Association and discriminative value of insulin resistance surrogate markers for aortic stiffness in asymptomatic adults

Abstract

Insulin resistance surrogate markers, including the triglyceride-glucose (TyG) index, TyG-BMI, and TG/HDL-C ratio, have been associated with aortic stiffness in high-risk populations. Their comparative associations and incremental discrimination in asymptomatic adults remain unclear. We therefore compared these markers and evaluated a simplified model for cfPWV-defined aortic stiffness. We conducted a cross-sectional study of 654 asymptomatic adults aged ≥18 years who underwent routine health examinations at two tertiary medical centers. After exclusions, 457 participants formed the modeling cohort and 101 formed the external validation cohort. Aortic stiffness was defined as cfPWV ≥10 m/s. We used multivariable logistic regression to estimate associations between the three surrogate markers and aortic stiffness. Restricted cubic spline regression assessed potential nonlinear associations. Incremental discrimination was evaluated using Δ AUC, NRI, and IDI. Six machine-learning models were compared, and the most interpretable model was evaluated in an independent institutional validation cohort. Aortic stiffness was present in 32.8% (150/457) of the modeling cohort. After full adjustment, the TyG index was independently associated with aortic stiffness (per-SD OR = 3.44, P  = 0.002), as were TG/HDL-C (OR = 3.11, P  = 0.039) and, more weakly, TyG-BMI (OR = 1.52, P  = 0.043). The model including TyG showed higher discrimination ( Δ AUC = 0.014, DeLong P  = 0.025) and reclassification (continuous NRI = 0.692 and IDI = 0.041; both P  < 0.001) than the base model. A data-derived TyG cutoff of 8.68 was identified as a potential marker for exploratory risk stratification. The five-variable model, comprising age, MAP, diabetes mellitus, smoking, and TyG, yielded AUCs of 0.931 in the modeling cohort and 0.909 in the external validation cohort. Subgroup and sensitivity analyses showed similar patterns. Among the three surrogate markers, the TyG index showed the strongest adjusted association with aortic stiffness and the greatest incremental discrimination beyond conventional clinical variables. The five-variable model showed good discrimination in an independent institutional validation cohort. However, these cross-sectional findings support only potential risk-stratification value and do not establish temporal sequence, causality, or clinical utility; prospective studies are required to assess broader generalizability.