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Original Research: Sleep Disorders |

Effect of Continuous Positive Airway Pressure on Cardiovascular Biomarkers: The Sleep Apnea Stress Randomized Controlled Trial

Hugo L. Paz y Mar, MD; Stanley L. Hazen, MD, PhD; Russell P. Tracy, PhD; Kingman P. Strohl, MD; Dennis Auckley, MD; James Bena, MS; Lu Wang, MS; Harneet K. Walia, MD; Sanjay R. Patel, MD; Reena Mehra, MD
Author and Funding Information

Some of the results of this study have been previously reported in the form of abstracts at the 28th Annual Meeting of Associated Professional Sleep Societies, June 2014, Minneapolis, MN.

FUNDING/SUPPORT: This study was supported by the National Heart, Lung and Blood Institute [Grant K23HL079114] and National Institutes of Health (NIH) National Center for Research Resources [Grant UL1 RR024989]. Dr Hazen was supported by NIH [Grant P01 HL076491]. Mass spectrometry studies were performed on instruments housed within a core partially supported by an AB SCIEX Center of Innovation grant.

aSleep Disorders Center, Neurological Institute, Cleveland Clinic, Cleveland, OH

bDepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH

cDepartments of Biochemistry and Pathology, University of Vermont, Burlington, VT

dDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH

eDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, MetroHealth Medical Center, Cleveland, OH

fDepartment of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH

gDivision 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

hDepartment of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH

CORRESPONDENCE TO: Reena Mehra, MD, Sleep Center, Neurologic Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;150(1):80-90. doi:10.1016/j.chest.2016.03.002
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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.

Trial Registration  ClinicalTrials.govNCT00607893.

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