Hemostatic implications of endothelial cell apoptosis in obstructive sleep apnea
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. Sleep And Breathing
(Impact Factor: 2.48).
04/2008; 12(4):331-7. DOI: 10.1007/s11325-008-0182-x
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.
Available from: Effie J Pereira
- "Several studies have revealed elevated or upregulated individual components of the haemostatic system in patients with OSA, including enhanced platelet activation, increased plasma levels of tissue factor, von Willebrand factor (VWF) and fibrinogen levels (Akinnusi et al., 2009; Bokinsky et al., 1995; El Solh et al., 2008; Liak and Fitzpatrick, 2011; Robinson et al., 2004). However, little information is known about the value of thromboelastography (TEG) as a global haemostatic tool in OSA. "
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ABSTRACT: Obstructive sleep apnoea (OSA) is associated with increased cardiovascular morbidity and mortality and hypercoagulability may be an underlying factor. We tested the hypotheses that patients with severe OSA are hypercoagulable and that two weeks of continuous positive airway pressure (CPAP) treatment reduces this hypercoagulability. In a prospective crossover study, twelve patients were randomized to either CPAP or no-CPAP for two weeks, a one week washout period, and then the other testing period for two weeks. Thromboelastography was used to assess coagulability at the start and end of each period and the apnoea-hypopnea indices (AHI) were measured at the end of each period. At baseline, ten patients had, compared to reference values, shorter clotting times, six increased rate of clot formation, twelve increased clot strength, and ten increased clotting indices. CPAP significantly reduced AHI (p=0.0003), clot strength (p=0.019) and clotting index (p=0.014). Hypercoagulability in patients with OSA can be detected by thromboelastography, and is reduced by CPAP.
Available from: PubMed Central
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ABSTRACT: Endothelial activation and inflammation are important mediators of accelerated atherogenesis and consequent increased cardiovascular morbidity in obstructive sleep apnea (OSA). Repetitive episodes of hypoxia/reoxygenation associated with transient cessation of breathing during sleep in OSA resemble ischemia/reperfusion injury and may be the main culprit underlying endothelial dysfunction in OSA. Additional factors such as repetitive arousals resulting in sleep fragmentation and deprivation and individual genetic susceptibility to vascular manifestations of OSA contribute to impaired endothelial function in OSA. The present review focuses on possible mechanisms that underlie endothelial activation and inflammation in OSA.
Available from: erj.ersjournals.com
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ABSTRACT: Obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is a highly prevalent breathing disorder in sleep that is an independent risk factor for cardiovascular morbidity and mortality. A large body of evidence, including clinical studies and cell culture and animal models utilising intermittent hypoxia, delineates the central role of oxidative stress in OSAHS as well as in conditions and comorbidities that aggregate with it. Intermittent hypoxia, the hallmark of OSAHS, is implicated in promoting the formation of reactive oxygen species (ROS) and inducing oxidative stress. The ramifications of increased ROS formation are pivotal. ROS can damage biomolecules, alter cellular functions and function as signalling molecules in physiological as well as in pathophysiological conditions. Consequently, they promote inflammation, endothelial dysfunction and cardiovascular morbidity. Oxidative stress is also a crucial component in obesity, sympathetic activation and metabolic disorders such as hypertension, dyslipidaemia and type 2 diabetes/insulin resistance, which aggregate with OSAHS. These conditions and comorbidities could result directly from the oxidative stress that is characteristic of OSAHS or could develop independently. Hence, oxidative stress represents the common underlying link in OSAHS and the conditions and comorbidities that aggregate with it.
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