title: HE4 Serum Levels Are Associated with Heart Failure Severity in Patients With Chronic Heart Failure.
abstract: BACKGROUND
  The novel biomarker human epididymis protein 4 (HE4) shows prognostic value in acute heart failure (HF) patients. We measured HE4 levels in patients with chronic heart failure (CHF) and correlated them to HF severity, kidney function, and HF biomarkers, and determined its predictive value.
  
  
  METHODS
  Serum HE4 levels in patients (n = 101) with stable CHF with reduced left ventricular ejection fraction (LVEF <45%) from the Vitamin D CHF (VitD-CHF) study (NCT01092130) were compared with those in age- and sex-matched healthy control subjects (n = 58) from the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study.
  
  
  RESULTS
  HE4 levels were higher in CHF compared with control subjects (69.2 pmol/L [interquartile range 55.6-93.8] vs 56.1 pmol/L [46.6-69.0]; P < .001) and were higher with increasing New York Heart Association functional class. Levels were associated with HF risk factors, including age, gender, diabetes, smoking and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP). HE4 demonstrated strong associations with kidney function and HF fibrosis biomarkers. In a multivariable model, we identified creatinine, NT-proBNP, galectin-3, high-sensitive troponin T, and smoking as factors associated with HE4. Independently from these factors, HE4 levels predicted death and HF rehospitalization (5-year follow-up, hazard ratio 3.8; confidence interval 1.31-11.1; P = .014).
  
  
  CONCLUSIONS
  HE4 levels are increased in CHF, correlate with HF severity and kidney function, and predict HF outcome.
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Arnold
authors.initials: A
authors.lastname: Piek
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Wouter C
authors.initials: WC
authors.lastname: Meijers
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; OLVG, Department of Internal Medicine, Amsterdam, The Netherlands.
authors.forename: Nicolas F
authors.initials: NF
authors.lastname: Schroten
authors.affiliation: Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Ron T
authors.initials: RT
authors.lastname: Gansevoort
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: de Boer
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Electronic address: h.h.w.sillje@umcg.nl.
authors.forename: Herman H W
authors.initials: HH
authors.lastname: Silljé
mesh_terms: D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D011379:Prognosis; D011506:Proteins / Q000378:metabolism*; D012720:Severity of Illness Index; D013318:Stroke Volume / Q000502:physiology*; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D000081102:WAP Four-Disulfide Core Domain Protein 2
chemical_list: D015415:Biomarkers; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human
keywords: HE4; WFDC2; chronic heart failure; fibrosis