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Novel disease mechanisms in pulmonary arterial hypertension
S96 Novel biomarkers in idiopathic pulmonary arterial hypertension
  1. C J Rhodes,
  2. J Wharton,
  3. L S Howard,
  4. J S R Gibbs,
  5. M R Wilkins
  1. Imperial College London, London, UK

Abstract

Background Circulatingosteopontin levels predict survival in right heart failure and lung tissue expression is increased in hypoxic animal models of pulmonary hypertension. Growth differentiation factor (GDF)-15 and red cell distribution width (RDW) are potential biomarkers in idiopathic pulmonary arterial hypertension (IPAH).

Objectives We assessed the prognostic value of these novel biomarkers, along with the more established N-terminal pro-brain natriuretic peptide (NT-proBNP) and other clinical indices, in treatment-naïve and treated patients with IPAH.

Methods Plasmaosteopontin, GDF-15, and NT-proBNP levels and RDW were determined in 126 patients with IPAH, who were followed for 4.0±2.2 years.

Results All four biomarkers correlated with WHO functional class and 6 min walk distance(6MWD) and cut-offs of osteopontin (53.4 ng/ml, p<0.05), GDF-15 (800 pg/ml)and RDW (15.65%) predicted significant differences in survival in patients with IPAH (Abstract S96 Figure 1). Raised NT-proBNP levels also predicted significantly poorer survival (p<0.01). A temporal increase in serially-measured levels ofGDF-15, osteopontin or RDW indicated poorer survival in IPAH. Patients with relatively low NT-proBNP levels (below median) who might normally be considered low risk, displayed higher mortality rates when GDF-15 levels or RDW were raised. Cox regression survival modelling confirmed RDW as a significant predictor of mortality, independent of established markers including NT-proBNP, 6MWD and WHO class. GDF-15, RDW and NT-proBNP predicted significant (p<0.05) survival differences in patients with reduced exercise capacity (6MWD <380 m); median survival with low 6MWD and raised RDW (>15.65%) was <1.5 year vs 3.6 year for low 6MWD irrespective of the RDW value.

Conclusions Osteopontin, GDF-15 and RDW all predicted survival in IPAH and were associated with poorer clinical status. Temporal changes in biomarkers appear to hold prognostic information. RDW and NT-proBNP may add the most value to 6MWD and WHO class.

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