Chitinase-3-like protein-1 (YKL-40) as a marker of endothelial dysfunction in obstructive sleep apnea

Sleep Med. 2016 Sep:25:87-92. doi: 10.1016/j.sleep.2016.08.001. Epub 2016 Aug 11.


Background: Obstructive sleep apnea (OSA) is a highly prevalent disorder affecting 15-24% of adults and triples the risk for hypertension independent of other risk factors. The exact mechanisms of endothelial dysfunction and variable susceptibility to hypertension in OSA are not entirely clear. No biomarker to date has been found to be associated with hypertension in OSA. Chitinase-3-like protein-1(YKL-40) is a circulating moiety with roles in injury, repair and angiogenesis that is dysregulated in atherosclerosis and correlates with increased cardiovascular morbidity and mortality. We sought to determine the role of YKL-40, as a biomarker, for endothelial dysfunction and hypertension in OSA.

Methods: All subjects underwent polysomnography for suspected sleep-disordered breathing. Endothelial-dependent vasodilatory capacity was assessed using flow-mediated vasodilation (FMD). YKL-40 was measured in plasma using ELISA methodology.

Results: We studied 95 subjects in four groups according to OSA and hypertension status. FMD was markedly impaired in hypertensive OSA (8.0% ± 0.5 vasodilation) compared to normotensive OSA (13.5% ± 0.5, P <0.0001) and non-OSA with hypertension (10.5% ± 0.8, P <0.01) and without hypertension (16.1% ± 1.0, P <0.0001). YKL-40 was significantly elevated only in hypertensive OSA compared to other three groups and had a negative correlation with FMD (r=-0.37, P = 0.0008). Receiver operating characteristic (ROC) curve analysis for YKL-40 in predicting endothelial dysfunction had a sensitivity of 71% and a specificity of 64% with AUC = 0.68, 0.57 to 0.80, P = 0.004.

Conclusions: Elevated circulating levels of YKL-40 are observed in only hypertensive OSA and have a significant negative correlation with endothelial function. This specificity suggests YKL-40 could be a potential biomarker for endothelial dysfunction in OSA.

Keywords: Chitinase-3-like protein-1; Endothelial dysfunction; Hypertension; Obstructive sleep apnea; YKL-40.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Biomarkers / blood
  • Chitinase-3-Like Protein 1 / blood
  • Chitinase-3-Like Protein 1 / metabolism*
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / pathology
  • Female
  • Humans
  • Hypertension / complications*
  • Hypertension / metabolism
  • Hypertension / pathology
  • Male
  • Middle Aged
  • Nitric Oxide / metabolism
  • Polysomnography / methods
  • Risk Factors
  • Sleep Apnea, Obstructive / complications
  • Sleep Apnea, Obstructive / epidemiology
  • Sleep Apnea, Obstructive / metabolism*
  • Sleep Apnea, Obstructive / pathology
  • Vasodilation


  • Biomarkers
  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1
  • Nitric Oxide