Cumulative exposure of the combined triglyceride-glucose and frailty index for incident hypertension prediction in middle-aged and older adults: a national cohort study

Abstract

Insulin resistance and frailty are both independently associated with elevated blood pressure, yet the combined and cumulative impact of these conditions on incident hypertension remains largely unexplored. This study aimed to evaluate the association between cumulative exposure to the combined triglyceride-glucose (TyG) and frailty index (FI), termed cumulative TyGFI, and the risk of incident hypertension among middle-aged and older Chinese adults. Data were derived from the China Health and Retirement Longitudinal Study (CHARLS), a nationally representative longitudinal cohort. After applying exclusion criteria, 3,846 participants aged 45 years or older without baseline hypertension were included. Cumulative TyGFI was calculated using TyG index and FI measurements at Wave 1 (2011–2012) and Wave 3 (2015). The primary outcome was incident hypertension, ascertained at Wave 4 (2018) and Wave 5 (2020). Multivariable Cox proportional hazards regression and logistic regression models were employed. Restricted cubic spline (RCS) analyses were conducted to assess dose-response relationships, and incremental predictive performance was evaluated using Harrell’s C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). In the fully adjusted Cox model, each 1-SD increase in cumulative TyGFI was associated with an 18% higher risk of incident hypertension (HR = 1.18, 95% CI: 1.10–1.27, P < 0.001). Compared with the lowest quartile (Q1), participants in Q4 had a 45% higher risk (HR = 1.45, 95% CI: 1.16–1.80, P < 0.001), with a significant dose-response trend (P for trend < 0.001). RCS analyses supported a linear positive association across all models (all P for non-linearity > 0.05). Logistic regression sensitivity analyses at 7-year and 9-year follow-up yielded broadly consistent results. Cumulative TyGFI yielded small but statistically significant improvements in predictive performance beyond conventional risk factors at 9-year follow-up (ΔC-index = 0.008; NRI = 13.53%; IDI = 0.43%; all P < 0.05). Compared with baseline TyG, cumulative TyGFI also provided modest improvements in C-index (ΔC-index = 0.006, P = 0.015; ΔIDI = 0.31%, P < 0.001). Subgroup analyses showed generally consistent associations across the examined strata (all P for interaction > 0.05). Cumulative TyGFI was independently and positively associated with incident hypertension in a linear dose-response manner and provided statistically significant but modest incremental predictive information beyond conventional risk factors and its individual components. These findings support further investigation of cumulative TyGFI as a complementary risk marker, although external validation and assessment of clinical utility are required before clinical use can be considered.