Abstract
Background: Hypertension remains a leading cause of cardiovascular morbidity and mortality globally, and insulin resistance (IR) and systemic inflammation are implicated in the pathogenesis of hypertension. Limited evidence exists on the predictive role of the triglyceride-glucose (TyG) index and its related indices (TyG-WHtR and TyG-WC) for hypertension. This study aimed to investigate these associations across multiple Chinese cohorts. Methods: Data from 31,224 participants (Fuqing, CHNS, CHARLS) were analyzed. TyG indices were calculated using fasting triglycerides, glucose, and anthropometrics. Hypertension was defined as SBP/DBP ≥ 140/90 mmHg, or physician diagnosis, or antihypertensive treatment. Logistic/Cox regression models were used to examine associations, adjusting for demographics, lifestyle, and metabolic factors. Mediation analysis quantified the role of neutrophil-to-lymphocyte ratio (NLR) in mediating the TyG-hypertension relationship. Results: Elevated TyG index and its obesity-adjusted variants consistently predicted incident hypertension across cohorts (all p < 0.001). Each 1-unit TyG increase was associated with 9-36% higher odds of hypertension in Fuqing (OR = 1.09-1.36). NLR mediated 20.4-29.4% of these associations (p < 0.001). Subgroup analyses revealed effect modifications by age, sex, and residence. Sensitivity analyses confirmed robustness when redefining hypertension thresholds (ACC/AHA criteria). Conclusions: TyG index and its related indices are robust predictors of (new-onset) hypertension, with NLR statistically accounting for approximately 25% of these associations in the mediation model. These findings underscore the interplay between metabolic dysregulation, inflammation, and hypertension and advocate for integrated biomarker strategies in risk stratification and prevention, while external validation in multi-ethnic populations is warranted.