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Hemostatic implications of endothelial cell apoptosis in obstructive sleep apnea
Authors:Ali A El Solh  Morohunfolu E Akinnusi  Ilya G Berim  A Misha Peter  Linda L Paasch  Kristie R Szarpa
Institution:(1) Western New York Respiratory Research Center, Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY, USA;(2) Division of Pulmonary, Critical Care, and Sleep Medicine, Erie County Medical Center, 462 Grider Street, Buffalo, NY 14215, USA
Abstract:Patients with obstructive sleep apnea (OSA) are at increased risk of atherothrombosis independent of the Framingham risk factors. Studies on hemostasis factors in OSA are scarce and inconsistent. We sought to understand the variation in atherothrombotic propensity as a function of apoptotic circulating endothelial cells (CECs) in OSA by investigating the relationship between CEC apoptosis and plasma levels of hemostatic factors tissue factor (TF) and von Willebrand Factor (vWF) in apneic subjects. Apoptotic CECs were detected by flow cytometry in 35 male subjects free of cardiovascular diseases (AHI range 8–43) and 12 healthy male controls (AHI range 2–5) before and after 8 weeks of nasal continuous positive airway pressure (nCPAP). Quantitative determination of TF and vWF was performed using an enzyme-linked immunosorbent assay (ELISA) kit. The mean levels of TF (66.78 ± 41.59 pg/ml) and vWF (189.70 ± 69.24 IU/dl) were significantly higher in OSA patients compared with those in healthy subjects (42.83 ± 14.18 pg/ml; and 124.48 ± 31.43 IU/dl). Apoptotic CECs were elevated in patients with OSA and correlated strongly with TF and vWF levels (p = 0.02 and p < 0.001; respectively). There were no correlations between TF, vWF and apnea hypopnea index, or arousal index. Only the percentage of time spent <90% oxygen saturation was inversely associated with TF (r = 0.38; p = 0.02). Following nCPAP therapy, there was significant decrease in TF levels that correlated with decrease in apoptotic CECs. In patients with OSA, increased prothrombotic factors are strongly determined by apoptotic CECs. Treatment with nCPAP may alleviate the coagulation propensity.
Keywords:Tissue factor  von Willebrand factor  Apoptosis  Endothelium  Sleep apnea
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