human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 
    Output:
    