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

- Hypertension is one of the most common complications of obstructive sleep apnea (OSA). However, approximately, one-third of patients with OSA do not have hypertension despite similar exposure to apneas, hypopneas, and intermittent hypoxia. The mechanism (s) of susceptibility or resilience to the development of hypertension in this population is unknown.
- Several studies demonstrate, that elevated serum Chitinase-3-like protein-1 (also known as YKL-40) levels are independently associated with the presence and extent of coronary artery disease and with all-cause as well as cardiovascular mortality.
- YKL-40 is a glycoprotein that is produced by macrophages, vascular smooth muscle cells and endothelial cells.
- We describe here over expression of YKL- 40 in patients with OSA and hypertension but not in those with hypertension or OSA alone. YKL-40 correlated inversely with endothelial function. Endothelial dysfunction is a pre-requisite for development of hypertension and atherosclerotic heart disease.
- YKL-40 has a potential for being a biomarker for endothelial dysfunction and hypertension in OSA.

BackgroundObstructive 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.MethodsAll 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.ResultsWe 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.ConclusionsElevated 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.