title: Objective, but Not Subjective, Sleepiness is Associated With Inflammation in Sleep Apnea.
abstract: Objective and subjective measures of excessive daytime sleepiness (EDS) are only weakly associated. No study, however, has examined whether these two measures of EDS differ in terms of underlying mechanisms and prognostic value. Pro-inflammatory cytokines, that is, interleukin-6 (IL-6) appear to promote sleepiness/fatigue, while the stress hormone cortisol promotes vigilance. We hypothesized that objective sleepiness is associated with increased levels of IL-6 and decreased levels of cortisol.
  
  
  
  We studied 58 obstructive sleep apnea (OSA) patients with clinical EDS and/or cardiovascular comorbidities who underwent 8-hour in-lab polysomnography for four consecutive nights. Objective and subjective daytime sleepiness were measured by Multiple Sleep Latency Test (MSLT), Epworth Sleepiness Scale (ESS), and Stanford Sleepiness Scale (SSS), respectively. Twenty-four-hour profiles of IL-6 and cortisol levels were assessed on the fourth day.
  
  
  
  The agreement between objective and subjective EDS in OSA patients was fair (kappa = 0.22). Objective EDS (lower MSLT) in OSA patients was associated with significantly elevated 24-hour (β = -0.34, p = .01), daytime (β = -0.30, p = .02) and nighttime (β = -0.38, p < .01) IL-6 levels, and significantly decreased daytime (β = 0.35, p = .01) cortisol levels. In contrast, subjective EDS (higher ESS/SSS) was not associated with either elevated IL-6 levels or decreased cortisol levels.
  
  
  
  Our findings suggest that OSA with objective EDS is the more severe phenotype of the disorder associated with low-grade inflammation, a link to cardiometabolic morbidity and mortality. Compared to subjective EDS, objective EDS is a stronger predictor of OSA severity and may be useful in the clinical management of the disorder.
authors.affiliation: Department of Psychiatry, Sleep Research and Treatment Center, Pennsylvania State University College of Medicine, Hershey, PA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Psychiatry, Sleep Research and Treatment Center, Pennsylvania State University College of Medicine, Hershey, PA.
authors.forename: Alexandros N
authors.initials: AN
authors.lastname: Vgontzas
authors.affiliation: Department of Psychiatry, Sleep Research and Treatment Center, Pennsylvania State University College of Medicine, Hershey, PA.
authors.forename: Julio
authors.initials: J
authors.lastname: Fernandez-Mendoza
authors.affiliation: Department of Psychiatry, Sleep Research and Treatment Center, Pennsylvania State University College of Medicine, Hershey, PA.
authors.forename: Ilia
authors.initials: I
authors.lastname: Kritikou
authors.affiliation: Department of Psychiatry, Sleep Research and Treatment Center, Pennsylvania State University College of Medicine, Hershey, PA.
authors.forename: Maria
authors.initials: M
authors.lastname: Basta
authors.affiliation: Department of Psychiatry, Sleep Research and Treatment Center, Pennsylvania State University College of Medicine, Hershey, PA.
authors.forename: Slobodanka
authors.initials: S
authors.lastname: Pejovic
authors.affiliation: Department of Psychiatry, Sleep Research and Treatment Center, Pennsylvania State University College of Medicine, Hershey, PA.
authors.forename: Jordan
authors.initials: J
authors.lastname: Gaines
authors.affiliation: Department of Psychiatry, Sleep Research and Treatment Center, Pennsylvania State University College of Medicine, Hershey, PA.
authors.forename: Edward O
authors.initials: EO
authors.lastname: Bixler
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D006970:Disorders of Excessive Somnolence / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007249:Inflammation / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D020181:Sleep Apnea, Obstructive / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology*
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D006854:Hydrocortisone
keywords: cortisol.; excessive daytime sleepiness; interleukin-6; objective daytime sleepiness; sleep apnea