Abstract
BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a major cause of morbidity and mortality. Insulin resistance and visceral adiposity play pivotal roles in its pathogenesis; however, the prognostic significance of the triglyceride glucose-body roundness index (TyG-BRI) and its interaction with nutritional status remain uncertain. METHODS: A total of 1,015 patients with HFpEF were prospectively enrolled. The TyG-BRI was calculated as the product of the triglyceride-glucose index (TyG index) and the body roundness index (BRI). Cox regression models were used to evaluate its prognostic value for adverse outcomes, with subgroup analyses stratified by nutritional status and mediation analysis assessing the role of exercise tolerance. RESULTS: During follow-up, 232 (22.9%) all-cause and 158 (15.6%) cardiovascular (CV) deaths occurred. In multivariate Cox regression analysis, patients in the highest TyG-BRI tertile exhibited significantly higher risks of all-cause (hazard ratio [HR] = 2.59, 95% confidence interval [CI]: 1.82-3.71; P for trend < 0.001) and CV mortality (HR = 2.43, 95% CI: 1.59-3.72; P for trend < 0.001) compared with those in the lowest tertile. The prognostic value of the TyG-BRI for all-cause mortality was more prominent among participants with impaired nutritional status (malnourished or at risk of malnutrition) (P for interaction < 0.1). Incorporation of the TyG-BRI into the baseline risk model for all-cause death significantly improved model discrimination (C-statistic = 0.701 vs. 0.626; P < 0.001) and outperformed its individual components (P < 0.05). Mediation analysis further revealed that the six-minute walk distance mediated 14.6% of the association between the TyG-BRI and all-cause mortality. CONCLUSIONS: In patients with HFpEF, the TyG-BRI was independently associated with adverse outcomes, with its prognostic value particularly evident among those with impaired nutritional status. Incorporating the TyG-BRI into the risk model modestly improved prognostic discrimination, and reduced exercise capacity appeared to partly mediate this association.