***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 —Endothelial function is impaired in coronary artery disease and may contribute to its clinical manifestations . Increased oxidative stress has been linked to impaired endothelial function in atherosclerosis and may play a role in the pathogenesis of cardiovascular events . This study was design ed to determine whether endothelial dysfunction and vascular oxidative stress have prognostic impact on cardiovascular event rates in patients with coronary artery disease . Methods and Results —Endothelium-dependent and -independent vasodilation was determined in 281 patients with documented coronary artery disease by measuring forearm blood flow responses to acetylcholine and sodium nitroprusside using venous occlusion plethysmography . The effect of the coadministration of vitamin C ( 24 mg/min ) was assessed in a subgroup of 179 patients .  Cardiovascular events , including death from cardiovascular causes , myocardial infa rct ion , ischemic stroke , coronary angioplasty , and coronary or peripheral bypass operation , were studied during a mean follow-up period of 4.5 years . Patients experiencing cardiovascular events ( n=91 ) had lower vasodilator responses to acetylcholine ( P < 0.001 ) and sodium nitroprusside ( P < 0.05 ) , but greater benefit from vitamin C ( P < 0.01 ) . The Cox proportional regression analysis for conventional risk factors demonstrated that blunted acetylcholine-induced vasodilation ( P = 0.001 ) , the effect of vitamin C ( P = 0.001 ) , and age ( P = 0.016 ) remained independent predictors of cardiovascular events . Conclusions —Endothelial dysfunction and increased vascular oxidative stress predict the risk of cardiovascular events in patients with coronary artery disease . These data support the concept that oxidative stress may contribute not only to endothelial dysfunction but also to coronary artery disease activity Allopurinol ameliorates endothelial dysfunction and arterial stiffness among patients without chronic kidney disease ( CKD ) , but it is unknown if it has similar effects among patients with CKD . Furthermore , because arterial stiffness increases left ventricular afterload , any allopurinol-induced improvement in arterial compliance might also regress left ventricular hypertrophy ( LVH ) . We conducted a r and omized , double-blind , placebo-controlled , parallel-group study in patients with stage 3 CKD and LVH . We r and omly assigned 67 subjects to allopurinol  at 300 mg/d  or placebo for 9 months ; 53 patients completed the study . We measured left ventricular mass index ( LVMI ) with cardiac magnetic resonance imaging ( MRI ) , assessed endothelial function by flow-mediated dilation ( FMD ) of the brachial artery , and evaluated central arterial stiffness by pulse-wave analysis . Allopurinol significantly reduced LVH ( P=0.036 ) , improved endothelial function ( P=0.009 ) , and improved the central augmentation index ( P=0.015 ) . This study demonstrates that allopurinol can regress left ventricular mass and improve endothelial function among patients with CKD . Because LVH and endothelial dysfunction associate with prognosis , these results call for further trials to examine whether allopurinol reduces cardiovascular events in patients with CKD and LVH Background —Forearm endothelial dysfunction , characterized by an impaired vasodilating response to acetylcholine ( ACh ) , may be associated with several cardiovascular risk factors , including essential hypertension . Although the prognostic value of coronary endothelial dysfunction has been demonstrated , that of forearm endothelial dysfunction is still unknown . Methods and Results —Endothelium-dependent and -independent vasodilation was investigated in 225 never-treated hypertensive patients ( age , 35 to 54 years ) by intra-arterial infusion of increasing doses of ACh and sodium nitroprusside . Patients were divided into tertiles on the basis of their increase in  ACh-stimulated forearm blood flow ( FBF ) from basal : group 1 , from 30 % to 184 % ; group 2 , from 185 % to 333 % ; and group 3 , from 339 % to 760 % increase from basal . During a mean follow-up of 31.5 of months ( range , 4 to 84 months ) , there were 29 major adverse events at the cardiac ( n=19 ) , cerebrovascular ( n=9 ) , or peripheral vascular ( n=1 ) level . Events included myocardial infa rct ion , angina , coronary revascularization procedures , stroke , transient cerebral ischemic attack , and aortoiliac occlusive disease . Event rate per 100 patient-years was 8.17 , 4.34 , and 2.02 in the first , second , and third tertiles of peak percent increase in FBF during ACh infusion . The excess risk associated with an FBF increase in the first tertile was significant ( relative risk , 2.084 ; 95 % CI , 1.25 to 3.48;P = 0.0049 ) after controlling for individual risk markers , including 24-hour ambulatory blood pressure . Conclusions —Our data suggest that forearm endothelial dysfunction is a marker of future cardiovascular events in patients with essential hypertension Background —In patients with chronic heart failure ( CHF ) , hyperuricemia is a common finding and is associated with reduced vasodilator capacity and impaired peripheral blood flow . It has been suggested that the causal link of this association is increased xanthine oxidase (XO)–derived oxygen free radical production and endothelial dysfunction . We therefore studied the effects of XO inhibition with allopurinol on endothelial function and peripheral blood flow in CHF patients after intra-arterial infusion and after oral administration in 2 independent placebo-controlled studies . Methods and Results —In 10 CHF patients with normal serum uric acid ( UA ) levels ( 315±42 & mgr;mol/L ) and 9 patients with elevated UA ( 535±54 & mgr;mol/L ) , endothelium-dependent ( acetylcholine infusion ) and endothelium-independent  ( nitroglycerin infusion ) vasodilation of the radial artery was determined . Coinfusion of allopurinol ( 600 & mgr;g/min ) improved endothelium-dependent but not endothelium-independent vasodilation in