***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: Chronic obstructive pulmonary disease ( COPD ) is characterized by low pulmonary function , inflammation , free radical production , vascular dysfunction , and subsequently a greater incidence of cardiovascular disease . By administering an acute oral antioxidant cocktail to patients with COPD ( n=30 ) and controls ( n=30 ) , we sought to determine the role of redox balance in the vascular dysfunction of these patients . Using a double-blind , r and omized , placebo-controlled , crossover design , patients with COPD and controls were ingested placebo or the antioxidant cocktail ( vitamin C , vitamin E , & agr;-lipoic acid ) after which brachial artery flow-mediated dilation and carotid-radial pulse wave velocity were assessed using ultrasound Doppler . The patients exhibited lower baseline antioxidant levels ( vitamin C and superoxide dismutase activity ) and higher levels of oxidative stress ( thiobarbituic acid reactive species ) in comparison with controls . The patients also displayed lower basal flow-mediated dilation ( P<0.05 ) , which was significantly improved with antioxidant cocktail ( 3.1±0.5 versus 4.7±0.6 % ; P<0.05 ; placebo versus antioxidant cocktail ) , but not controls ( 6.7±0.6 versus 6.9±0.7 % ; P>0.05 ; placebo versus antioxidant cocktail ) . The antioxidant cocktail also improved pulse wave velocity in patients with COPD ( 14±1 versus 11±1 m·s−1 ; P<0.05 ; placebo versus antioxidant cocktail ) while not affecting controls ( 11±2 versus 10±1 m·s−1 ; P>0.05 ; placebo versus antioxidant ) . Patients with COPD exhibit vascular dysfunction , likely mediated by an altered redox balance , which can be acutely mitigated by an oral antioxidant . Therefore , free radically mediated vascular dysfunction may be an important mechanism contributing to this population ’s greater risk and incidence of cardiovascular disease Rationale : Chronic obstructive pulmonary disease ( COPD ) is associated with a 2–3-fold increase in the risk of ischaemic heart disease , stroke and sudden death . The mechanisms responsible for this association are not clear and appear to be independent of smoking history . Objective : We test the hypothesis that patients with COPD have increased arterial stiffness and blood pressure in comparison with age and smoking matched controls . Methods : In a prospect i ve case control study , we recruited 102 patients with COPD and 103 healthy controls matched for age and smoking status . Patients were assessed by clinical history and spirometry , with  arterial stiffness and blood pressure  determined using radial artery applanation tonometry and sphygmomanometry . Results : Patients with COPD had increased arterial stiffness compared with matched controls , with elevated augmentation pressure ( 17 ( 1 ) vs 14 ( 1 ) mm Hg ; p = 0.005 ) and a reduced time to wave reflection ( 131 ( 1 ) vs 137 ( 2 ) ms ; p = 0.004 ) . These differences were associated with increases in both diastolic ( 82 ( 1 ) vs 78 ( 1 ) mm Hg ; p = 0.005 ) and systolic blood pressure ( 147 ( 2 ) vs 132 ( 2 ) mm Hg ; p<0.001 ) . Serum C reactive protein concentrations were threefold higher in patients ( 6.1 ( 0.9 ) vs 2.3 ( 0.4 ) mg/l ; p = 0.001 ) . Data are presented as mean ( SEM ) . Conclusions : Patients with COPD have increased arterial stiffness and blood pressure in comparison with controls matched for age and smoking status . We speculate that increased systemic inflammation and vascular dysfunction could potentially explain the excess cardiovascular morbidity and mortality associated with COPD OBJECTIVES The objective of this study was to examine whether statin therapy is associated with enhanced endothelium-dependent vascular function , improved pulmonary function and reduced systemic inflammation in patients with chronic obstructive pulmonary disease ( COPD ) . DESIGN AND SETTING This r and omized , placebo-controlled , double-blind , parallel trial including patients with COPD was performed at two University hospitals in Norway . SUBJECTS , INTERVENTION AND MEASUREMENTS Patients with stable COPD ( n = 99 ) were assigned r and omly to receive rosuvastatin 10 mg ( n = 49 ) or matching placebo ( n = 50 ) once daily for 12 weeks . The primary outcome measure was change in endothelium-dependent vascular function measured using peripheral arterial tonometry and expressed as the reactive hyperaemia index . Secondary end-points were change in pulmonary function , as assessed by forced expiratory volume in 1 s ( FEV1 ) and FEV1/forced vital capacity ( FVC ) , and change in the circulating levels of the inflammatory markers interleukin-6 ( IL6 ) and high-sensitivity C-reactive protein ( hsCRP ) . RESULTS In the overall study population , no significant between-group difference in change in endothelium-dependent vascular or pulmonary function was observed . Rosuvastatin therapy was associated with a reduction in hsCRP ( -20 % vs. 11 % , P = 0.017 ) and an attenuation of the rise in IL6 concentration ( 8 % vs. 30 % , P = 0.028 ) compared with placebo . In a prespecified subgroup analysis of patients with a supra-median circulating hsCRP concentration ( > 1.7 mg L(-1 ) ) , rosuvastatin was associated with improved endothelium-dependent vascular function ( 13 % vs. 2 % , P = 0.026 ) . CONCLUSIONS In stable COPD patients without the st and ard indications for statin therapy  , rosuvastatin treatment is associated with a significant attenuation of systemic inflammation and improvement in endothelial-dependent vascular function in patients with evidence of systemic inflammation Summary Patients with SCAD and concomitant COPD are at high risk of cardiovascular adverse events , due