Treatment-related biomarkers in pulmonary hypertension patients on oral therapies
العنوان: | Treatment-related biomarkers in pulmonary hypertension patients on oral therapies |
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المؤلفون: | Timothy J. McMahon, Terry Fortin, S. Nicholas Mason, Abby Poms, Elijah Gaspard, Hongmei Zhu, Yuliya Lokhnygina, Brian E. Fee, Karla Kennedy, Victor F. Tapson, Zach Kelleher, Kishan S. Parikh, Aparna Swaminathan |
المصدر: | Respiratory Research Respiratory Research, Vol 21, Iss 1, Pp 1-11 (2020) |
بيانات النشر: | Springer Science and Business Media LLC, 2020. |
سنة النشر: | 2020 |
مصطلحات موضوعية: | Male, medicine.medical_specialty, Hypertension, Pulmonary, Administration, Oral, 030204 cardiovascular system & hematology, Gastroenterology, Pulmonary hypertension, Nitric oxide, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Humans, Medicine, Longitudinal Studies, Prospective Studies, Prospective cohort study, Aged, lcsh:RC705-779, Endothelin-1, business.industry, Endothelin receptor antagonist, Research, lcsh:Diseases of the respiratory system, Middle Aged, Phosphodiesterase 5 Inhibitors, medicine.disease, Endothelin 1, Regimen, Treatment Outcome, 030228 respiratory system, chemistry, Concomitant, Cohort, Female, business, Biomarkers |
الوصف: | 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. |
تدمد: | 1465-993X |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f1158d0d3a1998aa3763441b68697503 https://doi.org/10.1186/s12931-020-01566-y |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....f1158d0d3a1998aa3763441b68697503 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 1465993X |
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