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Increased p-cresyl sulfate level is independently associated with poor outcomes in patients with heart failure

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Abstract

Amino acid-derived metabolites, including protein-bound uremic toxins, may have prognostic value for patients with heart failure (HF). The aim of this study was to investigate whether p-cresyl sulfate (PCS), indoxyl sulfate (IS), and arginine metabolites provided prognostic values in addition to the traditional biomarker, B-type natriuretic peptide (BNP), in patients with HF. Chromatography mass spectrometry was performed to measure tyrosine, tryptophan, arginine, PCS, IS, and asymmetric (ADMA) and symmetric dimethylarginine (SDMA) in the plasma from 51 normal controls and 136 HF patients. Compared to the normal controls, PCS levels significantly increased in HF patients (p = 0.003). During the follow-up (2.3 ± 1.1 years), 35 (25.7 %) patients experienced a composite event of death or HF-related re-hospitalization. In univariable analysis, PCS, estimated glomerular filtration rate (eGFR), BNP, DMA/arginine ratio, and ADMA/arginine ratio were associated with a higher rate of composite events. In the multivariable analysis, PCS was the only independent predictor of composite events [hazard ratio (HR) 1.06 (per 10 μM), 95 % confidence interval (CI) 1.01–1.11, p = 0.02]. Kaplan–Meier curves showed that a PCS level of ≥50 μM was significantly associated with a higher composite event rate than those with a PCS level of <50 μM (Log rank = 5.11, p = 0.024; HR 2.13, 95 % CI 1.09–4.16, p = 0.02). In conclusion, among protein-bound uremic toxins, eGFR, and DMA metabolites, increased PCS is the only independent predictor of HF-related events in patients with HF. A combination of PCS and BNP should better risk-stratify patients with HF.

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Acknowledgments

This study was supported in part by the National Science Council of Taiwan (102-2314-B-182-037-) and Chang Gung Memorial Hospital (CMRPG2C0312, 2C0351,2C0361, CMRPD1A0522, and CMRPG2A0172).

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Authors and Affiliations

  1. Division of Cardiology, Department of Internal Medicine, Heart Failure Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan

    Chao-Hung Wang, Min-Hui Liu & Yu-Yen Huang

  2. Chang Gung University College of Medicine, Taoyuan, Taiwan

    Chao-Hung Wang, Min-Hui Liu & Yu-Yen Huang

  3. Metabolomics Core Laboratory, Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan

    Mei-Ling Cheng, Ming-Shi Shiao & Jui-Fen Lin

  4. Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan

    Mei-Ling Cheng & Ming-Shi Shiao

  5. Department of Nursing, National Yang-Ming University, Taipei, Taiwan

    Min-Hui Liu

  6. Laboratory for Epidemiology, Department of Health Care Management, Chang Gung University College, Taoyuan, Taiwan

    Kuang-Hung Hsu

  7. Graduate Institute of Medical Biotechnology and Laboratory Sciences, Chang Gung University, Taoyuan, Taiwan

    Cheng-Cheng Lin

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  1. Chao-Hung Wang
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Correspondence to Mei-Ling Cheng.

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Wang, CH., Cheng, ML., Liu, MH. et al. Increased p-cresyl sulfate level is independently associated with poor outcomes in patients with heart failure. Heart Vessels 31, 1100–1108 (2016). https://doi.org/10.1007/s00380-015-0702-0

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  • DOI: https://doi.org/10.1007/s00380-015-0702-0

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