***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 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 Increased cardiovascular mortality has been associated with rheumatoid arthritis ( RA ) . There have been reports indicating that tumor necrosis factor blockers may exert favorable but transient effects on lipid profile , flow-mediated vasodilation ( FMD ) of the brachial artery , and common carotid intima – media thickness ( ccIMT ) in RA . In this study , we assessed the effects of rituximab on FMD , ccIMT , and lipid profile .  Five female RA patients received two infusions of 1000 mg rituximab i.v . High-resolution B-mode ultrasound was used to assess brachial FMD and ccIMT . We also determined plasma total cholesterol ( TC ) , HDL-C , LDL-C , and triglyceride ( Tg ) levels . Assessment s were performed at baseline , as well as at weeks 2 , 6 , and 16 after the first infusion . Rituximab ( RTX ) treatment result ed in a rapid and sustained improvement in FMD . The mean improvement was 30 % , 22 % , and 81 % at weeks 2 , 6 , and 16 , respectively . RTX had little effect on atherosclerosis within this short period of time ; however , we observed 10 % , 9 % , and 2 % decreases in ccIMT at weeks 2 , 6 , and 16 , respectively . RTX therapy result ed in 3–11 % decrease in TC , as well as 14–35 % increase in HDL-C levels . Two infusions of RTX exerted early and sustained favorable effects on endothelial dysfunction , as well as plasma TC and HDL-C levels .  RTX may also decrease ccIMT ; however , longer follow-up is needed to assess the prolonged effects of RTX on vascular function and lipid profile in RA patients Objectives : Rheumatoid arthritis ( RA ) is associated with increased cardiovascular disease ( CVD ) risk that has been attributed to endothelial dysfunction and inflammation . Non‐steroidal anti‐inflammatory drugs ( NSAIDs ) and cyclo‐oxygenase (COX)‐2 inhibitors have been shown in some studies to improve endothelial function in subjects without RA . The aim of this study was to investigate the effects of COX inhibition on endothelial function in patients with RA . Methods : Patients with RA ( n = 37 ) were r and omized to receive a 2‐week course of either indomethacin ( 75 mg bd ) , rofecoxib ( 12.5 mg bd ) , or placebo in a double‐blind study . Endothelial function was measured using flow‐mediated dilation ( FMD ) of the brachial artery in response to reactive hyperaemia . Arterial stiffness was also assessed using pulse wave analysis ( PWA ) through the measurement of the aortic augmentation index ( AIx ) . Measurements of vascular function and inflammatory markers were taken before and at the end of the treatment period . Results : There were no significant differences in changes in FMD , AIx , blood pressure ( BP ) , serum creatinine , erythrocyte sedimentation rate ( ESR ) , or high‐sensitivity C‐reactive protein ( hsCRP ) between groups . However , compared with the other treatment groups , there was a tendency for systolic BP to decrease in the placebo group ( p = 0.063 ) and for creatinine to increase in the indomethacin and rofecoxib groups after treatment ( p = 0.054 ) . Conclusions : This study suggests that COX inhibition by indomethacin or rofecoxib do not improve endothelial function in patients with RA 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 Objectives : Vascular endothelial function and common carotid artery intima – medial thickness ( CCA‐IMT ) are well‐established surrogate markers for early atherosclerotic disease , which accounts for 30–40 % of excess mortality in rheumatoid arthritis ( RA ) patients . Our aim was to investigate whether long‐term treatment with anti‐tumour necrosis factor (TNF)α agents can modulate endothelial function and CCA‐IMT . Methods : Twelve patients with RA ( mean age 54.8±15 years ) on anti‐TNFα treatment ( seven adalimumab , five infliximab ) due to uncontrolled disease activity , with mean Disease Activity Score ( DAS28 ) 5.7 ( range 4.6–6.9 ) despite disease‐modifying anti‐rheumatic drugs ( DMARDs )  , were studied prospect ively . Patients were assessed at baseline and after 3 and 18 