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 —Arterial distensibility measures , generally from pulse-wave velocity ( PWV ) , are widely used with little knowledge of relationships to patient outcome . We tested whether aortic PWV predicts cardiovascular and all-cause mortality in type 2 diabetes and glucose-tolerance – tested ( GTT ) multiethnic population sample s. Methods and Results — Participants were r and omly sample d from ( 1 ) a type 2 diabetes outpatient clinic and ( 2 ) primary care population registers , from which nondiabetic control subjects were given a GTT .  Brachial blood pressures  and Doppler-derived aortic PWV  were measured . Mortality data over 10 years ’ follow-up were obtained . At any level of systolic blood pressure ( SBP ) , aortic PWV was greater in subjects with diabetes than in controls . Mortality risk doubled in subjects with diabetes ( hazard ratio 2.34 , 95 % CI 1.5 to 3.74 ) and in those with glucose intolerance ( 2.12 , 95 % CI 1.11 to 4.0 ) compared with controls . For all groups combined , age , sex , and SBP predicted mortality ; the addition of PWV independently predicted all-cause and cardiovascular mortality ( hazard ratio 1.08 , 95 % CI 1.03 to 1.14 for each 1 m/s increase ) but displaced SBP . Glucose tolerance status and smoking were other independent contributors , with African-Caribbeans experiencing reduced mortality risk ( hazard ratio 0.41 , 95 % CI 0.25 to 0.69 ) . Conclusions —Aortic PWV is a powerful independent predictor of mortality in both diabetes and GTT population sample s. In displacing SBP as a prognostic factor , aortic PWV is probably further along the causal pathway for arterial disease and may represent a useful integrated index of vascular status and hence cardiovascular risk RATIONALE Cross-sectional association has been reported between sleep-disordered breathing ( SDB ) and insulin resistance , but no prospect i ve studies have been performed to determine whether SDB is causal in the development of diabetes . OBJECTIVES The purpose of our study was to investigate the prevalence and incidence of type II diabetes  in subjects with SDB and whether an independent relationship exists between them . METHODS A cross-sectional and longitudinal analysis was performed in 1,387 participants of the Wisconsin Sleep Cohort .  Full polysomnography was used to characterize SDB . Diabetes was defined in two ways : ( 1 ) physician-diagnosis alone or ( 2 ) for those with glucose measurements , either fasting glucose > or = 126 mg/dl or physician diagnosis . MEASUREMENTS AND MAIN RESULTS There was a greater prevalence of diabetes in subjects with increasing levels of SDB . A total of 14.7 % of subjects with an apnea-hypopnea index ( AHI ) of 15 or more had a diagnosis of diabetes compared with 2.8 % of subjects with an AHI of less than 5 . The odds ratio for having a physician diagnoses of diabetes mellitus with an AHI of 15 or greater versus an AHI of less than 5 was 2.30 ( 95 % confidence interval , 1.28 - 4.11 ; p = 0.005 ) after adjustment for age , sex , and body habitus . The odds ratio for developing diabetes mellitus within 4 yr with an AHI of 15 or more compared with an AHI of less than 5 was 1.62 ( 95 % confidence interval , 0.67 - 3.65 ; p = 0.24 ) when adjusting for age , sex , and body habitus . CONCLUSIONS Diabetes is more prevalent in SDB and this relationship is independent of other risk factors . However , it is not clear that SDB is causal in the development of diabetes OBJECTIVES The study was done to determine whether radial artery applanation tonometry can be used as a noninvasive method of assessing global endothelial function . BACKGROUND ; It is known that beta(2)-receptor stimulation results in endothelial release of nitric oxide . Furthermore , for over a century glyceryl trinitrate ( GTN ) has been known to markedly affect the arterial pressure waveform , even in the absence of significant blood pressure ( BP ) changes . Therefore , it was hypothesized that the change in the peripheral pressure waveform , as measured using tonometry and quantified using the augmentation index ( AIx ) and