Background: Although insulin resistance (IR) is associated with a higher risk of incident heart failure (HF), it is not fully understood whether IR could affect clinical outcomes in patients with established HF. We investigated the relationship between the triglyceride-glucose (TyG) index, a simple surrogate marker for IR, and clinical outcomes in patients with HF with preserved ejection fraction (HFpEF). Methods: This retrospective analysis from the PURSUIT-HFpEF registry included 917 patients hospitalized for decompensated HFpEF. The TyG index was calculated at discharge as ln(triglyceride [mg/dL] x fasting blood glucose [mg/dL]/2). The primary outcomes were all-cause death and major adverse cardiovascular events (MACEs; a composite of all-cause death, heart failure hospitalization, and stroke). Results: The median age of patients was 83 years, 44.7% was male, and 39.2% had diabetes. The median BMI was 21.5 kg/m2, with 20.9% having BMI <18.5 kg/m2. During a median follow-up of 387 days, 168 deaths and 343 MACEs occurred. A stepwise Cox hazard model revealed that higher TyG index was independently associated with lower risk of all-cause death (HR 0.53, 95% CI 0.38-0.75) and MACEs (HR 0.77, 95% CI 0.61-0.97). When patients were divided into quartiles based on TyG index, the incidences of both outcomes were significantly lower in higher TyG quartiles (all-cause death; p=0.0003, MACEs; p=0.007 by log-rank). Conclusions: In this predominantly elderly, low BMI cohort with established HFpEF, higher TyG index was paradoxically associated with better clinical outcomes. These findings imply a complex relationship between IR and HFpEF outcomes.

KI received honorarium from AstraZeneca, Eli Lilly, and Boehringer Ingelheim. SH received research support from Roche Diagnostics, Toyama Chemical, Acterlion Pharmacetical and honorarium from Daiichi Sankyo Company, Bayer, Astellas Pharma, Pfizer Pharmaceuticals, Boehringer Ingelheim. YS received research grant from Acterlion Pharmacetical and honoraria from Astellas Pharma, Daiichi Sankyo Company, Otsuka Pharmaceutical. The remaining authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.

UMIN-CTR ID: UMIN000021831

This work was funded by Roche Diagnostics K.K. and Fuji Film Toyama Chemical Co. Ltd.

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The IRB of Osaka University Graduate School of Medicine provided exemption for this research becuase this was a retrospective analysis of the registered database.

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