Angiopoietin-2 and D-dimer add prognostic information to clinical risk in pulmonary arterial hypertension
Background: Thrombosis and endothelial injury are pathologic hallmarks of pulmonary arterial hypertension (PAH). We aimed to evaluate whether markers of endothelial dysfunction and coagulation in the blood would provide insight into disease activity, treatment response, and outcomes in PAH. Methods:...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-02-01
|
| Series: | JHLT Open |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950133424001277 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1823864221311434752 |
|---|---|
| author | Heather L. Clark Daniel Lachant Allison N. Light Deborah Haight Samia Lopia Nigel Mackman R. James White |
| author_facet | Heather L. Clark Daniel Lachant Allison N. Light Deborah Haight Samia Lopia Nigel Mackman R. James White |
| author_sort | Heather L. Clark |
| collection | DOAJ |
| description | Background: Thrombosis and endothelial injury are pathologic hallmarks of pulmonary arterial hypertension (PAH). We aimed to evaluate whether markers of endothelial dysfunction and coagulation in the blood would provide insight into disease activity, treatment response, and outcomes in PAH. Methods: We prospectively collected baseline and 3-month follow-up blood samples from treatment-naïve patients with PAH (n = 22) and those who had a clinical indication to intensify therapy (n = 19). In addition, we recruited 12 healthy people and clinically stable patients with PAH (n = 45) as controls who had 2 blood samples collected twice within 14 days. We generated platelet-free plasma and measured D-dimer, angiopoietin-2, thrombin time, soluble P-selectin, von Willebrand factor, and vascular endothelial growth factor. We assessed treatment response with Reveal Lite 2 scores (all patients had N-terminal-pro-brain natriuretic peptide, 6-minute walk, and functional class assessment at both visits) and followed clinical outcomes for 3 years. Results: Angiopoietin-2 levels were elevated and fell in response to effective therapy (drop in Reveal Lite 2 score). At follow-up, persistently elevated angiopoietin-2 levels predicted clinical events and even identified low-risk participants who subsequently had events. D-dimer levels were also elevated in patients with PAH but did not change in response to therapy. Several other abnormalities in endothelial and platelet activation were identified (including elevated soluble P-selectin, elevated von Willebrand factor, and elevated vascular endothelial growth factor) but these did not change with treatment or predict outcome. Conclusions: Angiopoietin-2 and D-dimer are elevated in patients with PAH and may add prognostic information to routine clinical assessment. |
| format | Article |
| id | doaj-art-25d7c602f6f54a72a34a8dab4fcbf8fa |
| institution | Kabale University |
| issn | 2950-1334 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JHLT Open |
| spelling | doaj-art-25d7c602f6f54a72a34a8dab4fcbf8fa2025-02-09T05:01:55ZengElsevierJHLT Open2950-13342025-02-017100178Angiopoietin-2 and D-dimer add prognostic information to clinical risk in pulmonary arterial hypertensionHeather L. Clark0Daniel Lachant1Allison N. Light2Deborah Haight3Samia Lopia4Nigel Mackman5R. James White6Division of Pulmonary and Critical Care Medicine, University of Rochester Medical Center, Rochester, New YorkDivision of Pulmonary and Critical Care Medicine, University of Rochester Medical Center, Rochester, New YorkDivision of Pulmonary and Critical Care Medicine, University of Rochester Medical Center, Rochester, New YorkDivision of Pulmonary and Critical Care Medicine, University of Rochester Medical Center, Rochester, New YorkDepartment of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, New YorkDepartment of Medicine, UNC Blood Research Center, Division of Hematology, University of North Carolina at Chapel Hill, Chapel Hill, North CarolinaDivision of Pulmonary and Critical Care Medicine, University of Rochester Medical Center, Rochester, New York; Corresponding author: R. James White, Mary