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 — Patients with obstructive sleep apnea ( OSA ) experience repetitive episodic hypoxemia with consequent sympathetic activation and marked blood pressure surges , each of which may impair endothelial function . We tested the hypothesis that patients with OSA have impaired endothelium-dependent vasodilation , even in the absence of overt cardiovascular disease . Methods and Results —We studied 8 patients with OSA ( age 44±4 years ) and 9 obese control subjects ( age 48±3 years ) . Patients with OSA were newly diagnosed , never treated for OSA , on no medications , and free of any other known diseases . All obese control subjects underwent complete overnight polysomnographic studies to exclude occult OSA . Resistance-vessel function was tested by use of forearm blood flow responses to intra-arterial infusions of acetylcholine ( a vasodilator that stimulates endothelial release of nitric oxide ) , sodium nitroprusside ( an exogenous nitric oxide donor ) , and verapamil ( a calcium channel blocker ) . Conduit-vessel function was also evaluated by ultrasonography . Brachial artery diameter was measured under baseline conditions , during reactive hyperemia ( with flow increase causing endothelium-dependent dilatation ) , and after sublingual administration of nitroglycerin ( an endothelium-independent vasodilator ) . Patients with OSA had a blunted vasodilation in response to acetylcholine ( P < 0.007 ) , but responses to sodium nitroprusside and verapamil were not significantly different from those of control subjects . No significant difference in conduit-vessel dilation was evident between OSA patients and obese control subjects . Conclusions — Patients with OSA have an impairment of resistance-vessel endothelium-dependent vasodilation . This may be implicated in the pathogenesis of hypertension and heart failure in this condition Background : The obstructive sleep apnoea/hypopnoea syndrome ( OSAHS ) is associated with hypertension and increased cardiovascular risk , particularly when accompanied by marked nocturnal hypoxaemia . The mechanisms of these associations are unclear . We hypothesised that OSAHS combined with severe nocturnal hypoxaemia causes impaired vascular function that can be reversed by continuous positive airways pressure ( CPAP ) therapy . Methods : We compared vascular function in two groups of patients with OSAHS : 27 with more than 20 4 % desaturations/h ( desaturator group ) and 19 with no 4 % and less than five 3 % desaturations/h ( non-desaturator group ) . In a r and omised , double blind , placebo controlled , crossover trial , the effect of 6 weeks of CPAP therapy on vascular function was determined in the desaturator group . In all studies , vascular function was assessed invasively by forearm venous occlusion plethysmography during intra-arterial infusion of endothelium dependent ( acetylcholine 5–20 μg/min and substance P 2–8 pmol/min ) and independent ( sodium nitroprusside 2–8 μg/min ) vasodilators . Results : Compared with the non-desaturator group , patients with OSAHS and desaturations had reduced vasodilatation to all agonists ( p = 0.007 for all ) . The apnoea/hypopnoea index and desaturation frequency were inversely related to peak vasodilatation with acetylcholine ( r = −0.44 , p = 0.002 and r = −0.43 , p = 0.003 ) and sodium nitroprusside ( r = −0.42 , p = 0.009 and r = −0.37 , p = 0.02 ) . In comparison with placebo , CPAP  therapy improved forearm blood flow to all vasodilators ( p = 0.01 ) . Conclusions : Patients with OSAHS and frequent nocturnal desaturations have impaired endothelial dependent and endothelial independent vasodilatation that is proportional to hypoxaemia and is improved by CPAP therapy . Impaired vascular function establishes an underlying mechanism for the adverse cardiovascular consequences of OSAHS Background — Indirect evidence implicates endothelial dysfunction in the pathogenesis of vascular diseases associated with obstructive sleep apnea ( OSA ) . We investigated directly whether dysfunction and inflammation occur in vivo in the vascular endothelium of patients with OSA . The effects of continuous positive airway pressure ( CPAP ) therapy on endothelial