title: Extracellular matrix turnover and inflammatory markers independently predict functional status and outcome in chronic heart failure.
abstract: BACKGROUND
  Inflammatory pathways may promote extracellular matrix (ECM) remodeling and chronic heart failure (CHF) progression. The relationship between markers of inflammation and of ECM remodeling, and their influence on functional status and outcomes has not been examined in a large cohort of CHF patients.
  
  
  RESULTS
  We measured baseline blood serum collagen (amino-terminal propeptide of collagen III [PIIINP], metalloproteinase 1 [MMP-1], tissue inhibitor of metalloproteinase 1 [TIMP-1]), and inflammatory (high-sensitivity C-reactive protein [(hsCRP], interleukin [IL]-18, IL-10) markers in 1009 patients enrolled in the Research into Etanercept Cytokine Antagonism in Ventricular Dysfunction (RECOVER) trial. A positive correlation was detected between the 2 classes of markers (PIIINP to IL-18, MMP-1 and TIMP-1 to CRP, TIMP-1 to IL-18, MMP-1 to IL-10). In the adjusted multivariable model including all biomarkers, only PIIINP (P = .03) and MMP-1 (P = .048) were independent predictors of 6-minute walk test (6-MWT), whereas in another model including only inflammatory biomarkers, IL-18 was an independent predictor. PIIINP (P = .001) was the only biomarker independently associated with death and CHF hospitalization.
  
  
  CONCLUSIONS
  The independent associations of PIIINP and MMP-1 with 6-MWT and PIIINP with CHF morbi-mortality suggest that excessive ECM turnover may be associated with functional capacity deterioration and poor outcome.
authors.affiliation: Centre d'Investigation Clinique 9501, INSERM, Dommartin-lès-Toul, France.
authors.forename: Anca
authors.initials: A
authors.lastname: Radauceanu
authors.forename: Camille
authors.initials: C
authors.lastname: Ducki
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Virion
authors.forename: Patrick
authors.initials: P
authors.lastname: Rossignol
authors.forename: Ziad
authors.initials: Z
authors.lastname: Mallat
authors.forename: John
authors.initials: J
authors.lastname: McMurray
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Van Veldhuisen
authors.forename: Luigi
authors.initials: L
authors.lastname: Tavazzi
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Mann
authors.forename: Josette
authors.initials: J
authors.lastname: Capiaumont-Vin
authors.forename: Minjiang
authors.initials: M
authors.lastname: Li
authors.forename: Didier
authors.initials: D
authors.lastname: Hanriot
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D015331:Cohort Studies; D004311:Double-Blind Method; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006333:Heart Failure / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators