title: Fibrosis marker syndecan-1 and outcome in patients with heart failure with reduced and preserved ejection fraction.
abstract: BACKGROUND
  Syndecan-1 is a member of the proteoglycan family involved in cell-matrix interactions. Experimental studies showed that syndecan-1 is associated with inflammation in acute myocardial infarction and remodeling. The goal of this study was to explore the role of syndecan-1 in human heart failure (HF).
  
  
  RESULTS
  We analyzed plasma syndecan-1 levels in 567 patients with chronic HF. Primary end point was a composite of all-cause mortality and rehospitalization for HF at 18 months. Mean age was 71.0±11.0 years, 38% was women, and mean left ventricular ejection fraction was 32.5±14.0%. Median syndecan-1 levels were 20.1 ng/mL (interquartile range, 13.9-27.7 ng/mL). Patients with higher syndecan-1 levels were more often men, had higher N-terminal probrain-type natriuretic peptide levels, and worse renal function. Multivariable regression analyses showed a positive correlation between syndecan-1 levels and markers of fibrosis and remodeling but no correlation with inflammation markers. Interaction analysis revealed an interaction between left ventricular ejection fraction and syndecan-1 (P=0.047). A doubling of syndecan-1 was associated with an increased risk of the primary outcome in patients with HF with preserved ejection fraction (hazard ratio, 2.10; 95% confidence interval, 1.14-3.86; P=0.017) but not in patients with HF with reduced ejection fraction (hazard ratio, 0.95; 95% confidence interval, 0.71-1.27; P=0.729). Finally, syndecan-1 enhanced risk classification in patients with HF with preserved ejection fraction when added to a prediction model with established risk factors.
  
  
  CONCLUSIONS
  In patients with HF, syndecan-1 levels correlate with fibrosis biomarkers pointing toward a role in cardiac remodeling. Syndecan-1 was associated with clinical outcome in patients with HF with preserved ejection fraction but not in patients with HF with reduced ejection fraction.
authors.affiliation: From the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (J.T., A.v.d.P., I.T.K., R.A.d.B., W.H.v.G., A.A.V., D.J.v.V., P.v.d.M.); and Department of Social and Welfare Studies, Faculty of Health Sciences, Linköping University, Norrköping, Sweden (T.J.).
authors.forename: Jasper
authors.initials: J
authors.lastname: Tromp
authors.affiliation: From the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (J.T., A.v.d.P., I.T.K., R.A.d.B., W.H.v.G., A.A.V., D.J.v.V., P.v.d.M.); and Department of Social and Welfare Studies, Faculty of Health Sciences, Linköping University, Norrköping, Sweden (T.J.).
authors.forename: Atze
authors.initials: A
authors.lastname: van der Pol
authors.affiliation: From the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (J.T., A.v.d.P., I.T.K., R.A.d.B., W.H.v.G., A.A.V., D.J.v.V., P.v.d.M.); and Department of Social and Welfare Studies, Faculty of Health Sciences, Linköping University, Norrköping, Sweden (T.J.).
authors.forename: Ĳsbrand T
authors.initials: IT
authors.lastname: Klip
authors.affiliation: From the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (J.T., A.v.d.P., I.T.K., R.A.d.B., W.H.v.G., A.A.V., D.J.v.V., P.v.d.M.); and Department of Social and Welfare Studies, Faculty of Health Sciences, Linköping University, Norrköping, Sweden (T.J.).
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: de Boer
authors.affiliation: From the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (J.T., A.v.d.P., I.T.K., R.A.d.B., W.H.v.G., A.A.V., D.J.v.V., P.v.d.M.); and Department of Social and Welfare Studies, Faculty of Health Sciences, Linköping University, Norrköping, Sweden (T.J.).
authors.forename: Tiny
authors.initials: T
authors.lastname: Jaarsma
authors.affiliation: From the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (J.T., A.v.d.P., I.T.K., R.A.d.B., W.H.v.G., A.A.V., D.J.v.V., P.v.d.M.); and Department of Social and Welfare Studies, Faculty of Health Sciences, Linköping University, Norrköping, Sweden (T.J.).
authors.forename: Wiek H
authors.initials: WH
authors.lastname: van Gilst
authors.affiliation: From the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (J.T., A.v.d.P., I.T.K., R.A.d.B., W.H.v.G., A.A.V., D.J.v.V., P.v.d.M.); and Department of Social and Welfare Studies, Faculty of Health Sciences, Linköping University, Norrköping, Sweden (T.J.).
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.affiliation: From the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (J.T., A.v.d.P., I.T.K., R.A.d.B., W.H.v.G., A.A.V., D.J.v.V., P.v.d.M.); and Department of Social and Welfare Studies, Faculty of Health Sciences, Linköping University, Norrköping, Sweden (T.J.).
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.affiliation: From the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (J.T., A.v.d.P., I.T.K., R.A.d.B., W.H.v.G., A.A.V., D.J.v.V., P.v.d.M.); and Department of Social and Welfare Studies, Faculty of Health Sciences, Linköping University, Norrköping, Sweden (T.J.). p.van.der.meer@umcg.nl.
authors.forename: Peter
authors.initials: P
authors.lastname: van der Meer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D015897:Comorbidity; D005260:Female; D005355:Fibrosis; D005500:Follow-Up Studies; D006333:Heart Failure / Q000175:diagnosis* / Q000453:epidemiology* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D011379:Prognosis; D012044:Regression Analysis; D012189:Retrospective Studies; D012307:Risk Factors; D013318:Stroke Volume / Q000502:physiology*; D015996:Survival Rate; D053668:Syndecan-1 / Q000097:blood*; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis* / Q000453:epidemiology* / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D053668:Syndecan-1
keywords: fibrosis; heart failure; prognosis; syndecan-1