Obstructive sleep apnea: a cardiometabolic risk in obesity and the metabolic syndrome

Abstract

Obstructive sleep apnea (OSA) is an underdiagnosed condition characterized by recurrent episodes of obstruction of the upper airway leading to sleep fragmentation and intermittent hypoxia during sleep. Obesity predisposes to OSA, and the prevalence of OSA is increasing worldwide because of the ongoing epidemic of obesity. Recent evidence has shown that surrogate markers of cardiovascular risk, including sympathetic activation, systemic inflammation, and endothelial dysfunction, are significantly increased in obese patients with OSA versus those without OSA, suggesting that OSA is not simply an epiphenomenon of obesity. Moreover, findings from animal models and patients with OSA show that intermittent hypoxia exacerbates the metabolic dysfunction of obesity, augmenting insulin resistance and nonalcoholic fatty liver disease. In patients with the metabolic syndrome, the prevalence of moderate to severe OSA is very high (∼60%). In this population, OSA is independently associated with increased glucose and triglyceride levels as well as markers of inflammation, arterial stiffness, and atherosclerosis. A recent randomized, controlled, crossover study showed that effective treatment of OSA with continuous positive airway pressure for 3 months significantly reduced several components of the metabolic syndrome, including blood pressure, triglyceride levels, and visceral fat. Finally, several cohort studies have consistently shown that OSA is associated with increased cardiovascular mortality, independent of obesity. Taken together, these results support the concept that OSA exacerbates the cardiometabolic risk attributed to obesity and the metabolic syndrome. Recognition and treatment of OSA may decrease the cardiovascular risk in obese patients.

Keywords: BMI; CPAP; NAFLD; NO; OSA; body mass index; cardiovascular risk; continuous positive airway pressure; eNOS; endothelial nitric oxide synthase; metabolic syndrome; nitric oxide; nonalcoholic fatty liver disease; obesity; obstructive sleep apnea; sleep apnea.

Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1. Obesity Predisposes to Obstructive Sleep Apnea

Anatomic factors that predispose obese patients to obstructive sleep apnea.

Figure 2. Nonalcoholic Fatty Liver Disease in Severely Obese Individuals According to the Presence or Absence of OSA

(A) Representative image of the liver without inflammation in a subject without OSA. Macrovesicular hepatic steatosis is evident, but inflammation is absent (hematoxylin-eosin; original magnification ×100). (B) Representative image of the liver in a subject with OSA and severe nocturnal oxyhemoglobin desaturation. Macrovesicular hepatic steatosis is evident, and lobular inflammation is present (arrows) (hematoxylin-eosin; original magnification ×100). (C) Representative image of liver without pericellular fibrosis in an individual without OSA (Masson trichrome; original magnification ×100). (D) Representative image of liver in a subject with OSA and severe nocturnal oxyhemoglobin desaturation. Prominent pericellular perisinusoidal fibrosis is present. Collagen depositions are stained blue and have a chicken-wire appearance (Masson trichrome; original magnification ×100). Reprinted with permission from Polotsky et al. (43). Abbreviation as in Figure 1.

Figure 3. Sympathetic Activity in Lean and Obese Subjects According to the Presence or Absence of OSA

Muscle sympathetic nerve activity (MSNA) in lean (L) and obese (O) subjects according to the presence (+) or absence (−) of OSA. *p

Figure 4. Endothelial Dysfunction in Normal, Overweight, and Obese Subjects According to the Presence or Absence of OSA

Flow-mediated dilation (FMD) in normal (N), overweight (OV), and obese (O) stratified by body mass index (BMI) and as having central obesity by increased (I) vs normal (N) waist circumference or waist-to-hip ratio. Reprinted with permission from Jelic et al. (55). Abbreviation as in Figure 1.

Figure 5. Carotid Intima-Media Thickness in Patients With Metabolic Syndrome With and Without OSA

Carotid intima-media thickness (IMT) in patients with metabolic syndrome (MS) according to the presence or absence of OSA. Reprinted with permission from Drager et al. (58). Abbreviation as in Figure 1.