to chronic inflammation , responsible of endothelial dysfunction , oxidative stress and heightened platelet reactivity ( PR ) . The objective of this r and omised clinical trial was to test if ticagrelor is superior to clopidogrel in improving endothelial function in patients with stable coronary artery disease ( SCAD ) and concomitant chronic obstructive pulmonary disease ( COPD ) . Forty-six patients with SCAD and COPD undergoing percutaneous coronary intervention ( PCI ) were r and omly assigned to receive clopidogrel ( n=23 ) or ticagrelor ( n=23 ) on top of st and ard therapy with aspirin . The following parameters were assessed at baseline and after 1 month : i ) rate of apoptosis and ii ) nitric oxide ( NO ) levels in human umbilical vein endothelial cells ( HUVECs ) , iii ) levels of reactive oxygen species ( ROS ) in peripheral blood mononuclear cell , iv ) 29 cytokines/chemokines , v ) on-treatment PR . The primary endpoint of the study was the 1-month rate of HUVECs apoptosis . The rate of apoptosis after 1 month was significantly lower in patients treated with ticagrelor ( 7.4 ± 1.3 % vs 9.3 ± 1.5 % , p<0.001 ) , satisfying the pre-specified primary endpoint . In the ticagrelor arm , levels of NO were higher ( 10.1 ± 2.2 AU vs 8.5 ± 2.6 AU , p=0.03 ) while those of ROS ( 4 ± 1.8 AU vs 5.7 ± 2.8 AU , p=0.02 ) and P2Y 12 reactivity units ( 52 ± 70 PRU vs 155 ± 62 PRU , p<0.001 ) were lower . There were no differences in cytokines/chemokines levels and aspirin reactivity units between groups . In patients with SCAD and COPD undergoing PCI , ticagrelor , as compared to clopidogrel is superior in improving surrogate markers of endothelial function and on-treatment PR ( Clinical Trials.gov , NCT02519608 ) . Supplementary Material to this article is available online at www.thrombosis-online.com BACKGROUND : Smoking and COPD are risk factors for cardiovascular disease , and the pathogenesis may involve endothelial dysfunction . We tested the hypothesis that endothelium‐derived epoxyeicosatrienoic acid (EET)‐mediated endothelial function is impaired in patients with COPD and that a novel soluble epoxide hydrolase inhibitor , GSK2256294 , attenuates EET‐mediated endothelial dysfunction in human resistance vessels both in vitro and in vivo . METHODS : Endogenous and stimulated endothelial release of EETs was assessed in 12 patients with COPD , 11 overweight smokers , and two matched control groups , using forearm plethysmography with  intraarterial infusions of fluconazole , bradykinin , and the combination . The effects of GSK2256294 on EET‐mediated vasodilation in human resistance arteries were assessed in vitro and in vivo in a phase I clinical trial in healthy overweight smokers . RESULTS : Compared with control groups , there was reduced vasodilation with bradykinin ( P = .005 ) , a blunted effect of fluconazole on bradykinin‐induced vasodilation ( P = .03 ) , and a trend toward reduced basal EET/dihydroxyepoxyeicosatrienoic acid ratio in patients with COPD ( P = .08 ) . A similar pattern was observed in overweight smokers . In vitro , 10 & mgr;M GSK2256294  increased 11,12‐EET‐mediated vasodilation compared with vehicle ( 90 % ± 4.2 % vs 72.6 % ± 6.2 % maximal dilatation ) and shifted the bradykinin half‐maximal effective concentration ( EC50 ) ( –8.33 ± 0.172 logM vs –8.10 ± 0.118 logM ; P = .001 for EC50 ) . In vivo , 18 mg GSK2256294 improved the maximum bradykinin response from 338 % ± 46 % before a dose to 566 % ± 110 % after a single dose ( P = .02 ) and to 503 % ± 123 % after a chronic dose ( P = .003 ) . CONCLUSIONS : GSK2256294 attenuates smoking‐related EET‐mediated endothelial dysfunction , suggesting potential therapeutic benefits in patients with COPD . TRIAL REGISTRY : Clinical Trials.gov ; No. : NCT01762774 ; URL : www . clinical OBJECTIVES The purpose of this study was to determine whether smoking cessation improves flow-mediated dilation ( FMD ) of the brachial artery . BACKGROUND The long-term effects of continued smoking and smoking cessation on endothelial function have not been described previously . METHODS This was a 1-year , prospect i ve , double-blind , r and omized , placebo-controlled clinical trial of the effects of 5  smoking cessation pharmacotherapies .  FMD was measured by B-mode ultrasonography before and 1 year after the target smoking cessation date . Cessation was verified by exhaled carbon monoxide levels . DeltaFMD was compared among study arms and between subjects who successfully quit smoking and those who continued to smoke . Predictors of baseline FMD and DeltaFMD were identified by multivariable regression . RESULTS The 1,504 current smokers ( 58 % female , 84 % white ) were 44.7 + /- 11.1 years of age and smoked 21.4 + /- 8.9 cigarettes/day .  Baseline FMD was similar in each treatment arm ( p = 0.499 ) and was predicted by BA diameter ( p < 0.001 ) , reactive hyperemia blood flow ( p < 0.001 ) , high-density lipoprotein cholesterol ( p = 0.001 ) , and carbon monoxide ( p = 0.012 ) levels . After 1 year , 36.2 % quit smoking . FMD increased by 1 % ( 6.2 + /- 4.4 % to 7.2 + /- 4.2 % ) after 1 year ( p = 0.005 ) in those who quit , but did not change ( p = 0.643 ) in those who continued to smoke . Improved FMD among quitters remained significant ( p = 0.010 ) after controlling for changes in brachial artery diameter , reactive hyperemia , low-density lipoprotein cholesterol , and the presence of a home smoking ban . CONCLUSIONS Despite weight gain , smoking cessation leads to prolonged improvements in endothelial function , which may mediate part of the reduced cardi 
    Output:
    
This review provides evidence for impaired peripheral endothelial function in COPD .