Search

Purpose: Endocan is a biomarker of endothelial dysfunction, which is a precursor to cardiovascular disease. Obstructive sleep apnoea (OSA) is associated with elevated endocan levels but the effects of treatment on endocan levels in OSA are not fully established. We aimed to determine whether endocan levels could be detected by immunoassay and to determine the effect of supplemental oxygen during continuous positive airway pressure (CPAP) withdrawal on circulating endocan levels., Methods: We conducted an exploratory analysis from a randomised controlled crossover study which included participants with OSA. Participants stopped their CPAP therapy and were randomised to receive either supplemental oxygen or sham for 14 nights before crossing over. Supplemental oxygen blocked the rise in blood pressure seen in the sham group. We analysed plasma endocan levels by immunoassay at baseline and after 14 nights of intervention in both groups., Results: Twenty-five participants were included, with a total of 100 samples. Endocan levels were detectable at all time points in 22 participants (88%), and in 93 (93%) samples. Supplemental oxygen had no effect on endocan levels compared to sham (+ 0.52 ng/ml, 95%CI -0.21 to + 1.25, p = 0.16), and there was no significant difference in endocan levels from baseline to follow-up in either the sham (-0.30 ng/ml, 95%CI -0.89 to + 0.30, p = 0.31) or supplemental oxygen (+ 0.22 ng/ml, 95%CI 0.00 to + 0.44, p = 0.05) arm., Conclusions: We have shown that endocan levels are detectable before and after CPAP withdrawal. However, we found no effect of supplemental oxygen following CPAP withdrawal on circulating endocan levels., Trial Registration and Date: ISRCTN 17,987,510 19/02/2015., Competing Interests: Declarations Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the South Central Oxford B Research Ethics Committee (REC Reference 15/SC/0007) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Compliance with ethical standards Funding: This study was funded by the Oxford Radcliffe Hospital Charitable Funds and ResMed UK. Conflict of interest Dr. Chris Turnbull declares honoraria from Stowood, outside the scope of this work. Dr. Nayia Petousi, Prof John Stradling, and Dr Philippe Lassalle declare no conflict of interest. Informed consent Informed consent was obtained from all individual participants included in the study., (© 2024. The Author(s).)

Obstructive sleep apnea (OSA), a disease associated with excessive sleepiness and increased cardiovascular risk, affects an estimated 1 billion people worldwide. The present study examined proteomic biomarkers indicative of presence, severity, and treatment response in OSA. Participants (n = 1391) of the Stanford Technology Analytics and Genomics in Sleep study had blood collected and completed an overnight polysomnography for scoring the apnea−hypopnea index (AHI). A highly multiplexed aptamer-based array (SomaScan) was used to quantify 5000 proteins in all plasma samples. Two separate intervention-based cohorts with sleep apnea (n = 41) provided samples pre- and post-continuous/positive airway pressure (CPAP/PAP). Multivariate analyses identified 84 proteins (47 positively, 37 negatively) associated with AHI after correction for multiple testing. Of the top 15 features from a machine learning classifier for AHI ≥ 15 vs. AHI < 15 (Area Under the Curve (AUC) = 0.74), 8 were significant markers of both AHI and OSA from multivariate analyses. Exploration of pre- and post-intervention analysis identified 5 of the 84 proteins to be significantly decreased following CPAP/PAP treatment, with pathways involving endothelial function, blood coagulation, and inflammatory response. The present study identified PAI-1, tPA, and sE-Selectin as key biomarkers and suggests that endothelial dysfunction and increased coagulopathy are important consequences of OSA, which may explain the association with cardiovascular disease and stroke.

Rationale: Obstructive sleep apnea (OSA) is associated with systemic hypertension. Either overnight intermittent hypoxia, or the recurrent arousals that occur in OSA, could cause the daytime increases in blood pressure (BP)., Objectives: To establish the role of intermittent hypoxia in the increased morning BP in patients with OSA., Methods: Randomized, double-blinded, crossover trial assessing the effects of overnight supplemental oxygen versus air (sham) on morning BP, after continuous positive airway pressure (CPAP) withdrawal in patients with moderate to severe OSA. The primary outcome was the change in home morning BP after CPAP withdrawal for 14 nights, oxygen versus air. Secondary outcomes included oxygen desaturation index (ODI), apnea-hypopnea index (AHI), subjective sleepiness (Epworth Sleepiness Scale score), and objective sleepiness (Oxford Sleep Resistance Test)., Measurements and Main Results: Supplemental oxygen virtually abolished the BP rise after CPAP withdrawal and, compared with air, significantly reduced the rise in mean systolic BP (-6.6 mm Hg; 95% confidence interval [CI], -11.3 to -1.9; P = 0.008), mean diastolic BP (-4.6 mm Hg; 95% CI, -7.8 to -1.5; P = 0.006), and median ODI (-23.8/h; interquartile range, -31.0 to -16.3; P < 0.001) after CPAP withdrawal. There was no significant difference, oxygen versus air, in AHI, subjective sleepiness, or objective sleepiness., Conclusions: Supplemental oxygen virtually abolished the rise in morning BP during CPAP withdrawal. Supplemental oxygen substantially reduced intermittent hypoxia, but had a minimal effect on markers of arousal (including AHI), subjective sleepiness, or objective sleepiness. Therefore intermittent hypoxia, and not recurrent arousals, appears to be the dominant cause of daytime increases in BP in OSA.

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., (© 2016 Asian Pacific Society of Respirology.)