Obstructive Sleep Apnea

Clinical Principles Obstructive sleep apnea is an increasingly common disorder that is strongly linked to obesity. Neurocognitive sequelae, such as daytime sleepiness and impaired executive function, are important factors in motor vehicle accidents and probably contribute to loss of work-related productivity. Emerging clinical research studies suggest an increasing role of obstructive sleep apnea in cardiovascular disease, particularly systemic hypertension and congestive heart failure. Continuous positive airway pressure (CPAP) is very effective at reversing sleep-related disordered breathing events and consequent daytime symptoms, although maintaining patient adherence can be challenging. The role of CPAP and other modes of therapy in the management of systemic disease that coexists with obstructive sleep apnea is promising but remains to be determined by rigorous interventional controlled trials. Pathophysiologic Principles Obstructive sleep apnea is associated with a reduced-caliber upper airway, which, despite an increase in compensatory pharyngeal dilator muscle electromyographic output, is vulnerable to further narrowing or collapse. Acute and repetitive effects of apneas and hypopneas include oxygen desaturation, reductions in intrathoracic pressure, and central nervous system arousals, all of which may contribute to the cardiovascular diseases that frequently coexist with obstructive sleep apnea. Disruption of neural circulatory control in obstructive sleep apnea is demonstrated by heightened peripheral chemoreflex sensitivity and sympathetic overactivity during both sleep and wakefulness. Metabolic abnormalities in obstructive sleep apnea appear to be mediated in part by insulin resistance, which may be independent of body weight, and by the dysregulation of leptin. Along with an increasingly sophisticated scientific approach to obstructive sleep apnea has come controversy over its true definition. By convention, the apneahypopnea index has been used to characterize obstructive sleep apnea. This index measures the frequency of reductions in airflow associated with upper-airway collapse or narrowing that occurs with the state change from wakefulness to sleep. The term sleep-disordered breathing encompasses these phenomena. However, a rigid diagnostic standard has not been applied to the apneahypopnea index. As a result, its definition differs among sleep laboratories and in the medical literature. A consensus statement was developed over 5 years ago in an attempt to standardize these criteria in human research (1), and although many sleep laboratories have adopted these recommendations, diagnostic variability remains. According to this statement, an apnea involves upper-airway collapse and is defined as nearly complete cessation of airflow associated with oxygen desaturation or an arousal from sleep. Hypopneas, which are associated with partial collapse of the upper airway, should be considered as existing on a pathologic continuum with apneas and may be clinically more important because they may make up the majority of disordered breathing events in a given night (2). The apneahypopnea index measures the frequency of disordered breathing events but does not quantify other processes that may be operative in the pathophysiology of obstructive sleep apnea, such as the degree of oxygen desaturation. Moreover, the total number of arousals, some of which may occur in the absence of frank breathing abnormalities, may be a superior marker of sleep fragmentation than is the apneahypopnea index and may better explain daytime sleepiness (3). Nevertheless, no other metric has proven to be superior to the apneahypopnea index in assessing the overall effect of obstructive sleep apnea, even though it may prove to be inappropriate for characterizing obstructive sleep apnea in specific subsets of patients. For example, it may be that the frequency of arousal (perhaps independent of oxygen desaturation) has the greatest effect on daytime function. Or, perhaps the severity or duration of hypoxemic episodes will be found to have the greatest effect in terms of cardiovascular sequelae. The obstructive sleep apnea syndrome is defined as sleep-disordered breathing associated with daytime symptoms, most often excessive sleepiness. As accumulating data implicate obstructive sleep apnea in the pathogenesis of systemic disease, particularly in the pathophysiology of cardiovascular disease, the distinction between sleep-disordered breathing and the obstructive sleep apnea syndrome has become increasingly blurred. Epidemiology Inconsistencies in definitions of disease and sampling biases contribute to the wide range of prevalence of obstructive sleep apnea reported in the literature. The best evidence of the pervasiveness of obstructive sleep apnea derives from pooled data from 4 large prevalence studies that used similar in-laboratory monitoring, diagnostic criteria, and sampling methods. On the basis of these