function and repair capacity were assessed . Methods and Results — Thirty-two patients with newly diagnosed OSA and 15 control subjects were studied . Proteins that regulate basal endothelial nitric oxide ( NO ) production ( endothelial NO synthase [ eNOS ] and phosphorylated eNOS ) and inflammation ( cyclooxygenase-2 and inducible NOS ) and markers of oxidative stress ( nitrotyrosine ) were quantified by immunofluorescence in freshly harvested venous endothelial cells before and after 4 weeks of CPAP therapy . Vascular reactivity was measured by flow-mediated dilation . Circulating endothelial progenitor cell levels were quantified to assess endothelial repair capacity . Baseline endothelial expression of eNOS and phosphorylated eNOS was reduced by 59 % and 94 % , respectively , in patients with OSA compared with control subjects . Expression of both nitrotyrosine and cyclooxygenase-2 was 5-fold greater in patients with OSA than in control subjects , whereas inducible NOS expression was 56 % greater . Expression of eNOS and phosphorylated eNOS significantly increased , whereas expression of nitrotyrosine , cyclooxygenase-2 , and inducible NOS significantly decreased in patients who adhered to CPAP ≥4 hours daily . Baseline flow-mediated dilation and endothelial progenitor cell levels were lower in patients than in control subjects , and both significantly increased in patients who adhered to CPAP ≥4 hours daily . Conclusions — OSA directly affects the vascular endothelium by promoting inflammation and oxidative stress while decreasing NO availability and repair capacity . Effective CPAP therapy is associated with the reversal of these alterations BACKGROUND Endothelial vasodilator dysfunction is a characteristic feature of patients at risk for coronary atherosclerosis . Therefore , we prospect ively investigated whether coronary endothelial dysfunction predicts disease progression and cardiovascular event rates . METHODS AND RESULTS Coronary vasoreactivity was assessed in 147 patients using the endothelium-dependent dilator acetylcholine , sympathetic activation by cold pressor testing , dilator responses to increased blood flow , and dilation in response to nitroglycerin .  Cardiovascular events ( cardiovascular death , unstable angina , myocardial infa rct ion , percutaneous transluminal coronary angioplasty , coronary bypass grafting , ischemic stroke , or peripheral artery revascularization ) served as outcome variables over a median follow-up period of 7.7 years . Patients suffering from cardiovascular events during follow-up ( n=16 ) had significantly increased vasoconstrictor responses to acetylcholine infusion ( P=0 . 009 ) and cold pressor testing ( P=0.002 ) , as well as significantly blunted vasodilator responses to increased blood flow ( P<0.001 ) and the intracoronary injection of nitroglycerin ( P=0.001 ) . Impaired endothelial and endothelium-independent coronary vasoreactivity were associated with a significantly higher incidence of cardiovascular events by Kaplan-Meier analysis . By multivariate analysis , all tests of coronary vasoreactivity were significant , independent predictors of a poor prognosis , even after adjustment for traditional cardiovascular risk factors or the presence of atherosclerosis itself . CONCLUSIONS Coronary endothelial vasodilator dysfunction predicts long-term atherosclerotic disease progression and cardiovascular event rates . Thus , the assessment of coronary endothelial vasoreactivity can provide pivotal information as both a diagnostic and prognostic tool in patients at risk for coronary heart disease Background —Brachial artery endothelial function is impaired in individuals with atherosclerosis and coronary risk factors and improves with risk reduction therapy . However , the predictive value of brachial artery endothelial dysfunction for future cardiovascular events is unknown . Methods and Results —We preoperatively examined brachial artery vasodilation using ultrasound in 187 patients undergoing vascular surgery .  