***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Objectives : To assess the clinical relevance ( functional outcome ) of a 3-month allopurinol regimen in patients with high serum uric acid ( SUA ) levels and acute ischemic stroke without considering the changes in SUA levels . Material s and Methods : In a r and omized , double-blind , controlled study , 70 patients ( 45 females , 25 males ) with acute ischemic stroke who had elevated levels of SUA were included . They were divided in two 35-patient groups to investigate the effect of 3 months of an allopurinol ( 200 mg/day ) regimen versus placebo on their functional outcome , which was evaluated using a modified Rankin scale . Results : The overall mean age was 68.9 ± 11.33 years ( range 27 - 89 ) . The final favorable functional status ( mRS = 0 - 2 ) was 23 ( 65.7 % ) and 14 ( 40.0 % ) in the treated and placebo groups , respectively , which was strongly associated with allopurinol consumption ( OR = 4.646 , p = 0.014 ) and age ≤70 years ( OR = 0.139 , p = 0.005 ) in patients with ischemic stroke after adjusting for confounders . There was no significant difference in death  between allopurinol-treated cases ( 3 ; 8.6 % ) and placebo-treated ones ( 6 ; 17.2 % ; p = 0.278 ) . Conclusion : Allopurinol treatment was well tolerated and improved the 3-month functional status of patients with acute ischemic stroke who had high levels of SUA without considering the decreasing effect of allopurinol on SUA Background —Accumulating evidence suggests a critical role for increased reactive oxygen species ( ROS ) production in left ventricular ( LV ) remodeling and dysfunction after myocardial infa rct ion ( MI ) . Increased expression of xanthine oxidase ( XO ) , a major source of ROS , has recently been demonstrated in experimental and clinical heart failure ; however , a potential role for LV remodeling processes remains unclear . We therefore studied the effect of long-term treatment with allopurinol , a potent XO inhibitor , on myocardial ROS production and LV remodeling and dysfunction after MI . Methods and Results —Mice with extensive anterior MI ( n=105 ) were r and omized to treatment with either vehicle or allopurinol ( 20 mg · kg−1 · d−1 by gavage ) for 4 weeks starting on day 1 after surgery . Infa rct size was similar among the groups . XO expression and activity were markedly increased in the remote myocardium of mice after MI , as determined by electron spin resonance spectroscopy . Myocardial ROS production was increased after MI but markedly reduced after allopurinol treatment . Importantly , allopurinol treatment substantially attenuated LV cavity dilatation and dysfunction after MI , as assessed by echocardiography , and markedly reduced myocardial hypertrophy and interstitial fibrosis . Conclusion —The present study reveals a novel beneficial effect of treatment with allopurinol , ie , a marked attenuation of LV remodeling processes and dysfunction after experimental MI . Allopurinol treatment therefore represents a potential novel strategy to prevent LV remodeling and dysfunction after MI Background Many epidemiological studies analyze the relationship between hyperuricemia and cardiovascular outcomes . This observational prospect i ve study investigates the association of serum uric acid ( SUA ) levels with adverse cardiovascular events and deaths in an elderly population affected by advanced atherosclerosis . Methods Two hundred and seventy six elderly patients affected by advanced atherosclerosis ( 217 males and 59 females ; aged 71.2 ± 7.8 years ) were included . All patients were assessed for history of cardiovascular disease , cancer , obesity and traditional risk factors . Patients were followed for approximately 31 ± 11 months . Major events were recorded during follow-up , defined as myocardial infa rct ion , cerebral ischemia , myocardial and /or peripheral revascularization and death . Results Mean SUA level was 5.47 ± 1.43 mg/dL ; then we further divided the population in two groups , according to the median value ( 5.36 mg/dL ) . During a median follow up of 31 months ( 5 to 49 months ) , 66 cardiovascular events , 9 fatal cardiovascular