Joint effect of hepatic steatosis index and triglyceride glucose index on cardio-renal outcomes: a real-world study

Abstract Objective Hepatic steatosis index (HSI) and triglyceride glucose (TyG) index are emerging markers associated with metabolic health and cardiovascular risk. Their combined effects on cardio-renal outcomes remain poorly understood. This study evaluated the joint effect of HSI and TyG index on cardio-renal outcomes in a real-world population. Methods We analyzed 16,109 participants, stratified by tertiles of TyG index and HSI groups (≤ 36 vs. >36). Cardio-renal outcomes included composite major adverse cardiovascular events (MACE: cerebrovascular events, coronary artery disease, heart failure, myocardial infarction) and renal events (eGFR decline ≥ 50%, end-stage kidney disease [ESKD], proteinuria). Hazard ratios (HRs) were calculated using multivariable Cox proportional hazards models adjusted for demographics and clinical covariates. Results Higher TyG tertiles were associated with a significantly increased risk of composite cardio-renal outcomes (HR for tertile 3 vs. tertile 1: 1.58; 95% CI: 1.37–1.83). Subgroup analysis showed that individuals with HSI > 36 and TyG tertile 3 had the highest risks for composite MACE (HR: 1.62; 95% CI: 1.34–1.96) and composite renal outcomes (HR: 3.13; 95% CI: 2.10–4.68) compared with other subgroups. Both higher TyG and HSI levels showed a particularly strong association with proteinuria (HR for HSI > 36 and TyG tertile 3: 3.69; 95% CI: 2.26–6.02). Conclusions The combined assessment of HSI and TyG index provides a valuable tool for identifying individuals at high risk for cardio-renal outcomes. These findings highlighted the importance of metabolic markers in predicting complications and underscore the need for early interventions targeting these populations.