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Decreases in hepatokine Fetuin-A levels are associated with hepatic hypoperfusion and predict cardiac outcomes in patients with heart failure

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Abstract

Background

Interactions of the heart and the liver remain to be fully understood in the pathophysiology of heart failure (HF). Hepatokines are proteins synthesized and secreted from the liver and regulate systemic metabolisms of peripheral tissues. This study sought to clarify the clinical relevance of hepatokine Fetuin-A in patients with HF.

Methods and results

We enrolled 217 participants including 187 hospitalized patients with HF and 30 control subjects who were sought with a comparable age- and sex profile and who had never had HF or structural cardiac abnormalities. First, we examined the levels of Fetuin-A and found that its levels were significantly lower in patients with HF than in the controls. Next, HF patients were categorized into four groups based on hepatic hemodynamics assessed by abdominal ultrasonography which determines liver hypoperfusion by peak systolic velocity (PSV) of the celiac artery and liver stiffness by shear wave elastography (SWE). Fetuin-A levels were significantly decreased in HF patients with liver hypoperfusion compared to those without, but were not different between HF patients with and without elevated liver stiffness. Correlation analysis revealed that circulating Fetuin-A was positively correlated with PSV of the celiac artery but not with SWE of the liver. Kaplan–Meier analysis demonstrated that HF patients with lower Fetuin-A levels were significantly associated with increased adverse outcomes including cardiac deaths and decompensated HF.

Conclusions

Liver-derived hepatokine Fetuin-A may be a novel target involved in the cardio-hepatic interactions, as well as a useful biomarker for predicting the prognosis in patients with HF.

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Acknowledgements

The authors thank Ms. Tomiko Miura, Ms. Shoko Takahashi, Ms. Kumiko Watanabe and Ms. Yumi Yoshihisa for their technical assistance. Graphical abstract was created with BioRender.com.

Funding

This work was supported in part by JSPS KAKENHI grants No. 20K07828 to AY and No. MO20K16529 to YI.

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Correspondence to Tomofumi Misaka.

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The authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the Ethics Committee of Fukushima Medical University (approval number, 823), and was complied with the Declaration of Helsinki. All patients provided written informed consent for study participation.

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Tomita, Y., Misaka, T., Yoshihisa, A. et al. Decreases in hepatokine Fetuin-A levels are associated with hepatic hypoperfusion and predict cardiac outcomes in patients with heart failure. Clin Res Cardiol 111, 1104–1112 (2022). https://doi.org/10.1007/s00392-022-02023-0

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  • DOI: https://doi.org/10.1007/s00392-022-02023-0

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