***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 
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    Input: Background and Purpose — The role of uric acid as a risk factor for myocardial infa rct ion is controversial , and little is known about its role as a risk factor for stroke . Recent evidence suggests that uric acid may be an important causal agent in cardiovascular disease , for example , by inducing renal disease and hence hypertension . We investigated the association between serum uric acid and coronary heart disease and stroke in a large prospect i ve population -based study . Methods — The study was based on 4385 participants of the Rotterdam Study who , at baseline ( 1990 to 1993 ) , were ≥55 years of age , free from stroke and coronary heart disease , and had blood taken . Follow-up for incident stroke and myocardial infa rct ion was complete until January 1 , 2002 . Data were analyzed with Cox proportional hazards models with adjustment for relevant confounders . Results — Average follow-up was 8.4 years . High serum uric acid levels were associated with risk of myocardial infa rct ion and stroke ; age- and sex-adjusted hazard ratios ( 95 % CIs ) for highest versus lowest quintile of uric acid were 1.68 ( 1.24 to 2.27 ) for cardiovascular disease ( 515 cases ) , 1.87 ( 1.12 to 3.13 ) for myocardial infa rct ion ( 194 cases ) , 1.57 ( 1.11 to 2.22 ) for stroke ( 381 cases ) , 1.77 ( 1.10 to 2.83 ) for ischemic stroke ( 205 cases ) , and 1.68 ( 0.68 to 4.15 ) for hemorrhagic stroke ( 46 cases ) . Adjustment for other vascular risk factors only slightly attenuated these associations . Associations were stronger in persons without hypertension than in those with hypertension . Conclusions — Uric acid is a strong risk factor for myocardial infa rct ion and stroke BACKGROUND The role of serum uric acid ( SUA ) as a risk factor for cardiovascular disease ( CVD ) remains controversial . Little is known about its predictive value for mortality from congestive heart failure ( CHF ) and stroke , particularly in elderly , post-menopausal women . METHODS The relation of SUA to risk of death from total CVD , CHF , stroke and coronary heart disease ( CHD ) was examined prospect ively in a large cohort of 28613 elderly Austrian women ( mean age 62.3 years ) , followed-up for a median of 15.2 years . Adjusted Cox proportional hazards models were calculated to evaluate SUA as an independent predictor for fatal CVD events . RESULTS SUA in the highest quartile ( > or=5.41 mg/dL ) was significantly associated with mortality from total CVD ( p<0.0001 ) , showing a clear dose-response relationship ; the adjusted hazard ratio ( 95%CI ) in comparison to the lowest SUA quartile was 1.35 ( 1.20 - 1.52 ) . In subgroup analyses SUA was independently predictive for deaths from acute and subacute ( p<0.0001 ) and chronic forms ( p=0.035 ) of CHD , yielding adjusted hazard ratios for the highest versus lowest SUA quartile of 1.58 ( 1.19 - 2.10 ) and 1.25 ( 1.01 - 1.56 ) , respectively . SUA was further significantly related to fatal CHF ( p<0.0001 ) and stroke ( p=0.018 ) ; the adjusted hazard ratios for the highest versus lowest SUA quartile were 1.50 ( 1.04 - 2.17 ) and 1.37 ( 1.09 - 1.74 ) , respectively . CONCLUSIONS These findings , for the first time , demonstrate that SUA is an independent predictor for all major forms of death from CVD including acute , subacute and chronic forms of CHD , CHF and stroke in elderly , post-menopausal women BACKGROUND The role of serum uric acid ( SUA ) as an independent risk factor for cardiovascular disease ( CVD ) remains controversial , and little is known about its prognostic importance for mortality from congestive heart failure ( CHF ) and stroke . Few large-scale epidemiologic studies with sufficient follow-up have addressed the association of SUA and CVD mortality in apparently healthy men across a wide age range . METHODS A cohort of 83 683 Austrian men ( mean age , 41.6 years ) was prospect ively followed for a median of 13.6 years . We used Cox proportional hazards models adjusted for established risk factors to evaluate SUA as an independent predictor for CVD mortality . RESULTS The highest quintile of SUA concentration ( > 398.81 mumol/L ) was significantly related to mortality from CHF ( P = 0.03 ) and stroke ( P < 0.0001 ) ; adjusted hazard ratios ( 95 % confidence interval ) for the highest vs lowest quintiles of SUA were 1.51 ( 1.03 - 2.22 ) and 1.59 ( 1.23 - 2.04 ) , respectively . SUA was not associated , however , with mortality from acute , subacute , or chronic forms of coronary heart disease ( CHD ) after adjustment for potential confounding factors ( P = 0.12 ) . Age was a significant effect modifier for the relation of SUA to fatal CHF ( P = 0.05 ) , with markedly stronger associations found in younger individuals . CONCLUSIONS Our study demonstrates for the first time in a large prospect i ve male cohort that SUA is independently related to mortality from CHF and stroke . Although increased SUA is not necessarily a causal risk factor , our results suggest the clinical