M. Parkes Center for Asthma, Allergy, and Pulmonary Care, University of Rochester Medical Center, 400 Red Creek Drive, Rochester, NY 14623.Background: Thrombosis and endothelial injury are pathologic hallmarks of pulmonary arterial hypertension (PAH). We aimed to evaluate whether markers of endothelial dysfunction and coagulation in the blood would provide insight into disease activity, treatment response, and outcomes in PAH. Methods: We prospectively collected baseline and 3-month follow-up blood samples from treatment-naïve patients with PAH (n = 22) and those who had a clinical indication to intensify therapy (n = 19). In addition, we recruited 12 healthy people and clinically stable patients with PAH (n = 45) as controls who had 2 blood samples collected twice within 14 days. We generated platelet-free plasma and measured D-dimer, angiopoietin-2, thrombin time, soluble P-selectin, von Willebrand factor, and vascular endothelial growth factor. We assessed treatment response with Reveal Lite 2 scores (all patients had N-terminal-pro-brain natriuretic peptide, 6-minute walk, and functional class assessment at both visits) and followed clinical outcomes for 3 years. Results: Angiopoietin-2 levels were elevated and fell in response to effective therapy (drop in Reveal Lite 2 score). At follow-up, persistently elevated angiopoietin-2 levels predicted clinical events and even identified low-risk participants who subsequently had events. D-dimer levels were also elevated in patients with PAH but did not change in response to therapy. Several other abnormalities in endothelial and platelet activation were identified (including elevated soluble P-selectin, elevated von Willebrand factor, and elevated vascular endothelial growth factor) but these did not change with treatment or predict outcome. Conclusions: Angiopoietin-2 and D-dimer are elevated in patients with PAH and may add prognostic information to routine clinical assessment.http://www.sciencedirect.com/science/article/pii/S2950133424001277pulmonary arterial hypertensionangiopoietin-2D-dimerthrombosisREVEALscore |
| spellingShingle | Heather L. Clark Daniel Lachant Allison N. Light Deborah Haight Samia Lopia Nigel Mackman R. James White Angiopoietin-2 and D-dimer add prognostic information to clinical risk in pulmonary arterial hypertension JHLT Open pulmonary arterial hypertension angiopoietin-2 D-dimer thrombosis REVEAL score |
| title | Angiopoietin-2 and D-dimer add prognostic information to clinical risk in pulmonary arterial hypertension |
| title_full | Angiopoietin-2 and D-dimer add prognostic information to clinical risk in pulmonary arterial hypertension |
| title_fullStr | Angiopoietin-2 and D-dimer add prognostic information to clinical risk in pulmonary arterial hypertension |
| title_full_unstemmed | Angiopoietin-2 and D-dimer add prognostic information to clinical risk in pulmonary arterial hypertension |
| title_short | Angiopoietin-2 and D-dimer add prognostic information to clinical risk in pulmonary arterial hypertension |
| title_sort | angiopoietin 2 and d dimer add prognostic information to clinical risk in pulmonary arterial hypertension |
| topic | pulmonary arterial hypertension angiopoietin-2 D-dimer thrombosis REVEAL score |
| url | http://www.sciencedirect.com/science/article/pii/S2950133424001277 |
| work_keys_str_mv | AT heatherlclark angiopoietin2andddimeraddprognosticinformationtoclinicalriskinpulmonaryarterialhypertension AT daniellachant angiopoietin2andddimeraddprognosticinformationtoclinicalriskinpulmonaryarterialhypertension AT allisonnlight angiopoietin2andddimeraddprognosticinformationtoclinicalriskinpulmonaryarterialhypertension AT deborahhaight angiopoietin2andddimeraddprognosticinformationtoclinicalriskinpulmonaryarterialhypertension AT samialopia angiopoietin2andddimeraddprognosticinformationtoclinicalriskinpulmonaryarterialhypertension AT nigelmackman angiopoietin2andddimeraddprognosticinformationtoclinicalriskinpulmonaryarterialhypertension AT rjameswhite angiopoietin2andddimeraddprognosticinformationtoclinicalriskinpulmonaryarterialhypertension |