Treatment-related biomarkers in pulmonary hypertension patients on oral therapies
- PDF / 1,282,556 Bytes
- 11 Pages / 595.276 x 790.866 pts Page_size
- 67 Downloads / 176 Views
Open Access
RESEARCH
Treatment‑related biomarkers in pulmonary hypertension patients on oral therapies Aparna C. Swaminathan1, Hongmei Zhu1, Victor Tapson2, Yuliya Lokhnygina3, Abby Poms1, Zach Kelleher1, Elijah Gaspard1, Karla Kennedy1, Brian E. Fee1, Terry Fortin1, S. Nicholas Mason1, Kishan Parikh1 and Tim J. McMahon1,4*
Abstract 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. Keywords: Pulmonary hypertension, Biomarkers, Nitric oxide, Endothelin-1 Background Pulmonary arterial hypertension (PAH) carries significant morbidity and mortality and is characterized by progressive elevation of pulmonary arterial pressures *Correspondence: [email protected] 1 Department of Medicine, Duke University Medical Center, DUMC 2650, 203 Research Drive, Durham, NC 27710, USA Full list of author information is available at the end of the article
and secondary right heart failure [1]. The pathogenesis of PAH is complex and involves metabolic and cellular dysfunction, inflammation, fibrosis and dysregulation of vasoactive and
Data Loading...
