title: Effect of OSA on hypoxic and inflammatory markers during CPAP withdrawal: Further evidence from three randomized control trials.
abstract: Obstructive sleep apnoea (OSA) is associated with cardiovascular disease. Intermittent hypoxia, endothelial dysfunction and adipose tissue-mediated inflammation have all been linked to cardiovascular disease in OSA. We therefore explored the effect of OSA on relevant associated blood markers: adrenomedullin (ADM), endocan, endothelin-1 (ET-1), resistin and vascular endothelial growth factor (VEGF).
  
  
  
  Patients with OSA, established on and compliant with continuous positive airways pressure (CPAP) therapy for >1 year were included from three randomized controlled trials, conducted at two centres. Patients were randomized to either continued therapeutic CPAP or sham CPAP (CPAP withdrawal) for 2 weeks. Blood markers were measured at baseline and at 14 days and the treatment effect between sham CPAP and therapeutic CPAP was analysed.
  
  
  
  A total of 109 patients were studied (therapeutic CPAP n = 54, sham CPAP n = 55). Sham CPAP was associated with a return of OSA (between-group difference in oxygen desaturation index (ODI) 36.0/h, 95% CI 29.9-42.2, P < 0.001). Sham CPAP was associated with a reduction in ADM levels at 14 days (-26.0 pg/mL, 95% CI -47.8 to -4.3, P = 0.02), compared to therapeutic CPAP. Return of OSA was not associated with changes in endocan, ET-1, resistin or VEGF.
  
  
  
  Whilst CPAP withdrawal was associated with return of OSA, it was associated with an unexpected significant reduction in the vasodilator ADM and not with expected increases in hypoxia-induced markers, markers of endothelial function or resistin. We propose that the vascular effects occurring in OSA may be brought about by other mechanisms, perhaps partly through a reduction in ADM.
authors.affiliation: Oxford Centre for Respiratory Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.|NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
authors.forename: Chris D
authors.initials: CD
authors.lastname: Turnbull
authors.affiliation: Division of Pulmonology and Sleep Disorders Center, University Hospital of Zurich, Zurich, Switzerland.
authors.forename: Valentina A
authors.initials: VA
authors.lastname: Rossi
authors.affiliation: NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.|Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Santer
authors.affiliation: Division of Pulmonology and Sleep Disorders Center, University Hospital of Zurich, Zurich, Switzerland.
authors.forename: Esther I
authors.initials: EI
authors.lastname: Schwarz
authors.affiliation: Oxford Centre for Respiratory Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.|NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
authors.forename: John R
authors.initials: JR
authors.lastname: Stradling
authors.affiliation: Oxford Centre for Respiratory Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.|Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Nayia
authors.initials: N
authors.lastname: Petousi
authors.affiliation: Division of Pulmonology and Sleep Disorders Center, University Hospital of Zurich, Zurich, Switzerland.|Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Kohler
mesh_terms: D053607:Adrenomedullin / Q000097:blood*; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D045422:Continuous Positive Airway Pressure / Q000379:methods*; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood*; D010349:Patient Compliance; D011509:Proteoglycans / Q000097:blood*; D052243:Resistin / Q000097:blood*; D020181:Sleep Apnea, Obstructive / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D015300:Ventilator Weaning / Q000379:methods*
chemical_list: D015415:Biomarkers; C101134:ESM1 protein, human; D019332:Endothelin-1; D009363:Neoplasm Proteins; D011509:Proteoglycans; C499624:RETN protein, human; D052243:Resistin; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D053607:Adrenomedullin
keywords: cardiovascular disease; continuous positive airways pressure; intermittent hypoxia; obstructive sleep apnoea