Abstract 5657: Growth Differentiation Factor-15 as a Biomarker in Pulmonary Arterial Hypertension and Hypoxia-induced Pulmonary Hypertension

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Circulating growth differentiation factor (GDF)-15 is a possible biomarker in idiopathic pulmonary arterial hypertension (IPAH). We sought to verify its prognostic value and evaluate GDF-15 in other forms of pulmonary hypertension (PH). GDF-15 and N-terminal pro-brain natriuretic peptide (NT-proBNP) were assayed in 127 IPAH patients, 83 of whom received targeted therapy. GDF-15 was also measured in 16 connective tissue disease-associated PAH (CTD) patients, 64 healthy controls and 89 Kyrgyz highlanders (2500 –3600 m), 35 of whom had PH (HAPH; mean pulmonary artery pressure (mPAP) >25 mmHg). GDF-15 levels were greater in IPAH (mean±SEM 987 ±81 pg/ml) and CTD (978 ±144 pg/ml) versus controls (306 ±16 pg/ml; P<0.001). GDF-15 levels >800 pg/ml were associated with decreased exercise capacity (p=0.002) and cardiac index (p=0.02), and increased NT-proBNP (p<0.001), age (p<0.001) and mean right atrial pressure (p=0.02), but did not correlate with mixed venous or arterial (SaO 2 ) oxygen saturation. 3 year mortality in IPAH was 21% (GDF-15 <800 pg/ml) and 58% (GDF-15 >800 pg/ml), with a hazard ratio of 5.12 (95% CI 1.89 –13.9; P<0.001). GDF-15 remained an independent predictor of mortality after adjusting for clinical/haemodynamic measurements and combining NT-proBNP data improved risk stratification. SaO 2 was significantly lower in high altitude (90.4±0.4%) and HAPH subjects (87.3±0.7%) versus IPAH patients (93.3±0.6%; P<0.001). GDF-15 was raised in HAPH, not high altitude residents (548±64 vs. 307±14 pg/ml; P<0.001), and correlated with mPAP (p<0.001). The data support the use of GDF-15 as a prognostic marker in IPAH and question whether hypoxia stimulates GDF-15 in PH.