hyperuricemic patients ( P < 0.05 ) . In a double-blind , crossover design , hyperuricemic CHF patients were r and omly allocated to allopurinol 300 mg/d or placebo for 1 week . In 14 patients ( UA 558±21 & mgr;mol/L , range 455 to 743 & mgr;mol/L ) , treatment reduced UA by > 120 & mgr;mol/L in all patients ( mean reduction 217±15 & mgr;mol/L , P < 0.0001 ) . Compared with placebo , allopurinol  improved peak blood flow ( venous occlusion plethysmography ) in arms ( + 24 % , P = 0.027 ) and legs ( + 23 % , P = 0.029 ) . Flow-dependent flow improved by 58 % in arms ( P = 0.011 ) . Allantoin , a marker of oxygen free radical generation , decreased by 20 % after allopurinol treatment ( P < 0.001 ) . There was a direct relation between change of UA and improvement of flow-dependent flow  after allopurinol treatment ( r = 0.63 , P < 0.05 ) . Conclusions —In hyperuricemic CHF patients , XO inhibition with allopurinol improves peripheral vasodilator capacity and blood flow both locally and systemically Background —Impaired flow-dependent , endothelium-mediated vasodilation ( FDD ) in patients with chronic heart failure ( CHF ) results , at least in part , from accelerated degradation of nitric oxide by oxygen radicals . The mechanisms leading to increased vascular radical formation , however , remain unclear . Therefore , we determined endothelium-bound activities of extracellular superoxide dismutase ( ecSOD ) , a major vascular antioxidant enzyme , and xanthine-oxidase , a potent radical producing enzyme , and their relation to FDD in patients with CHF . Methods and Results —ecSOD and xanthine-oxidase activities , released from endothelium into plasma by heparin bolus injection , were determined in 14 patients with CHF and 10 control subjects .  FDD of the radial artery was measured using high-resolution ultrasound and was assessed before and after administration of the antioxidant vitamin C ( 25 mg/min ; IA ) . In patients with CHF , endothelium-bound ecSOD activity was substantially reduced ( 5.0±0.7 versus 14.4±2.6 U · mL−1 · min−1;P < 0.01 ) and closely related to FDD ( r = 0.61 ) . Endothelium-bound xanthine-oxidase activity was increased by > 200 % ( 38±10 versus 12±4 nmol O2·− · & mgr;L−1;P < 0.05 ) and inversely related to FDD ( r = −0.35 ) in patients with CHF . In patients with low ecSOD and high xanthine-oxidase activity , a greater benefit of vitamin C on FDD was observed , ie , the portion of FDD inhibited by radicals correlated negatively with ecSOD ( r = −0.71 ) but positively with xanthine-oxidase ( r = 0.75 ) . Conclusions —These results demonstrate that both increased xanthine-oxidase and reduced ecSOD activity are closely associated with increased vascular oxidative stress in patients with CHF . This loss of vascular oxidative balance likely represents a novel mechanism contributing to endothelial dysfunction in CHF Therapeutic strategies against free radicals have mostly focused on the augmentation of antioxidant defenses ( eg , vitamins C and E ) . A novel approach is to prevent free radical generation by the enzyme system xanthine oxidase . We examined whether the inhibition of xanthine oxidase with allopurinol can improve endothelial function in subjects with type 2 diabetes and coexisting mild hypertension compared with control subjects of a similar age . We examined 23 subjects ( 11 patients with type 2 diabetes and 12 healthy age-matched control subjects ) in 2 parallel groups . The subjects were administered 300 mg allopurinol in a r and omized , placebo-controlled study in which both therapies were administered for 1 month . Endothelial function was assessed with bilateral venous occlusion plethysmography , in which the forearm blood flow responses to intra-arterial infusions of endothelium-dependent and -independent vasodilators were measured . Allopurinol significantly increased the mean forearm blood flow response to acetylcholine by 30 % ( 3.16+/-1.21 versus 2.54+/-0.76 mL. 100 mL(-1 ) . min(-1 ) allopurinol versus placebo ; P=0.012 , 95 % CI 0.14 , 1.30 ) but did not affect the nitroprusside response in patients with type 2 diabetes . There was no significant impact on either endothelium-dependent or -independent vascular responses in age-matched control subjects . Allopurinol improved endothelial function to near-normal levels . Regarding markers of free radical activity , the level of malondialdehyde was significantly reduced ( 0.30+/-0.04 versus 0 . 34+/-0.05 micromol/L for allopurinol versus placebo , P=0.03 ) in patients with type 2 diabetes but not in control subjects . The xanthine oxidase inhibitor allopurinol improves endothelial dysfunction in patients with type 2 diabetes with mild hypertension but not in matched control subjects . In the former group , allopurinol restored endothelial function to near-normal levels Background — Allopurinol has been shown to improve endothelial function in chronic heart failure . This study aim ed to establish its mechanism of action and to construct a dose – response curve for the effect of allopurinol . Methods and Results — Two r and omized , placebo-controlled , double-blind , crossover studies were performed for 1 month on patients with New York Heart Association Class II – III chronic heart failure , comparing 300 mg allopurinol , 600 mg allopurinol , and placebo for the first study and 1000 mg probenecid versus placebo in the second study . Endothelial function was assessed by st and ard forearm venous occlusion plethysmography . Allopurinol 600 mg/d significantly increased forearm blood flow response to acetylcholine compared with both allopurinol 300 mg/d and placebo ( % change in forearm blood flow [ mean±SEM ] : 240.31±38.19 % versus 152.10±18.21 % versus 7 
    Output:
    
Allopurinol has an antioxidant property that might partially reverse endothelial dysfunction  in patients with certain comorbidities .
The importance of this property and the magnitude of the beneficial effect are likely to be related to the relative contribution of xanthine oxidase into the oxidative stress associated with different underlying pathologies