***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: CONTEXT Observational studies have shown that psychosocial factors are associated with increased risk for cardiovascular morbidity and mortality , but the effects of behavioral interventions on psychosocial and medical end points remain uncertain . OBJECTIVE To determine the effect of 2 behavioral programs , aerobic exercise training and stress management training , with routine medical care on psychosocial functioning and markers of cardiovascular risk . DESIGN , SETTING , AND PATIENTS R and omized controlled trial of 134 patients ( 92 male and 42 female ; aged 40 - 84 years ) with stable ischemic heart disease ( IHD ) and exercise-induced myocardial ischemia . Conducted from January 1999 to February 2003 . INTERVENTIONS Routine medical care ( usual care ) ; usual care plus supervised aerobic exercise training for 35 minutes 3 times per week for 16 weeks ; usual care plus weekly 1.5-hour stress management training for 16 weeks . MAIN OUTCOME MEASURES Self-reported measures of general distress ( General Health Question naire [ GHQ ] ) and depression ( Beck Depression Inventory [ BDI ] ) ; left ventricular ejection fraction ( LVEF ) and wall motion abnormalities ( WMA ) ; flow-mediated dilation ; and cardiac autonomic control ( heart rate variability during deep breathing and baroreflex sensitivity ) . RESULTS Patients in the exercise and stress management groups had lower mean ( SE ) BDI scores ( exercise : 8.2 [ 0.6 ] ; stress management : 8.2 [ 0.6 ] ) vs usual care ( 10.1 [ 0.6 ] ; P = .02 ) ; reduced distress by GHQ scores ( exercise : 56.3 [ 0.9 ] ; stress management : 56.8 [ 0.9 ] ) vs usual care ( 53.6 [ 0.9 ] ; P = .02 ) ; and smaller reductions in LVEF during mental stress testing ( exercise : -0.54 % [ 0.44 % ] ; stress management : -0.34 % [ 0.45 % ] ) vs usual care ( -1.69 % [ 0.46 % ] ; P = .03 ) . Exercise and stress management were associated with lower mean ( SE ) WMA rating scores ( exercise : 0.20 [ 0.07 ] ; stress management : 0.10 [ 0.07 ] ) in a subset of patients with significant stress-induced WMA at baseline vs usual care ( 0.36 [ 0.07 ] ; P = .02 ) . Patients in the exercise and stress management groups had greater mean ( SE ) improvements in flow-mediated dilation ( exercise : mean [ SD ] , 5.6 % [ 0.45 % ] ; stress management : 5.2 % [ 0.47 % ] ) vs usual care patients ( 4.1 % [ 0.48 % ] ; P = .03 ) . In a subgroup , those receiving stress management showed improved mean ( SE ) baroreflex sensitivity ( 8.2 [ 0.8 ] ms/mm Hg ) vs usual care ( 5.1 [ 0.9 ] ms/mm Hg ; P = .02 ) and significant increases in heart rate variability ( 193.7 [ 19.6 ] ms ) vs usual care ( 132.1 [ 21.5 ] ms ; P = .04 ) . CONCLUSION For patients with stable IHD , exercise and stress management training reduced emotional distress and improved markers of cardiovascular risk more than usual medical care alone BACKGROUND Improved endothelial function may contribute to the beneficial effects of cholesterol-lowering therapy . METHODS AND RESULTS In this r and omized , double-blind study , we compared the effect of 6 months of simvastatin ( 40 mg/d ) treatment with that of placebo on coronary endothelial vasomotor function in 60 patients with coronary artery disease .  Simvastatin lowered LDL-cholesterol by 40+/-12 % from 130+/-28 mg/dL ( P<0.001 ) . Peak intracoronary acetylcholine infusion produced epicardial coronary constriction at baseline in both the simvastatin ( -17+/-13 % ) and placebo ( -24+/-16 % ) groups . After treatment , acetylcholine produced less constriction in both groups ( -12+/-19 % and -15+/-14 % , respectively , P=0.97 ) . The increase in coronary blood flow during infusion of the peak dose of substance P was blunted at baseline in both the simvastatin ( 42+/-50 % ) and placebo ( 55+/-71 % ) groups , reflecting impaired endothelium-dependent dilation of coronary microvessels . After treatment , the flow increase was 82+/-81 % in the simvastatin group and 63+/-53 % in the placebo group ( P=0.16 ) . CONCLUSIONS Six months of cholesterol-lowering therapy has no significant effect on coronary endothelial vasomotor function in the study population of patients with coronary artery disease and mildly elevated cholesterol