Obesity in heart failure with preserved ejection fraction with and without diabetes: risk factor or innocent bystander?

ABSTRACT

AIMS: 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. METHODS AND RESULTS: 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. A total of 6744 individuals with HFpEF were included, of which 1702 (25%) had T2DM. Patients with T2DM had higher BMI values (29.4 kg/m2 vs. 27.1 kg/m2, P < 0.001), higher N-terminal pro-brain natriuretic peptide values (864 mg/dL vs. 724 mg/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 with 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 22.5-24.9 kg/m2 as the reference group, the unadjusted hazard ratio (HR) for all-cause death was increased in patients with BMI <22.5 kg/m2 [HR 1.27 (confidence interval 1.09-1.48), P = 0.003] and decreased in BMI categories ≥25 kg/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. CONCLUSION: Among the various phenotypes of HFpEF, the T2DM phenotype is specifically associated with a 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.

Individuals with HFpEF and concomitant diabetes show a distinct phenotype particularly associated with a higher disease burden and worse outcome. The obesity paradox observed in individuals with heart failure may not be generalized to HFpEF patients with concomitant diabetes.