title: Independent and additive prognostic ability of serum carboxy-terminal telopeptide of collagen type-I in heart failure patients: a multi-marker approach with high-negative predictive value to rule out long-term adverse events.
abstract: BACKGROUND
  Altered myocardial extracellular matrix turnover has been proposed as a major determinant of myocardial remodelling. Carboxy-terminal telopeptide of collagen type-I (CITP) represents a collagen type-I degradation-derived serum peptide. In this study we examined the independent and additive prognostic value of serum concentrations of CITP compared with well-known mortality predictors such as the N-terminal pro-brain natriuretic peptide (NT-proBNP) in chronic heart failure (CHF) patients.
  
  
  METHODS
  We studied 196 consecutive patients (126 male, mean age 69 ± 10 years), who were admitted for acute decompensation of the CHF syndrome. The study entry point was determined at the discharge of the patients after achieving a stable compensated status. The primary endpoint was cardiac mortality during a 12-month follow-up.
  
  
  RESULTS
  In the multivariate Cox proportional hazard model the levels of CITP remained a predictor of survival (hazards ratio 0.4 95% confidence interval 0.21-0.76, P = 0.005), independent of NT-proBNP levels. The stratified log-rank test (P < 0.001) showed that CHF patients characterized by low levels of both biomarkers had better survival (hazards ratio 0.12 95% confidence interval 0.04-0.35, P < 0.001) compared with patients characterized by high levels of both biomarkers. The negative predictive value of the combined measure for long-term adverse events was 94%.
  
  
  CONCLUSIONS
  Serum levels of CITP were shown to be an independent and strong prognostic marker regarding survival in CHF patients. Furthermore, CITP levels had an additive prognostic value compared with NT-proBNP levels. These findings underline the detrimental role of myocardial fibrosis in the progression of heart failure and suggest a novel multi-marker approach for risk stratification in the CHF syndrome.
authors.affiliation: University Cardiology Department, Medical School, Democritus University of Thrace, Alexandroupolis, Greece. dtziakas@med.duth.gr
authors.forename: Dimitrios N
authors.initials: DN
authors.lastname: Tziakas
authors.forename: Georgios K
authors.initials: GK
authors.lastname: Chalikias
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Stakos
authors.forename: Sofia V
authors.initials: SV
authors.lastname: Chatzikyriakou
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Papazoglou
authors.forename: Konstantina
authors.initials: K
authors.lastname: Mitrousi
authors.forename: Asimina
authors.initials: A
authors.lastname: Lantzouraki
authors.forename: Adina
authors.initials: A
authors.lastname: Thomaidi
authors.forename: Harisios
authors.initials: H
authors.lastname: Boudoulas
authors.forename: Stavros
authors.initials: S
authors.lastname: Konstantinides
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D002908:Chronic Disease; D024042:Collagen Type I / Q000097:blood*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005355:Fibrosis; D006115:Greece; D006333:Heart Failure / Q000097:blood* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013997:Time Factors
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain