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

Background and objectiveObstructive 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). MethodsPatients with OSA, established on and compliant with continuous positive airways pressure (CPAP) therapy for >1year 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. ResultsA total of 109 patients were studied (therapeutic CPAPn=54, sham CPAPn=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 (-26.0pg/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. ConclusionWhilst 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. Intermittent hypoxia, endothelial dysfunction and adipose tissue-mediated inflammation have been proposed as mechanisms in the development of cardiovascular disease in obstructive sleep apnoea (OSA). We explored changes in associated biomarkers after continuous positive airways pressure (CPAP) withdrawal. Return of OSA led to a small reduction in adrenomedullin with no significant change in other cardiovascular markers.