***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 Abstract — Flow-mediated dilatation ( FMD ) of conduit arteries is dependent on an intact endothelium , although the mechanisms are not fully understood . Using high-resolution ultrasound , we examined the role of endothelial mediators in radial artery dilatation in response to transient ( short period of reactive hyperemia ) and sustained ( prolonged period of reactive hyperemia , h and warming , or an incremental infusion of acetylcholine into the distal radial artery ) hyperemia . After short episodes of reactive hyperemia , FMD was abolished by local infusion of the nitric oxide synthesis inhibitor NGmonomethyl-l-arginine ( 5.3±1.2 % versus 0.7±0.7 % , P < 0.001 ) . In contrast , basal vessel diameter and dilatation after prolonged episodes of reactive hyperemia , h and warming , and distal infusion of acetylcholine were not attenuated by nitric oxide synthesis inhibition . Inhibition of cyclooxygenase or local autonomic nervous system blockade also had no effect on FMD .  Patients with hypercholesterolemia exhibited reduced FMD in response to transient hyperemia , but the response to sustained hyperemia was normal . These data suggest heterogeneity of endothelial responses to blood flow that are dependent on the characteristics of the flow stimulus . Dilatation after brief episodes of hyperemia is mediated by release of nitric oxide , whereas dilatation during sustained hyperemia is unaffected by NO synthesis inhibition . Hypercholesterolemia seems to differentially affect these pathways with impairment of the nitric oxide – dependent pathway and preservation of non nitric oxide – mediated dilatation to sustained flow stimuli BACKGROUND Since inflammation is believed to have a role in the pathogenesis of cardiovascular events , measurement of markers of inflammation has been proposed as a method to improve the prediction of the risk of these events . METHODS We conducted a prospect i ve , nested case-control study among 28,263 apparently healthy postmenopausal women over a mean follow-up period of three years to assess the risk of cardiovascular events associated with base-line levels of markers of inflammation . The markers included high-sensitivity C-reactive protein ( hs-CRP ) , serum amyloid A , interleukin-6 , and soluble intercellular adhesion molecule type 1 ( sICAM-1 ) . We also studied homocysteine and a variety of lipid and lipoprotein measurements .  Cardiovascular events were defined as death from coronary heart disease , nonfatal myocardial infa rct ion or stroke , or the need for coronary-revascularization procedures . RESULTS Of the 12 markers measured , hs-CRP was the strongest univariate predictor of the risk of cardiovascular events ; the relative risk of events for women in the highest as compared with the lowest quartile for this marker was 4.4 ( 95 percent confidence interval , 2.2 to 8.9 ) . Other markers significantly associated with the risk of cardiovascular events were serum amyloid A ( relative risk for the highest as compared with the lowest quartile , 3.0 ) , sICAM-1 ( 2.6 ) , interleukin-6 ( 2.2 ) , homocysteine ( 2.0 ) , total cholesterol ( 2.4 ) , LDL cholesterol ( 2.4 ) , apolipoprotein B-100 ( 3.4 ) , HDL cholesterol ( 0.3 ) , and the ratio of total cholesterol to HDL cholesterol ( 3.4 ) . Prediction models that incorporated markers of inflammation in addition to lipids were significantly better at predicting risk than models based on lipid levels alone ( P<0.001 ) . The levels of hs-CRP and serum amyloid A were significant predictors of risk even in the subgroup of women with LDL cholesterol levels below 130 mg per deciliter ( 3.4 mmol per liter ) , the target for primary prevention established by the National Cholesterol Education Program . In multivariate analyses , the only plasma markers that independently predicted risk were hs-CRP ( relative risk for the highest as compared with the lowest quartile , 1.5 ; 95 percent confidence interval , 1.1 to 2.1 ) and the ratio of total cholesterol to HDL cholesterol ( relative risk , 1.4 ; 95 percent confidence interval , 1.1 to 1.9 ) . CONCLUSIONS The addition of the measurement of C-reactive protein to screening based on lipid levels may provide an improved method of identifying persons at risk for cardiovascular events BACKGROUND Brachial artery flow-mediated dilation ( FMD ) may predict cardiovascular events in selected high-risk patients . Whether FMD testing predicts cardiovascular events in asymptomatic , lower risk individuals from the general population is unknown . METHODS AND RESULTS As a part of a multi-ethnic , prospect i ve cohort study , the Northern Manhattan Study , we examined FMD by high-resolution ultrasonography in 842 community participants who were free of stroke or myocardial infa rct ion . Lower FMD levels predicted cardiovascular events ( myocardial infa rct ion , stroke and vascular death ) at 36 months of follow-up ( hazard ratio (HR)=1.12 for every 1 % decrease in FMD , 95 % CI 1.01 - 1.25 , p=0.03 ) . The risk of events in patients with FMD in the lower two tertiles ( FMD<7.5 % ) was significantly higher than those in the highest tertile ( HR=3.28 , 95 % CI 1.07 - 10.06 , p=0.04 for lowest versus highest tertile , and HR=3.05 , 95 % CI 1.03 - 9.66 , p=0.04 for middle versus highest