Association between cytokines and functional, hemodynamic parameters, and clinical outcomes in pulmonary arterial hypertension
To assess the relationship of cytokines with functional and clinical outcomes in pulmonary arterial hypertension (PAH). Endothelial dysfunction and vascular inflammation are characteristic of PAH. We investigated whether markers of angiogenesis and inflammation associated with functional, hemodynami...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2018-09-01
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| Series: | Pulmonary Circulation |
| Online Access: | https://doi.org/10.1177/2045894018794051 |
| _version_ | 1811327285328871424 |
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| author | Aditya A. Joshi Ryan Davey Youlan Rao Kai Shen Raymond L. Benza Amresh Raina |
| author_facet | Aditya A. Joshi Ryan Davey Youlan Rao Kai Shen Raymond L. Benza Amresh Raina |
| author_sort | Aditya A. Joshi |
| collection | DOAJ |
| description | To assess the relationship of cytokines with functional and clinical outcomes in pulmonary arterial hypertension (PAH). Endothelial dysfunction and vascular inflammation are characteristic of PAH. We investigated whether markers of angiogenesis and inflammation associated with functional, hemodynamic parameters, and clinical outcomes in PAH. PAH patients (n = 206) were pooled from two clinical trials: TRUST-1 and FREEDOM-C2. Baseline and post-treatment cytokine levels were correlated to baseline clinical and hemodynamic parameters, were assessed in clinical subgroups, and were associated with clinical outcomes. In 206 patients (mean age = 48 years; 74% women) with WHO group-1 PAH, most cytokine levels were higher in those with 6-min walking distance (6MWD) < median (335 m) vs. those above median, including Ang-1 (11.9 ± 10.1 vs. 5.9 ± 6.0 ng/mL), Ang-2 (14.3 ± 11.8 vs. 12.2 ± 11.2 ng/mL), and MMP-9 (221 ± 262.3 vs. 119 ± 171 ng/mL). Baseline 6MWD inversely correlated with Ang-1 (r = −0.27, P < 0.0001), Ang-2 (r = −0.20, P = 0.004), and MMP-9 (r = −0.27, P < 0.0001). MMP-9 levels differed significantly by NYHA functional class ( P = 0.001) suggesting an association between MMP-9 and subjective PAH severity. Mean Ang-2 levels were higher in those with baseline right atrial pressure (RAP) > 15 mmHg compared to those with RAP < 15 mmHg (23,841 vs. 11,020 pg/mL). Baseline RAP was associated with change in MMP-9 levels (r = −0.53, P = 0.03). Finally, baseline Ang-1, VEGF and MMP-9 levels were associated with risk of death and hospitalization at 16-week follow-up. Inflammatory cytokines and vascular angiogenesis markers are associated with baseline functional, hemodynamic parameters in PAH, and predict death and hospitalization. Larger prospective studies are needed to confirm the utility of cytokines in PAH. |
| first_indexed | 2024-04-13T15:05:05Z |
| format | Article |
| id | doaj.art-01059f71940d4f13a5f8f3c1337e873d |
| institution | Directory Open Access Journal |
| issn | 2045-8940 |
| language | English |
| last_indexed | 2024-04-13T15:05:05Z |
| publishDate | 2018-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pulmonary Circulation |
| spelling | doaj.art-01059f71940d4f13a5f8f3c1337e873d2022-12-22T02:42:11ZengWileyPulmonary Circulation2045-89402018-09-01810.1177/2045894018794051Association between cytokines and functional, hemodynamic parameters, and clinical outcomes in pulmonary arterial hypertensionAditya A. Joshi0Ryan Davey1Youlan Rao2Kai Shen3Raymond L. Benza4Amresh Raina5Department of Internal Medicine, Allegheny General Hospital, Pittsburgh, PA, USADivision of Cardiology, Western University, London, ON, CanadaUnited Therapeutics Corporation, Research Triangle, NC, USAUnited Therapeutics Corporation, Research Triangle, NC, USASection of Heart Failure/Transplant/MCS & Pulmonary Hypertension, Cardiovascular Institute, Allegheny General Hospital, Pittsburgh, PA, USASection of Heart Failure/Transplant/MCS & Pulmonary Hypertension, Cardiovascular Institute, Allegheny General Hospital, Pittsburgh, PA, USATo assess the relationship of cytokines with functional and clinical outcomes in pulmonary arterial hypertension (PAH). Endothelial dysfunction and vascular inflammation are characteristic of PAH. We investigated whether markers of angiogenesis and inflammation associated with functional, hemodynamic parameters, and clinical outcomes in PAH. PAH patients (n = 206) were pooled from two clinical trials: TRUST-1 and FREEDOM-C2. Baseline and post-treatment cytokine levels were correlated to baseline clinical and hemodynamic parameters, were assessed in clinical subgroups, and were associated with clinical outcomes. In 206 patients (mean age = 48 years; 74% women) with WHO group-1 PAH, most cytokine levels were higher in those with 6-min walking distance (6MWD) < median (335 m) vs. those above median, including Ang-1 (11.9 ± 10.1 vs. 5.9 ± 6.0 ng/mL), Ang-2 (14.3 ± 11.8 vs. 12.2 ± 11.2 ng/mL), and MMP-9 (221 ± 262.3 vs. 119 ± 171 ng/mL). Baseline 6MWD inversely correlated with Ang-1 (r = −0.27, P < 0.0001), Ang-2 (r = −0.20, P = 0.004), and MMP-9 (r = −0.27, P < 0.0001). MMP-9 levels differed significantly by NYHA functional class ( P = 0.001) suggesting an association between MMP-9 and subjective PAH severity. Mean Ang-2 levels were higher in those with baseline right atrial pressure (RAP) > 15 mmHg compared to those with RAP < 15 mmHg (23,841 vs. 11,020 pg/mL). Baseline RAP was associated with change in MMP-9 levels (r = −0.53, P = 0.03). Finally, baseline Ang-1, VEGF and MMP-9 levels were associated with risk of death and hospitalization at 16-week follow-up. Inflammatory cytokines and vascular angiogenesis markers are associated with baseline functional, hemodynamic parameters in PAH, and predict death and hospitalization. Larger prospective studies are needed to confirm the utility of cytokines in PAH.https://doi.org/10.1177/2045894018794051 |
| spellingShingle | Aditya A. Joshi Ryan Davey Youlan Rao Kai Shen Raymond L. Benza Amresh Raina Association between cytokines and functional, hemodynamic parameters, and clinical outcomes in pulmonary arterial hypertension Pulmonary Circulation |
| title | Association between cytokines and functional, hemodynamic parameters, and clinical outcomes in pulmonary arterial hypertension |
| title_full | Association between cytokines and functional, hemodynamic parameters, and clinical outcomes in pulmonary arterial hypertension |
| title_fullStr | Association between cytokines and functional, hemodynamic parameters, and clinical outcomes in pulmonary arterial hypertension |
| title_full_unstemmed | Association between cytokines and functional, hemodynamic parameters, and clinical outcomes in pulmonary arterial hypertension |
| title_short | Association between cytokines and functional, hemodynamic parameters, and clinical outcomes in pulmonary arterial hypertension |
| title_sort | association between cytokines and functional hemodynamic parameters and clinical outcomes in pulmonary arterial hypertension |
| url | https://doi.org/10.1177/2045894018794051 |
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