Circulating cardiovascular risk factors in obstructive sleep apnoea: data from randomised controlled trials Selective Activation of Inflammatory Pathways by Intermittent Hypoxia in Obstructive Sleep Apnea Syndrome Improvement of factor VII clotting activity following long-term NCPAP treatment in obstructive sleep apnoea syndrome. The Impact of CPAP on Cardiovascular Biomarkers in Minimally Symptomatic Patients with Obstructive Sleep Apnea: A Pilot Feasibility Randomized Crossover Trial High plasminogen activator inhibitor and tissue plasminogen activator levels in plasma precede a first acute myocardial infarction in both men and women: evidence for the fibrinolytic system as an independent primary risk factor. Increased prevalence of sleep apnea in patients with recurring ischemic stroke compared with first stroke victims Platelet activation, epinephrine, and blood pressure in obstructive sleep apnea syndrome Hematocrit levels in sleep apnea. Association between sleep apnea severity and blood coagulability: treatment effects of nasal continuous positive airway pressure Activated factor 12 (FXIIa) predicts recurrent coronary events after an acute myocardial infarction. Coagulation factor VII and the risk of coronary heart disease in healthy men. Effect of continuous positive airway pressure treatment on serum cardiovascular risk factors in patients with obstructive sleep apnea-hypopnea syndrome. Snoring and the risk of obstructive sleep apnea in patients with pulmonary embolism. An association between oxygen desaturation and D-dimer in patients with obstructive sleep apnea syndrome. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group.
Background : Obstructive sleep apnoea ( OSA ) is associated with high cardiovascular morbidity and mortality and is an independent risk factor for hypertension . Novel circulating cardiovascular risk markers enabling a more accurate prediction of cardiovascular risk have been identified . Examination of these markers may clarify the increased risk in OSA and contribute to an analysis of the benefits of treatment . Methods : Plasma levels of total cholesterol and triglyceride and activated coagulation factors XIIa and VIIa , factors VII , VIII , XII , fibrinogen , thrombin-antithrombin ( TAT ) , von Willebr and factor antigen ( vWFAg ) , soluble P-selectin ( sP-sel ) , and homocysteine  were measured before and after treatment for 1 month with therapeutic or subtherapeutic ( control ) continuous positive airways pressure ( CPAP ) in 220 patients with OSA . Results : Levels of activated coagulation factors XIIa , VIIa , TAT and sP-sel were higher in OSA patients at baseline than in unmatched controls , but did not fall with 1 month of therapeutic CPAP treatment . The raised sP-sel levels correlated only with body mass index ( p = 0.002 ) . There was a trend towards a significant fall in total cholesterol with therapeutic CPAP ( p = 0.06 ) compared with the control group . In the therapeutic group there was a clinical ly significant mean fall in total cholesterol of 0.28 mmol/l ( 95 % confidence interval 0.11 to 0.45 , p = 0.001 ) which may reduce cardiovascular risk by about 15 % . Conclusion : A number of activated coagulation factors are increased in untreated OSA patients , potentially contributing to vascular risk , but they do not fall with 1 month of CPAP treatment . Nasal CPAP may produce a clinical ly relevant fall in total cholesterol level , potentially reducing cardiovascular risk , but this needs to be verified in a larger prospect i ve study Background — Obstructive sleep apnea syndrome ( OSAS ) , characterized by intermittent hypoxia/reoxygenation ( IHR ) , is an independent risk factor for cardiovascular disease . We investigated the underlying molecular mechanisms of this association in a translational study . Methods and Results — In a novel in vitro model of IHR , we used HeLa cells transfected with reporter constructs and DNA binding assays for the master transcriptional regulators of the inflammatory and adaptive pathways ( NF&kgr;B and HIF-1 , respectively ) to investigate underlying transcriptional events initiated by repeated cell exposure to IHR . Furthermore , we prospect ively studied 19 male OSAS patients ( median apnea-hypopnea frequency , 48.5 episodes per hour ; interquartile range [ IQR ] , 28.5 to 72.9 ) and 17 matched normal control subjects . Circulating levels of the proinflammatory cytokine tumor necrosis factor-&agr ; and the adaptive factor erythropoietin were assayed in all subjects at baseline and again