fibrin and Sleep-Apnea--Obstructive

Obstructive sleep apnoea (OSA) is associated with increased cardiovascular disease (CVD) risk. In the general population, CVD events peak at 9:00-10:00 AM, associated with diurnal changes in thrombotic potential. However in OSA, these CVD events occur frequently at night. Measuring thrombotic potential across the sleep-wake cycle may provide insight into the temporal association of OSA with CVD. This study aimed to determine diurnal changes in fibrin generation in OSA and whether treatment of OSA with continuous positive airway pressure (CPAP) alters fibrin generation across the sleep-wake cycle. In a randomised placebo-controlled crossover trial, patients with OSA were assigned to two months each of therapeutic CPAP and placebo. After each treatment period, fibrin generation was determined by overall haemostatic potential assay at seven time points over 24 hours (h). Twenty-eight patients (25 men, 3 women) with severe OSA (Apnoea Hypopnoea Index = 37.9 ± 23.9/h, Oxygen Desaturation Index 31.3 ± 22.4/h) completed the study. All parameters, except lag time to fibrin generation, showed significant diurnal changes, both on CPAP and placebo. Compared to 9:00 AM, fibrin generation parameters were significantly lower at midnight and 3:00 AM for overall coagulation potential (OCP), overall haemostasis potential (OHP), maximum optical density, and maximum slope (all p≤0.001). CPAP produced no change in fibrin generation parameters compared to placebo. In severe OSA patients, fibrin generation peaked at 6:00 AM and 9:00 AM rather than during the sleep period (midnight and 3:00 AM). These findings suggest a prothrombotic shift in the morning similar to individuals without OSA. There was no difference between CPAP and placebo on fibrin generation.

Topics: Adult; Arousal; Cardiovascular Diseases; Circadian Rhythm; Continuous Positive Airway Pressure; Cross-Over Studies; Female; Fibrin; Humans; Male; Middle Aged; Sleep; Sleep Apnea, Obstructive; Thrombosis

Topics: Cardiovascular Diseases; Fibrin; Humans; Hypertension; Risk Factors; Sleep Apnea, Obstructive; Thrombosis

We investigated plasma fibrin clot properties in high-risk hypertensive patients with obstructive sleep apnoea (OSA) and assessed the impact of continuous positive airway pressure (CPAP) treatment on clot phenotype.. We studied 50 hypertensive patients with clinically significant OSA (age 50.0 ± 8.8 years, 39 M, 11 F). In total, 38 hypertensive patients without OSA balanced for age, sex, blood pressure, cardiovascular risk factors, and metabolic status served as controls. Plasma fibrin clot properties, including clot permeability coefficient, clot lysis time (CLT), and turbidimetric parameters of clot formation were determined. Patients underwent transthoracic echocardiography, carotid ultrasonography, evaluation of endothelial function and calcium score index of coronary arteries, and Doppler imaging of renal arteries.. Compared with controls, OSA patients were characterized by more compact fibrin structure (lower median clot permeability coefficient, 6.00 vs. 7.25 10 cm; P < 0.001), impaired fibrinolysis (longer median CLT, 108.00 vs. 92.50 min; P < 0.001), and by faster clot formation (shorter median lag phase, 40.50 vs. 42.50 s; P = 0.041), and higher median maximum clot absorbency indicating denser fibrin networks (0.87 vs. 0.81; P = 0.028). Clot permeability coefficient and CLT correlated with apnoea-hypopnoea index (r = -0.46; P < 0.001 and r = 0.44; P < 0.001, respectively) as well with mean (r = 0.31; P = 0.003; r = -0.36; P = 0.001, respectively) and minimal oxygen saturation (r = 0.46; P < 0.001; r = -0.49; P < 0.001, respectively). After 3 months of CPAP treatment we observed an increase in clot permeability coefficient (5.95 vs. 7.60 10 cm; P = 0,001), shortened CLT (107.00 vs. 87.00; P = 0.006), a longer lag phase of fibrin formation (40.00 vs. 43.50 s; P = 0.013), and a trend toward lower maximum clot absorbency (0.86 vs. 0.81; P = 0.058).. In hypertensive patients at high cardiovascular risk, OSA was associated with unfavourable prothrombotic fibrin clot characteristics, including hypofibrinolysis, which significantly improve as early as after 3 months of CPAP treatment.

Topics: Adult; Aged; Carotid Arteries; Continuous Positive Airway Pressure; Echocardiography; Female; Fibrin; Fibrin Clot Lysis Time; Fibrinolysis; Humans; Hypertension; Male; Middle Aged; Oxygen; Permeability; Renal Artery; Severity of Illness Index; Sleep Apnea, Obstructive; Thrombosis; Ultrasonography, Doppler

Obstructive sleep apnea syndrome (OSAS) has been associated with high cardiovascular morbidity and mortality, and patients suffer from repeated episodes of hypoxia. Platelet-derived microparticles (PDMPs) are released via platelet activation by various agonists, including inflammatory cytokines or high shear stress. Plasminogen activator inhibitor -1 (PAI-1) is a fibrinolytic marker and soluble fibrin (SF) is a coagulation activation marker. We examined plasma levels of PDMPs, PAI-1 and SF in patients with OSAS. We also examined the effects of continuous positive airway pressure (CPAP) on plasma levels of PDMPs.. Full polysomnography (PSG) monitoring was performed on 27 patients. The apneahypopnea index (AHI) of 5 events/h or less than 30 events/h indicated mild to moderate OSAS, and an AHI of 30 events/h or more indicated severe OSAS. Plasma levels of PDMPs were measured using an ELISA kit, and PAI and SF were determined by a latex immunoassay. In addition, the effects of CPAP treatment were studied in 7 patients.. The plasma level of PDMPs was significantly higher in patients with severe OSAS (15.8±10.4 U/mL) than normal controls (10.8±7.1 U/mL, p < 0.05) and patients with mild to moderate OSAS (9.2±3.5 U/mL, p < 0.05). The plasma levels of PDMPs correlated with the AHI (r = 0.39, p < 0.05). In addition, CPAP treatment decreased the plasma level of PDMPs (11.9±5.6 U/mL to 6.7±3.2 U/mL, p < 0.05).. Patients with OSAS might be at increased cardiovascular risk due to elevated PDMPs. Moreover a decrease in the plasma level of PDMPs by treatment with CPAP might reduce cardiovascular risk.

Topics: Blood Platelets; Case-Control Studies; Cell-Derived Microparticles; Female; Fibrin; Humans; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Platelet Activation; Polysomnography; Prognosis; Sleep Apnea, Obstructive