Serum Angiopoietin-1 and Angiopoietin-2 as Biomarkers of Pulmonary Hemodynamic Burden in COPD-Associated Pulmonary Hypertension: A Cross-Sectional Study

Purpose: Pulmonary hypertension (PH) is a serious complication of COPD associated with worse outcomes. Reliable circulating biomarkers of pulmonary vascular involvement are lacking. Angiopoietin-1 (ANGP-1) and angiopoietin-2 (ANGP-2) regulate endothelial homeostasis, but their relationship with echocardiographically estimated pulmonary pressure in COPD remains uncertain. Methods: This prospective cross-sectional study included 70 consecutively recruited adults with COPD, stratified using a study-specific echocardiographic threshold into the COPD PH group (mPAP > 20 mmHg; n = 46) and the COPD without PH (mPAP < 20 mmHg; n = 24), together with 20 additional controls. This non-invasive stratification was not considered equivalent to PH confirmed by right heart catheterization. Serum ANGP-1 and ANGP-2 were measured using ELISA. Group differences and associations with e-mPAP and right atrial pressure (RAP) were assessed. Results: Median ANGP-1 was higher in the elevated e-mPAP group [8780.06 (IQR 7955.29–9902.88) pg/mL] than in the lower e-mPAP group [3065.14 (1170.69–6200.41)] and controls [2997.19 (1292.13–3278.18); p < 0.001]. ANGP-2 showed a similar pattern [6152.92 (5380.27–8652.50), 2669.77 (1802.18–4744.00), and 2405.54 (1779.73–3751.76) pg/mL; p < 0.001]. Among COPD participants, ANGP-1 and ANGP-2 correlated with e-mPAP (r = 0.64 and r = 0.54) and RAP (r = 0.54 and r = 0.52; all Holm-adjusted p < 0.001). In multivariable models, e-mPAP and RAP were independently associated with ANGP-1, whereas RAP was independently associated with ANGP-2. Conclusions: Higher circulating ANGP-1 and ANGP-2 were associated with an elevated echo-estimated pulmonary-pressure phenotype in COPD. These findings are exploratory and require validation in larger cohorts using direct hemodynamic assessment.