after 6 weeks of continuous positive airway pressure therapy in patients . Full blood count was measured as part of a detailed baseline evaluation . HeLa cells exposed to IHR demonstrated selective activation of the proinflammatory transcription factor NF&kgr;B ( P<0.001 by ANOVA ) , whereas the adaptive regulator HIF-1 was not activated , as demonstrated by luciferase reporter assays and DNA binding studies . Circulating tumor necrosis factor-&agr ; levels were higher in OSAS patients ( 2.56 pg/mL ; IQR , 2.01 to 3.42 pg/mL ) than in control subjects ( 1.25 pg/mL ; IQR , 0.94 to 1.87 ; P<0.001 ) but normalized with continuous positive airway pressure therapy ( 1.24 pg/mL ; IQR , 0.78 to 2.35 pg/mL ; P=0.002 ) . In contrast , erythropoietin levels were similar throughout . Furthermore , circulating neutrophil levels were higher in OSAS patients than in control subjects , whereas the hematocrit was unaltered . Conclusions — These data demonstrate selective activation of inflammatory over adaptive pathways in IHR and OSAS , which may be an important molecular mechanism of cardiovascular disease Obstructive sleep apnoea syndrome ( OSAS ) is a very common disorder . Patients with OSAS are at an increased risk for cardiovascular events . It has also been reported that a 25 % rise in factor VII clotting activity ( FVIIc ) is associated with a 55 % increase in ischaemic heart disease death during the first 5 years . We examined the effects of nasal continuous positive airway pressure ( NCPAP ) treatment on FVIIc in patients with OSAS .  FVIIc was investigated prospect ively in 15 patients with OSAS before ( mean + /- SEM apnoea and hypopnoea index ( AHI ) 61.5 + /- 4.2 and after ( AHI 3.0 + /- 0.9 ) NCPAP treatment for immediate relief , at 1 month after treatment and at over 6 months . FVIIc levels gradually decreased after NCPAP treatment . After 6 months of NCPAP treatment , FVIIc levels had decreased significantly ( before 141.1 + /- 11.7 % vs. after 6 months 110.7 + /- 6.2 % ; p < 0.01 ) . Six of the seven patients whose FVIIc levels were over 140 % before the NCPAP treatment had FVIIc levels below 130 % after 6 months or 1 year of NCPAP treatment . This decrease in FVIIc after long-term NCPAP treatment could improve mortality in OSAS patients . If patients , especially obese ones , present with high FVIIc of unknown origin , it would be prudent to check for OSAS Background Previous , largely uncontrolled studies demonstrated the substantial effects of continuous positive airway pressure ventilation ( CPAP ) on a variety of physiologic and biochemical markers known to be risk factors for cardiovascular disease in patients with obstructive sleep apnea ( OSA ) . In this pilot crossover study , we assessed ( 1 ) the feasibility of using CPAP in a group of minimally symptomatic patients with OSA , assessed through patient compliance and ( 2 ) CPAP therapy ’s effect on biomarkers in these patients . Methods We studied patients with minimal daytime sleepiness who were referred to the University of British Columbia ’s Hospital Sleep Clinic with suspected OSA and an apnea-hypopnea index ( AHI ) > 15 events/h . Patients were r and omized to either CPAP or no therapy for 4 weeks followed by a washout of 4 weeks , and then a crossover to the other intervention . Fasting morning blood and urine , 24-h blood pressure ( BP ) measurements , and endothelial function ( peak flow-mediated dilation to nitroglycerin-mediated dilation ratio ) were assessed before and after each study intervention . Results Nine adult male and four female patients were studied . Mean ( SD ) age was 55 ( 7 ) years , mean AHI = 27.9/h , mean Epworth Sleepiness Score = 6.8 ( 11/13 had a score < 10 ) , and mean BMI = 31.1 kg/m2 .  Mean compliance with CPAP therapy was 5.53 h/night . Compared to no therapy , potential improvements were observed with CPAP for urinary microalbumin , norepinephrine , and epinephrine to creatinine ratios ( decreased by 3.51 mg/mmol , 1.70 nmol/mmol , and 0.95 nmol/mmol , respectively ) ; 24-h BP ( systolic decreased by 3.60 mmHg , diastolic by 0.70 mmHg ) ; homeostasis model for insulin resistance score ( decreased by 1.11 ) ; and endothelial function ( increased by 7.4 % ) . However , none of the above differences was significant ( p > 0.10 ) . Conclusion In this pilot study there were potential improvements in a variety of cardiovascular biomarkers with CPAP . CPAP compliance was reasonably good even though patients were not particularly sleepy . Accordingly , larger r and omized controlled