title: Comprehensive biomarker profiling in patients with obstructive sleep apnea.
abstract: OBJECTIVE
  The pathophysiological links between obstructive sleep apnea syndrome (OSAS) and cardiovascular mortality are incompletely understood. We aimed to contribute to a better characterization by using comprehensive biomarker profiling quantifying hemodynamic cardiac stress, cardiomyocyte injury, inflammation, endothelial function, matrix turnover and metabolism.
  
  
  METHODS
  In 65 patients with moderate or severe OSAS [apnea-hypopnea index (AHI) 39±20/h] and 33 patients with no or mild OSAS (AHI 8+4/h), B-type natriuretic peptide (BNP), N-terminal-pro-BNP (NT-proBNP), high-sensitivity cardiac troponin I (hs-cTnI), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and insulin were measured before and after sleep. In a subgroup measurements were repeated in a second night with continuous positive airway pressure (CPAP).
  
  
  RESULTS
  Patients with moderate/severe OSAS had higher insulin before sleep [median (interquartile range), 36.4 (21.9-52.1) vs. 20.8 (10.6-32.8)mU/mL; p=0.006], higher IL-6 after sleep [1.00 (0.73-1.58) vs. 0.72 (0.48-0.94)pg/mL; p=0.005], and larger relative overnight reduction in BNP [-9 (-35-0) vs. -3 (-21-13)%; p=0.04] than those with mild/no OSAS. Insulin before sleep was the only independent predictor of moderate/severe OSAS. Insulin before and IL-6 after sleep were independent predictors of severe OSAS, and when combined provided high diagnostic accuracy for severe OSAS (area under the receiver operator characteristic curve 0.80; 95%-confidence interval 0.69-0.91). In contrast, there were no significant differences in NT-proBNP, hs-cTnI, VEGF, and MMP-9 between moderate/severe and mild/no OSAS. Short-term CPAP had no impact on biomarker concentrations before and after sleep.
  
  
  CONCLUSIONS
  Significant OSAS is characterized by a distinct biomarker profile including high insulin before and high IL-6 after sleep.
authors.affiliation: Division of Cardiology, University Hospital Basel, Switzerland; Division of Cardiology, Kantonsspital St. Gallen, Switzerland. Electronic address: micha.maeder@kssg.ch.
authors.forename: Micha T
authors.initials: MT
authors.lastname: Maeder
authors.affiliation: Division of Respiratory Medicine, University Hospital Basel, Switzerland.
authors.forename: Werner
authors.initials: W
authors.lastname: Strobel
authors.affiliation: Division of Internal Medicine, University Hospital Basel, Switzerland; Department of Emergency and Critical Care Medicine, City Hospital Nuremberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Christ
authors.affiliation: Singulex, Inc., Alameda, CA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Todd
authors.affiliation: Singulex, Inc., Alameda, CA, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Estis
authors.affiliation: Division of Cardiology, University Hospital Basel, Switzerland; Division of Internal Medicine, University Hospital Basel, Switzerland.
authors.forename: Karin
authors.initials: K
authors.lastname: Wildi
authors.affiliation: Division of Cardiology, University Hospital Basel, Switzerland; Division of Internal Medicine, University Hospital Basel, Switzerland.
authors.forename: Gregor
authors.initials: G
authors.lastname: Thalmann
authors.affiliation: Division of Cardiology, University Hospital Basel, Switzerland; Division of Internal Medicine, University Hospital Basel, Switzerland.
authors.forename: Jonas
authors.initials: J
authors.lastname: Hilti
authors.affiliation: Division of Respiratory Medicine, University Hospital Basel, Switzerland; Division of Respiratory Medicine, Kantonsspital St. Gallen, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Brutsche
authors.affiliation: Division of Cardiology, University Hospital Basel, Switzerland; Division of Internal Medicine, University Hospital Basel, Switzerland.
authors.forename: Raphael
authors.initials: R
authors.lastname: Twerenbold
authors.affiliation: Division of Cardiology, Kantonsspital St. Gallen, Switzerland.
authors.forename: Hans
authors.initials: H
authors.lastname: Rickli
authors.affiliation: Division of Cardiology, University Hospital Basel, Switzerland; Division of Internal Medicine, University Hospital Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Mueller
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D017286:Polysomnography / Q000379:methods; D011446:Prospective Studies; D020181:Sleep Apnea, Obstructive / Q000097:blood* / Q000175:diagnosis*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D007328:Insulin; D015850:Interleukin-6; D042461:Vascular Endothelial Growth Factor A
keywords: Biomarkers; Diurnal changes; Multimarker; Obstructive sleep apnea syndrome