Effects of short-term continuous positive airway pressure withdrawal on cerebral vascular reactivity measured by blood oxygen level-dependent magnetic resonance imaging in obstructive sleep apnoea: a randomised controlled trial

Impaired cerebral vascular reactivity (CVR) increases long-term stroke risk. Obstructive sleep apnoea (OSA) is associated with peripheral vascular dysfunction and vascular events. The aim of this trial was to evaluate the effect of continuous positive airway pressure (CPAP) withdrawal on CVR. 41 OSA patients (88% male, mean age 57±10 years) were randomised to either subtherapeutic or continuation of therapeutic CPAP. At baseline and after 2 weeks, patients underwent a sleep study and magnetic resonance imaging (MRI). CVR was estimated by quantifying the blood oxygen level-dependent (BOLD) MRI response to breathing stimuli. OSA did recur in the subtherapeutic CPAP group (mean treatment effect apnoea–hypopnoea index +38.0 events·h−1, 95% CI 24.2–52.0; p<0.001) but remained controlled in the therapeutic group. Although there was a significant increase in blood pressure upon CPAP withdrawal (mean treatment effect +9.37 mmHg, 95% CI 1.36–17.39; p=0.023), there was no significant effect of CPAP withdrawal on CVR assessed via BOLD MRI under either hyperoxic or hypercapnic conditions. Short-term CPAP withdrawal did not result in statistically significant changes in CVR as assessed by functional MRI, despite the recurrence of OSA. We thus conclude that, unlike peripheral endothelial function, CVR is not affected by short-term CPAP withdrawal. Withdrawing continuous positive airway pressure therapy and the resulting recurrence of obstructive sleep apnoea did not result in a significant reduction in cerebral vascular reactivity, despite clinically relevant increases in blood pressure http://ow.ly/T2QD30mU6L2

[1]  O. Riesterer,et al.  Dependency of the blood oxygen level dependent-response to hyperoxic challenges on the order of gas administration in intracranial malignancies , 2019, Neuroradiology.

[2]  C. J. Gauthier,et al.  BOLD signal physiology: Models and applications , 2019, NeuroImage.

[3]  E. Kaluski,et al.  A meta-analysis of continuous positive airway pressure therapy in prevention of cardiovascular events in patients with obstructive sleep apnoea , 2018, European heart journal.

[4]  A. Crawley,et al.  Cerebrovascular Resistance: The Basis of Cerebrovascular Reactivity , 2018, Front. Neurosci..

[5]  J. Stradling,et al.  Nocturnal cerebral hypoxia in obstructive sleep apnoea: a randomised controlled trial , 2018, European Respiratory Journal.

[6]  M. Kohler,et al.  Con: continuous positive airway pressure and cardiovascular prevention , 2018, European Respiratory Journal.

[7]  S. Javaheri,et al.  Pro: continuous positive airway pressure and cardiovascular prevention , 2018, European Respiratory Journal.

[8]  E. Rostrup,et al.  Impaired cerebrovascular reactivity in obstructive sleep apnea: a case-control study. , 2017, Sleep medicine.

[9]  A. Crawley,et al.  The role of vascular resistance in BOLD responses to progressive hypercapnia , 2017, Human brain mapping.

[10]  S. Eickhoff,et al.  Functional reorganization in obstructive sleep apnoea and insomnia: A systematic review of the resting-state fMRI , 2017, Neuroscience & Biobehavioral Reviews.

[11]  K. Chou,et al.  Systemic inflammation and alterations to cerebral blood flow in obstructive sleep apnea , 2017, Journal of sleep research.

[12]  H. Gong,et al.  Resting cerebral blood flow alteration in severe obstructive sleep apnoea: an arterial spin labelling perfusion fMRI study , 2017, Sleep and Breathing.

[13]  Rui Chen,et al.  CPAP for Prevention of Cardiovascular Events in Obstructive Sleep Apnea. , 2016, The New England journal of medicine.

[14]  J. Stradling,et al.  Effect of CPAP Withdrawal on BP in OSA: Data from Three Randomized Controlled Trials. , 2016, Chest.

[15]  Keith W. Muir,et al.  Respiratory challenge MRI: Practical aspects , 2016, NeuroImage: Clinical.

[16]  Danny J. J. Wang,et al.  Water Exchange across the Blood‐Brain Barrier in Obstructive Sleep Apnea: An MRI Diffusion‐Weighted Pseudo‐Continuous Arterial Spin Labeling Study , 2015, Journal of Neuroimaging.

[17]  Carrie R. H. Innes,et al.  Decreased Regional Cerebral Perfusion in Moderate-Severe Obstructive Sleep Apnoea during Wakefulness. , 2015, Sleep.

[18]  M. Preisig,et al.  Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study. , 2015, The Lancet. Respiratory medicine.

[19]  S. Parthasarathy,et al.  Cerebrovascular reactivity in young subjects with sleep apnea. , 2015, Sleep.

[20]  D J Mikulis,et al.  Cerebrovascular Reactivity Mapping: An Evolving Standard for Clinical Functional Imaging , 2015, American Journal of Neuroradiology.

