Diagnostic and prognostic significance of serum angiopoietin-1 and-2 concentrations in patients with pulmonary hypertension

Several biomarkers for detecting pulmonary hypertension (PH) have been reported. However, these biomarkers are deemed insufficient to detect PH in its early stages. We evaluated the utility of serum angiopoietin (ANGP), a glycoprotein related to angiogenesis, as a diagnostic and prognostic biomarker of PH. Patients with PH who underwent right-heart catheterization, were retrospectively studied. Serum concentrations of ANGP-1 and ANGP-2 were measured using an enzyme-linked immunosorbent assay in patients with PH (n=32), those with idiopathic pulmonary fibrosis (IPF) without PH (as a disease control, n=75), and age-matched healthy controls (HC, n=60). Nineteen patients (59.4%) with PH had World Health Organization group 3 PH. Serum ANGP-2 concentration, but not ANGP-1, in patients with PH was significantly higher compared with that in HC (p=0.025) and in patients with IPF without PH (p=0.008). Serum ANGP-2 concentration in patients with PH positively and significantly correlated with N-terminal pro-B-type natriuretic peptide (r=0.769, p<0.001), right ventricular diameter on echocardiography (r=0.565, p=0.035), and mean pulmonary arterial pressure (r=0.449, p=0.032) and pulmonary vascular resistance (r=0.451, p=0.031) on right-heart catheterization. ANGP-1 and ANGP-2 were expressed on lung vascular endothelial cells, as shown by immunohistochemistry. Patients with PH with higher ANGP-2 concentration (2.48 ng/mL) had significantly worse survival (p=0.022). Higher ANGP-2 concentration was a significant worse prognostic factor (hazard ratio=6.063, p=0.037), while serum ANGP-1 concentration was not. In conclusion, serum ANGP-2 may be a useful diagnostic and prognostic biomarker in patients with PH, especially in patients with group 3 PH.

Automated summary

The study evaluated the utility of serum angiopoietin (ANGP) as a diagnostic and prognostic biomarker in patients with pulmonary hypertension (PH), showing that serum ANGP-2 concentration was significantly higher in patients with PH and correlated with parameters related to PH. Higher ANGP-2 concentration was associated with worse survival in PH patients, making it a potential prognostic factor especially in patients with group 3 PH.