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Clinical Research

Cachectic biomarkers as confounders behind the obesity paradox in patients with acute decompensated heart failure

International Journal of Obesity volume 49, pages 888–895 (2025)Cite this article

Subjects

Abstract

Background

Obesity is a risk factor for heart failure (HF) development but is associated with a lower incidence of mortality in HF patients. This obesity paradox may be confounded by unrecognized comorbidities, including cachexia.

Methods

A retrospective assessment was conducted using data from a prospectively recruiting multicenter registry, which included consecutive acute heart failure patients. A low, normal, and high body mass index (BMI) was defined as <20 kg/m2, 20–25 kg/m2, and ≥25 kg/m2, respectively. Cachexia was defined as a combination of BMI < 20 kg/m2 and any biochemical abnormalities including albumin, hemoglobin, or C-reactive protein. Patients with either of the three biochemical abnormalities were categorized as those with cachectic biomarkers. Two-year all-cause, cardiac, and noncardiac mortality were evaluated.

Results

This study evaluated 3314 patients (mean BMI, 22 ± 4 kg/m2 [low BMI with cachexia, 828 (25%); low BMI without cachexia, 273 (8%); normal BMI, 1584 (48%); high BMI, 629 (19%)]). Overall, an increase of 1 point in BMI was associated with a decreased incidence of all-cause mortality (adjusted hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.90–0.94; p < 0.001). Regardless of the mode of death, the low BMI with cachexia indicated the worst prognosis, while the low BMI without cachexia showed a similar prognosis to the normal BMI. Cachectic biomarkers, which were observed more frequently in the low BMI, predicted a higher incidence of 2-year all-cause mortality across the BMI categories (adjusted HR for the low BMI, 1.90; 95% CI, 1.30–2.77; p = 0.001; adjusted HR for the normal BMI, 1.94; 95% CI, 1.34–2.79; p < 0.001; adjusted HR for the high BMI, 3.60; 95% CI, 1.61–8.08; p = 0.002).

Conclusions

BMI could be only a surrogate marker. The cachectic biomarkers may reflect the underlying conditions and contribute to elucidating the obesity paradox.

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Fig. 1: Association of BMI with two-year all-cause mortality.
Fig. 2: Association of BMI with the mode of death.
Fig. 3: Two-year mortality based on the BMI categories with and without the cachectic biomarkers.

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Data availability

The data that support the findings of this study are available on request from the corresponding author.

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Acknowledgements

We appreciate all participants in the WET-HF registry for their contribution to the investigation and data acquisition.

Funding

The West Tokyo Heart Failure Registry was supported by a Grant-in-Aid for Young Scientists [Japan Society for the Promotion of Science KAKENHI, #18K15860 (YS), #23K15168 (YS)], a Grant-in-Aid for Scientific Research (C) [#23591062 (TY), #26461088 (TY), #16K09469 (YN), #17K09526 (TK), #18K08056 (TY), #20K08408 (TK), #21K08142 (TY), #21K08087 (AG), #23K07591 (MK), #23K07584 (TK)], a Grant-in-Aid for Scientific Research (B) [16H05215 (SK), 20H03915 (SK), 24K02674 (SK)], a Health Labour Sciences Research Grant [#14528506 (SK)], the Sakakibara Clinical Research Grant for the Promotion of Sciences [TY 2012–2020], the Japan Agency for Medical Research and Development [201439013 C (SK)], and the Grant-in-Aid for Clinical Research from the Japanese Circulation Society [2019 (YS)].

Author information

Author notes

  1. These authors contributed equally: Yusuke Miura, Satoshi Higuchi.

Authors and Affiliations

  1. Department of Cardiovascular Medicine, Kyorin University Hospital, Tokyo, Japan

    Yusuke Miura, Takashi Kohno, Kyoko Soejima & Ayumi Goda

  2. Division of Cardiology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan

    Satoshi Higuchi

  3. Department of Cardiology, Keio University School of Medicine, Tokyo, Japan

    Yasuyuki Shiraishi & Shun Kohsaka

  4. Department of Cardiology, Sakakibara Heart Institute, Tokyo, Japan

    Mitsunobu Kitamura & Tsutomu Yoshikawa

  5. Department of Cardiology, National Defense Medical College, Saitama, Japan

    Yuji Nagatomo

  6. Department of Cardiology, Tokyo Saiseikai Central Hospital, Tokyo, Japan

    Yumiko Kawakubo Ichihara

  7. Department of Cardiology, St Luke’s International Hospital, Tokyo, Japan

    Atsushi Mizuno

  8. Department of Cardiology, Saitama Medical University, International Medical Center, Saitama, Japan

    Shintaro Nakano

Authors
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Consortia

West Tokyo Heart Failure (WET-HF) Registry Investigators

  • Yusuke Miura
  • , Satoshi Higuchi
  • , Takashi Kohno
  • , Yasuyuki Shiraishi
  • , Mitsunobu Kitamura
  • , Yuji Nagatomo
  • , Yumiko Kawakubo Ichihara
  • , Atsushi Mizuno
  • , Shintaro Nakano
  • , Kyoko Soejima
  • , Ayumi Goda
  • , Shun Kohsaka
  •  & Tsutomu Yoshikawa

Contributions

Conceptualization: YM and SH; Methodology: YM, SH, TK, YS, and SK; Software: YM and SH; Validation: TK, YS, SK, and TY; Formal analysis: YM and SH; Investigation: SH, TK, YS, YN, AM, AG, SK, TY; Resources: TK, YS, MK, YN, YI, AM, SN, AG, SK, TY; Data Curation: YS and SK; Writing—original draft: YM, SH, and TK; Review and editing: YS, MK, YN, YI, AM, SN, KS, AG, SK, TY; Visualization: YM and SH; Supervision: TK, SK, and TY; Project administration: SK and TY; Funding acquisition: TK, YS, AG, SK, and TY.

Corresponding authors

Correspondence to Satoshi Higuchi or Takashi Kohno.

Ethics declarations

Competing interests

Dr. Shiraishi has received lecture fees from Otsuka Pharma-ceuticals Co., Ltd. and Ono Pharmaceuticals Co., Ltd. S. Nakano reports speaking fees and consulting fees from Pfizer and Otsuka. S. Kohsaka reports an investigator-initiated grant from Novartis, and personal fees from Bristol-Myers Squibb. All other authors report no conflicts of interest.

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Miura, Y., Higuchi, S., Kohno, T. et al. Cachectic biomarkers as confounders behind the obesity paradox in patients with acute decompensated heart failure. Int J Obes 49, 888–895 (2025). https://doi.org/10.1038/s41366-025-01716-6

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