Treatment-related biomarkers in pulmonary hypertension patients on oral therapies.
Abstract
<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.
Type
Journal articlePermalink
https://hdl.handle.net/10161/22471Published Version (Please cite this version)
10.1186/s12931-020-01566-yPublication Info
Swaminathan, Aparna C; Zhu, Hongmei; Tapson, Victor; Lokhnygina, Yuliya; Poms, Abby;
Kelleher, Zach; ... McMahon, Tim J (2020). Treatment-related biomarkers in pulmonary hypertension patients on oral therapies.
Respiratory research, 21(1). pp. 304. 10.1186/s12931-020-01566-y. Retrieved from https://hdl.handle.net/10161/22471.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Terry Ann Fortin
Associate Professor of Medicine
Yuliya Vladimirovna Lokhnygina
Associate Professor of Biostatistics & Bioinformatics
Statistical methods in clinical trials, survival analysis, adaptive designs, adaptive
treatment strategies, causal inference in observational studies, semiparametric inference
Timothy Joseph McMahon
Professor of Medicine
The McMahon Lab at Duke University and Durham VA Medical Center is investigating novel
roles of the red blood cell (RBC) in the circulation. The regulated release of the
vasodilator SNO (a form of NO, nitric oxide) by RBCs within the respiratory cycle
in mammals optimizes nutrient delivery at multiple levels, especially in the lung
(gas exchange) and the peripheral microcirculation (O2 transport to tissues). Deficiency
of RBC SNO bioactivity (as in human RBCs banked for transfusion),
Kishan S Parikh
Assistant Professor of Medicine
Duke University Medical CenterDuke Clinical Research Institute
Aparna Swaminathan
Assistant Professor of Medicine
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