months for endothelial‐dependent vasodilatation , assessed by flow‐mediated vasodilatation ( FMD ) , endothelial‐independent vasodilatation and CCA‐IMT . RA disease activity and response to therapy were assessed by the DAS28 index . Results : After 18 months of treatment , 67 % of the patients were responders according to European League Against Rheumatism ( EULAR ) response criteria  . Anti‐TNFα treatment improved FMD ( from 7±4.3 % to 11.1±3.8 % , p = 0.026 ) whereas CCA‐IMT did not change significantly [ from 0.67 ( 0.4–1 ) to 0.68 ( 0.39–1.2 ) mm ; mean change 0.01 ( −0.06 to 0.08 ) mm ] . Endothelial‐independent vasodilatation remained stable ( 20.4±7.3 % to 22.9±6.5 % , p = 0.4 ) . Conclusions : In this small cohort of patients with RA and no clinical ly overt cardiovascular disease ( CVD ) , after 18 months of treatment with anti‐TNFα agents , endothelial function improved significantly while CCA‐IMT remained stable . Longitudinal studies using more patients are needed to determine the clinical significance of these findings in relation to the risk of atherosclerosis OBJECTIVE To vali date the European League Against Rheumatism ( EULAR ) , the American College of Rheumatology ( ACR ) , and the World Health Organization (WHO)/International League Against Rheumatism ( ILAR ) response criteria for rheumatoid arthritis ( RA ) . METHODS EULAR response criteria were developed combining change from baseline and level of disease activity attained during follow up . In a trial comparing hydroxychloroquine and sulfasalazine , we studied construct ( radiographic progression ) , criterion ( functional capacity ) , and discriminant validity . RESULTS EULAR response criteria had good construct , criterion , and discriminant validity , ACR and WHO/ILAR criteria showed only good criterion validity . CONCLUSION EULAR response criteria showed better construct and discriminant validity than did the ACR and the WHO/ILAR response criteria for RA NG monomethyl-L-arginine ( L-NMMA ) , a specific inhibitor of the synthesis of endothelium-derived nitric oxide ( NO ) , was infused into the brachial arteries of healthy volunteers to study the role of NO in the control of forearm blood flow .  L-NMMA caused a 50 % fall in basal blood flow and attenuated the dilator response to infused acetylcholine but not that to glyceryl trinitrate . These results indicate that the dilator action of endothelium-derived NO contributes to the control of basal and stimulated regional blood flow in man . Impairment of production of NO might account for the abnormalities in vascular reactivity that characterise a wide variety of disease states Introduction In this study we aim ed to investigate whether there are indications of premature atherosclerosis , as measured by endothelial dependent flow-mediated dilation ( ED-FMD ) and intima media thickness ( IMT ) , in patients with very early RA , and to analyze its relation to biomarkers of endothelial dysfunction , taking inflammation and traditional cardiovascular disease ( CVD ) risk factors into account . Methods Patients from the three northern counties of Sweden diagnosed with early RA are followed in an ongoing prospect i ve study of CVD co-morbidity . Of these , all patients aged ≤60 years were consecutively included in this survey of CVD risk factors ( n = 79 ) . Forty-four age and sex matched controls were included . IMT of common carotid artery and ED-FMD of brachial artery were measured using ultrasonography . Blood was drawn for analysis of lipids , erythrocyte sedimentation rate ( ESR ) , C-reactive protein ( CRP ) , plasminogen activator inhibitor-1 ( PAI-1 ) , tissue plasminogen activator (tPA)-mass , VonWillebr and factor ( VWF ) , soluble intercellular adhesion molecule-1 ( sICAM ) , soluble vasc 
    Output:
    
RESULTS Vascular function and morphology was impaired in RA relative to healthy controls .
The majority of studies reported no associations between systemic inflammation and vascular function .
CONCLUSION The link between systemic inflammation and vascular function and morphology is not wholly supported by the available literature .