Paradoxical prognostic value of the triglyceride-glucose index in predicting adverse outcomes in acute heart failure patients

Abstract Background Metabolic dysfunction is a key factor influencing the prognosis of acute heart failure (AHF). The triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, has emerged as a potential predictor of adverse cardiovascular outcomes. However, its prognostic value in AHF patients still needs to be explored. Purpose This study aimed to evaluate the association between TyG index tertiles and adverse clinical outcomes in a large multicenter cohort of AHF patients. Methods We analyzed data from 5,581 AHF patients admitted to 10 tertiary hospitals in South Korea between March 2011 and February 2014. The TyG index was calculated and categorized into tertiles. The primary outcome was a composite of cardiac death and heart failure readmission. Multivariate Cox proportional hazard regression models were used to evaluate the association between TyG index tertiles and outcomes, adjusting for potential confounders. Subgroup analyses were conducted based on diabetes mellitus (DM) status. Results Among 5,581 patients, the incidence of the primary outcome was significantly higher in Tertile 1 compared to Tertile 3 (36.87% vs. 30.88%, p = 0.005). Cardiac death was also more frequent in Tertile 1 than in Tertile 3 (10.91% vs. 8.73%, p = 0.039). In multivariate analysis, those in the highest TyG index tertile (Tertile 3) exhibited a significantly lower risk of the primary outcome compared to Tertile 1 (HR: 0.769; 95% CI: 0.654–0.905; p=0.002). Other predictors of the primary outcome included prior heart failure, DM, and lower hemoglobin levels. In subgroup analyses, the protective effect of a higher TyG index was more pronounced in patients without DM (p for trend 0.001). Kaplan-Meier survival curves further illustrated these findings, showing that patients without DM in Tertile 3 had significantly better event-free survival compared to those in Tertile 1 (log-rank p 0.001) (Figure). Conclusion The TyG index, typically associated with increased metabolic risk, was paradoxically related to a lower risk of cardiac death and heart failure readmission in this large cohort of acute heart failure patients. This unexpected finding suggests that the predictive value of the TyG index in AHF may differ from other populations, potentially reflecting distinct metabolic adaptations or treatment strategies in this high-risk group. Further research is warranted to clarify the underlying mechanisms and validate these findings in various patient populations.Figure