Decreased Plasma Levels of Orexin-A in Sleep Apnea

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Abstract
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. To evaluate plasma levels of orexin-A in patients with OSAS and the effect of CPAP treatment. 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)). 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.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). 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.