Intermittent Hypoxemia and OSA Implications for Comorbidities

[ Contemporary Reviews in Sleep Medicine ]

IntermittentHypoxemiaandOSA Implications for Comorbidities

Naresh A. Dewan , MD, FCCP ; F. Javier Nieto , MD, MPH, PhD ; and Virend K. Somers , MD, PhD, FCCP

OSA is a common chronic disorder that is associated with signi cant morbidity and mortality including cardiovascular, metabolic, and neurocognitive disease and increased cancer-related deaths. OSA is characterized by recurrent episodes of apneas and hypopneas associated with repetitive episodes of intermittent hypoxemia, intrathoracic pressure changes, and arousals. Intermittent hypoxemia (IH) is now being recognized as a potential major factor contributing to the pathogenesis of OSA-related comorbidities. OSA-related high-frequency IH is charac-terized by cycles of hypoxemia with reoxygenation that is distinctly di erent than sustained low-frequency hypoxia and contributes to ischemia-reperfusion injury. Data from both animal and human studies support mechanistic links between IH and its adverse impact at the tissue level. IH promotes oxidative stress by increased production of reactive oxygen species and angiogenesis, increased sympathetic activation with BP elevation, and systemic and vascular in ammation with endothelial dysfunction that contributes to diverse multiorgan chronic mor-bidity and mortality a ecting cardiovascular disease, metabolic dysfunction, cognitive decline, and progression of cancer. Data from observational studies in large population groups also support the role for hypoxia in the pathogenesis of OSA comorbidity. Treatment with CPAP to reverse OSA-related symptoms and comorbidities has been shown to provide variable bene t in some but not all patient groups. Early treatment with CPAP makes intuitive sense to promote maximal functional recovery and minimize residual injury. More studies are needed to deter-mine the interacting e ects of IH and obesity, di erential e ects of both short-term and long-term hypoxemia, and the e ect of CPAP treatment.

ABBREVIATIONS : AF 5 atrial fibrillation;CHEST 2015; 147 ( 1) : 266 - 274

AHI 5 apnea-hypopnea index ;HIF 5 hypoxia-inducible factor ;IH 5 intermittenthypoxemia;NADPH 5 reducednicotinamideadeninedinucleotidephosphate; NO 5 nitricoxide;ROS 5 reactiveoxygenspecies;Spo2 5 pulseoximetrybloodoxygensaturation;VEGF 5 vascularendothelialgrowthfactorOSA is a common chronic disorder with an

estimated prevalence of moderate to severe sleep apnea in 6% to 13% of the adult popu-1 It is lation aff ecting . 20 million Americans. also associated with signifi cant morbidity

and mortality that includes cardiovascular,

2 metabolic, and neurocognitive impairment.

Emerging data also suggest an increased

ManuscriptreceivedFebruary28,2014;revisionacceptedSeptember6,2014. FFILIATIONS: AFrom the Division of Pulmonary, Critical Care, and Sleep Medicine (Dr Dewan), Department of Medicine, Creighton University and Pulmonary Section, Omaha VA Medical Center, US Department of Veterans Aff airs, Omaha, NE; Population Health Sciences, School of Medicine and Public Health (Dr Nieto), University of Wisconsin-Madison, Board of Regents of the University of Wisconsin System, Madison, WI; and Sleep and Cardiovascular Clinical Research Unit, College of Medicine (Dr Somers), Mayo Clinic, Mayo Foundation for Medical Education and Research, Rochester, MN. P arts of this article were presented as a Sleep Network Highlight session at CHEST 2013, October 26-31, 2013, Chicago, IL.

FUNDING/SUPPORT: Dr Nieto’s contributions were supported in part

by the National Institutes of Health (NIH) [Grant R01HL062252-11] and by the University of Wisconsin Helfaer Endowed Chair of Public Health. Dr Somers’ contribution to this work was sup ported by the NIH [Grant HL-65176].

ORRESPONDENCE TO: Naresh A. Dewan, MD, FCCP, Division of Pul-C

monary, Critical Care and Sleep Medicine, Department of Medicine, Creighton University and Pulmonary Section, Omaha VA Medical Center, Omaha, NE 68178; e-mail: ndewan@creighton.edu © 2015 AMERICAN COLLEGE OF CHEST PHYSICIANS. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.14-0500

266 Contemporary Reviews in Sleep Medicine

[ 147#1 CHEST JANUARY 2015 ]

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