title: Circulating collagen biomarkers as indicators of disease severity in pulmonary arterial hypertension.
abstract: OBJECTIVE
  The goal of this study was to determine if biomarkers of collagen metabolism in PAH identify patients with worse disease and higher risk of death.
  
  
  BACKGROUND
  The relationship between circulating markers of collagen metabolism, degree of disease severity, and outcome in pulmonary arterial hypertension (PAH) is unknown.
  
  
  METHODS
  Patients with stable idiopathic, anorexigen-associated, and hereditary PAH were prospectively enrolled. Levels of the following collagen biomarkers were measured: N-terminal pro-peptide of type III procollagen (PIIINP), C-terminal telopeptide of collagen type I (CITP), matrix metalloproteinase (MMP)-9, and tissue inhibitor of metalloproteinase (TIMP)-1. Patients were divided into mild, moderate, and severe PAH groups. Data were compared between tertiles of each biomarker. Pearson correlation and Spearman rank coefficient analyses were performed. Data on time to death or transplantation were examined by Kaplan-Meier survival curves.
  
  
  RESULTS
  Circulating levels of PIIINP, CITP, MMP-9, and TIMP-1 were higher in the PAH group (n = 68) as compared with age- and sex-matched healthy controls (n = 37) (p < 0.001 for each). PIIINP levels increased with the severity of disease (p = 0.002). PIIINP tertile data indicated that with increasing levels, 6-min walk distance and cardiac index decreased, World Health Organization functional classification worsened, and resting heart rate increased. A significant correlation existed between PIIINP levels and worsening World Health Organization functional classification (rs = 0.320; p < 0.01), and there was a negative correlation between cardiac index and 6-min walk distance (r = -0.304 and r = -0.362, respectively; p < 0.05). PIIINP tertiles showed a trend toward worse outcome in patients with higher tertiles (lung transplant or death) (p = 0.07; log-rank test).
  
  
  CONCLUSIONS
  Markers of collagen metabolism were associated with worse disease in patients with PAH.
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, Baylor College of Medicine, and Houston Methodist Hospital, Houston, Texas. Electronic address: safdar@bcm.edu.
authors.forename: Zeenat
authors.initials: Z
authors.lastname: Safdar
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, Baylor College of Medicine, and Houston Methodist Hospital, Houston, Texas.
authors.forename: Emilio
authors.initials: E
authors.lastname: Tamez
authors.affiliation: University of Texas School of Public Health, Houston, Texas.
authors.forename: Wenyaw
authors.initials: W
authors.lastname: Chan
authors.affiliation: Department of Cardiology, Baylor College of Medicine, Houston, Texas.
authors.forename: Basant
authors.initials: B
authors.lastname: Arya
authors.affiliation: Houston Methodist Hospital, Houston, Texas.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Ge
authors.affiliation: Department of Cardiology, Baylor College of Medicine, Houston, Texas.
authors.forename: Anita
authors.initials: A
authors.lastname: Deswal
authors.affiliation: Department of Cardiology, Baylor College of Medicine, Houston, Texas.
authors.forename: Biykem
authors.initials: B
authors.lastname: Bozkurt
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, Baylor College of Medicine, and Houston Methodist Hospital, Houston, Texas.
authors.forename: Adaani
authors.initials: A
authors.lastname: Frost
authors.affiliation: Department of Cardiology, Baylor College of Medicine, Houston, Texas.
authors.forename: Mark
authors.initials: M
authors.lastname: Entman
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000503:physiopathology; D016027:Heart Transplantation / Q000706:statistics & numerical data; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis* / Q000503:physiopathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D010490:Pericardial Effusion / Q000175:diagnosis / Q000503:physiopathology; D011347:Procollagen / Q000378:metabolism*; D011379:Prognosis; D011446:Prospective Studies; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; D019715:Tissue Inhibitor of Metalloproteinase-1; C052929:collagen type I trimeric cross-linked peptide; C041876:procollagen Type III-N-terminal peptide; D020780:Matrix Metalloproteinase 9
keywords: BNP; PIIINP; heart failure; vascular remodeling