thromboplastin and Sleep-Apnea--Obstructive

Topics: Aged; Capsules; Corn Oil; Dietary Supplements; Docosahexaenoic Acids; Double-Blind Method; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Female; Healthy Volunteers; Humans; Male; Middle Aged; Sleep Apnea, Obstructive; Sleep Quality; Thromboplastin

Obstructive sleep apnea (OSA) has been associated with an increased risk of atherothrombotic events. A prothrombotic state might partially explain this link. This study investigated OSA patients' day/night rhythm of several prothrombotic markers and their potential changes with therapeutic continuous positive airway pressure (CPAP).. The study included 51 OSA patients [apnea hypopnea index (AHI) ⩾10] and 24 non-OSA controls (AHI<10). Of the 51 OSA patients, 25 were randomized to CPAP and 26 to placebo-CPAP. Twelve blood samples were collected over a 24h period to measure prothrombotic markers. For the apneic patients these samples were collected before treatment and after 3weeks of treatment with either CPAP or placebo-CPAP. Day/night variation in prothrombotic markers was examined using a cosinor analysis.. Compared with controls, OSA patients showed lower mesor (mean) and amplitude (difference between maximum and minimum activity) of D-dimer. In unadjusted (but not in adjusted) analysis, patients showed higher mesor of plasminogen activator inhibitor-1 (p<0.05 in all cases). No significant group differences were seen in mesor and amplitude for either soluble tissue factor or von Willebrand factor, or the acrophase (time of the peak) and periodic pattern for any prothrombotic markers. There were no significant differences in changes of periodic pattern and in day/night rhythm parameters of prothrombotic markers pre- to post-treatment between the CPAP and placebo condition.. There may be altered day/night rhythm of some prothrombotic markers in OSA patients compared with controls. CPAP treatment for 3weeks did not affect day/night rhythm of prothrombotic markers in OSA patients differently from placebo-CPAP.

Topics: Biomarkers; Case-Control Studies; Circadian Rhythm; Continuous Positive Airway Pressure; Female; Fibrin Fibrinogen Degradation Products; Humans; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Sleep Apnea, Obstructive; Thromboplastin; Thrombosis; von Willebrand Factor

A prothrombotic state may contribute to the elevated cardiovascular risk in patients with obstructive sleep apnea (OSA). We investigated the relationship between apnea severity and hemostasis factors and effect of continuous positive airway pressure (CPAP) treatment on hemostatic activity. We performed full overnight polysomnography in 44 OSA patients (mean age 47+/-10 years), yielding apnea-hypopnea index (AHI) and mean nighttime oxyhemoglobin saturation (SpO2) as indices of apnea severity. For treatment, subjects were double-blind randomized to 2 weeks of either therapeutic CPAP (n = 18), 3 l/min supplemental nocturnal oxygen (n = 16) or placebo-CPAP (<1 cm H2O) (n = 10). Levels of von Willebrand factor antigen (VWF:Ag), soluble tissue factor (sTF), D-dimer, and plasminogen activator inhibitor (PAI)-1 antigen were measured in plasma pre- and posttreatment. Before treatment, PAI-1 was significantly correlated with AHI (r = 0.47, p = 0.001) and mean nighttime SpO2 (r = -0.32, p = 0.035), but these OSA measures were not significantly related with VWF:Ag, sTF, and D-dimer. AHI was a significant predictor of PAI-1 (R2 = 0.219, standardized beta = 0.47, p = 0.001), independent of mean nighttime SpO2, body mass index (BMI), and age. A weak time-by-treatment interaction for PAI-1 was observed (p = 0.041), even after adjusting for age, BMI, pre-treatment AHI, and mean SpO2 (p = 0.046). Post hoc analyses suggested that only CPAP treatment was associated with a decrease in PAI-1 (p = 0.039); there were no changes in VWF:Ag, sTF, and D-dimer associated with treatment with placebo-CPAP or with nocturnal oxygen. Apnea severity may be associated with impairment in the fibrinolytic capacity. To the extent that our sample size was limited, the observation that CPAP treatment led to a decrease in PAI-1 in OSA must be regarded as tentative.

Topics: Adult; Antigens; Continuous Positive Airway Pressure; Double-Blind Method; Female; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Humans; Male; Middle Aged; Oxyhemoglobins; Plasminogen Activator Inhibitor 1; Polysomnography; Reference Values; Sleep Apnea, Obstructive; Statistics as Topic; Thrombophilia; Thromboplastin; Treatment Outcome; von Willebrand Factor

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.

