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.