data, it is estimated that 1 of 5 white adults with an average body mass index of 25 to 28 kg/m2 has an apneahypopnea index of 5 or greater (at least mild disease) and 1 of 15 has an apneahypopnea index of 15 or greater (at least moderate disease) (4-8). Up to 5% of adults in western countries probably have the obstructive sleep apnea syndrome (7). Data on the natural history of sleep-disordered breathing from the Wisconsin Sleep Cohort suggest that factors important in progression of disease include baseline obesity, older age, and the presence of snoring (7) (Figure 1). Figure 1. Mean apneahypopnea index at baseline and the increase 8 years later in 282 participants in the Wisconsin Sleep Cohort. Longitudinal data from the Wisconsin Sleep Cohort show that among persons with mild obstructive sleep apnea (apneahypopnea index, 5 to 15 ) at baseline, a 10% increase in body weight leads to a 6-fold risk for developing moderate or severe obstructive sleep apnea and a 1% change in body weight predicts a concordant 3% change in the apneahypopnea index (9). The mechanism underlying the risk imparted by obesity is thought to be related, at least in part, to airway narrowing as a result of excess regional soft tissue. The association between neck circumference and the apneahypopnea index supports this theory (10). Men have a higher risk for obstructive sleep apnea than do women. The reason for this is not entirely clear, but hormonal influences may offer a partial explanation. Postmenopausal women are at higher risk for obstructive sleep apnea than are premenopausal women (7), an effect that hormone replacement therapy may ameliorate (11). The association between age and obstructive sleep apnea is complex. Several studies have shown a higher prevalence of obstructive sleep apnea in elderly persons compared with middle-aged persons, although daytime symptoms may be less common with advancing age (12). The Sleep Heart Health Study demonstrated that the influence of male sex and body mass index on obstructive sleep apnea tends to wane with age. For unclear reasons, the overall prevalence of obstructive sleep apnea plateaus after 65 years of age (13). Data are limited on the occurrence of sleep apnea in nonwhite populations. The prevalence among African-American persons, after adjustment for body mass index, seems to be at least equal to and may exceed that among white persons (14). The prevalence among men in urban India and men and women in Korea is similar to that observed in western countries (15, 16). Clinical Presentation The cardinal symptom of obstructive sleep apnea is excessive daytime sleepiness. It can be difficult to quantify because patients may use varied adjectives to describe sleepiness, and they may confuse sleepiness with fatigue. The challenge for the clinician is to identify sleepiness that warrants further evaluation. Subjective tools, such as the Epworth Sleepiness Scale, are quick and simple to complete but do not correlate well with the severity of the apneahypopnea index. It may be the mere presence of sleepiness rather than its quantification that is critical because obstructive sleep apnea correlates with motor vehicle accidents, the risk for which is related to the severity of the apneahypopnea index in some (17), but not all (18), studies. Excessive daytime sleepiness appears to result from sleep fragmentation related to recurrent central nervous system arousals in response to disordered breathing events. However, the relationship among these events may be more complex. Experimental disruption of sleep, as manifested by transient blood pressure or heart rate elevations without visible electroencephalographic alterations that traditionally indicate arousal (so-called autonomic arousals), produces evidence of sleepiness on subsequent objective testing (19). Moreover, although the severity of the apneahypopnea index appears to correlate with the degree of subjective sleepiness (20), many people with an apneahypopnea index greater than 5 do not report daytime symptoms. Perception and reporting of daytime sleepiness seem to vary greatly among individuals. When a validated sleep questionnaire was used, a subgroup analysis of the Sleep Heart Health Study showed that 35% of persons with severe obstructive sleep apnea (apneahypopnea index 30) reported sleepiness, as did 21% of those without clinical obstructive sleep apnea (apneahypopnea index < 5) (20). Obstructive sleep apnea is strongly associated with snoring. Notwithstanding the limitations of quantifying this subjective finding, data from the Sleep Heart Health Study suggest that snoring is associated with daytime sleepiness independently of the severity of the apneahypopnea index (21). Diagnosis Several prediction rules have been devised to aid the clinician in determining the pretest probability of obstructive sleep apnea. Such information may allow more efficient use of bed space in sleep laboratories. Validated tools include morphometric examination of