The severity of OSA is typically defined by the use of disordered breathing indices (1). There are a number of different types of breathing events, and they may have different significance with regard to physiologic effects. The strict definitions of these events have varied over the years; however, in 2007, the American Academy of Sleep Medicine released “The AASM Manual for the Scoring of Sleep and Associated Events” (2). This was important as the manual defined recommended standards for sleep centers on equipment, filter settings, and scoring of sleep studies. Adoption of these standards should decrease the variability in scoring events between laboratories. Nonetheless, counting events to define severity remains problematic on several fronts. There is little correlation between these respiratory disturbance indices and sleepiness (3). Furthermore, it has not been shown to correlate well with the quality-of-life measure or other disease-specific outcomes (4). This may in part be related to the equivalence of the events in the index. All events may not result in comparable physiologic responses, for example, a 45-second apnea in rapid eye movement (REM) may result in cardiac arrhythmias, severe oxygen desaturation, and marked blood pressure fluctuation; however, it would have equal weight with a hypopnea that caused an oxygen desaturation from 95% to 91%.

Another issue is that sleep centers may use different equipments to measure respiratory variables. Again, the manual should be very helpful in standardizing the equipment between sleep centers (2).

To summarize, using a polysomnographically defined AHI alone is fraught with problems and should not be used in isolation to determine the diagnosis and management of a patient with OSA.

Another issue relates to treating disease that may be confined or particularly severe in one stage of sleep (usually REM), but is not significant overall, based on total sleep time (TST). REM-related OSA is an understudied phenomenon. It is well known that obstructive sleep-disordered breathing (SDB) is worse (longer events and lower oxygen desaturations) in REM sleep because of a more collapsible upper airway (muscle atonia) and a blunted response to chemical stimuli (5). It is clear that some patients have most of their SDB during this stage of sleep (Fig. 19-1). This phenomenon of REM-related OSA is
three times more common in women than in men (6,7). This is likely due to inherent differences in the upper airway between men and women (8). It is also more likely to occur in younger populations and less-obese patients (9). There are conflicting data as to whether REM-related OSA alone can result in significant daytime sleepiness (10,11). It has been shown that pulmonary artery pressures are more elevated during REM- than nonrapid eye movement (NREM)-related events, even after adjusting for oxygen saturation levels (12). However, no data exist as to whether REM-related OSA can cause long-term morbidity or mortality. Therefore, there is little to guide us as to how to treat this condition.

Similar to REM-related OSA, it is commonly observed that patients have worsening of both frequency and number of SDB events when they are in the supine position. There are subgroups of patients that have OSA only when supine (13). They tend to be both thinner and younger than “nonpositional” patients with OSA, which leads one to wonder whether, with time, some of these patients may progress to the “nonpositional” status. Although there are significantly more data on this phenomenon than on REM-related OSA, little data exist on long-term effects on those patients whose SDB is predominantly in the supine position. There are treatment options aside from nasal continuous positive airway pressure (CPAP) in these patients, as will be discussed later.

In the past decade, a number of cardiovascular diseases have been shown to occur frequently in association with OSA (Table 19-2). Although these are mostly associations, epidemiologic studies would suggest that many of these associations are more than coincidental. Perhaps the most studied cardiovascular disease associated with OSA is systemic hypertension. It has been shown that approximately 30% of the patients in essential hypertension clinics have OSA (46,47 and 48), and it is estimated that 50% to 60% of patients with OSA have hypertension (49). The difficulty with showing causality, that is, OSA can cause hypertension, lies in the fact that the population having hypertension is similar to the population having OSA: middle-aged, overweight males. Animal models have been instructive in showing that both recurrent apneas and hyporemia during sleep will result in elevated blood pressure over time (50,51 and 52). Two large epidemiologic studies, one longitudinal and the other cross-sectional, showed an increasing dose response for the severity of OSA, defined by AHI and the presence of hypertension (53,54). Another study showed that patients with refractory hypertension, defined by persistent elevation of blood pressure, despite the use of three or more antihypertensives, had a very high prevalence of OSA—96% of men and 65% of women (55).

It is generally agreed upon that treatment of OSA improves hypertension. Two meta-analyses from reviewed randomized, controlled trials compared CPAP with placebo. Bazzano et al. (56) evaluated 16 trials ranging from 2 to 24 weeks in length. They found an overall mean net change of -1.83 mm Hg (95% CI: -3.05 to -0.61) in diastolic blood pressure (DBP) and a mean net change of -2.46 mm Hg (95% CI: -4.31 to -0.62) in systolic blood pressure (SBP). Haentjens et al. (57) evaluated 12 trials, 10 of which were included in the Bazzano article, and found a mean net change of -1.79 mm Hg (95% CI: -2.87 to -0.71) in DBP and of -1.77 mm Hg (95% CI: -3.00 to -0.54) in SBP. In general, most articles suggest that patients with a higher AHI had a more marked change in blood pressure.

