Serum Angiopoietin-1 and Angiopoietin-2 as Biomarkers of Pulmonary Hemodynamic Burden in COPD-Associated Pulmonary Hypertension: A Cross-Sectional Study.
Bajpai J, Pradhan A, et al. • Advances in respiratory medicine • 2026
Higher circulating ANGP-1 and ANGP-2 were associated with an elevated echo-estimated pulmonary-pressure phenotype in COPD, suggesting these angiopoietins may serve as exploratory biomarkers of pulmonary hemodynamic burden requiring validation in larger cohorts using direct hemodynamic assessment.
Key Findings
Results
Serum ANGP-1 levels were significantly higher in COPD patients with elevated echocardiographically estimated mean pulmonary arterial pressure (e-mPAP > 20 mmHg) compared to those without elevated e-mPAP and healthy controls.
Median ANGP-1 in the elevated e-mPAP group was 8780.06 pg/mL (IQR 7955.29–9902.88)
Median ANGP-1 in the lower e-mPAP group was 3065.14 pg/mL (IQR 1170.69–6200.41)
Median ANGP-1 in controls was 2997.19 pg/mL (IQR 1292.13–3278.18)
Difference was statistically significant at p < 0.001 across all three groups
Study included 46 COPD patients with elevated e-mPAP, 24 COPD patients without elevated e-mPAP, and 20 controls
Results
Serum ANGP-2 levels were significantly higher in COPD patients with elevated e-mPAP compared to those without elevated e-mPAP and healthy controls.
Median ANGP-2 in the elevated e-mPAP group was 6152.92 pg/mL (IQR 5380.27–8652.50)
Median ANGP-2 in the lower e-mPAP group was 2669.77 pg/mL (IQR 1802.18–4744.00)
Median ANGP-2 in controls was 2405.54 pg/mL (IQR 1779.73–3751.76)
Difference was statistically significant at p < 0.001 across all three groups
Results
Both ANGP-1 and ANGP-2 showed moderate positive correlations with echocardiographically estimated mean pulmonary arterial pressure among COPD participants.
ANGP-1 correlated with e-mPAP with r = 0.64 (Holm-adjusted p < 0.001)
ANGP-2 correlated with e-mPAP with r = 0.54 (Holm-adjusted p < 0.001)
Correlations were assessed across all 70 COPD participants
Holm correction was applied to account for multiple comparisons
Results
Both ANGP-1 and ANGP-2 showed moderate positive correlations with right atrial pressure (RAP) among COPD participants.
ANGP-1 correlated with RAP with r = 0.54 (Holm-adjusted p < 0.001)
ANGP-2 correlated with RAP with r = 0.52 (Holm-adjusted p < 0.001)
All four correlations (ANGP-1 and ANGP-2 with e-mPAP and RAP) remained significant after Holm adjustment
Results
In multivariable models, e-mPAP and RAP were independently associated with ANGP-1, while RAP alone was independently associated with ANGP-2.
Multivariable regression was used to assess independence of associations
e-mPAP was independently associated with ANGP-1 but not ANGP-2 in these models
RAP was independently associated with both ANGP-1 and ANGP-2
Results suggest differential hemodynamic determinants for the two angiopoietins
Methods
The study used a non-invasive echocardiographic threshold (mPAP > 20 mmHg) for stratification, which was explicitly noted as not equivalent to pulmonary hypertension confirmed by right heart catheterization.
70 consecutively recruited adults with COPD were stratified using a study-specific echocardiographic threshold
Authors stated: '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
Conclusions
The authors characterized the findings as exploratory and called for validation in larger cohorts using direct hemodynamic assessment.
The study design was prospective and cross-sectional
Authors noted that reliable circulating biomarkers of pulmonary vascular involvement in COPD are currently lacking
Conclusions explicitly stated: 'These findings are exploratory and require validation in larger cohorts using direct hemodynamic assessment'
The study represents a preliminary investigation into angiopoietins as biomarkers in COPD-associated pulmonary hypertension
What This Means
This research suggests that two proteins involved in blood vessel regulation — angiopoietin-1 (ANGP-1) and angiopoietin-2 (ANGP-2) — are found at significantly higher levels in the blood of people with chronic obstructive pulmonary disease (COPD) who also have elevated pressure in the blood vessels of their lungs. The study enrolled 70 COPD patients and 20 healthy controls and used echocardiography (an ultrasound of the heart) to estimate lung blood vessel pressure. Patients with estimated pressures above a threshold had ANGP-1 levels roughly three times higher and ANGP-2 levels roughly two-and-a-half times higher than those with lower pressures or healthy controls. Both proteins also showed moderate correlations with right atrial pressure, another measure of cardiac strain.
These findings matter because pulmonary hypertension — high pressure in the lung blood vessels — is a serious complication of COPD that worsens outcomes, yet there are currently no well-established blood tests to detect or monitor it non-invasively. Identifying biomarkers like ANGP-1 and ANGP-2 that track with pulmonary pressure could potentially offer a simpler way to flag which COPD patients have more severe vascular involvement. The proteins are involved in maintaining the health of blood vessel linings, and their elevation may reflect the kind of vascular remodeling and endothelial dysfunction seen in pulmonary hypertension.
However, the study has important limitations that the authors themselves highlight. The pressure measurements were estimated from echocardiography rather than confirmed by the gold-standard method (right heart catheterization), the sample size was relatively small (70 COPD patients), and the study was cross-sectional, meaning it cannot show whether changes in these proteins over time predict outcomes. The authors describe these results as exploratory and call for larger studies with direct hemodynamic measurements to confirm whether ANGP-1 and ANGP-2 can be clinically useful biomarkers in this setting.
Bajpai J, Pradhan A, Ahmad M, Kant S, Verma A, Bajaj D, et al.. (2026). Serum Angiopoietin-1 and Angiopoietin-2 as Biomarkers of Pulmonary Hemodynamic Burden in COPD-Associated Pulmonary Hypertension: A Cross-Sectional Study.. Advances in respiratory medicine. https://doi.org/10.3390/arm94040059