trials in this area appear feasible and warranted BACKGROUND In patients with established ischemic heart disease , prospect i ve cohort studies have indicated that plasminogen activator inhibitor ( PAI-1 ) , the inhibitor of the fibrinolytic system , may predict cardiovascular events . So far , there have been no primary prospect i ve studies of PAI-1 . METHODS AND RESULTS The aim of the present study was to test whether plasma levels of PAI-1 , tissue-type plasminogen activator ( tPA ) , von Willebr and factor ( vWF ) , and thrombomodulin ( TM )  could predict the occurrence of a first acute myocardial infa rct ion ( AMI ) in a population with high prevalence of coronary heart disease by use of a prospect i ve nested case-control design . Mass concentrations of PAI-1 and tPA  were significantly higher for the 78 subjects who developed a first AMI compared with the 156 references matched for age , sex , and sampling time ; for tPA , this increase was independent of smoking habits , body mass index , hypertension , diabetes , cholesterol , and apolipoprotein A-I. The ratio of quartile 4 to 1 for tPA was 5.9 for a patient to develop a first AMI . The association between tPA and AMI was seen in both men and women .  Increased levels of vWF were associated with AMI in a univariate analysis . High levels of TM were associated with AMI in women but not in men . CONCLUSIONS The plasma levels of PAI-1 , tPA , and vWF are associated with subsequent development of a first AMI ; for PAI-1 and tPA , this relation was found in both men and women . For tPA but not for PAI-1 and vWF , this association is independent of established risk factors Abstract Since sleep apnea ( SA ) and stroke have many shared risk factors an independent contribution of SA to the overall risk of stroke is not easily proven and has been question ed recently . To contribute to this controversy , we analysed the frequency of SA  in groups of patients with first and recurring ischemic stroke . We prospect ively studied 102 patients admitted to our stroke unit . The prevalence of vascular risk factors and a history of previous stroke were recorded . All patients received cardio – respiratory polygraphy during the first 72 hours after admission .  CT and MRI scans were evaluated for the location of the acute stroke and the presence of older vascular lesions . Thirty – four women and 68 men with a mean age of 64.5 ± 13.7 years were included in the study . Cerebral lesions attributable to a previous stroke were identified in 25 patients , of whom 19 reported to have suffered a stroke before . Patients with stroke recurrence had a higher mean apnea – hypopnea index ( AHI ) ( 26.6/h vs. 15.1/h , p<0.05 ) and more often presented with a sleep apnea syndrome ( SA ) defined by an AHI ≥ 10/h ( 80 vs. 52 % , p < 0.05 ) than patients with first ever stroke . Logistic regression analysis including the variables " age " , " gender " , " cumulative risk factors " , " AHI ≥ 10/h " , and " diabetes " identified diabetes ( Odd ’s ratio [ OR ] = 4.5 ) and AHI ≥ 10/h ( OR = 3.5 ) as independent risk – factors for stroke recurrence . According to our results SA is an independent risk factor for stroke recurrence . We therefore advocate routine sleep – apnea screening in all patients having suffered an ischemic stroke Objective : There is an increased risk of patients with obstructive sleep apnea syndrome ( OSAS ) to have stroke or cardiac infa rcts . Besides hypertension , epinephrine-induced platelet activation could be a further reason for the increased cardiovascular morbidity and mortality in OSAS . Methods : During a 4-month period ( August 1994 to December 1994 ) we recruited prospect ively 76 patients referred for polysomnograms because of a suspected sleep disorder such as OSAS . Results : Fifty patients had no respiratory events during sleep ( non-OSAS ) , 19 patients had more than five but less than 50 obstructive apneas or hypopneas per hour of total sleep time ( mild-to-moderate OSAS group ) , and seven patients had an apnea hypopnea index of more than 50 per hour of total sleep time ( severe OSAS group ) . Blood pressure , plasma epinephrine levels , and P-selectin expression ( as a marker for platelet activation ) were measured in every patient at 9 PM and 6 AM ( before and after the polysomnogram ) . There was a significant correlation of the apnea hypopnea index with 9 PM and 6 AM systolic and diastolic blood pressure , with 9 PM platelet activation , and with 6 AM epinephrine levels mainly due to high values in the severe