in response to Salbutamol ( Salb ) , would allow assessment of global endothelial function . METHODS The study contained three parts . In the first study , Salb ( 400 microg ) was administered to 11 healthy subjects via inhalation after either intravenous N-omega-nitro-monomethyl-L-arginine ( L-NMMA ) ( 3 mg/kg over 5 min ) or control solution ( normal saline ) in the supine , rested , fasted condition . The BP , heart rate and waveform responses were recorded each 5 min following Salb for 20 min . Next , GTN was given and responses recorded 5 min later . In the second study , both the reproducibility of Salb and the GTN responses were assessed in 9 subjects studied twice on separate days . In the third study , the Salb and GTN responses of 12 subjects with angiographic coronary artery disease ( CAD ) were compared with 10 age-matched control subjects with no atherosclerotic risk factors . RESULTS After control infusion , AIx decreased following Salb , from 50.8 + /- 4.3 % to 44.8 + /- 4.2 % , a change of -11.8 + /- 3.7 % , p < 0.01 . After L-NMMA , AIx did not significantly change following Salb ( 54.2 + /- 5.1 % vs. 52.9 + /- 5.3 % , -2.0 + /- 3.1 % ) . The GTN-induced decreases in AIx were similar after either infusion ( 35.1 + /- 3.3 % vs. 36.5 + /- 3.3 % ) . Reproducibility of Salb-induced changes in AIx between studies performed on separate days was good ( r = 0.80 , p < 0.01 ) . Salb-induced changes in AIx in CAD patients were significantly less compared to control subjects ( -2.4 + /- 1.9 % vs. -13.2 + /- 2.4 % , respectively , p < 0.002 ) . The GTN-induced changes were not significantly different ( -27.6 + /- 4.2 vs. -38.9 + /- 4.4 % , p = 0.07 ) . CONCLUSIONS The peripheral arterial pressure waveform is sensitive to beta(2)-stimulation . Changes are related to nitric oxide release , are reproducible and can distinguish between clinical subject groups . Arterial waveform changes following Salb may thus provide a noninvasive method of measuring " global " arterial endothelial function Background —Obstructive sleep apnea ( OSA ) has been increasingly linked to cardiovascular and cerebrovascular disease . Inflammatory processes associated with OSA may contribute to cardiovascular morbidity in these patients . We tested the hypothesis that OSA patients have increased plasma C-reactive protein ( CRP ) . Methods and Results —We studied 22 patients ( 18 males and 4 females ) with newly diagnosed OSA , who were free of other diseases , had never been treated for OSA , and were taking no medications . We compared CRP measurements in these patients to measurements obtained in 20 control subjects ( 15 males and 5 females ) who were matched for age and body mass index , and in whom occult OSA was excluded .  Plasma CRP levels were significantly higher in patients with OSA than in controls ( median [ range ] 0.33 [ 0.09 to 2.73 ] versus 0.09 [ 0.02 to 0.9 ] mg/dL , P < 0.0003 ) . In multivariate analysis , CRP levels were independently associated with OSA severity ( F=6.8 , P = 0.032 ) . Conclusions —OSA is associated with elevated levels of CRP , a marker of inflammation and of cardiovascular risk . The severity of OSA is proportional to the CRP level AIMS Increased arterial wave reflections are associated with the presence and extent of coronary atherosclerosis and with cardiovascular mortality in selected population s. We prospect ively evaluated their prognostic value in the short- and long-term following percutaneous coronary interventions ( PCIs ) . METHODS AND RESULTS We non-invasively quantified wave reflections [ expressed as augmentation index corrected for heart rate of 75 b.p.m . ( AIx@75 ) ] using applanation tonometry of the radial artery and a vali date d transfer function to obtain the corresponding aortic values in 262 patients undergoing PCI .  