Hypertension, Insulin Resistance and Right Ventricular Dysfunction: Insights from a Single-Center Study and Mendelian Randomization Analysis

BackgroundRight ventricular (RV) dysfunction is increasingly recognized in hypertensive patients, often linked to metabolic abnormalities. The triglyceride glucose-body mass index (TyG-BMI), a marker of insulin resistance (IR), has been associated with cardiovascular outcomes, but its role in RV dysfunction remains unclear. ObjectivesThis study aimed to evaluate the association between TyG-BMI and right ventricular free wall longitudinal strain (RVFWLS) in hypertensive patients using two-dimensional speckle tracking echocardiography. Key risk factors influencing RVFWLS were identified, and the contributions of TyG-BMI and its components-fasting plasma glucose (FPG), triglycerides (TG), and BMI-were examined. Causality was verified via multivariable Mendelian randomization (MVMR). MethodsA total of 280 hypertensive patients underwent echocardiographic and clinical assessments. RVFWLS was used to evaluate RV function, with -21% as the threshold for normal. Predictor of RVFWLS were identified using LASSO regression and random forest models. Multiple linear regression and mediation analysis were performed to assess the direct and indirect effects of TyG-BMI on RVFWLS, while weighted quantile sum regression was conducted to quantify the contributions of TyG-BMI components. MVMR was utilized to explore causal relationships between TyG-BMI components, hypertension, and RV ejection fraction (RVEF). ResultsTyG-BMI emerged as the strongest predictor of RVFWLS, followed by HDL-C, SBP, hs-CRP, heart rate, and diabetes history. TyG-BMI was independently associated with RVFWLS ({beta} = 0.03, P < 0.001). Mediation analysis revealed hs-CRP partially mediated this association (indirect effect: 0.002; 95% CI: 0.001-0.001; P=0.02). Among TyG-BMI components, FPG contributed most to RVFWLS (50%), followed by BMI (33%) and TG (17%). MVMR confirmed a causal role of FPG in reduced RVEF (P < 0.05). ConclusionTyG-BMI is strongly associated with subclinical RV dysfunction in hypertension, with hs-CRP acting as a partial mediator and FPG as the dominant contributor. Clinical PerspectiveO_ST_ABSWhat is new?C_ST_ABSO_LIThis study identifies TyG-BMI as a novel and robust predictor of right ventricular free-wall longitudinal strain (RVFWLS) in hypertensive patients, emphasizing its significance as a marker of metabolic and cardiovascular health. C_LIO_LIAmong TyG-BMI components, fasting plasma glucose (FPG) emerges as the strongest contributor to RV dysfunction, supported by clinical data and Mendelian randomization analysis. C_LI What are the clinical implications?O_LIAssessing TyG-BMI can help clinicians identify hypertensive patients at higher risk for subclinical RV dysfunction. C_LIO_LIEarly metabolic interventions targeting FPG and systemic inflammation may prevent or mitigate RV remodeling progression, minimizing further cardiovascular complications. C_LI