Association between the cumulative average triglyceride-glucose-waist circumference index and new-onset hypertension among Chinese middle-aged and older adults-a national prospective study

INTRODUCTION: Hypertension is one of the most important chronic diseases among middle-aged and older adults in China, characterized by high prevalence, low control rates, and a substantial burden of complications. Insulin resistance (IR) is considered a key metabolic pathway in the development and progression of hypertension; however, traditional IR measurements (e.g., the hyperinsulinemic-euglycemic clamp and HOMA-IR) have limited accessibility in large community-based samples. The triglyceride-glucose index (TyG) and its combinations with adiposity/central obesity indicators (e.g., TyG-WC) have been proposed as simple surrogate markers of IR, with advantages of low cost and easy availability. Nevertheless, prospective evidence remains relatively limited regarding the relationship between the cumulative average TyG-WC-an indicator of long-term exposure-and the risk of new-onset hypertension. METHODS: This prospective cohort study used data from the China Health and Retirement Longitudinal Study (CHARLS). We first excluded participants with hypertension at baseline (2011) and then excluded those who met hypertension criteria at the second exposure assessment in 2015 or lacked hypertension information in 2020; therefore, the final analytic cohort included 2571participants aged ≥ 45 years who were hypertension-free before the 2015 TyG-WC measurement. The exposure was the cumulative average TyG-WC, calculated as the mean of TyG-WC measured in 2011 and 2015. New-onset hypertension was ascertained at the 2020 follow-up after the second exposure measurement and was defined by self-reported physician diagnosis, antihypertensive treatment status, or measured blood pressure thresholds. Multivariable Cox proportional hazards models were used as the primary association analysis, and logistic regression models were used as complementary analyses of cumulative incidence because exact calendar dates of hypertension onset were unavailable. Restricted cubic spline (RCS), subgroup and interaction, and exploratory receiver operating characteristic (ROC) curve analyses were performed. RESULTS: By the 2020 follow-up, 226 participants (8.8%) developed new-onset hypertension after the exposure window. Compared with those who remained normotensive, participants with incident hypertension were older, more likely to reside in rural areas, and had significantly higher baseline BMI, waist circumference, fasting blood glucose, systolic/diastolic blood pressure, and cumulative average TyG-WC (all P < 0.05). In the fully adjusted Cox proportional hazards model, each 1-IQR increase in cumulative average TyG-WC was associated with a higher risk of hypertension (HR = 1.40, 95% CI 1.13-1.73, P = 0.002); compared with the lowest quartile (Q1), the highest quartile (Q4) had the highest risk (HR = 2.00, 95% CI 1.27-3.14, P = 0.003). Logistic regression produced directionally consistent odds estimates (per 1-IQR increase: OR = 1.44, 95% CI 1.15-1.79, P = 0.001; Q4 vs. Q1: OR = 2.12, 95% CI 1.32-3.42, P = 0.002), but these ORs were interpreted cautiously as odds ratios rather than risk ratios. RCS analysis indicated a significant positive and approximately linear dose-response relationship (P for overall association < 0.01; P for nonlinearity > 0.05). Subgroup analyses demonstrated a generally consistent association across most strata, with a significant interaction observed only in the heart disease subgroup (P for interaction < 0.05). Adding cumulative average TyG-WC to the base model modestly increased the AUC from 0.628 to 0.642. CONCLUSIONS: Among Chinese adults aged ≥ 45 years who remained free of hypertension through the 2015 exposure assessment, the cumulative average TyG-WC was positively associated with the risk of new-onset hypertension by 2020 and showed an approximately linear dose-response pattern(Fig. 1). As a composite metabolic risk indicator derived from routine clinical measurements, cumulative average TyG-WC may help inform community-level risk stratification and primary prevention; however, the causal and clinical predictive interpretation of this study requires further validation. CLINICAL TRIAL NUMBER: Not applicable.