During 2-year follow-up , 61 patients reached the primary endpoint [ death , myocardial infa rct ion ( MI ) , and restenosis ] . Increasing tertiles of Alx@75 were related to the rate of patients reaching the primary endpoint [ 15.2 , 20 and 35.3 % , respectively ( P = 0.001 ) ] , as well as the secondary endpoints total mortality , myocardial infa rct ion and death plus myocardial infa rct ion ( RR for the third vs. the first tertile 4.33 , 3.25 and 3.46 , respectively , P < 0.05 ) . In a multivariable Cox-regression model , AIx@75 added prognostic value above and beyond clinical risk factors , angiographic variables , and medications ( RR 1.8 , 95%CI 1.18 - 2.76 per increasing AIx@75-tertile , P < 0.01 ) . CONCLUSION Increased arterial wave reflections are independently associated with an increased risk for severe short- and long-term cardiovascular events in patients undergoing PCI 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 Continuous positive airway pressure ( CPAP ) treatment improves endothelial function and sympathetic activity in patients with obstructive sleep apnea ( OSA ) . However , the long-term effects of CPAP on pulse wave velocity ( PWV ) , which reflects arterial stiffness that is associated with cardiovascular events , have not been evaluated in OSA patients with or without hypertension ( HT ) . In this study , 212 male OSA patients who had been receiving CPAP treatment for 2 years and were divided into two groups , those with HT ( n=114 ) and those without ( n=98 ) , were studied . In both HT and normotensive ( NT ) patients , PWV decreased significantly over the first 6 months of treatment ( P=0.005 and 0.010 , respectively ) , before increasing gradually from 6 to 24 months . Body mass index ( BMI ) , body weight , heart rate ( HR ) , systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) levels decreased significantly in the HT group over the 2 years of CPAP treatment ( P<0.001 for all ) . In contrast , only HR decreased significantly in the NT group over the 2 years of treatment ( P<0.001 ) . Multivariate regression analysis revealed that age ( P=0.008 ) , decreases in DBP ( P<0.001 ) and HR ( P<0.001 ) and higher initial levels of serum high-density lipoprotein – cholesterol ( P=0.040 ) were independent factors related to changes in PWV over the 2 years of CPAP treatment in all patients . In conclusion 
    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 —Arterial distensibility measures , generally from pulse-wave velocity ( PWV ) , are widely used with little knowledge of relationships to patient outcome . We tested whether aortic PWV predicts cardiovascular and all-cause mortality in type 2 diabetes and glucose-tolerance – tested ( GTT ) multiethnic population sample s. Methods and Results — Participants were r and omly sample d from ( 1 ) a type 2 diabetes outpatient clinic and ( 2 ) primary care population registers , from which nondiabetic control subjects were given a GTT .  Brachial blood pressures  and Doppler-derived aortic PWV  were measured . Mortality data over 10 years ’ follow-up were obtained . At any level of systolic blood pressure ( SBP ) , aortic PWV was greater in subjects with diabetes than in controls . Mortality risk doubled in subjects with diabetes ( hazard ratio 2.34 , 95 % CI 1.5 to 3.74 ) and in those with glucose intolerance ( 2.12 , 95 % CI 1.11 to 4.0 ) compared with controls . For all groups combined , age , sex , and SBP predicted mortality ; the addition of PWV independently predicted all-cause and cardiovascular mortality ( hazard ratio 1.08 , 95 % CI 1.03 to 1.14 for each 1 m/s increase ) but displaced SBP . Glucose tolerance status and smoking were other independent contributors , with African-Caribbeans experiencing reduced mortality risk ( hazard ratio 0.41 , 95 % CI 0.25 to 0.69 ) . Conclusions —Aortic PWV is a powerful independent predictor of mortality in both diabetes and GTT population sample s. In displacing SBP as a prognostic factor , aortic PWV is probably further along the causal pathway for arterial disease and may represent a useful integrated index of vascular status and hence cardiovascular risk RATIONALE Cross-sectional association has been reported between sleep-disordered breathing ( SDB ) and insulin resistance , but no prospect i ve studies have been performed to determine whether SDB is causal in the development of diabetes . OBJECTIVES The purpose of our study was to investigate the prevalence and incidence of type II diabetes  in subjects with SDB and whether an independent relationship exists between them . METHODS A cross-sectional and longitudinal analysis was performed in 1,387 participants of the Wisconsin Sleep Cohort .  