OSAS group . Conclusions : Our results suggest that platelet activation , epinephrine , and high blood pressure play a role in the high prevalence of cerebrovascular and cardiovascular events in patients with OSAS This study addresses the hypothesis that patients with obstructive sleep apnea , who exhibit recurrent episodes of oxygen desaturation at night , have higher hematocrit levels than nonapneic control subjects . We prospect ively studied 624 patients referred to the sleep disorders center at St. Michael 's Hospital because of suspicion of sleep apnea . All patients had nocturnal polysomnography and measurements of hematocrit level , hemoglobin value , WBC count , and platelet count . Smoking history and  awake oxygen saturation ( SaO2 )  was recorded in all of them . Nocturnal oxygenation was assessed using three indices : lowest nocturnal SaO2  ( LoSaO2 ) , mean nocturnal SaO2  ( MnSaO2 ) and percent of total sleep time spent at SaO2 lower than 85 percent ( TST85 % ) . Patients with TST85 % in the lowest quartile ( TST85 % = 0 ) had minimally lower hematocrit levels than patients with TST85 % in the highest quartile ( 8 < or = TST85 % < or = 90 ) : 0.41 + /- 0.03 vs 0.40 + /- 0.02 in female subjects and 0.45 + /- 0.05 vs 0.43 + /- 0.05 in male subjects , respectively ( p < 0.05 ) . Multiple linear regression analysis revealed that MnSaO2 , age , and pack-years of smoking were significant predictors of hematocrit level , but they accounted for only 9 percent of the variability in hematocrit level ( multiple R2 = 0.087 ; p < 0.05 ) . We conclude that intermittent nocturnal hypoxemia during episodes of apnea does not lead to clinical polycythemia , but is associated with minor elevations in hematocrit value . These small elevations are unlikely to be useful as markers of hypoxic stress associated with sleep apnea 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 r and omized 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 Willebr and 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 , st and ardized β=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 BACKGROUND Activated factor XII ( FXIIa ) is involved in vascular injury and repair , participating in inflammation , thrombosis , and fibrinolysis . We wanted to test the hypothesis that FXIIa may predict an  acute coronary syndrome ( ACS ) after a myocardial infa rct ion ( MI ) and to evaluate whether FXIIa is related to global markers of end-stage coagulation and inflammation , including fibrin monomer ( FM ) and ultrasensitive C-reactive protein ( microCRP ) . METHODS In a prospect i ve study of 300 patients with acute MI , we evaluated the predictive value of FXIIa in blood sample s drawn 4 to 6 days after admission . Cardiac death , re-MI , and troponin-T-positive unstable angina pectoris were registered during a median follow-up period of 1.5 years . RESULTS In the upper quartile of FXIIa ( Q4 ) ( > or = 2.23 ng/mL ) 32.0 % of patients had an ACS as compared with 16.9 % of patients with FXIIa in the three lower quartiles ( Q1 - 3 , P = .008 ) . Relative risk of recurrent ACS for patients with FXIIa in the Q4 as compared with Q1 - 3 was 1.89 ( 95 % CI , 1.22 to 2.93 ) . A secondary ACS occurred earlier in patients with FXIIa in the Q4 as compared with those with FXIIa in the Q1 - 3 ( P = .0039 ) . Conventional risk factors as potential confounders were not associated with time to event . FXIIa did not correlate with FM or microCRP , and the FM and microCRP levels were of a similar magnitude in the Q4 as compared with the Q1 and the Q1 - 3 of FXIIa . CONCLUSIONS FXIIa predicts recurrent coronary events after MI . The prognostic ability of FXIIa was not reflected by markers of hypercoagulability or inflammation Numerous investigations have demonstrated the role of thrombus formation in the pathogenesis of coronary heart disease ( CHD ) . A tendency to thrombosis may also be indicated by elevated levels of coagulation factor VII clotting activity ( FVIIc ) . Significant associations of FVIIc with increased coronary risk , however , have been found only in the Northwick Park Heart Study . Here we present the results of the 8-year follow-up of FVIIc measurements in 2780 healthy men of the Prospect i ve Cardiovascular Münster study . In the study population ( age at entry , 49.3 + /- 6.1 years , mean + /- SD ) , 130 CHD events occurred during follow-up . FVIIc was significantly higher in subjects with coronary events than in those without ( 112.4 + /- 20.1 % vs 108.7 + /- 21.4 % , P = .023 ) . Compared with