Another cardiovascular disease associated with OSA is pulmonary hypertension. This has been shown to be present in approximately 15% to 20% of the patients with OSA (58,59). In patients with OSA, it tends to be mild (average mean pulmonary artery pressures of 20-25 mm Hg) or exercise induced. It is controversial whether pulmonary hypertension can occur in OSA independent of obesity or underlying lung disease (60,61). It has, however, been shown that the treatment of OSA can improve pulmonary hemodynamics (62,63 and 64). The long-term effects of pulmonary hypertension on the course of patients with OSA are unknown.

Aside from systemic and pulmonary hypertension, other cardiovascular diseases have been associated with OSA, including coronary artery disease (CAD) and stroke. It has been shown that patients with OSA have elevated levels of risk markers such as C-reactive protein (65), leptin (66), and homocysteine (67), all of which have been associated with increased risk of cardiovascular disease. Case control studies of male and female patients who have had recent acute coronary syndrome show an association between the conditions with significantly elevated odds ratios (68,69). Nocturnal arrhythmias are also common in patients with OSA. The risk of arrhythmia with OSA appears to be related to severity. Analysis of electrocardiographic recordings during sleep studies in >450 patients showed a 58% (vs. 42% in patients without OSA) prevalence of arrhythmias in patients with OSA, with most arrhythmias occurring in those with an AHI of >40 per hour (70). Bradycardia, sinus pauses, and nocturnal paroxysmal asystole are the most common arrhythmias seen, and these increase in frequency with increasing severity of the syndrome. Nonsustained supraventricular tachycardias may also occur in patients with severe OSA; however, ventricular arrhythmias are very uncommon (71). Treatment of OSA with CPAP improves most nocturnal arrhythmias (72).

The risk for stroke appears to be even more compelling than the risk for CAD in patients with OSA. In the Sleep Heart Health study in which overnight PSG was done in >6,000 adults, the relative odds ratio of self-reported stroke was elevated when comparing the upper AHI quartiles with the lower ones (1.58) (73). It has also been shown that the prevalence of SDB is very high in patients with recent stroke or transient ischemic attack, in some series as high as 95% (74,75). Patients with concomitant OSA and stroke have been shown to have early neurologic worsening and oxygen desaturation compared with controls (76). One study suggests that those with stroke and OSA are at risk for higher mortality. Sahlin et al. (77) diagnosed OSA in 23 of 132 patients admitted for stroke rehabilitation and using those with an AHI of <15 as controls, individuals with OSA had a higher 10-year mortality, with an adjusted hazard ratio of 1.76.

In conclusion, deciding on when to treat a patient with SDB requires several considerations: (1) the severity of the condition as defined by the disordered breathing indexes or oxygen desaturation, understanding that there
is considerable variability from one sleep laboratory to the next; (2) the symptoms the patient has, and how those symptoms impact on day-to-day functioning; and (3) the presence of concomitant diseases, particularly cardiovascular diseases, namely, systemic hypertension, pulmonary hypertension, heart disease, and stroke.

Nasal CPAP has become the current treatment of choice for the majority of adult patients with OSA. The mechanism by which nasal CPAP works is predominantly by creating a “pneumatic splint” in the upper airway, hence, preventing collapse (78). Other effects of CPAP include diminishing muscle tone in the upper airway and increasing functional residual capacity (79,80). The pressure required by an individual patient is usually determined during a sleep study, in which the pressure is gradually increased until obstructive events and snoring are eliminated and oxygen saturation is maintained above 90%. Nasal CPAP has been shown to be very successful in the treatment of OSA. Approximately 95% of the patients can be definitively treated with this device, including patients with mild disease (81). Nasal CPAP has been shown to improve many aspects of the OSA syndrome including daytime sleepiness (82) and quality of life (83), and after the initiation of CPAP, patients with OSA have fewer hospitalizations (84). An excellent review of all the randomized trials comparing CPAP with placebo or other treatments in adults is published in the Cochrane Library (85). This review concluded that although CPAP is more effective than placebo in improving sleepiness, multiple quality of life measures, and health status, further work is required to determine which specific groups of patients are most likely to benefit, how much benefit can be obtained, and at what cost.

The biggest drawback of nasal CPAP is the adherence to nightly usage. Originally, physicians had to depend upon patient’s report regarding usage. However, with the advent of CPAP machines containing timers to measure hours of usage, it was found that the apparatus is used an average of 5 hours per night (86,87 and 88). Depending on the definition of compliance to therapy, 46% to 89% of the patients continue to use their nasal CPAP after obtaining it (89,90 and 91). A number of techniques have been used to try to improve adherence to CPAP. However, no one measure has been shown to consistently do so. Such efforts include the following: giving patients proper instruction and follow-up on the use of the apparatus (92,93), assuring mask fit and comfort is maximal (94), and humidification to decrease dryness (95). A new feature for many CPAP devices is expiratory pressure relief. Internal monitoring that senses when the patient switches from inhalation to exhalation allows a decrease in the CPAP level during exhalation without any substantial impact on the efficacy of CPAP. Studies have shown improved tolerance of CPAP and increased usage over the short term, but longer-term acceptance has not been proven in studies to date (96,97).