Abstract 6168: Growth-Differentiation Factor-15 Is an Independent Prognostic Indicator in Idiopathic Pulmonary Arterial Hypertension
Circulating levels of the TGFβ-related cytokine, growth-differentiation factor-15 (GDF-15), provide independent prognostic information in patients with pulmonary embolism and left-sided heart failure. This study is the first to investigate GDF-15 as a possible biomarker in idiopathic pulmonary arterial hypertension. GDF-15 levels were determined in 76 patients at the time of baseline right heart catheterization (1st cohort). Patients were followed for a median of 48 months. In addition, 22 patients were studied at baseline and 3– 6 months after initiation of therapy (2nd cohort). 55% of the patients in the 1st cohort presented with GDF-15 levels ≥1200 ng/L, the previously defined upper reference limit. The risk of death or lung transplantation at 3 years was 15% and 44% in patients with GDF-15 levels below or above 1200 ng/L, respectively (P=0.006). Elevated levels of GDF-15 were associated with increased mean right atrial and pulmonary capillary wedge pressures, a lower SvO2, and higher levels of NT-proBNP (all P<0.02). After adjustment for hemodynamic and biochemical variables, GDF-15 remained an independent predictor of adverse outcomes (HR 2.6 per 1 SD of lnGDF-15 [95% CI 1.4 – 4.8]; P=0.001). Changes (Δ) in GDF-15 over time in the 2nd cohort were related to changes in NT-proBNP (rho = 0.47; P=0.031) and inversely related to changes in SvO2 (rho = −0.74; P<0.001; Figure⇓). These data identify GDF-15 as a promising biomarker for risk stratification and, possibly, monitoring of patients with idiopathic pulmonary arterial hypertension.