Decreased plasma levels of orexin-A in sleep apnea

Background: Orexin-A, also known as hypocretin, is a neuropeptide implicated in appetite and sleep regulation. Because the obstructive sleep apnea syndrome (OSAS) is characterized by obesity and excessive daytime sleepiness, we hypothesized that orexin-A levels may be abnormal in patients with OSAS. Further, since treatment with continuous positive airway pressure ( CPAP) in patients with OSAS is very effective in normalizing daytime sleepiness, we also hypothesized that the chronic use of CPAP may influence plasma levels of orexin-A in these patients. Objective: To evaluate plasma levels of orexin-A in patients with OSAS and the effect of CPAP treatment. Patients and Methods: We compared the plasma levels of orexin-A in 13 healthy controls, 27 untreated patients with OSAS and 14 patients treated with CPAP during at least 1 year (4.5 +/- 0.5 h/night; mean +/- SEM). All patients had severe OSAS (apnea-hypopnea index, 57 +/- 4 h(-1)). Results: Orexin-A plasma levels were significantly lower in untreated (9.4 +/- 1.9 pg . ml(-1), p < 0.01) and treated patients with OSAS (4.2 +/- 1.5 pg center dot ml(-1), p < 0.001) than in healthy subjects (20.6 +/- 4.5 pg . ml(-1)). In untreated patients, orexin-A levels were not significantly related to daytime somnolence assessed by Epworth scale ( r = - 0.18, p = 0.37) or the body mass index ( r = - 0.13, p = 0.52). Conclusions: Orexin-A plasma levels are abnormally low in patients with OSAS, independently of the level of somnolence and/or presence of obesity. These results suggest that these low orexin-A levels may be related to the pathogenesis of OSAS. Copyright (C) 2004 S. Karger AG, Basel.