Obesity in HFpEF with and without diabetes - Risk factor or innocent bystander?

Abstract

Heart failure with preserved ejection fraction (HFpEF) is a condition that commonly coexists with type 2 diabetes mellitus (T2DM) and obesity. Whether the obesity-related survival benefit generally observed in HFpEF extends to individuals with concomitant T2DM is unclear. This study sought to examine the prognostic role of overweight and obesity in a large cohort of HFpEF with and without T2DM. This large-scale cohort study included patients with HFpEF enrolled between 2010 and 2020. The relationship between body mass index (BMI), T2DM and survival was assessed. 6,744 individuals with HFpEF were included, of which 1,702 (25%) had T2DM. Patients with T2DM had higher BMI values (29.4kg/m2 vs. 27.1kg/m2, p<0.001), higher NT-proBNP values (864mg/dl vs. 724mg/dl, p<0.001) and a higher prevalence of numerous risk factors/comorbidities than those without T2DM. During a median follow-up time of 47 months (Q1-Q3: 20-80), 2014 (30%) patients died. Patients with T2DM had a higher incidence of fatal events compared to those without T2DM, with a mortality rate of 39.2% and 26.7% respectively (p<0.001). In the overall cohort, using the BMI category 22.5 to 24.9 kg/m2 as the reference group, the unadjusted hazard ratio (HR) for all-cause death was increased in patients with BMI <22.5kg/m2 (HR: 1.27 [CI 1.09-1.48], p=0.003) and decreased in BMI categories ≥25kg/m2. After multivariate adjustment, BMI remained significantly inversely associated with survival in non-T2DM, whereas survival was unaltered at a wide range of BMI in patients with T2DM. Among the various phenotypes of HFpEF, the T2DM phenotype is specifically associated with greater disease burden. Higher BMI is linked to improved survival in HFpEF overall, while this effect neutralises in patients with concomitant T2DM. Advising BMI-based weight targets and weight loss may be pursued with different intensity in the management of HFpEF, particularly in the presence of T2DM.