Results: Over a median follow-up of 5.2 years, 625 participants (8.33%) experienced a first stroke (incidence rate 102.18 per 10,000 person-years). In fully adjusted models, each 1-SD increase in TyG-BRI, TyG-ABSI, TyG-WWI, and TyG-CVAI was associated with stroke hazards of 1.16 (95% CI, 1.06-1.27), 1.10 (1.01-1.21), 1.13 (1.03-1.25), and 1.20 (1.10-1.31), respectively. Participants in the highest TyG-CVAI quartile had a 67% higher risk than those in the lowest (HR, 1.67; 95% CI, 1.28-2.18). Nonlinear thresholds were identified at TyG-BRI 18.16 and TyG-WWI 78.93. ROC analysis indicated that TyG-CVAI had the greatest discriminative ability for predicting stroke. SBP mediated 26.3-32.9% of these associations. The findings were consistent across multiple subgroup and sensitivity analyses.

Conclusion: Novel TyG-related indices, particularly TyG-CVAI, showed significant and incremental predictive value for stroke risk among individuals with CKM syndrome stages 0-3. Their incorporation into risk stratification frameworks may enhance early detection and prevention of cerebrovascular events in metabolically vulnerable populations.

Keywords: CKM syndrome; Stroke risk, systolic blood pressure; TyG-related indices; Visceral adiposity..

Fig. 1

Flowchart of participant selection

Fig. 2

Kaplan–Meier curves for new-onset stroke across quartiles of TyG-related indices: (A) TyG-BRI, (B) TyG-ABSI, (C) TyG-WWI, and (D) TyG-CVAI

Fig. 3

Restricted cubic spline curves illustrating the associations between TyG-related indices and new-onset stroke risk. (A) TyG-BRI, (B) TyG-ABSI, (C) TyG-WWI, and (D) TyG-CVAI. Solid lines represented adjusted hazard ratios derived from multivariable Cox models, and shaded areas denote 95% confidence intervals. Adjusted for age, gender, education level, alcohol intake, smoking, hypertension, DM, antidiabetic agents, antihypertensive agents, SBP, DBP, PLT, BUN, Cr, LDL_C, CRP, HbA1C, UA, Hb, eGFR

Fig. 4

Comparison of the discriminatory performance of different IR indices for predicting new-onset stroke

Fig. 5

Mediation analysis of SBP in the association between TyG-related indices and new-onset stroke

Fig. 6

Subgroup analyses of the association between TyG-related indices and new-onset stroke. (A) TyG-BRI, (B) TyG-ABSI, (C) TyG-WWI, and (D) TyG-CVAI. Models were adjusted based on Model 3, with the stratification variable itself excluded from adjustment