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Background <p>The presence of higher body mass index (BMI) accompanied by better outcomes in patients with heart failure with reduced ejection fraction (HFrEF) is described as the obesity paradox. However, recent evidence has 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 patients with the use of contemporary guideline-directed medical therapy (GDMT), including SGLT2is, is scarce.</p> Aim <p>To assess the association between BMI and mortality in patients with HFrEF treated with modern GDMT across a wide BMI spectrum.</p> Patients and methods <p>The data of 420 consecutive patients (male sex: 75%, age: 62 [51–71] years, NT-proBNP at admission: 5678 [2647–10501] pg/mL, LVEF: 24 [20–30] %, coronary artery disease: 44%, atrial fibrillation: 45%, normal weight: 33% [group 1: BMI &lt; 25&#xa0;kg/m<sup>2</sup>], overweight: 31% [group 2: BMI: 25–29.9&#xa0;kg/m<sup>2</sup>], obese: 36% [group 3: BMI ≥ 30&#xa0;kg/m<sup>2</sup>], type 2 diabetes [T2D]: 35%, eGFR &lt; 60&#xa0;mL/min/1.73m<sup>2</sup>: 55%) hospitalised for HFrEF in 2021–2024 with available BMI were analysed retrospectively. The application of GDMT at hospital discharge was compared between three groups of patients (group 1, 2, and 3). All-cause mortality (ACM) was assessed using Kaplan–Meier curves and the log-rank test. Predictors of ACM were estimated with uni- and multivariate Cox proportional hazards regression. In a sensitivity analysis, BMI groups were propensity score-matched (PSM) at a 1:1:1 ratio, adjusting for possible confounders.</p> Results <p>At hospital discharge, triple therapy (TT: RASi + βB + MRA) was applied in 82% (RASi: 92%, βB: 85%, MRA: 95%), while quadruple therapy (QT: TT + SGLT2i) was implemented in 58% of the total cohort (SGLT2i use: 64%). At discharge, higher BMI category was significantly (p &lt; 0.05) 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%).</p> <p>During a median follow-up of 534&#xa0;days, ACM was lower with increasing BMI subgroup category (p = 0.021). In the multivariate analysis, BMI subgroup category was not associated with ACM, whereas age, T2D, peripheral artery disease, NT-proBNP at discharge, and use of QT at discharge were independent predictors of ACM. In the sensitivity analysis, no significant differences were seen in the ACM of each BMI category after PSM.</p> Conclusions <p>In a consecutive cohort of patients hospitalised due to HFrEF with high rates of modern GDMT use across a wide BMI spectrum, higher BMI subgroup category was not associated with better survival after adjustment for comorbidities and prognostic factors.</p> Graphical Abstract <p></p>

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Revisiting the obesity paradox in patients with heart failure with reduced ejection fraction in the light of contemporary guideline-directed medical therapy

  • 期刊论文

  • 发表日期：

    2026年3月24日

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  • Tamás G. Gergely,
  • Zsolt Forrai,
  • Ádám Kazay,
  • Pál Péter Schäffer,
  • Máté Vámos,
  • Dávid Pilecky,
  • Tamás Péter Füzesi,
  • Laura Fanni Hanuska,
  • Noémi Nyolczas,
  • Miklós Dékány,
  • Péter Andréka,
  • Zsolt Piróth,
  • Fanni Bánfi-Bacsárdi,
  • Balázs Muk

摘要

Background

The presence of higher body mass index (BMI) accompanied by better outcomes in patients with heart failure with reduced ejection fraction (HFrEF) is described as the obesity paradox. However, recent evidence has 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 patients with the use of contemporary guideline-directed medical therapy (GDMT), including SGLT2is, is scarce.

Aim

To assess the association between BMI and mortality in patients with HFrEF treated with modern GDMT across a wide BMI spectrum.

Patients and methods

The data of 420 consecutive patients (male sex: 75%, age: 62 [51–71] years, NT-proBNP at admission: 5678 [2647–10501] pg/mL, LVEF: 24 [20–30] %, coronary artery disease: 44%, atrial fibrillation: 45%, normal weight: 33% [group 1: BMI < 25 kg/m2], overweight: 31% [group 2: BMI: 25–29.9 kg/m2], obese: 36% [group 3: BMI ≥ 30 kg/m2], type 2 diabetes [T2D]: 35%, eGFR < 60 mL/min/1.73m2: 55%) hospitalised for HFrEF in 2021–2024 with available BMI were analysed retrospectively. The application of GDMT at hospital discharge was compared between three groups of patients (group 1, 2, and 3). All-cause mortality (ACM) was assessed using Kaplan–Meier curves and the log-rank test. Predictors of ACM were estimated with uni- and multivariate Cox proportional hazards regression. In a sensitivity analysis, BMI groups were propensity score-matched (PSM) at a 1:1:1 ratio, adjusting for possible confounders.

Results

At hospital discharge, triple therapy (TT: RASi + βB + MRA) was applied in 82% (RASi: 92%, βB: 85%, MRA: 95%), while quadruple therapy (QT: TT + SGLT2i) was implemented in 58% of the total cohort (SGLT2i use: 64%). At discharge, higher BMI category was significantly (p < 0.05) 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%).

During a median follow-up of 534 days, ACM was lower with increasing BMI subgroup category (p = 0.021). In the multivariate analysis, BMI subgroup category was not associated with ACM, whereas age, T2D, peripheral artery disease, NT-proBNP at discharge, and use of QT at discharge were independent predictors of ACM. In the sensitivity analysis, no significant differences were seen in the ACM of each BMI category after PSM.

Conclusions

In a consecutive cohort of patients hospitalised due to HFrEF with high rates of modern GDMT use across a wide BMI spectrum, higher BMI subgroup category was not associated with better survival after adjustment for comorbidities and prognostic factors.

Graphical Abstract