levels . These findings suggest that the effects of cholesterol lowering on endothelial function are more complex than previously thought Abstract Objective To establish the predictive accuracy of the Framingham risk score for coronary heart disease in a representative British population . Design Prospect i ve cohort study . Setting 24 towns in the United Kingdom . Participants 6643 British men aged 40 - 59 years and free from cardiovascular disease at entry into the British regional heart study . Main outcome measures Comparison of observed 10 year coronary heart disease mortality and event rates with predicted rates for each individual , using the relevant Framingham risk equation . Results Of 6643 men , 2.8 % ( 95 % confidence interval 2.4 % to 3.2 % ) died from coronary heart disease compared with 4.1 % predicted ( relative overestimation 47 % , P < 0.0001 ) . A fatal or non-fatal coronary heart disease event occurred in 10.2 % ( 9.5 % to 10.9 % ) of the men compared with 16.0 % predicted ( relative overestimation 57 % , P < 0.0001 ) . These relative degrees of overestimation were similar at all levels of coronary heart disease risk , so that overestimation of absolute risk was greatest for those at highest risk . A simple adjustment provided an improved level of accuracy . In a “ high risk score ” approach , most cases occur in the low risk group . In this case , 84 % of the deaths from coronary heart disease and non-fatal events occurred in the 93 % of men classified at low risk ( < 30 % in 10 years ) by the Framingham score . Conclusion Guidelines for the primary prevention of coronary heart disease advocate offering preventive measures to individuals at high risk . Currently recommended risk scoring methods derived from the Framingham study significantly overestimate the absolute coronary risk assigned to individuals in the United Kingdom OBJECTIVE The aim of this study was to determine whether HMGCoA reductase inhibitor with atorvastatin can modulate endothelial function in type II diabetics having average cholesterol and no prior cardiovascular disease . MATERIAL AND METHOD Type II diabetics , with no prior cardiovascular events and total cholesterol at admission of < or = 200 mg/dl or LDL < or = 140 mg/dl , were r and omized to placebo ( n = 20 ) or atorvastatin 20 mg daily ( n = 22 ) for 30 weeks . Brachial artery endothelium-dependent dilatation or flow-mediated dilatation ( FMD ) and endothelium-independent dilatation or nitroglycerine-mediated dilatation ( NTGMD ) were measured at baseline and after thirty weeks of treatment . RESULTS Baseline clinical characteristics were similar at admission in both groups . After thirty weeks of treatment , the FMD did not significantly change in either the atorvastatin or placebo group ( 4.11 + /- 1.05 % to 3.01 + /- 1.27 % vs 5.75 + /- 1.93 % to 6.45 + /- 1.41 % , respectively ; p = 0.46 by analysis of covariance ) . Similarly , the NTGM did not change in either group . CONCLUSION The addition of HMGCoA reductase inhibitor with atorvastatin did not improve endothelial function in type 2 diabetes having average cholesterol with no prior cardiovascular disease , despite an improvement of the lipid profile BACKGROUND The endothelium modulates vascular tone through release of vasodilating substances , such as endothelium-derived relaxing factors , and vasoconstricting substances , such as endothelin . Endothelin concentrations are elevated in humans with atherosclerosis and in hypercholesterolemic pigs . Furthermore , the endothelium-dependent vasodilator acetylcholine increases endothelin in hypercholesterolemia in association with coronary vasoconstriction . The present study was design ed to test the hypotheses that coronary endothelial dysfunction in humans is characterized by enhanced coronary and circulating endothelin and that the vasoconstriction associated with acetylcholine results in further release of coronary endothelin . METHODS AND RESULTS Coronary and circulating endothelin concentrations were measured at baseline and during intracoronary acetylcholine administration in 20 patients undergoing diagnostic coronary angiography .  