[21]  J. Gati,et al.  Cerebral blood flow velocity underestimates cerebral blood flow during modest hypercapnia and hypocapnia. , 2014, Journal of applied physiology.

[22]  Albert Dahan,et al.  Assessment of middle cerebral artery diameter during hypocapnia and hypercapnia in humans using ultra-high-field MRI. , 2014, Journal of applied physiology.

[23]  Rajesh Kumar,et al.  Global Brain Blood-Oxygen Level Responses to Autonomic Challenges in Obstructive Sleep Apnea , 2014, PloS one.

[24]  James Duffin,et al.  Factors affecting the determination of cerebrovascular reactivity , 2014, Brain and behavior.

[25]  C. Guilleminault,et al.  An fMRI study of cerebrovascular reactivity and perfusion in obstructive sleep apnea patients before and after CPAP treatment. , 2014, Sleep medicine.

[26]  Dinu S. Chandran,et al.  Correction for blood pressure improves correlation between cerebrovascular reactivity assessed by breath holding and 6% CO(2) breathing. , 2014, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[27]  J. Duffin,et al.  Normal hypercapnic cerebrovascular conductance in obstructive sleep apnea , 2014, Respiratory Physiology & Neurobiology.

[28]  D J Mikulis,et al.  Measuring cerebrovascular reactivity: what stimulus to use? , 2013, The Journal of physiology.

[29]  J. Le Bas,et al.  Functional imaging of cerebral perfusion. , 2013, Diagnostic and interventional imaging.

[30]  Danny J. J. Wang,et al.  Regional cerebral blood flow alterations in obstructive sleep apnea , 2013, Neuroscience Letters.

[31]  Rajesh Kumar,et al.  Heart Rate Responses to Autonomic Challenges in Obstructive Sleep Apnea , 2013, PloS one.

[32]  J. Stradling,et al.  CPAP improves endothelial function in patients with minimally symptomatic OSA: results from a subset study of the MOSAIC trial. , 2013, Chest.

[33]  T. Young,et al.  Increased prevalence of sleep-disordered breathing in adults. , 2013, American journal of epidemiology.

[34]  David J Mikulis,et al.  CO2 blood oxygen level-dependent MR mapping of cerebrovascular reserve in a clinical population: safety, tolerability, and technical feasibility. , 2013, Radiology.

[35]  S. Quan,et al.  Rules for scoring respiratory events in sleep: update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events. Deliberations of the Sleep Apnea Definitions Task Force of the American Academy of Sleep Medicine. , 2012, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[36]  Y. Loke,et al.  Association of Obstructive Sleep Apnea With Risk of Serious Cardiovascular Events: A Systematic Review and Meta-Analysis , 2012, Circulation. Cardiovascular quality and outcomes.

[37]  T. Young,et al.  Effects of sleep-disordered breathing on cerebrovascular regulation: A population-based study. , 2010, American journal of respiratory and critical care medicine.

[38]  Jeff H. Duyn,et al.  Characterization of regional heterogeneity in cerebrovascular reactivity dynamics using novel hypocapnia task and BOLD fMRI , 2009, NeuroImage.

[39]  D P Auer,et al.  Precision of Cerebrovascular Reactivity Assessment with Use of Different Quantification Methods for Hypercapnia Functional MR Imaging , 2009, American Journal of Neuroradiology.

[40]  Terry Young,et al.  Association of sleep-disordered breathing and the occurrence of stroke. , 2005, American journal of respiratory and critical care medicine.

[41]  Jose M Marin,et al.  Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study , 2005, The Lancet.

[42]  J. Pickard,et al.  Pressure Autoregulation and Positron Emission Tomography-derived Cerebral Blood Flow Acetazolamide Reactivity in Patients with Carotid Artery Stenosis , 2004, Neurosurgery.

[43]  Takashi Inoue,et al.  Prediction and monitoring of cerebral hyperperfusion after carotid endarterectomy by using single-photon emission computerized tomography scanning. , 2003, Journal of neurosurgery.

[44]  Maximilian Reiser,et al.  Oxygen‐enhanced MRI of the brain , 2002, Magnetic resonance in medicine.

[45]  P. Jennum,et al.  Intracranial pressure and obstructive sleep apnea. , 1989, Chest.

[46]  S. Kety,et al.  THE EFFECTS OF ALTERED ARTERIAL TENSIONS OF CARBON DIOXIDE AND OXYGEN ON CEREBRAL BLOOD FLOW AND CEREBRAL OXYGEN CONSUMPTION OF NORMAL YOUNG MEN. , 1948, The Journal of clinical investigation.

[47]  D. Mikulis,et al.  Evaluation of Cerebrovascular Reactivity in Subjects with and without Obstructive Sleep Apnea. , 2018, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[48]  T. Neumann-Haefelin,et al.  Assessment of cerebrovascular reactivity with functional magnetic resonance imaging: comparison of CO(2) and breath holding. , 2001, Magnetic resonance imaging.