Effect of OSA on hypoxic and inflammatory markers during CPAP withdrawal: Further evidence from three randomized control trials

Respirology. 2017 May;22(4):793-799. doi: 10.1111/resp.12946. Epub 2016 Nov 18.

Abstract

Background and objective: 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).

Methods: 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.

Results: 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.

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT01797653.

Keywords: cardiovascular disease; continuous positive airways pressure; intermittent hypoxia; obstructive sleep apnoea.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adrenomedullin / blood*
  • Adult
  • Aged
  • Biomarkers / blood*
  • Continuous Positive Airway Pressure / methods*
  • Endothelin-1 / blood*
  • Female
  • Humans
  • Hypoxia / metabolism
  • Inflammation / metabolism
  • Male
  • Middle Aged
  • Neoplasm Proteins / blood*
  • Patient Compliance
  • Proteoglycans / blood*
  • Resistin / blood*
  • Sleep Apnea, Obstructive / physiopathology*
  • Vascular Endothelial Growth Factor A / blood*
  • Ventilator Weaning / methods*

Substances

  • Biomarkers
  • ESM1 protein, human
  • Endothelin-1
  • Neoplasm Proteins
  • Proteoglycans
  • RETN protein, human
  • Resistin
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Adrenomedullin

Associated data

  • ClinicalTrials.gov/NCT01797653
  • ISRCTN/ISRCTN93153804
  • ISRCTN/ISRCTN73047833