Endocan, Obstructive Sleep Apnea, and Vascular Risk

Abstract

Obstructive sleep apnea (OSA) is characterized by interruptions of breathing during sleep caused by partial or complete obstruction of the upper airways. Obstructive sleep apnea is associated with an increased risk of cardiovascular disease (CVD). The mechanisms involved may include several, interrelated, but not completely defined mechanisms, for example, dyslipidemia, inflammation, insulin resistance, and oxidative stress. In addition, animal models suggest that OSA can exert proatherogenic effects (eg, inflammation, oxidative stress, vascular smooth cell activation, adhesion molecule expression, monocyte/lymphocyte activation, increased lipid loading of macrophages, lipid peroxidation, and endothelial dysfunction). Platelets may also be activated, and this effect correlated with some indicators of breathing function during sleep. Continuous positive airway pressure (CPAP) is an effective treatment for OSA. Apart from behavioral treatment (eg, weight loss and increased physical activity), CPAP is the most common treatment for moderate to severe OSA. Treating OSA with CPAP improves symptoms and quality of life and may decrease cardiovascular morbidity. Continuous positive airway pressure therapy could improve cardiovascular outcomes by reducing oxidative stress and preventing endothelial damage. In this issue of Angiology, Altintas et al measured serum endocan levels in patients with OSA and healthy controls and after 3 months of CPAP treatment in those with OSA. Endocan levels were significantly higher in the patients with OSA. After 3 months of CPAP treatment, endocan levels decreased significantly. In multivariate logistic regression analysis, endocan was an independent and significant indicator of OSA and its severity. Inflammatory markers and responses from vascular endothelial cells play a role in the initiation and progression of atheroma and plaque instability. Endothelial dysfunction is considered as the initial lesion in the development of atherosclerosis. Endocan has been shown to increase the production of proinflammatory cytokines by endothelial cells, enhance microvascular permeability, and modulate leukocyte migration. Endocan can be detected in the blood and is a marker of angiogenesis and endothelial cell activation in response to proangiogenic signals. Endocan participates in molecular interactions with several mediators that are essential for the regulation of biological processes such as cell adhesion, migration, proliferation, and neovascularization. Endocan may contribute to organ-specific inflammation and endothelium-dependent pathological disorders and may represent a novel endothelial cell dysfunction marker. In a recent study, we reported that serum endocan levels were significantly higher in a hypertension (HT) group compared to the controls. This may be relevant since there is an association between OSA and HT. Serum endocan levels positively correlated with carotid intima–media thickness and highsensitivity C-reactive protein levels. Wang et al concluded that serum endocan levels were independently correlated with the presence and severity of coronary artery disease (CAD) in patients with HT. Kose et al reported a significant increase in serum endocan levels in patients with acute coronary syndrome (ACS) compared with controls, but the CAD burden in patients with ACS was not correlated with serum endocan levels. Kose et al also reported that endocan levels were significantly higher in diabetic patients with ACS than in nondiabetic patients with ACS. This finding may reflect greater severity of vessel involvement in diabetic patients. Endothelial dysfunction or activation may significantly contribute to the increased risk of CVD in patients with chronic kidney disease (CKD). Yilmaz et al concluded that endocan levels are inversely correlated with renal function and that they influenced all-cause mortality and CVD events in a CKD population independent of other risk factors. As for OSA, there is also evidence of endothelial dysfunction in Behcet disease. These patients have significantly higher serum levels of endocan, especially if systemic involvement is present. Patients with psoriasis also had significantly higher serum levels of endocan, and these levels correlated with CVD risk and disease activity. Obstructive sleep apnea may be more common in patients with psoriasis; in turn, psoriasis may be associated with increased risk of CVD. Finally, medication may affect endocan levels. For example, endocan levels are significantly decreased after antihypertensive therapy with valsartan and amlodipine. It follows that medication should be considered if endocan is assessed. In conclusion, since endocan release probably reflects vascular damage and risk factors, its measurement may provide