individuals without coronary events , FVIIc was not significantly higher in men with nonfatal events ( 111.7 + /- 20.4 % ; P = .196 , n = 93 ) , but there was a tendency toward higher FVIIc activity in subjects with fatal events ( 114.6 + /- 19.5 % ; P = .076 , n = 37 ) . In the multiple logistic regression analysis , we did not find FVIIc to be an independent risk factor for CHD , and the significance of FVIIc disappeared after total cholesterol , LDL-cholesterol , and triglycerides were taken into account . The increase in the number of CHD events through higher levels of FVIIc was more pronounced in the presence of additional cardiovascular risk factors : smoking ; myocardial infa rct ion events in family ; angina pectoris ; high levels of fibrinogen , total cholesterol , LDL cholesterol , and triglycerides ; and a low level of HDL cholesterol . We conclude that FVIIc is a risk factor for CHD , especially in the presence of additional risk factors , and must be taken into account when assessing cardiovascular risk in men BACKGROUND Serum levels of circulating markers associated with cardiovascular morbidity are elevated in patients with obstructive sleep apnea-hypopnea syndrome ( OSAHS ) . These factors are studied in patients mainly before the application of therapy with continuous positive airway pressure ( CPAP )  , and the effects of CPAP treatment on them have not been thoroughly studied . Therefore , the aim of the study was to examine the effect of compliance to CPAP therapy on these factors . METHODS Patients with newly diagnosed OSAHS , nonsmokers , without comorbidities or medication use , at baseline and during the follow-up period , were included . Serum cardiovascular risk factors ( ie , high-sensitivity C-reactive protein [ hs-CRP ] , homocysteine , total cholesterol , triglycerides , high-density lipoprotein cholesterol [ HDL-C ] , low-density lipoprotein cholesterol , apolipoprotein A-I [ ApoA-I ] , and apolipoprotein B [ ApoB ] ) were measured at baseline and 6 months after CPAP application . Patients were classified into the following three groups according to CPAP use : group 1 ( n = 20 ) , good compliance ( > or= 4 h use per night ) ; group 2 ( n = 19 ) , poor compliance ( < 4 h use per night ) ; and group 3 ( n = 14 ) , refusal of CPAP treatment .  RESULTS Fifty-three patients ( 47 male patients and 6 female patients ; mean [ + /- SD ] age , 46.09 + /- 10.87 years ) were included in the study . In all groups , body mass index remained stable . In group 1 , significant decreases in the levels of hs-CRP ( p = 0.03 ) , homocysteine ( p = 0.005 ) , total cholesterol ( p = 0.021 ) , total cholesterol/HDL-C ratio ( p = 0.018 ) , and ApoB/ApoA-I ratio ( p = 0.021 ) was observed . The patients in group 2 showed a decrease in homocysteine levels ( p = 0.021 ) only , while no significant changes were observed in the patients in group 3 . CONCLUSIONS Good compliance to CPAP treatment lowers the serum levels of cardiovascular risk factors , indicating a beneficial effect on the overall cardiovascular risk BACKGROUND Obstructive sleep apnea ( OSA ) is associated with prothrombotic effects that could lead to venous thromboembolic disease . We performed a prospect i ve cross-sectional study to determine the prevalence of snoring and risk of OSA in patients with acute pulmonary embolism ( PE ) . METHODS We evaluated 270 consecutive patients who underwent a computed tomographic angiogram for suspected PE . Patients without PE served as a control group . Demographic and clinical characteristics were analyzed . The Berlin Question naire was used to determine the presence of snoring and the risk of OSA .  A subset of patients also underwent formal  nocturnal polysomnography . RESULTS PE was present in 71 ( 26 % ) of the 270 patients who underwent a computed tomographic angiogram .  When compared with patients without PE , patients with PE had a significantly higher prevalence of snoring ( 75 % vs 50 % , odds ratio = 2.91 , 95 % confidence interval : 1.60 , 5.33 , P = 0.001 ) and an increased risk of having OSA , as defined by the Berlin Question naire ( 65 % vs 36 % , odds ratio = 3.25 , confidence interval : 1.84 , 5.72 , P < 0.001 ) . Results from the multivariate analysis showed that PE was independently associated with risk of OSA ( OR = 2.78 , P = 0.001 ) . CONCLUSIONS We found a higher prevalence of snoring and high risk of OSA in patients diagnosed with acute PE , in comparison with patients in whom PE was suspected but ruled out . This association might be independent