Full polysomnography was used to characterize SDB . Diabetes was defined in two ways : ( 1 ) physician-diagnosis alone or ( 2 ) for those with glucose measurements , either fasting glucose > or = 126 mg/dl or physician diagnosis . MEASUREMENTS AND MAIN RESULTS There was a greater prevalence of diabetes in subjects with increasing levels of SDB . A total of 14.7 % of subjects with an apnea-hypopnea index ( AHI ) of 15 or more had a diagnosis of diabetes compared with 2.8 % of subjects with an AHI of less than 5 . The odds ratio for having a physician diagnoses of diabetes mellitus with an AHI of 15 or greater versus an AHI of less than 5 was 2.30 ( 95 % confidence interval , 1.28 - 4.11 ; p = 0.005 ) after adjustment for age , sex , and body habitus . The odds ratio for developing diabetes mellitus within 4 yr with an AHI of 15 or more compared with an AHI of less than 5 was 1.62 ( 95 % confidence interval , 0.67 - 3.65 ; p = 0.24 ) when adjusting for age , sex , and body habitus . CONCLUSIONS Diabetes is more prevalent in SDB and this relationship is independent of other risk factors . However , it is not clear that SDB is causal in the development of diabetes OBJECTIVES The study was done to determine whether radial artery applanation tonometry can be used as a noninvasive method of assessing global endothelial function . BACKGROUND ; It is known that beta(2)-receptor stimulation results in endothelial release of nitric oxide . Furthermore , for over a century glyceryl trinitrate ( GTN ) has been known to markedly affect the arterial pressure waveform , even in the absence of significant blood pressure ( BP ) changes . Therefore , it was hypothesized that the change in the peripheral pressure waveform , as measured using tonometry and quantified using the augmentation index ( AIx ) and in response to Salbutamol ( Salb ) , would allow assessment of global endothelial function . METHODS The study contained three parts . In the first study , Salb ( 400 microg ) was administered to 11 healthy subjects via inhalation after either intravenous N-omega-nitro-monomethyl-L-arginine ( L-NMMA ) ( 3 mg/kg over 5 min ) or control solution ( normal saline ) in the supine , rested , fasted condition . The BP , heart rate and waveform responses were recorded each 5 min following Salb for 20 min . Next , GTN was given and responses recorded 5 min later . In the second study , both the reproducibility of Salb and the GTN responses were assessed in 9 subjects studied twice on separate days . In the third study , the Salb and GTN responses of 12 subjects with angiographic coronary artery disease ( CAD ) were compared with 10 age-matched control subjects with no atherosclerotic risk factors . RESULTS After control infusion , AIx decreased following Salb , from 50.8 + /- 4.3 % to 44.8 + /- 4.2 % , a change of -11.8 + /- 3.7 % , p < 0.01 . After L-NMMA , AIx did not significantly change following Salb ( 54.2 + /- 5.1 % vs. 52.9 + /- 5.3 % , -2.0 + /- 3.1 % ) . The GTN-induced decreases in AIx were similar after either infusion ( 35.1 + /- 3.3 % vs. 36.5 + /- 3.3 % ) . Reproducibility of Salb-induced changes in AIx between studies performed on separate days was good ( r = 0.80 , p < 0.01 ) . Salb-induced changes in AIx in CAD patients were significantly less compared to control subjects ( -2.4 + /- 1.9 % vs. -13.2 + /- 2.4 % , respectively , p < 0.002 ) . The GTN-induced changes were not significantly different ( -27.6 + /- 4.2 vs. -38.9 + /- 4.4 % , p = 0.07 ) . CONCLUSIONS The peripheral arterial pressure waveform is sensitive to beta(2)-stimulation . Changes are related to nitric oxide release , are reproducible and can distinguish between clinical subject groups . Arterial waveform changes following Salb may thus provide a noninvasive method of measuring " global " arterial endothelial function Background —Obstructive sleep apnea ( OSA ) has been