title: Effect of Continuous Positive Airway Pressure on Cardiovascular Biomarkers: The Sleep Apnea Stress Randomized Controlled Trial.
abstract: BACKGROUND
  Although existing research highlights the relationship of OSA and cardiovascular disease, the effect of OSA treatment on cardiovascular biomarkers remains unclear. We evaluated the effect of OSA treatment on oxidative stress/inflammation measures.
  
  
  METHODS
  We conducted a parallel, randomized controlled trial in moderate to severe OSA (apnea-hypopnea index ≥ 15) patients to examine effects of 2-month CPAP vs sham-CPAP on the primary outcome of oxidative stress/inflammation (F2-isoprostanes: ng/mg) and myeloperoxidase: pmol/L) and secondary oxidative stress measures. Exploratory secondary analyses included vascular and systemic inflammation markers. Linear models adjusted for baseline values examined effect of CPAP on biomarker change (least squares means, 95% CI) including secondary stratified analyses examining CPAP adherence and degree of hypoxia.
  
  
  RESULTS
  Of 153 participants, 76 were randomized to CPAP and 77 to sham-CPAP. In an intent-to-treat analyses, no significant change was observed in the sham and CPAP groups respectively: F2-isoprostanes (-0.02 [-0.12 to 0.10] vs -0.08 [-0.18 to 0.03]) or myeloperoxidase (-3.33 [-17.02 to 10.37] vs -5.15 [-18.65 to 8.35]), nor other oxidative markers; findings that persisted in analyses stratified by adherence and hypoxia. Exploratory analyses revealed percentage reduction of soluble IL-6 receptor (ng/mL) levels (-0.04 [-0.08 to -0.01] vs 0.02 [-0.02 to 0.06], P = .019) and augmentation index (%) (-6.49 [-9.32 to -3.65] vs 0.44 [-2.22 to 3.10], P < .001) with CPAP compared with sham, respectively.
  
  
  CONCLUSIONS
  In moderate to severe OSA, 2-month CPAP vs sham did not reduce oxidative stress despite consideration of a broad range of measures, positive airway pressure adherence, and hypoxia burden. These findings suggest that nonoxidative stress pathways primarily modulate OSA-related cardiovascular consequences.
  
  
  BACKGROUND
  ClinicalTrials.govNCT00607893.
authors.affiliation: Sleep Disorders Center, Neurological Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Hugo L
authors.initials: HL
authors.lastname: Paz Y Mar
authors.affiliation: Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Stanley L
authors.initials: SL
authors.lastname: Hazen
authors.affiliation: Departments of Biochemistry and Pathology, University of Vermont, Burlington, VT.
authors.forename: Russell P
authors.initials: RP
authors.lastname: Tracy
authors.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH.
authors.forename: Kingman P
authors.initials: KP
authors.lastname: Strohl
authors.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, MetroHealth Medical Center, Cleveland, OH.
authors.forename: Dennis
authors.initials: D
authors.lastname: Auckley
authors.affiliation: Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: James
authors.initials: J
authors.lastname: Bena
authors.affiliation: Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Sleep Disorders Center, Neurological Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Harneet K
authors.initials: HK
authors.lastname: Walia
authors.affiliation: Division of Sleep and Circadian Disorders, Brigham and Women's Hospital and Division of Pulmonary, Critical Care and Sleep Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Sanjay R
authors.initials: SR
authors.lastname: Patel
authors.affiliation: Sleep Disorders Center, Neurological Institute, Cleveland Clinic, Cleveland, OH; Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH. Electronic address: mehrar@ccf.org.
authors.forename: Reena
authors.initials: R
authors.lastname: Mehra
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology; D045422:Continuous Positive Airway Pressure / Q000379:methods*; D028441:F2-Isoprostanes / Q000097:blood*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D009195:Peroxidase / Q000097:blood*; D019947:Receptors, Interleukin-6 / Q000097:blood; D012307:Risk Factors; D020181:Sleep Apnea, Obstructive / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy; D013223:Statistics as Topic
chemical_list: D015415:Biomarkers; D028441:F2-Isoprostanes; D019947:Receptors, Interleukin-6; D009195:Peroxidase
keywords: CPAP; inflammation; obstructive sleep apnea