Clinical Value of Asymmetrical Dimethylarginine Detection in Patients with Connective Tissue Disease-Associated Pulmonary Arterial Hypertension

Liu, Juan; Fu, Qiang; Jiang, Lili; Wang, Youlian

doi:10.1155/2019/3741909

Cited by 10 publications

(8 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A more potent inhibitor of NO synthesis than SDMA (30), ADMA has been shown to associate with hemodynamic indices and survival in prior studies of PAH patients (25,31). In the current study, we found that that high ADMA levels associated with lower 6MWD in PAH patients on ERAs but not in PAH patients on either PDE-5i or on PDE-5i/ ERA combination therapy.…”

Section: Discussionsupporting

confidence: 54%

Treatment-related biomarkers in pulmonary hypertension patients on oral therapies

Swaminathan

Zhu

Tapson

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Multiple classes of oral therapy are available for the treatment of pulmonary arterial hypertension (PAH), but there is little to guide clinicians in choosing a specific regimen or therapeutic class. We aimed to investigate whether treatment-relevant blood biomarkers can predict therapy response in prevalent PAH patients.Methods: This prospective cohort study longitudinally assessed biomarkers along the endothelin-1 (ET-1) and nitric oxide (cGMP, ADMA, SDMA, nitrite, and S-nitrosohemoglobin) pathways along with the cGMP/NT-proBNP ratio over 12 months in patients with WHO Group 1 PAH on oral PAH-specific therapies. The relationship between biomarkers and 6MWD at the same and future visits was examined using mixed linear regression models adjusted for age. As cGMP can be elevated when NT-proBNP is elevated, we also tested the relationship between 6MWD and the cGMP/NT-pro BNP ratio. Patients with PAH with concomitant heart or lung disease or chronic thromboembolic pulmonary hypertension (CTEPH) were included in a sensitivity analysis.Results: The study cohort included 58 patients with PAH treated with either an endothelin receptor antagonist (27.6%), phosphodiesterase-5 inhibitor (29.3%) or a combination of the two (43.1%). Among biomarkers along the current therapeutic pathways, ET-1 and the cGMP/NT-proBNP ratio associated with same visit 6MWD (p = 0.02 and p=0.03 respectively), and ET-1 predicted future 6MWD (p=0.02). ET-1 (p=0.01) and cGMP/NT-proBNP ratio (p=0.04) also predicted future 6MWD in the larger cohort (n = 108) of PAH patients with concomitant left heart disease (n = 17), lung disease (n = 20), or CTEPH (n = 13). Finally, in the larger cohort, SDMA associated with 6MWD at the same visit (p = 0.01) in all subgroups and ADMA associated with 6MWD in PAH patients with concomitant lung disease (p=0.03) and PAH patients on ERA therapy (p = 0.01).Conclusions: ET-1, cGMP/NTproBNP ratio, and dimethylarginines ADMA and SDMA are mediators along pathways targeted by oral PAH therapies that associate with or predict 6MWD.

show abstract

Section: Discussionsupporting

confidence: 54%

Treatment-related biomarkers in pulmonary hypertension patients on oral therapies

Swaminathan

Zhu

Tapson

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…A more potent inhibitor of NO synthesis than SDMA [30], ADMA has been shown to associate with hemodynamic indices and survival in prior studies of PAH patients [25,31]. In the current study, we found that that high ADMA levels associated with lower 6MWD in PAH patients on ERAs but not in PAH patients on either PDE-5i or on PDE-5i/ ERA combination therapy.…”

Section: Discussionsupporting

confidence: 51%

Treatment-related biomarkers in pulmonary hypertension patients on oral therapies

