Association of Baseline and Longitudinal Changes in Frailty Burden and Risk of Heart Failure in Type 2 Diabetes - Findings from the Look AHEAD Trial

Background: Individuals with diabetes have a high frailty burden and increased risk of heart failure (HF). In this study, we evaluated the association of baseline and longitudinal changes in frailty with risk of HF and its subtypes: HF with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF). Methods: Participants (age: 45-76 years) of the Look AHEAD trial without prevalent HF were included. The frailty index (FI) was used to assess frailty burden using a 35-variable deficit model. The association between baseline and longitudinal changes (1- and 4-year follow-up) in FI with risk of overall HF, HFpEF (ejection fraction [EF] ≥ 50%), and HFrEF (EF < 50%) independent of other risk factors and cardiorespiratory fitness was assessed using adjusted Cox models. Results: The study included 5 100 participants with type 2 diabetes mellitus, of which 257 developed HF. In adjusted analysis, higher frailty burden was significantly associated with a greater risk of overall HF. Among HF subtypes, higher baseline FI was significantly associated with risk of HFpEF (hazard ratio [HR] [95% CI] per 1-SD higher FI: 1.37 [1.15-1.63]) but not HFrEF (HR [95% CI]: 1.19 [0.96-1.46]) after adjustment for potential confounders, including traditional HF risk factors. Among participants with repeat measures of FI at 1- and 4-year follow-up, an increase in frailty burden was associated with a higher risk of HFpEF (HR [95% CI] per 1-SD increase in FI at 4 years: 1.78 [1.35-2.34]) but not HFrEF after adjustment for other confounders. Conclusions: Among individuals with type 2 diabetes mellitus, higher baseline frailty and worsening frailty burden over time were independently associated with higher risk of HF, particularly HFpEF after adjustment for other confounders.