Abstract 4370015: Associations of baseline and longitudinal changes in MASLD with risk of heart failure events in type 2 diabetes and overweight or obesity: the Look Action for Health in Diabetes (Look AHEAD) Trial Liver Ancillary Study

Introduction: Adults with type 2 diabetes (T2D) and overweight or obesity have a high prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD). MASLD is associated with risk of atherosclerotic cardiovascular disease (ASCVD). However, the relationship between MASLD and risk of heart failure (HF), including HF subtypes, in T2D is less well-established. Methods: We included participants with T2D and overweight/obesity from the Look AHEAD (Action for Health in Diabetes) trial who had available AST, ALT, and GGT data. The probability of MASLD was estimated using the Dallas Steatosis Index and classified as low, intermediate, or high based on probabilities <40%, ≥40 to <70%, and ≥70%, respectively. Adjusted Cox models were created to evaluate the associations of baseline and 1-year longitudinal changes in probability of MASLD with risk of overall HF, HF with preserved and reduced ejection fraction (HFpEF and HFrEF, respectively). Results: The present study included 3,938 participants (mean age 59 years, 59% female, 67% White race). During follow-up, 211 HF events occurred (107 HFpEF, 84 HFrEF). Compared with a low probability of MASLD at baseline, high probability of MASLD at baseline was associated with overall HF risk ( Table ). In HF subtype analyses, higher probability of MASLD was significantly associated with higher risk of HFpEF but not HFrEF. In longitudinal analysis, 1-year increase in the probability of MASLD was significantly associated with higher risk of overall HF with a similar, non-significant pattern of association observed for both HF subtypes. Conclusions: Among adults with T2D and overweight or obesity in the Look AHEAD trial, higher probability of MASLD at baseline and increase in MASLD probability over 1-year follow-up were associated with higher risk of overall HF. Baseline MASLD probability was significantly associated with risk of HFpEF but not HFrEF. These findings underscore the prognostic implications of MASLD and its importance in HF risk assessment in T2D.