et al. 2020

View full text Add to dashboard Cite

Background Multiple classes of oral therapy are available for the treatment of pulmonary arterial hypertension (PAH), but there is little to guide clinicians in choosing a specific regimen or therapeutic class. We aimed to investigate whether treatment-relevant blood biomarkers can predict therapy response in prevalent PAH patients. Methods This prospective cohort study longitudinally assessed biomarkers along the endothelin-1 (ET-1) and nitric oxide (cGMP, ADMA, SDMA, nitrite, and S-nitrosohemoglobin) pathways along with the cGMP/NT-proBNP ratio over 12 months in patients with WHO Group 1 PAH on oral PAH-specific therapies. The relationship between biomarkers and 6MWD at the same and future visits was examined using mixed linear regression models adjusted for age. As cGMP can be elevated when NT-proBNP is elevated, we also tested the relationship between 6MWD and the cGMP/NT-pro BNP ratio. Patients with PAH with concomitant heart or lung disease or chronic thromboembolic pulmonary hypertension (CTEPH) were included in a sensitivity analysis. Results The study cohort included 58 patients with PAH treated with either an endothelin receptor antagonist (27.6%), phosphodiesterase-5 inhibitor (25.9%) or a combination of the two (43.1%). Among biomarkers along the current therapeutic pathways, ET-1 and the cGMP/NT-proBNP ratio associated with same visit 6MWD (p = 0.02 and p = 0.03 respectively), and ET-1 predicted future 6MWD (p = 0.02). ET-1 (p = 0.01) and cGMP/NT-proBNP ratio (p = 0.04) also predicted future 6MWD in the larger cohort (n = 108) of PAH patients with concomitant left heart disease (n = 17), lung disease (n = 20), or CTEPH (n = 13). Finally, in the larger cohort, SDMA associated with 6MWD at the same visit (p = 0.01) in all subgroups and ADMA associated with 6MWD in PAH patients with concomitant lung disease (p = 0.03) and PAH patients on ERA therapy (p = 0.01). Conclusions ET-1, cGMP/NTproBNP ratio, and dimethylarginines ADMA and SDMA are mediators along pathways targeted by oral PAH therapies that associate with or predict 6MWD.

show abstract

“…A more potent inhibitor of NO synthesis than SDMA (24), ADMA has been shown to associate with hemodynamic indices and survival in prior studies of PAH patients (19,25). In the current study, we found that that high ADMA levels associated with lower 6MWD in PAH patients on ERAs but not in PAH patients on either PDE-5i or on PDE-5i/ ERA combination therapy.…”

Section: Discussionsupporting

confidence: 51%

Treatment-related Biomarkers in Pulmonary Hypertension Patients on Oral Therapies

Swaminathan

Zhu

Tapson

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Multiple classes of oral therapy are available for the treatment of pulmonary arterial hypertension (PAH), but there is little to guide clinicians in choosing a specific regimen or therapeutic class. We aimed to investigate whether treatment-relevant blood biomarkers can predict therapy response in prevalent PAH patients.Methods: This prospective cohort study longitudinally assessed biomarkers along the endothelin-1 (ET-1) and nitric oxide (cGMP, ADMA, SDMA, nitrite, and S-nitrosohemoglobin) pathways along with the cGMP/NT-proBNP ratio over 12 months in patients with WHO Group 1 PAH on oral PAH-specific therapies. The relationship between biomarkers and 6MWD at the same and future visits was examined using mixed linear regression models. As cGMP can be elevated when NT-proBNP is elevated, we also tested the relationship between 6MWD and the cGMP/NT-pro BNP ratio. Patients with PAH with concomitant heart or lung disease or chronic thromboembolic pulmonary hypertension (CTEPH) were included in a sensitivity analysis. Results: The study cohort included 58 patients with PAH treated with either an endothelin receptor antagonist (27.6%), phosphodiesterase-5 inhibitor (29.3%) or a combination of the two (43.1%). Among biomarkers along the current therapeutic pathways, ET-1 and the cGMP/NT-proBNP ratio associated with same visit 6MWD (p = 0.04 and p=0.009 respectively). ET-1 (p=0.01) and cGMP/NT-proBNP ratio (p < 0.001) also predicted future 6MWD in the larger cohort (n = 108) of PAH patients with concomitant left heart disease (n = 17), lung disease (n = 20), or CTEPH (n = 13). Finally, in the larger cohort, SDMA associated with 6MWD at the same visit (p = 0.003) in all subgroups and ADMA associated with 6MWD in PAH patients with concomitant lung disease (p=0.027) and PAH patients on ERA therapy (p = 0.01). Conclusions: ET-1, cGMP/NTproBNP ratio, and dimethylarginines ADMA and SDMA are mediators along pathways targeted by oral PAH therapies that associate with or predict 6MWD.

show abstract

Clinical Value of Asymmetrical Dimethylarginine Detection in Patients with Connective Tissue Disease-Associated Pulmonary Arterial Hypertension

Cited by 10 publications

References 16 publications

Treatment-related biomarkers in pulmonary hypertension patients on oral therapies

Treatment-related biomarkers in pulmonary hypertension patients on oral therapies

Treatment-related biomarkers in pulmonary hypertension patients on oral therapies

Treatment-related Biomarkers in Pulmonary Hypertension Patients on Oral Therapies

Contact Info

Product

Resources

About