Association between insulin resistance indices and outcomes in patients with heart failure with preserved ejection fraction.

BACKGROUND

Insulin resistance (IR) plays a pivotal role in the interplay between metabolic disorders and heart failure with preserved ejection fraction (HFpEF). Various non-insulin-based indices emerge as reliable surrogate markers for assessing IR, including the triglyceride-glucose (TyG) index, the TyG index with body mass index (TyG-BMI), atherogenic index of plasma (AIP), and the metabolic score for insulin resistance (METS-IR). However, the ability of different IR indices to predict outcome in HFpEF patients has not been extensively explored.

METHODS

Patients having HFpEF were recruited from January 2012 and December 2023. The outcome was defined as major adverse cardiovascular event (MACE), encompassing all-cause mortality and rehospitalization for heart failure. The potential linear relationship was visualized by the restricted cubic spline (RCS) curve. Both univariable and multivariable Cox proportional hazards models were employed to examine the association between the IR indexes and MACE. Furthermore, to assess the incremental prognostic value of the TyG index, we conducted comprehensive analyses using area under the curve (AUC), the continuous net reclassification index (cNRI), and the integrated discrimination index (IDI).

RESULTS

A total of 8693 patients met the inclusion criteria and were included in the final analysis. The mean age of the patients was 70.59 ± 10.6 years, with 5045 (58.04%) being male. The Kaplan-Meier survival analysis revealed that higher degree of the four IR indexes was associated with higher risk of MACE (all log-rank P < 0.05). When treated as a continuous variable, the TyG index showed a significant association with MACE (HR 2.1, 95% CI 1.98-2.23, P < 0.001 in model 1; HR 1.81, 95% CI 1.73-1.9, P < 0.001 in model 2; HR 1.68, 95% CI 1.6-1.76, P < 0.001 in model 3). When categorized into quartiles, the highest quartile of the TyG index (Q4) was significantly associated with MACE (HR 2.48, 95% CI 2.24-2.76, P < 0.001 in model 3). Similar significant associations were found between TyG-BMI, AIP, METS-IR, and MACE. The TyG index was found to enhance the risk stratification capability of the MAGGIC score (AUC from 0.601 to 0.666). When compared to other IR indicators, the TyG index exhibited superior discrimination and reclassification abilities in predicting MACE. Additionally, the TyG-BMI index revealed a U-shaped correlation with MACE, indicating that both an elevated and a lower TyG-BMI index were associated with an increased risk.

CONCLUSION

All four IR indices are independently associated with MACE in patients with HFpEF. Notably, these IR indices significantly enhance the predictive accuracy of the MAGGIC score, a widely used risk assessment tool in HFpEF. Among these indices, the TyG index demonstrated the highest discriminatory and reclassification abilities, providing the greatest incremental value in predicting MACE and exhibiting significant superiority compared to the other indices. These findings highlight the importance of assessing IR indices, particularly the TyG index, in the risk assessment and management strategies for HFpEF patients. However, it should be noted that our findings need to be validated in diverse populations to ensure their applicability and generalizability.