Higher BMI category was not associated with all-cause mortality in HFrEF patients after adjustment for confounders, despite lower unadjusted mortality in obese versus normal weight patients (21% vs 33%).
Cohort (n=420)
Does higher BMI improve survival in HFrEF patients treated with contemporary guideline-directed medical therapy?
The historical 'obesity paradox' in HFrEF is no longer observed when adjusting for comorbidities and the implementation of modern guideline-directed medical therapy.
Absolute Event Rate: 21% vs 33%
p-value: p=<0.05
Abstract Background The presence of higher body mass index (BMI) accompanied with better outcomes in patients (pts) with heart failure with reduced ejection fraction (HFrEF) is described as the obesity paradox. However, recent evidence questioned the existence of this phenomenon by adjusting for better prognostic factors and using superior anthropometric measures of obesity. Nevertheless, data regarding the association between BMI and mortality in HFrEF pts with the use of contemporary guideline-directed medical therapy (GDMT), including SGLT2is is scarce. Aim To assess the association between BMI and mortality in pts with HFrEF treated with modern GDMT across a wide BMI spectrum. Patients and methods The data of 420 consecutive pts hospitalised (male sex: 75%, age: 62 51-71 years, NT-proBNP at admission: 5678 2647-10501 pg/mL, LVEF: 24 20-30 %, hypertension: 65%, coronary artery disease: 44%, atrial fibrillation: 45%, normal weight: 33% group 1: BMI 25 kg/m2, overweight: 31% group 2: 25 ≤ BMI 30 kg/m2, obese: 36% group 3: BMI ≥ 30 kg/m2, type 2 diabetes T2DM: 35%, eGFR 60 mL/min/1.73m2: 53%) for HFrEF in 2021-2024 with available BMI were analysed retrospectively. The application of GDMT at hospital discharge was compared between group 1, 2, and 3 pts. All-cause mortality (ACM) was assessed via Kaplan-Meier curves and log-rank test for trend. Independent predictors of ACM were estimated with multivariate Cox proportional hazards regression. In a sensitivity analysis, BMI groups were propensity-score-matched (PSM) with 1:1:1 ratio, adjusting for possible confounders. Results At hospital discharge, triple therapy (TT: RASi + βB + MRA) was applied in 82% (RASi: 91%, βB: 85%, MRA: 95%), while quadruple therapy (QT: TT + SGLT2i) was implemented in 54% of the total cohort (SGLT2i use: 59%). At discharge, higher BMI category was significantly (p0.05) associated with increased use of MRA (group 1, 2, 3: 93%, 92%, and 100%), SGLT2i medications (group 1, 2, 3: 58%, 61%, and 71%), and QT (group 1, 2, 3: 51%, 56%, and 65%). With a median follow-up of 534 days, ACM was lower with increasing BMI category (mortality of group 1,2,3: 33%, 29%, 21%, p0.05). In the multivariate analysis, BMI category was not associated with ACM, whereas age, T2DM, NT-proBNP at discharge, and use of QT at discharge were independent predictors of ACM. In the sensitivity analysis, no differences were seen in the ACM of each BMI category after PSM. Conclusions In a consecutive cohort of pts hospitalised due to HFrEF with high rates of modern GDMT use across a wide BMI spectrum, higher BMI category was no longer associated with better survival after adjustment for comorbidities and prognostic factors. However, age, T2DM, and elevated NT-proBNP proved to be negative-, while the implementation of modern GDMT was a positive independent predictor of ACM. Hence, GDMT implementation has to be prioritised in all patients regardless of BMI category to improve prognosis.
Gergely et al. (2025) conducted a cohort in Heart failure with reduced ejection fraction (HFrEF) (n=420). Higher body mass index (BMI) vs. Normal weight (BMI < 25 kg/m2) was evaluated on All-cause mortality (p=<0.05). Higher BMI category was not associated with all-cause mortality in HFrEF patients after adjustment for confounders, despite lower unadjusted mortality in obese versus normal weight patients (21% vs 33%).