LAUSR

Obstructive Sleep Apnea (OSA) is a widespread and heterogeneous sleep disorder. Studies have identified reproducible subtypes of OSA based on patient-reported symptoms that have different cardiovascular outcomes. Prior data showed similar apnea-hypopnea index (AHI) across subtypes; however, other physiological characteristics have not been comprehensively compared among these subtypes. 1,285 participants from the Sleep Apnea Global Interdisciplinary Consortium (SAGIC) with moderate-severe OSA (AHI≥15) were included. Differences in traditional and novel physiological traits were compared among the Disturbed Sleep (n=183 [14.2%]), Minimally Symptomatic (n=581 [45.2%]), and Excessively Sleepy (n=521 [40.5%]) subtypes using analysis of covariance (ANCOVA) adjusted for age, sex, BMI and race/ethnicity. Measures included AHI and other respiratory event indices, hypoxic burden, oxygen characteristics, sleep/wake amounts, electroencephalogram (EEG) spectral characteristics, including metrics related to the odds ratio product (ORP; a validated index of sleep depth ranging from 0.0 [deep sleep] to 2.5 [full wakefulness]), arousal intensity, and heart rate response to arousal. Compared to other subtypes, the Disturbed Sleep subtype demonstrated increased wakefulness (more wake time [p< 0.001] and wake after sleep onset [p=0.001]), higher beta frequency EEG power (14.33-20.0 Hz [p=0.025] and 20.33-35.0 Hz [p=0.004]), and less deep sleep (higher average [p=0.001] and NREM-specific [p=0.044] ORP, less time with ORP from 0.50-0.75 [p=0.004] and 0.75-1.00 [p=0.015], and more time from 2.20-2.25 [p=0.017] and 2.25-2.50 [p=0.0005]). The Excessively Sleepy subtype had more severe hypoxemia, including greater hypoxic burden (p=0.002) and lower average SpO2 (p=0.002) and minimum SpO2 (p=0.0002) compared to other subtypes. Differences in physiological characteristics, including ORP-related traits, were observed among symptom subtypes. Results suggest that characteristics indicative of increased wakefulness may distinguish those with the Disturbed Sleep subtype, whereas more severe hypoxemia may characterize the Excessively Sleepy subtype. Future investigations into underlying molecular causes of symptom subtypes, particularly the Excessively Sleepy, are warranted given evidence of associations with outcomes such as cardiovascular disease. SAGIC Investigators (Ayas N, Chen NH, Cistulli P, de Chazal P, Gislason TG, Han F, Hirsch-Allen AJ, Keenan BT, Li QY, Magalang UJ, Maislin G, Mazzotti DR, McArdle N, Mindel J, Pack AI, Penzel T, Schwab RJ, Singh B, Sutherland K); NIH P01 HL094307