Patients were prospect ively followed for 30 days after surgery . Forty-five patients had a postoperative event , including cardiac death ( 3 ) , myocardial infa rct ion ( 12 ) , unstable angina/ischemic ventricular fibrillation ( 2 ) , stroke ( 3 ) , or elevated troponin I , reflecting myocardial necrosis ( 25 ) . Preoperative endothelium-dependent flow-mediated dilation was significantly lower in patients with an event ( 4.9±3.1 % ) than in those without an event ( 7.3±5%;P < 0.001 ) , whereas endothelium-independent vasodilation to nitroglycerin was similar in both groups . In a Cox proportional-hazards model , the independent predictors of events were age ( P = 0.001 ) , renal insufficiency ( P = 0.03 ) , noncarotid surgery ( P = 0.05 ) , and lower brachial artery flow-mediated dilation ( P = 0.007 ) . If troponin I elevation was not considered an event , low flow-mediated dilation remained an independent predictor of risk ( odds ratio 9.0 , 95 % CI 1.2 to 68;P = 0.03 ) . When a flow-mediated dilation cutpoint of 8.1 % was used , endothelial function had a sensitivity of 95 % , specificity of 37 % , and negative predictive value of 98 % for events . Conclusions —Impaired brachial artery endothelial function independently predicts postoperative cardiac events , which supports a role for endothelial dysfunction in the pathogenesis of cardiovascular disease . The strong negative predictive value of preserved endothelial function raises the possibility that assessment of brachial artery flow-mediated dilation will be useful in the management of patients undergoing vascular surgery 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 —Endothelial dysfunction plays a key role in atherogenesis . We prospect ively investigated the impact of noninvasive measurement of endothelial function on cardiovascular risk in peripheral arterial disease ( PAD ) . The study was specially aim ed at assessing whether brachial artery flow-mediated dilation ( FMD ) added to the predictive value of  ankle-brachial pressure index  ( ABPI ) . Methods and Results —Of 131 patients monitored for a mean of 23±10 months , 18 had a coronary event , 12 a cerebrovascular event , and 9 a peripheral event .  The median FMD was lower in patients with an event than in those without ( 5.8 % versus 7.6 % , P 
    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 — Patients with obstructive sleep apnea ( OSA ) experience repetitive episodic hypoxemia with consequent sympathetic activation and marked blood pressure surges , each of which may impair endothelial function . We tested the hypothesis that patients with OSA have impaired endothelium-dependent vasodilation , even in the absence of overt cardiovascular disease . Methods and Results —We studied 8 patients with OSA ( age 44±4 years ) and 9 obese control subjects ( age 48±3 years ) . Patients with OSA were newly diagnosed , never treated for OSA , on no medications , and free of any other known diseases . All obese control subjects underwent complete overnight polysomnographic studies to exclude occult OSA . Resistance-vessel function was tested by use of forearm blood flow responses to intra-arterial infusions of acetylcholine ( a vasodilator that stimulates endothelial release of nitric oxide ) , sodium nitroprusside ( an exogenous nitric oxide donor ) , and verapamil ( a calcium channel blocker ) . Conduit-vessel function was also evaluated by ultrasonography . Brachial artery diameter was measured under baseline conditions , during reactive hyperemia ( with flow increase causing endothelium-dependent dilatation ) , and after sublingual administration of nitroglycerin ( an endothelium-independent vasodilator ) . Patients with OSA had a blunted vasodilation in response to acetylcholine ( P < 0.007 ) , but responses to sodium nitroprusside and verapamil were not significantly different from those of control subjects . No significant difference in conduit-vessel dilation was evident between OSA patients and obese control subjects . Conclusions — Patients with OSA have an impairment of resistance-vessel endothelium-dependent vasodilation . This may be implicated in the pathogenesis of hypertension and heart failure in this condition Background : The obstructive sleep apnoea/hypopnoea syndrome ( OSAHS ) is associated with hypertension and increased cardiovascular risk , particularly when accompanied by marked nocturnal hypoxaemia . The mechanisms