# Overweight and obesity association with mortality in patients with heart failure and reduced or preserved ejection fraction-a cohort study

**Authors:** Nicolas Garin, David Carballo, Jonathan Dash, Jérôme Stirnemann, Jean-Luc Reny, Nicolas Vuilleumier, Sebastian Carballo, Yoshiaki Taniyama, Yoshiaki Taniyama, Yoshiaki Taniyama

PMC · DOI: 10.1371/journal.pone.0341606 · PLOS One · 2026-02-03

## TL;DR

This study finds that the survival benefit of being overweight in heart failure patients is likely due to other factors like age and disease severity, not actual weight benefits.

## Contribution

The study demonstrates that the obesity paradox in heart failure is fully explained by confounding factors after adjustment.

## Key findings

- Overweight and obese patients had lower unadjusted mortality in heart failure.
- After adjusting for factors like age and disease severity, the survival benefit disappeared.
- The obesity paradox is explained by confounding variables, not a direct protective effect of excess weight.

## Abstract

Obesity is a risk factor for incident heart failure, but patients with excess weight and heart failure have lower mortality. This “obesity paradox” may be explained either by a favourable effect of the adipose tissue or by confounding.

We aimed to assess if body mass index (BMI) is associated with lower mortality after extensive adjustment for prognostic factors in patients with reduced (HFrEF) or preserved (HFpEF) ejection fraction.

Prospective, observational study including consecutive patients hospitalized for acute heart failure. Two years hazard of mortality was assessed in a multivariable Cox model, in the whole population and separately for HFrEF and HFpEF.

Among 957 included patients (mean age 76 years, 41% women), 500 (47%) had HFrEF and 443 (53%) HFpEF. Four hundred (39%) were in the normoweight, 301(30%) in the overweight, and 256(25%) in the obese category (Class I obesity:144 patients; class II or III: 112). Corresponding mortality was 37%, 26% and 22%. Unadjusted hazard ratio (HR) for mortality was 0.96 (95% CI 0.94–0.98) for each BMI point in the whole population, 0.97 (95% CI 0.94–1.02) in patients with HFrEF, and 0.94 (95% CI 0.92–0.97) in HFpEF. After adjustment for age, sex, atrial fibrillation, diabetes, chronic obstructive pulmonary disease, chronic anaemia, hypertension, glomerular filtration rate, and NT-proBNP, HR was 1.00 (95% CI 0.96–1.02) in the whole population, 1.02 (0.96–1.07) in HFrEF, and 0.98 (95% CI 0.94–1.01) in HFpEF.

Excess weight was associated with an apparent survival benefit in patients with acute heart failure, particularly in patients with HFpEF. This advantage disappeared completely after adjustment for confounding factors including NT-proBNP. The obesity paradox can be completely explained by differences in demographics, co-morbidities, and severity of heart failure.

## Linked entities

- **Diseases:** heart failure (MONDO:0005252), atrial fibrillation (MONDO:0004981), diabetes (MONDO:0005015), chronic obstructive pulmonary disease (MONDO:0005002)

## Full-text entities

- **Genes:** NPPB (natriuretic peptide B) [NCBI Gene 4879] {aka BNP, Iso-ANP}, GIP (gastric inhibitory polypeptide) [NCBI Gene 2695], EHMT1 (euchromatic histone lysine methyltransferase 1) [NCBI Gene 79813] {aka EHMT1-IT1, EUHMTASE1, Eu-HMTase1, FP13812, GLP, GLP1}, IDE (insulin degrading enzyme) [NCBI Gene 3416] {aka INSULYSIN}, AP2B1 (adaptor related protein complex 2 subunit beta 1) [NCBI Gene 163] {aka ADTB2, AP105B, AP2-BETA, CLAPB1}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, GLP1R (glucagon like peptide 1 receptor) [NCBI Gene 2740] {aka GLP-1, GLP-1-R, GLP-1R}, LEP (leptin) [NCBI Gene 3952] {aka LEPD, OB, OBS}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, MME (membrane metalloendopeptidase) [NCBI Gene 4311] {aka CALLA, CD10, CMT2T, NEP, SCA43, SFE}
- **Diseases:** Inflammation (MESH:D007249), chronic renal failure (MESH:D007676), coronary artery disease (MESH:D003324), adiposity (MESH:D018205), HF (MESH:D006333), Overweight (MESH:D050177), death (MESH:D003643), DM (MESH:D009223), weight (MESH:D015431), HFrEF (MESH:D054143), COPD (MESH:D029424), atrial fibrillation (MESH:D001281), diabetes (MESH:D003920), oedema (MESH:C536897), Pulmonary rales (MESH:D012135), loss in (MESH:D016388), cachexia (MESH:D002100), cancer (MESH:D009369), anaemia (MESH:D000743), Hyperaldosteronism (MESH:D006929), Chronic anaemia (MESH:C536761), Underweight (MESH:D013851), abdominal obesity (MESH:D056128), hypertension (MESH:D006973), frailty (MESH:D000073496), Obese (MESH:D009765), infections (MESH:D007239)
- **Chemicals:** cholesterol (MESH:D002784), MRA (MESH:C502936), ARNI (-), Natriuretic peptides (MESH:D045265)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12867239/full.md

## References

40 references — full list in the complete paper: https://tomesphere.com/paper/PMC12867239/full.md

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Source: https://tomesphere.com/paper/PMC12867239