Obstructive sleep apnoea syndrome.

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Abstract
Abstract • References • Author information Obstructive sleep apnoea syndrome (OSAS) is a common clinical condition in which the throat narrows or collapses repeatedly during sleep, causing obstructive sleep apnoea events. The syndrome is particularly prevalent in middle-aged and older adults. The mechanism by which the upper airway collapses is not fully understood but is multifactorial and includes obesity, craniofacial changes, alteration in upper airway muscle function, pharyngeal neuropathy and fluid shift towards the neck. The direct consequences of the collapse are intermittent hypoxia and hypercapnia, recurrent arousals and increase in respiratory efforts, leading to secondary sympathetic activation, oxidative stress and systemic inflammation. Excessive daytime sleepiness is a burden for the majority of patients. OSAS is also associated with cardiovascular co-morbidities, including hypertension, arrhythmias, stroke, coronary heart disease, atherosclerosis and overall increased cardiovascular mortality, as well as metabolic dysfunction. Whether treating sleep apnoea can fully reverse its chronic consequences remains to be established in adequately designed studies. Continuous positive airway pressure (CPAP) is the primary treatment modality in patients with severe OSAS, whereas oral appliances are also widely used in mild to moderate forms. Finally, combining different treatment modalities such as CPAP and weight control is beneficial, but need to be evaluated in randomized controlled trials. For an illustrated summary of this Primer, visit: http://go.nature.com/Lwc6te Subject terms: Cardiovascular diseases • Respiratory tract diseases • Sleep disorders Figures at a glance Displaying 7 of 7 figures | Figures index Figure 1: Maxillofacial and soft tissue changes occurring in OSAS. a | Normal anatomy. b | Typical anatomical changes in obstructive sleep apnoea syndrome (OSAS): a long soft palate and enlarged uvula (1); a reduced retroglossal pharyngeal airway space (2); an increased distance between the hyoid bone and the mandible (3); a shorter and more vertical mandible (4); a retro-position of the mandible, which is measured by the angle (retrognathia) (5); dental overbite or loss of normal dental occlusion (6); tonsillar hypertrophy (7); adenoid hypertrophy (8); and macroglossia (unusual large tongue) (9). Figure 2: Global prevalence of sleep apnoea. Schematic representation of the apnoea and hypopnoea frequency per hour (apnoea–hypopnoea index; AHI) worldwide. US data are based on the Bixler study in general population cohorts in Pennsylvania277,278 and the population prevalence estimates obtained from longitudinal data of the Wisconsin cohort study17. Obstructive sleep apnoea syndrome (OSAS) is also prevalent in Asian populations279,280; a contributing factor might be differences in craniofacial structure compared with white people281. The data from Australia were based on one community population report282,283 and were biased in favour of snorers. The Brazilian data were obtained from a general population study of predominantly middle-aged adults, 60% of whom had a body mass index >25 kg per m2 (Ref. 129). The data in India are based on a cross-sectional prevalence study in healthy urban Indian males aged 35–65 years. Although there are no published data on the prevalence among African populations, OSAS is at least as prevalent in African Americans as in Americans of European descent284,285. Care should be taken when attempting to perform inter-study comparisons because of varying definitions of daytime sleepiness, differences in sampling schemes, disparities in techniques used for monitoring sleep and breathing16. *‘Sleep disorder clinic’ criteria include a apnoea–hypopnoea index of ≥10 plus daytime sleepiness, hypertension or another cardiovascular complication. ‡Daytime hypersomnolence (excessive daytime sleepiness) was not related to the severity of OSAS. Figure 3: Schematic outlining the hypothesized pathways by which intermittent hypoxia activates the autonomic nervous system and leads to hypertension. Intermittent hypoxia activates the peripheral chemoreceptors (located in the carotid bodies), which partly control the ventilator responses to reductions in blood oxygen content (hypoxic ventilator response) and to increases in blood partial pressure in carbon dioxide (hypercapnic ventilator response). Also, these chemoreflexes increase the outflow of the sympathetic nervous system, activates the renin, angiotensin II and aldosterone system, and enhances vasoconstrictor activity. Impaired baroreflex, reduction in the levels of the vasodilator nitric oxide (NO), increased endothelin production and receptor expression might also alter vasoconstrictor activity and promote an increase in systemic blood pressure. In addition, it has been evidenced that intermittent hypoxia associated with intermittent hypercapnia does not only lead to increased sensitivity to the vasoconstrictor endothelin 1 but also to increased calcium sensitivity in the vessels of exposed animals compared with controls. Broken line; indirect pathway. Figure adapted from Ref. 61, Wiley. Figure 4: Oxidative stress promotes sympathetic activation, cellular and systemic inflammation, and vascular co-morbidities in OSAS. Intermittent hypoxia induces the production of reactive oxygen species (ROS), resulting in oxidative stress by inducing mitochondrial dysfunction, activating NADPH oxidase (NOX) and xanthine oxidase (XOX), and inducing nitric oxide synthase (NOS) uncoupling. Interaction of ROS with nitric oxide (NO) further promotes oxidative stress while diminishing the bioavailability of NO and thus promoting hypertension, inflammation, endothelial dysfunction, hypercoagulability and atherosclerosis. The ROS-dependent increase in sympathetic activation, and in angiotensin II and endothelin 1 levels contribute to hypertension. Concomitantly, ROS can...