Topics: Adult; Apoptosis; Atherosclerosis; Continuous Positive Airway Pressure; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Hemostasis; Humans; Male; Oxygen; Polysomnography; Reference Values; Risk Factors; Sleep Apnea, Obstructive; Thrombophilia; Thromboplastin; Thrombosis; von Willebrand Factor

Subjective sleep disturbances have been associated with increased risk of coronary artery disease (CAD). We hypothesized that disrupted sleep as verified by polysomnography is associated with increased levels of prothrombotic hemostasis factors previously shown to predict CAD risk.. Full-night polysomnography was performed in 135 unmedicated men and women (mean age +/- SD, 36.8 +/- 7.8 years) without a history of sleep disorders. Morning fasting plasma levels of von Willebrand Factor (VWF) antigen, soluble tissue factor (sTF) antigen, d-dimer, and plasminogen activator inhibitor (PAI)-1 antigen were determined. Statistical analyses were adjusted for age, gender, ethnicity, body mass index, BP, and smoking history.. Higher total arousal index (ArI) was associated with higher levels of VWF (beta = 0.25, p = 0.011, DeltaR(2) = 0.045), and longer wake after sleep onset was associated with higher levels of sTF (beta = 0.23, p = 0.023, DeltaR(2) = 0.038). More nighttime spent at mean oxygen saturation < 90% (beta = 0.20, p = 0.020, DeltaR(2) = 0.029) and higher apnea-hypopnea index (AHI) [beta = 0.19, p = 0.034, DeltaR(2) = 0.024] were associated with higher PAI-1. There was a trend for a relationship between mean oxygen desaturation < 90% and PAI-1 (p = 0.053), even after controlling for AHI. Total ArI (beta = 0.28, p = 0.005, DeltaR(2) = 0.056) and WASO (beta = 0.25, p = 0.017, DeltaR(2) = 0.042) continued to predict VWF and sTF, respectively, even after controlling for AHI.. Polysomnographically verified sleep disruptions were associated with prothrombotic changes. Measures of sleep fragmentation and sleep efficiency were related to VWF and sTF, respectively. Apnea-related measures were related to PAI-1. Our findings suggest that sleep disruptions, even in a relatively healthy population, are associated with potential markers of prothrombotic cardiovascular risk.

Topics: Adult; Antigens; Arousal; Coronary Thrombosis; Female; Fibrin Fibrinogen Degradation Products; Humans; Male; Middle Aged; Oxygen; Plasminogen Activator Inhibitor 1; Polysomnography; Risk Factors; Sleep Apnea, Obstructive; Sleep Deprivation; Sleep Stages; Thrombophilia; Thromboplastin; von Willebrand Factor

Obstructive sleep apnoea hypopnoea syndrome (OSAHS) is associated with increased morbidity and mortality due to cardiovascular disease. In order to examine the association between OSAHS and cardiovascular disease, this study measured hypoxia-inducible and atherosclerosis-associated molecules in the peripheral blood.. In this study peripheral blood was obtained early in the morning from 60 consecutive male patients with OSAHS (AHI > or =10 events/h) and 30 male control subjects without OSAHS (AHI <5 events/h). Serum levels of heat shock protein-70 (Hsp-70), tissue factor (TF), monocyte chemotactic protein-1 (MCP-1), highly sensitive C-reactive protein (hs-CRP), hepatocyte growth factor and plasma vascular endothelial growth factor were measured and their relationship with severity and hypoxaemia in OSAHS examined.. Serum hs-CRP, TF, MCP-1 and Hsp-70 levels were significantly higher in OSAHS compared with control subjects. Categorization of the patients into mild (10 < or = AHI < 30 events/h), moderate (30 < or = AHI < 60 events/h) and severe (AHI > or = 60 events/h) OSAHS subgroups showed that serum levels of hs-CRP, TF and Hsp-70 increased with severity. The hs-CRP, TF, MCP-1 and Hsp-70 levels in the non-obese OSAHS group were also significantly higher than those in the control group whereas there was no difference in BMI between the two groups. Repetitive hypoxaemia significantly correlated with hs-CRP, TF and Hsp-70 levels and appeared to be a significant determinant for these molecules.. These findings suggest that CRP, TF and Hsp-70 may be upregulated by repetitive hypoxaemia in OSAHS and may be involved in the development of the atherogenic process in OSAHS.

Topics: Analysis of Variance; Atherosclerosis; C-Reactive Protein; Case-Control Studies; HSP70 Heat-Shock Proteins; Humans; Hypoxia; Intercellular Signaling Peptides and Proteins; Linear Models; Male; Middle Aged; Polysomnography; Risk Factors; Severity of Illness Index; Sleep Apnea, Obstructive; Thromboplastin