REM-related obstructive sleep apnea: to treat or not to treat?

T term REM-related obstructive sleep apnea (OSA) is used loosely by sleep clinicians when the polysomnogram (PSG) reveals obstructive apneas and hypopneas that occur predominantly or exclusively during REM sleep. In addition to being poorly characterized, various set of criteria have been used to describe REM-related OSA.1 It is therefore not surprising that the reported prevalence of REM-related OSA is quite variable, ranging from as little as 10% to as much as 36% of the patient population with OSA undergoing PSG.1-5 Despite the wide variation in prevalence, studies have consistently shown that REM-related OSA occurs more commonly in younger individuals, women, children, and in patients with mild or moderate OSA.1-6 More importantly, the clinical signifi cance of REM-related OSA remains controversial.7 Although a few studies have reported a link between obstructive respiratory events during REM sleep and hypersomnolence,2,8 several large cross-sectional clinic-based and prospective epidemiologic studies have suggested that only obstructive events during NREM sleep are associated with excessive daytime sleepiness (EDS). 9-12 The Sleep Heart Health Study investigators reported that in a large community-based sample of middle-aged and older adults, REMAHI was not independently associated with daytime sleepiness or quality of life after adjusting for NREMAHI. 11 These fi ndings were also confi rmed in a large clinical cohort.12 Patients with REM-related OSA tend to have an overall low AHI by virtue of the disproportionately lower percent of REM sleep as a function of total sleep duration. However, it remains unknown whether obstructive respiratory events that are isolated to REM sleep have a differential neurocognitive and cardiometabolic impact compared to events that occur in NREM sleep. It is now well established that compared to NREM sleep, REM sleep is associated with greater sympathetic activity and cardiovascular instability in healthy human subjects and patients with OSA.13,14 The hemodynamic and sympathetic changes during REM sleep cause a surge in the blood pressure and heart rate. These acute hemodynamic changes could play a part in triggering ischemic events in patients with cardiovascular disease.14-17 Indeed, obstructive apneas and hypopneas during REM sleep lead to greater degrees of hypoxemia18,19 and higher levels of sympathetic activity compared to events in NREM sleep.13 While numerous studies have established a robust association between OSA and adverse neurocognitive and cardiometabolic outcomes, there is a major gap of knowledge on the risks associated with untreated REM-related OSA. To date it remains a clinical conundrum whether asymptomatic or minimally symptomatic patients with REM-related OSA—who typically have an overall low severity of disease as measured by the AHI—should be treated and whether they would derive any benefi t from CPAP therapy. Given the paucity of clinical research in REM-related OSA, the study by Su and colleagues in this issue of the Journal is an important and timely contribution to the fi eld and may help shed some light to the uncertainty faced by clinicians. In a retrospective observational study the authors evaluated a cohort of patients with REM-related OSA and compared them to nonstage specifi c OSA. They found that symptomatic patients with REM predominant—but not REM exclusive—OSA benefi ted equally from CPAP therapy compared to patients with nonstage specifi c OSA as it relates to sleepiness, fatigue, and quality of life. The authors measured relevant outcomes with several validated questionnaires. Moreover, an attempt was made to obtain objective CPAP adherence in a large proportion of patients. The authors are to be commended for providing the fi rst line of evidence that symptomatic patients with REM-related OSA can achieve similar degree of improvement in functional outcomes with CPAP therapy compared to patients with nonstage specifi c OSA. Notwithstanding the strengths and novelty of the study, there are several limitations that are noteworthy. The defi nition used for classifying REM-related OSA was fairly permissive with regards to the NREMAHI (NREMAHI < 15 events per hour). 1,7