Circulating Collagen Biomarkers as Indicators of Disease Severity in Pulmonary Arterial Hypertension

Zeenat Safdar, Emilio Tamez, Wenyaw Chan, Basant Arya, Yimin Ge, Anita Deswal, Biykem Bozkurt, Adaani Frost, Mark Entman

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Objectives: 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.

Original languageEnglish (US)
Pages (from-to)412-421
Number of pages10
JournalJACC: Heart Failure
Volume2
Issue number4
DOIs
StatePublished - Aug 2014

Keywords

  • BNP
  • Heart failure
  • PIIINP
  • Vascular remodeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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