tertile ) . In a multivariate analysis including cardiovascular risk factors , the increase in risk associated with FMD was no longer statistically significant . CONCLUSIONS Non-invasive FMD testing predicts incident cardiovascular events in this multi-ethnic , population -based sample , but its predictive value is not independent of cardiovascular risk factors Background Previous studies have suggested that long-term use of β agonists to treat chronic obstructive pulmonary disease ( COPD ) may increase the risk of cardiovascular adverse events . In this post hoc analysis , data from the TOwards a Revolution in COPD Health ( TORCH ) study were used to investigate whether use of the long-acting β2 agonist salmeterol over 3 years increased the risk of cardiovascular adverse events in patients with moderate to severe COPD . Methods TORCH was a r and omised , double-blind , placebo controlled study conducted at 444 centres in 42 countries . Patients ( n=6184 ; safety population ) received twice daily combined salmeterol 50 μg plus fluticasone propionate 500 μg ( SFC ) , either component alone , or placebo . Adverse events were recorded every 12 weeks for 3 years . Results The probability of having a cardiovascular adverse event by 3 years was 24.2 % for placebo , 22.7 % for salmeterol , 24.3 % for fluticasone propionate and 20.8 % for SFC . Although a history of myocardial infa rct ion doubled the probability of cardiovascular adverse events , the event rates remained similar across treatment groups . Conclusion Post hoc analysis of the 3-year TORCH data set showed that salmeterol alone or in combination ( SFC ) did not increase the risk of cardiovascular events in patients with moderate to severe COPD BACKGROUND Ischemic heart disease and peripheral vascular diseases are prevalent in COPD and it is estimated that any 10 % decrease in forced expiratory volume in 1 second ( FEV1 ) is associated with 30 % increased cardiovascular risk of death . Endothelial dysfunction may be one of the mechanistic pathways that link between COPD and cardiovascular mortality . Our aim was to study the vascular reactivity of patients with stable COPD and to try to correlate endothelial dysfunction , vascular reactivity and functional capacity of these patients that eventually may lead to cardiovascular mortality . METHODS This was a prospect i ve study . Twenty-three consecutive ambulatory COPD patients were enrolled . All were smoking men , aged 64.4 ± 8.4 years . Twenty-two healthy volunteers aged 44.7 ± 11.7 years , BMI of 25.2 ± 4.2 , height of 172 ± 8 cm served as the control group  . Vascular studies included endothelial function and ankle brachial index . RESULTS Baseline diameter of the brachial artery was larger in COPD patients compared with controls . The absolute change in diameter post hyperemia was significantly less in patients ( 0.004 ± 0.02 cm vs. 0.05 ± 0.02 cm , p<0.001 ) and COPD patients responded to hyperemia by constriction instead of dilatation ( FMD% was -0.6 ± 6.3 % in patients vs. 15.6 ± 7.6 % in controls , p<0.001 ) . There was no difference in ABI in patients and controls ( 0.95 ± 0.26 vs. 1.06 ± 0.16 , p=0.07 ) . DISCUSSION We found that patients with COPD have dilated arteries , have impaired ability to respond to high shear stress that triggers nitric oxide dependent flow mediated dilatation , and have also impaired ability to function - represented by the poor 6 minute walk test Background : Cardiovascular diseases are prevalent in people with chronic obstructive pulmonary disease ( COPD ) . We hypothesized that endothelial dysfunction could be a marker of the proatherogen status in COPD . Methods and results : We measured endothelial dysfunction by flow-mediated dilation ( FMD ) and after sublingual administration of nitroglycerin ( nitrate-mediated dilation : NMD ) in 44 COPD patients and 48 controls . Compared with controls COPD patients had worse mean FMD ( 5.4 % vs 8.2 % , P < .001 ) and NMD ( 12.0 % vs 13.9 % , P = .007 ) . FMD was inversely related to FEV1/VC ratio ( r = −0.327 , P = .030 ) . The negative association between COPD and FMD was confirmed after correction for potential confounders in a multiple linear regression model ( β = −0.019 , P = .002 ) . In the same model NMD ( β = 0.396 , P < .001 ) was positively associated with FMD . Conclusions : Endothelial-dependent and , to a lesser extent , endothelial-independent dilations are significantly impaired in COPD , and the impairment is proportional to the severity of bronchial obstruction BACKGROUND Long-acting beta-agonists and inhaled corticosteroids are used to treat chronic obstructive pulmonary disease ( COPD ) , but their effect on survival is unknown . METHODS We conducted a r and omized , double-blind trial comparing salmeterol at a dose of 50 microg plus fluticasone propionate at a dose of 500 microg twice daily ( 
    Output:
    
Meta-regression models show that a more severe degree of airway obstruction is associated with a more severe FMD impairment in COPD patients than in controls .
Regression analyses confirm that the association between COPD and endothelial dysfunction is independent of baseline smoking status and most traditional cardiovascular risk factors .
In conclusion , COPD is significantly and independently associated with endothelial dysfunction .