of other risks factors common to both OSA and PE . Therefore , OSA may represent a risk factor for the development of PE D-dimer , a degradation product of fibrin , is being increasingly used as a marker and prognostic factor in various thrombotic diseases . Previous reports have shown that obstructive sleep apnea is associated with platelet activation and hypercoagulability . The aim of the study was to assess the potential role of the plasma D-dimer test in patients with obstructive sleep apnea . We design ed a prospect i ve group comparison study in a tertiary-care , university-affiliated medical center . One hundred and three patients of mean age 57 years ( range 50 - 76 years ) with symptoms suggestive of obstructive sleep apnea were included .  Polysomnography was performed in all cases , and blood was collected for plasma D-dimer measurement by MiniQuant turbidmetric assay . The demographic and polysomnograph data were compared between patients with normal and high ( > 250 ng/ml ) D-dimer levels . The group with higher D-dimer values had lower mean minimal oxygen saturation ( 72.1 + /- 16.4 vs. 81.7 + /- 11.6 % , p = 0.008 ) and a longer mean period of oxygen saturation below 90 % ( 84.1 + /- 86.2 vs. 38.5 + /- 70.8 minutes , p = 0.032 ) . There was no correlation of respiratory disturbance index and sleep architecture with D-dimer values . We concluded that sleep apnea syndrome is associated with fibrinolytic activity . Oxygen desaturation seems to be one of the mediatory factors in the putative connection between obstructive sleep apnea and hypercoagulability state BACKGROUND Increased levels of certain hemostatic factors may play a part in the development of acute coronary syndromes and may be associated with an increased risk of coronary events in patients with angina pectoris . METHODS We conducted a prospect i ve multicenter study of 3043 patients with angina pectoris who underwent coronary angiography and were followed for two years . Base-line measurements included the concentrations of selected hemostatic factors indicative of a thrombophilic state or endothelial injury . The results were analyzed in relation to the subsequent incidence of myocardial infa rct ion or sudden coronary death . RESULTS After adjustment for the extent of coronary artery disease and other risk factors , an increased incidence of myocardial infa rct ion or sudden death was associated with higher base-line concentrations of fibrinogen ( mean + /- SD , 3.28 + /- 0.74 g per liter in patients who subsequently had coronary events , as compared with 3.00 + /- 0.71 g per liter in those who did not ; P = 0.01 ) , von Willebr and factor antigen ( 138 + /- 49 percent vs. 125 + /- 49 percent , P = 0.05 ) , and tissue plasminogen activator ( t-PA ) antigen ( 11.9 + /- 4.7 ng per milliliter vs. 10.0 + /- 4.2 ng per milliliter , P = 0.02 ) . The concentration of C-reactive protein was also directly correlated with the incidence of coronary events ( P = 0.05 ) , except when we adjusted for the fibrinogen concentration . In patients with high serum cholesterol levels , the risk of coronary events rose with increasing levels of fibrinogen and C-reactive protein , but the risk remained low even given high serum cholesterol levels in the presence of low fibrinogen concentrations . CONCLUSIONS In patients with angina pectoris , the levels of fibrinogen , von Willebr and factor antigen , and t-PA antigen are independent predictors of subsequent acute coronary syndromes . In addition , low fibrinogen concentrations characterize patients at low risk for coronary events despite increased serum cholesterol levels . Our data are consistent with a pathogenetic role of impaired fibrinolysis , endothelial-cell injury , and inflammatory activity in the progression of coronary artery disease
BACKGROUND Obstructive sleep apnea ( OSA ) is a common disorder that affects both quality of life and cardiovascular health .
The causal link between OSA and cardiovascular morbidity⁄mortality remains elusive .
One possible explanation is that repeated episodes of nocturnal hypoxia lead to a hypercoagulable state that predisposes patients to thrombotic events .
There is evidence supporting a wide array of hematological changes that affect hemostasis ( eg , increased hematocrit , blood viscosity , platelet activation , clotting factors and decreased fibrinolytic activity ) .
OBJECTIVE To provide a comprehensive review of the current evidence associating OSA with increased coagulability , and to highlight areas for future research .