of these associations are unclear . We hypothesised that OSAHS combined with severe nocturnal hypoxaemia causes impaired vascular function that can be reversed by continuous positive airways pressure ( CPAP ) therapy . Methods : We compared vascular function in two groups of patients with OSAHS : 27 with more than 20 4 % desaturations/h ( desaturator group ) and 19 with no 4 % and less than five 3 % desaturations/h ( non-desaturator group ) . In a r and omised , double blind , placebo controlled , crossover trial , the effect of 6 weeks of CPAP therapy on vascular function was determined in the desaturator group . In all studies , vascular function was assessed invasively by forearm venous occlusion plethysmography during intra-arterial infusion of endothelium dependent ( acetylcholine 5–20 μg/min and substance P 2–8 pmol/min ) and independent ( sodium nitroprusside 2–8 μg/min ) vasodilators . Results : Compared with the non-desaturator group , patients with OSAHS and desaturations had reduced vasodilatation to all agonists ( p = 0.007 for all ) . The apnoea/hypopnoea index and desaturation frequency were inversely related to peak vasodilatation with acetylcholine ( r = −0.44 , p = 0.002 and r = −0.43 , p = 0.003 ) and sodium nitroprusside ( r = −0.42 , p = 0.009 and r = −0.37 , p = 0.02 ) . In comparison with placebo , CPAP  therapy improved forearm blood flow to all vasodilators ( p = 0.01 ) . Conclusions : Patients with OSAHS and frequent nocturnal desaturations have impaired endothelial dependent and endothelial independent vasodilatation that is proportional to hypoxaemia and is improved by CPAP therapy . Impaired vascular function establishes an underlying mechanism for the adverse cardiovascular consequences of OSAHS Background — Indirect evidence implicates endothelial dysfunction in the pathogenesis of vascular diseases associated with obstructive sleep apnea ( OSA ) . We investigated directly whether dysfunction and inflammation occur in vivo in the vascular endothelium of patients with OSA . The effects of continuous positive airway pressure ( CPAP ) therapy on endothelial function and repair capacity were assessed . Methods and Results — Thirty-two patients with newly diagnosed OSA and 15 control subjects were studied . Proteins that regulate basal endothelial nitric oxide ( NO ) production ( endothelial NO synthase [ eNOS ] and phosphorylated eNOS ) and inflammation ( cyclooxygenase-2 and inducible NOS ) and markers of oxidative stress ( nitrotyrosine ) were quantified by immunofluorescence in freshly harvested venous endothelial cells before and after 4 weeks of CPAP therapy . Vascular reactivity was measured by flow-mediated dilation . Circulating endothelial progenitor cell levels were quantified to assess endothelial repair capacity . Baseline endothelial expression of eNOS and phosphorylated eNOS was reduced by 59 % and 94 % , respectively , in patients with OSA compared with control subjects . Expression of both nitrotyrosine and cyclooxygenase-2 was 5-fold greater in patients with OSA than in control subjects , whereas inducible NOS expression was 56 % greater . Expression of eNOS and phosphorylated eNOS significantly increased , whereas expression of nitrotyrosine , cyclooxygenase-2 , and inducible NOS significantly decreased in patients who adhered to CPAP ≥4 hours daily . Baseline flow-mediated dilation and endothelial progenitor cell levels were lower in patients than in control subjects , and both significantly increased in patients who adhered to CPAP ≥4 hours daily . Conclusions — OSA directly affects the vascular endothelium by promoting inflammation and oxidative stress while decreasing NO availability and repair capacity . Effective CPAP therapy is associated with the reversal of these alterations BACKGROUND Endothelial vasodilator dysfunction is a characteristic feature of patients at risk for coronary atherosclerosis . Therefore , we prospect ively investigated whether coronary endothelial dysfunction predicts disease progression and cardiovascular event rates . METHODS AND RESULTS Coronary vasoreactivity was assessed in 147 patients using the endothelium-dependent dilator acetylcholine , sympathetic activation by cold pressor testing , dilator responses to increased blood flow , and dilation in response to nitroglycerin .  