events and 14 cancer-related deaths have occurred . The patients with increased SUA level presented a higher significant incidence of total cardiovascular events ( HR : 1.867 , P = 0.014 , 95 % CI : 1.134–3.074 ) . The same patients showed a significant increased risk of cancer-related death ( HR : 4.335 , P = 0.025 , 95 % CI : 1.204–15.606 ) . Conclusions Increased SUA levels are independently and significantly associated with risk of cardiovascular events and cancer related death in a population of mainly elderly patients affected by peripheral vasculopathy A plethora of experimental evidence indicates that allopurinol reduces the formation of cytotoxic free radicals during myocardial ischemia and reperfusion . The purpose of this study was to evaluate the effect of allopurinol on cardiac performance and early mortality after coronary bypass surgery .  Allopurinol ( n = 89 ) or placebo ( n = 80 ) was administered to 169 patients before surgery . R and omization produced groups evenly matched for surgical risk factors . Hospital mortality rate in the placebo group was 14 of 80 ( 18 % ) in the allopurinol group 4 of 89 ( 4 % ) , p = 0.014 . Cardiac performance , scored by cardiac index and the need for ionotropic or mechanical support , was significantly better in the allopurinol group . More nonfatal complications occurred in the allopurinol group . When either a complication or death is termed an event , the proportion of events was equal in the two groups . No side effects were identified . We now administer allopurinol to all patients who are undergoing bypass surgery unless specifically contraindicated Background —Dilated cardiomyopathy is characterized by an imbalance between left ventricular performance and myocardial energy consumption . Experimental models suggest that oxidative stress result ing from increased xanthine oxidase ( XO ) activity contributes to this imbalance . Accordingly , we hypothesized that XO inhibition with intracoronary allopurinol improves left ventricular efficiency in patients with idiopathic dilated cardiomyopathy . Methods and Results — Patients ( n=9 ; ejection fraction , 29±3 % ) were instrumented to assess myocardial oxygen consumption ( M&OV0312;o2 ) , peak rate of rise of left ventricular pressure ( dP/dtmax ) , stroke work ( SW ) , and efficiency ( dP/dtmax/M&OV0312 ; o2 and SW/M&OV0312;o2 ) at baseline and after sequential infusions of intracoronary allopurinol ( 0.5 , 1.0 , and 1.5 mg/min , each for 15 minutes ) . Allopurinol caused a significant decrease in M&OV0312;o2 ( peak effect , −16±5%;P < 0.01 ; n=9 ) with no parallel decrease in dP/dtmax or SW and no change in ventricular load . The net result was a substantial improvement in myocardial efficiency ( peak effects : dP/dtmax/M&OV0312 ; o2 , 22±9 % , n=9 ; SW/M&OV0312 ; o2 , 40±17 % , n=6 ; both P < 0.05 ) . These effects were apparent despite concomitant treatment with st and ard heart failure therapy , including ACE inhibitors and & bgr;-blockers . XO and its parent enzyme xanthine dehydrogenase were more abundant in failing explanted human myocardium on immunoblot . Conclusions —These findings indicate that XO activity may contribute to abnormal energy metabolism in human cardiomyopathy . By reversing the energetic inefficiency of the failing heart , pharmacological XO inhibition represents a potential novel therapeutic strategy for the treatment of human heart failure Background — Oxidative stress may contribute to heart failure ( HF ) progression . Inhibiting xanthine oxidase in hyperuricemic HF patients may improve outcomes . Methods and Results — We r and omly assigned 253 patients with symptomatic HF , left ventricular ejection fraction ⩽40 % , and serum uric acid levels ≥9.5 mg/dL to receive allopurinol ( target dose , 600 mg daily ) or placebo  in a double-blind , multicenter trial . The primary composite end point at 24 weeks was based on survival , worsening HF , and patient global assessment . Secondary end points included change in quality of life , submaximal exercise capacity , and left ventricular ejection fraction . Uric acid levels were significantly reduced with allopurinol in comparison with placebo ( treatment difference , –4.2 [ –4.9 , –3.5 ] mg/dL and –3.5 [ –4.2 , –2.7 ] mg/dL at 12 and 24 weeks , respectively , both P<0.0001 ) . At 24 weeks , there was no significant difference in clinical status between the allopurinol- and placebo-treated patients ( worsened 45 % versus 46 % , unchanged 42 % versus 34 % , improved 13 % versus 19 % , respectively ; P=0.68 ) . At 12 and 24 weeks , there was no significant difference in change in Kansas City Cardiomyopathy Question naire scores or 6-minute walk distances between the 2 groups . At 24 weeks , left ventricular ejection fraction did not change in either group or between groups . Rash occurred more frequently with allopurinol ( 10 % versus 2 % , P=0.01 ) , but there was no difference in serious adverse event rates between the groups ( 20 % versus 15 % , P=0.36 ) . Conclusions — In high-risk HF patients with reduced ejection fraction and elevated uric acid levels , xanthine oxidase inhibition with allopurinol failed to improve clinical status , exercise capacity , quality of life , or left ventricular ejection fraction at 24 weeks . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00987415 The association of serum uric acid with cardiovascular disease  has been appreciated for nearly half a century ( 1 ) . Several prospect i ve studies have shown an association between baseline hyperuricemia and incident coronary heart disease , cardiovascular disease , and death ( 2 - 10 ) . Despite the strength of these associations , uric acid has not been established as a causal risk factor for cardiovascular disease . Instead , uric acid seems inextricably linked to hypertension , dyslipidemia , and disordered glucose metabolism , which play a causal role in the pathogenesis of cardiovascular disease . As such , uric acid may be merely a marker of risk for cardiovascular disease . Several recent reports , however , have attempted to dispel this notion ( 3 , 9 , 11 - 14 ) . Using data from the First National Health and Nutrition Examination Study ( NHANES I ) , Freedman and colleagues ( 3 ) demonstrated that each 60-mol/L increment in uric acid level was associated with a 48 % increase in risk for  incident ischemic heart disease among women . Furthermore , a growing body of laboratory and clinical evidence suggests that uric acid plays a role in platelet adhesiveness ( 15 - 17 ) , formation of free radicals ( 18 ) , and oxidative stress ( 19 , 20 ) . As a result of this growing controversy , we revisited this question in the Framingham Heart Study sample . Longer and more contemporary follow-up and more outcome events allowed us to exp and on a previous Framingham report [ 2 ] . In this paper , we describe the relation of baseline serum uric acid level to 1 ) incident coronary heart disease events [ death from coronary heart disease , recognized myocardial infa rct ion , and coronary insufficiency ] , 2 ) death from cardiovascular disease , and 3 ) death from all causes . Because previous studies ( 2 , 3 , 7 , 21 ) have suggested that uric acid is more strongly associated with adverse events in women than in men , we chose a priori to perform sex-specific analyses . Methods Study Sample The selection criteria and study design of the Framingham Heart Study and the Framingham Offspring Study have been described elsewhere ( 22 , 23 ) . Original participants of the Framingham Heart Study who took part in the 13th biennial examination ( 1972 to 1976 ) and adult participants in the first examination of the Framingham Offspring Study ( 1971 to 1975 ) were eligible for this investigation ( n=7940 ) . Blood sample s for uric acid measurement were obtained in 7650 ( 96.3 % ) persons . Participants were excluded ( n=887 ) for the following reasons : use of more than 2 g of salicylates per day ( n=17 ) , missing covariate or follow-up data ( n=117 ) , and prevalent cardiovascular disease ( n=753 ) . The remaining 6763 participants were followed prospect ively until 1994 . Baseline 
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This up date d meta- analysis does not suggest that XOI exert a large reduction in mortality but also can not exclude the possibility of substantial harm or benefit