Patients were divided into two groups on the basis of their response to intracoronary acetylcholine . Group 1 ( n = 7 ) demonstrated a normal vasodilatory response , but group 2 ( n = 13 ) demonstrated coronary vasoconstriction . Baseline coronary and circulating endothelin concentrations ( as determined by coronary sinus and femoral artery measurements , respectively ) were higher in patients who responded to acetylcholine with coronary vasoconstriction ( group 2 ) than in group 1 patients ( coronary sinus , 15.9 + /- 1.0 pg/mL versus 7.1 + /- 1.0 pg/mL ; femoral , 14.1 + /- 0.9 pg/mL versus 6.8 + /- 1.0 pg/mL , respectively ; P < .01 ) . In response to intracoronary acetylcholine , a further increase in coronary endothelin was observed only in group 2 ; this increase correlated with changes in coronary artery diameter . CONCLUSIONS This study demonstrates that endothelin immunoreactivity is enhanced in the coronary and systemic circulation in humans with coronary endothelial dysfunction . Moreover , acetylcholine further increased coronary endothelin concentration in patients with coronary endothelial dysfunction and was associated with coronary vasoconstriction . These observations strongly support a role for endothelin as an early participant in and marker for coronary endothelial dysfunction in humans Background Coronary endothelial function and vasomotion are impaired in smokers without coronary disease , and this is thought to be due to increased oxidative stress . Methods and Results We used positron emission tomography to measure the coronary flow reserve , an integrated measure of coronary flow , through both the large epicardial coronary arteries and the microcirculation in 11 smokers and 8 control subjects before and after administration of the antioxidant vitamin C. At baseline , coronary flow reserve was reduced by 21 % in smokers compared with control subjects ( P < 0.05 ) but was normalized after vitamin C , whereas the drug had no effect in control subjects . Conclusions The present study is the first to demonstrate that the noxious prooxidant effects of smoking extend beyond the epicardial arteries to the coronary microcirculation and affect the regulation of myocardial blood flow .  Vitamin C restores coronary microcirculatory responsiveness and impaired coronary flow reserve in smokers , which provides evidence that the damaging effect of smoking is at least in part accounted for by an increased oxidative stress OBJECTIVE Endothelial dysfunction is considered an important early marker of atherosclerosis and cardiovascular risk and is currently used as a surrogate end point for cardiovascular risk in clinical trials . Type 2 diabetic patients show a characteristic dyslipidemia . Aggressive lipid lowering might be an effective method to improve endothelial function in these patients . RESEARCH DESIGN AND METHODS A r and omized , double-blind , placebo-controlled trial was completed to study the effect of 30 weeks ' administration of atorvastatin 10 mg and 80 mg on endothelial function , as assessed by B-mode ultrasound of the brachial artery , in 133 patients with type 2 diabetes without a history of cardiovascular disease . RESULTS Patients with diabetes and diabetic dyslipidemia had considerable endothelium-dependent and endothelium-independent dysfunction ; mean flow-mediated vasodilation ( SD ) was 3.16 % ( 3.56 ) , and mean response on sublingual nitroglycerin was 6.58 % ( 6.04 ) . Despite substantial lowering of all atherogenic lipid parameters , no improvement of endothelium-dependent vasodilatation was found ( P > 0.8 ) . CONCLUSIONS We observed considerable baseline endothelium-dependent and endothelium-independent dysfunction in patients with diabetes and diabetic dyslipidemia without a history of cardiovascular disease . Aggressive lipid lowering by administration of atorvastatin , result ing in substantial improvement of the lipid profile , did not reverse endothelial dysfunction This study assesses the prognost 
    Output:
    
Endothelial dysfunction , a functional expression of the inherent atherosclerotic risk representing an integrated index of both the overall CV risk-factor burden and the sum of all vasculoprotective factors in an individual , may serve as the missing link between CV risk factors and atherosclerotic disease .