Cardiovascular events ( cardiovascular death , unstable angina , myocardial infa rct ion , percutaneous transluminal coronary angioplasty , coronary bypass grafting , ischemic stroke , or peripheral artery revascularization ) served as outcome variables over a median follow-up period of 7.7 years . Patients suffering from cardiovascular events during follow-up ( n=16 ) had significantly increased vasoconstrictor responses to acetylcholine infusion ( P=0 . 009 ) and cold pressor testing ( P=0.002 ) , as well as significantly blunted vasodilator responses to increased blood flow ( P<0.001 ) and the intracoronary injection of nitroglycerin ( P=0.001 ) . Impaired endothelial and endothelium-independent coronary vasoreactivity were associated with a significantly higher incidence of cardiovascular events by Kaplan-Meier analysis . By multivariate analysis , all tests of coronary vasoreactivity were significant , independent predictors of a poor prognosis , even after adjustment for traditional cardiovascular risk factors or the presence of atherosclerosis itself . CONCLUSIONS Coronary endothelial vasodilator dysfunction predicts long-term atherosclerotic disease progression and cardiovascular event rates . Thus , the assessment of coronary endothelial vasoreactivity can provide pivotal information as both a diagnostic and prognostic tool in patients at risk for coronary heart disease Background —Brachial artery endothelial function is impaired in individuals with atherosclerosis and coronary risk factors and improves with risk reduction therapy . However , the predictive value of brachial artery endothelial dysfunction for future cardiovascular events is unknown . Methods and Results —We preoperatively examined brachial artery vasodilation using ultrasound in 187 patients undergoing vascular surgery .  Patients were prospect ively followed for 30 days after surgery . Forty-five patients had a postoperative event , including cardiac death ( 3 ) , myocardial infa rct ion ( 12 ) , unstable angina/ischemic ventricular fibrillation ( 2 ) , stroke ( 3 ) , or elevated troponin I , reflecting myocardial necrosis ( 25 ) . Preoperative endothelium-dependent flow-mediated dilation was significantly lower in patients with an event ( 4.9±3.1 % ) than in those without an event ( 7.3±5%;P < 0.001 ) , whereas endothelium-independent vasodilation to nitroglycerin was similar in both groups . In a Cox proportional-hazards model , the independent predictors of events were age ( P = 0.001 ) , renal insufficiency ( P = 0.03 ) , noncarotid surgery ( P = 0.05 ) , and lower brachial artery flow-mediated dilation ( P = 0.007 ) . If troponin I elevation was not considered an event , low flow-mediated dilation remained an independent predictor of risk ( odds ratio 9.0 , 95 % CI 1.2 to 68;P = 0.03 ) . When a flow-mediated dilation cutpoint of 8.1 % was used , endothelial function had a sensitivity of 95 % , specificity of 37 % , and negative predictive value of 98 % for events . Conclusions —Impaired brachial artery endothelial function independently predicts postoperative cardiac events , which supports a role for endothelial dysfunction in the pathogenesis of cardiovascular disease . The strong negative predictive value of preserved endothelial function raises the possibility that assessment of brachial artery flow-mediated dilation will be useful in the management of patients undergoing vascular surgery 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 —Endothelial dysfunction plays a key role in atherogenesis . We prospect ively investigated the impact of noninvasive measurement of endothelial function on cardiovascular risk in peripheral arterial disease ( PAD ) . The study was specially aim ed at assessing whether brachial artery flow-mediated dilation ( FMD ) added to the predictive value of  ankle-brachial pressure index  ( ABPI ) . Methods and Results —Of 131 patients monitored for a mean of 23±10 months , 18 had a coronary event , 12 a cerebrovascular event , and 9 a peripheral event .  The median FMD was lower in patients with an event than in those without ( 5.8 % versus 7.6 % , P 
    Output:
    