TyG Index and Related Indices Predicting Hypertension: Mediation by Neutrophil-to-Lymphocyte Ratio in Multiple Chinese Cohorts

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.

Keywords: cohort study; hypertension; neutrophil-to-lymphocyte ratio; triglyceride-glucose index.

Figure 1

Flowchart of participant selection. ^a The Fuqing Cohort survey ended 16 December 2022; TyG, triglyceride-glucose.

Figure 2

Restricted cubic spline curve for the association of TyG and its related indices with hypertension. Solid lines represent hazard ratios, and dashed lines represent 95% confidence intervals; Adjusted for sex, age, education, urban, baseline SBP and DBP (except for Fuqing cohort), smoking, drinking, uric acid, HDL-C, TC, and HbA1c; The red solid lines represent the effect estimates, and the shadowed parts are 95% confidence intervals; two-piece Cox proportional hazards models were used to estimate the risk inflection point; TyG, triglyceride-glucose; WHtR, waist to height ratio; WC, waist circumference.

Figure 3

Subgroup analyses of the relationship between TyG index and its related indices and hypertension. ^a The Fuqing Cohort survey ends 16 December 2022; ^b The odds/hazard ratios were adjusted for sex, age, education, urban, BMI, baseline SBP and DBP (except for Fuqing cohort), smoking, drinking, uric acid, HDL-C, TC, and HbA1c; In this study, wave 8 (in 2009) of CHNS and wave 1 (in 2011) of CHARLS were regarded as the baseline, respectively. Subsequent follow-up surveys were used to follow the outcome until the final follow-up survey, which was wave 10 of CHNS (in 2015) and wave 4 (in 2018) of CHARLS; FBG, fasting blood glucose; TG, triglyceride.