importance of monitoring and intervention based on the presence of an increased SUA concentration , especially because SUA is routinely measured 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 Measurements and Definitions Medical histories and physical examinations were performed for each participant at every clinic visit . Systolic and diastolic blood pressure were measured twice in the left arm of seated participants by using a mercury-column sphygmomanometer positioned near eye level . The average of the two readings was used for each blood pressure variable . The diagnosis of hypertension was based on a systolic blood pressure of 140 mm Hg or higher , a diastolic blood pressure of 90 mm Hg or higher , or the current use of antihypertensive drugs ( 24 ) . Height and weight were measured at each examination , and body mass index was calculated as the weight in kilograms divided by the square of the height in meters . Participants who reported smoking at least one cigarette per day during the year before the examination were classified as current smokers . Alcohol use was ascertained by self-report and was categorized as ounces of ethanol consumed per week . Menopause was defined as the absence of menses for 1 year or more . Diabetes was defined on the basis of a nonfasting blood glucose level of 11.1 mmol/L ( 200 mg/dL ) or greater , a fasting blood glucose level of 7.8 mmol/L ( 140 mg/dL ) or greater , or the use of insulin or an oral hypoglycemic agent . Serum uric acid levels were measured with an autoanalyzer that used a phosphotungstic acid reagent ( 25 ) . Cholesterol levels were determined according to the Abell-Kendall method ( 26 ) . Outcome Events The primary outcome measures were incident coronary heart disease events , death from cardiovascular disease ( coronary heart disease , congestive heart failure , stroke , or other cardiovascular disease ) , and death from all causes . Coronary heart disease events included the following : death from coronary heart disease ( available information suggested coronary heart disease as the probable cause ) , recognized myocardial infa rct ion ( serial electrocardiographic changes leading to development of new pathologic Q waves , characteristic increase and decrease in serum myocardial markers with a suggestive clinical history , or evidence at necropsy of new or recent infa rct ion ) , and coronary insufficiency ( prolonged ischemic chest discomfort associated with transient repolarization abnormality , without criteria for myocardial infa rct ion ) . Events that were more equivocal , such as unrecognized myocardial infa rct ion and angina pectoris , were not included as coronary heart disease events for this analysis . A panel of three physicians determined the outcome events according to previously published criteria ( 27 ) after review ing Framingham Heart Study and outside hospital and physician records . Statistical Analysis Separate analyses were performed for men and women . All participants were divided according to sex-specific uric acid quintiles . Crude event rates were calculated for each quintile . Cox proportional-hazards regression models ( 28 ) were used to examine the relations of uric acid quintiles ( with quintile 1 as the reference category ) and the relation of uric acid level as a continuous variable to incidence of coronary heart disease events , cardiovascular disease mortality rates , and all-cause mortality rates . For comparative purpose s , hazard ratios were calculated without adjustment . For inferential purpose s , hazard ratios were calculated with adjustment for age only and also with adjustment for age and other clinical variables associated with uric acid level or atherosclerotic events : body mass index ( kg/m2 ) , diabetes ( yes/no ) , systolic blood pressure ( mm Hg ) , current diuretic use ( yes/no ) , use of antihypertensive medications other than diuretics ( yes/no ) , left ventricular hypertrophy shown on electrocardiography ( yes/no ) , total cholesterol level ( mmol/L ) , smoking status ( yes/no ) , alcohol use ( ounces consumed per week ) , and menopausal status in women ( yes/no ) . Post hoc subgroup analyses were done to determine any possible relations between quintiles of uric acid and the outcome events in participants stratified according to diuretic use and hypertension status . All analyses were performed on a Sun UltraSPARC computer ( Sun Microsystems , Mountain View , California ) using SAS software ( SAS Institute , Cary , North Carolina ) ( 29 ) . A two-sided P value less than 0.05 was the criterion for statistical significance . Results Participant Characteristics Table 1 shows the baseline clinical characteristics for men and women . The mean uric acid level was 379 mol/L in men ( range , 119 to 738 mol/L ) and 285 mol/L in women ( range , 24 to 696 mol/L ) . The effect of age on mean serum uric acid level is illustrated in the Figure . In men , uric acid levels changed minimally with age . In women , mean 
    Output:
    
Hyperuricemia may modestly increase the risks of both stroke incidence and mortality .