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

Chao Hung Wang, Mei Ling Cheng*, Min Hui Liu, Ming-Shih Shiao, Kuang Hung Hsu, Yu Yen Huang, Cheng Cheng Lin, Jui Fen Lin

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

24 Scopus citations


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.

Original languageEnglish
Pages (from-to)1100-1108
Number of pages9
JournalHeart and Vessels
Issue number7
StatePublished - 01 07 2016

Bibliographical note

Publisher Copyright:
© 2015, Springer Japan.


  • Dimethylarginine
  • Heart failure
  • Indoxyl sulfate
  • Prognosis
  • p-Cresyl sulfate


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