increasingly linked to cardiovascular and cerebrovascular disease . Inflammatory processes associated with OSA may contribute to cardiovascular morbidity in these patients . We tested the hypothesis that OSA patients have increased plasma C-reactive protein ( CRP ) . Methods and Results —We studied 22 patients ( 18 males and 4 females ) with newly diagnosed OSA , who were free of other diseases , had never been treated for OSA , and were taking no medications . We compared CRP measurements in these patients to measurements obtained in 20 control subjects ( 15 males and 5 females ) who were matched for age and body mass index , and in whom occult OSA was excluded .  Plasma CRP levels were significantly higher in patients with OSA than in controls ( median [ range ] 0.33 [ 0.09 to 2.73 ] versus 0.09 [ 0.02 to 0.9 ] mg/dL , P < 0.0003 ) . In multivariate analysis , CRP levels were independently associated with OSA severity ( F=6.8 , P = 0.032 ) . Conclusions —OSA is associated with elevated levels of CRP , a marker of inflammation and of cardiovascular risk . The severity of OSA is proportional to the CRP level AIMS Increased arterial wave reflections are associated with the presence and extent of coronary atherosclerosis and with cardiovascular mortality in selected population s. We prospect ively evaluated their prognostic value in the short- and long-term following percutaneous coronary interventions ( PCIs ) . METHODS AND RESULTS We non-invasively quantified wave reflections [ expressed as augmentation index corrected for heart rate of 75 b.p.m . ( AIx@75 ) ] using applanation tonometry of the radial artery and a vali date d transfer function to obtain the corresponding aortic values in 262 patients undergoing PCI .  During 2-year follow-up , 61 patients reached the primary endpoint [ death , myocardial infa rct ion ( MI ) , and restenosis ] . Increasing tertiles of Alx@75 were related to the rate of patients reaching the primary endpoint [ 15.2 , 20 and 35.3 % , respectively ( P = 0.001 ) ] , as well as the secondary endpoints total mortality , myocardial infa rct ion and death plus myocardial infa rct ion ( RR for the third vs. the first tertile 4.33 , 3.25 and 3.46 , respectively , P < 0.05 ) . In a multivariable Cox-regression model , AIx@75 added prognostic value above and beyond clinical risk factors , angiographic variables , and medications ( RR 1.8 , 95%CI 1.18 - 2.76 per increasing AIx@75-tertile , P < 0.01 ) . CONCLUSION Increased arterial wave reflections are independently associated with an increased risk for severe short- and long-term cardiovascular events in patients undergoing PCI 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 Continuous positive airway pressure ( CPAP ) treatment improves endothelial function and sympathetic activity in patients with obstructive sleep apnea ( OSA ) . However , the long-term effects of CPAP on pulse wave velocity ( PWV ) , which reflects arterial stiffness that is associated with cardiovascular events , have not been evaluated in OSA patients with or without hypertension ( HT ) . In this study , 212 male OSA patients who had been receiving CPAP treatment for 2 years and were divided into two groups , those with HT ( n=114 ) and those without ( n=98 ) , were studied . In both HT and normotensive ( NT ) patients , PWV decreased significantly over the first 6 months of treatment ( P=0.005 and 0.010 , respectively ) , before increasing gradually from 6 to 24 months . Body mass index ( BMI ) , body weight , heart rate ( HR ) , systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) levels decreased significantly in the HT group over the 2 years of CPAP treatment ( P<0.001 for all ) . In contrast , only HR decreased significantly in the NT group over the 2 years of treatment ( P<0.001 ) . Multivariate regression analysis revealed that age ( P=0.008 ) , decreases in DBP ( P<0.001 ) and HR ( P<0.001 ) and higher initial levels of serum high-density lipoprotein – cholesterol ( P=0.040 ) were independent factors related to changes in PWV over the 2 years of CPAP treatment in all patients . In conclusion 
    Output:
    