human
***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: OBJECTIVE This study was performed to characterize the risk of stroke in elderly patients with recurrent intermittent atrial fibrillation ( AF ) . BACKGROUND Although intermittent AF is common , relatively little is known about the attendant risk of stroke . METHODS A longitudinal cohort study was performed comparing 460 participants with intermittent AF with 1,552 with sustained AF treated with aspirin in the Stroke Prevention in Atrial Fibrillation studies and followed for a mean of two years . Independent risk factors for ischemic stroke were identified by multivariate analysis . RESULTS Patients with intermittent AF were , on average , younger ( 66 vs. 70 years , p < 0.001 ) , were more often women ( 37 % vs. 26 % p < 0.001 ) and less often had heart failure ( 11 % vs. 21 % , p < 0.001 ) than those with sustained AF . The annualized rate of ischemic stroke was similar for those with intermittent ( 3.2 % ) and sustained AF ( 3.3 % ) . In patients with intermittent AF , independent predictors of ischemic stroke were advancing age ( relative risk [ RR ] = 2.1 per decade , p < 0.001 ) , hypertension ( RR = 3.4 , p = 0.003 ) and prior stroke ( RR = 4.1 , p = 0.01 ) . Of those with intermittent AF predicted to be high risk ( 24 % ) , the observed stroke rate was 7.8 % per year ( 95 % confidence interval 4.5 to 14 ) . CONCLUSIONS In this large cohort of AF patients given aspirin , those with intermittent AF had stroke rates similar to patients with sustained AF and similar stroke risk factors . Many elderly patients with recurrent intermittent AF have substantial rates of stroke and likely benefit from anticoagulation . High-risk patients with intermittent AF can be identified using the same clinical criteria that apply to patients with sustained AF BACKGROUND AND PURPOSE Nonvalvular atrial fibrillation ( AF ) is a strong , independent risk factor for stroke , but the absolute rate of stroke varies widely among AF patients , importantly influencing the potential benefit of antithrombotic prophylaxis . We explore factors associated with ischemic stroke in AF patients taking aspirin .  METHODS We performed multivariate logistic regression analysis of 2012 participants given aspirin alone or in combination with low , inefficacious doses of warfarin in the Stroke Prevention in Atrial Fibrillation I-III trials followed for a mean of 2.0 years , during which 130 ischemic strokes were observed . RESULTS Age ( relative risk [RR]=1.8 per decade , P<0.001 ) , female sex ( RR=1.6 , P=0.01 ) , history of hypertension ( RR=2.0 , P<0.001 ) , systolic blood pressure > 160 mm Hg ( RR=2.3 , P<0.001 ) , and prior stroke or transient ischemic attack ( RR=2.9 , P<0.001 ) were independently associated with increased stroke risk . Regular consumption of > /=14 alcohol-containing drinks per week was associated with reduced stroke risk ( adjusted RR=0.4 , P=0.04 ) . Among SPAF III participants , estrogen hormone replacement therapy was associated with a higher risk of ischemic stroke ( adjusted RR=3.2 , P=0.007 ) . With the use of these variables , a risk stratification scheme for primary prevention separated participants into those with high ( 7.1%/y , 22 % of the cohort ) , moderate ( 2.6%/y , 37 % of the cohort ) , and low ( 0.9%/y , 41 % of the cohort ) rates of stroke . Ischemic strokes in low-risk participants were less often disabling ( P<0.001 ) . CONCLUSIONS Patients with AF who have high and low rates of stroke during treatment with  aspirin can be identified . However , validation of our risk stratification scheme is necessary before it can be applied with confidence to clinical management . Postmenopausal estrogen replacement therapy and moderate alcohol consumption may additionally modify the risk of stroke in AF , but these findings require confirmation In a prospect i ve study of 312 older patients with chronic atrial fibrillation , at 36-month follow-up evaluation , new thromboembolic stroke developed in 162 of 312 patients ( 52 % ) . Significant independent risk factors for new thromboembolic stroke were prior stroke ( risk ratio = 1.6 ) , rheumatic mitral stenosis ( risk ratio = 2.0 ) , left ventricular ( LV ) hypertrophy ( risk ratio = 2.8 ) , abnormal LV ejection fraction ( risk ratio = 1.8 ) , serum total cholesterol ( risk ratio = 1.005 ) , and serum high-density lipoprotein cholesterol ( risk ratio = 0.96 ) OBJECTIVE To identify echocardiographic predictors of arterial thromboembolism in patients with nonrheumatic atrial fibrillation and to determine whether these add to clinical variables for risk stratification . DESIGN Cohort study of patients assigned to placebo in a r and omized clinical trial . SETTING Five hundred sixty-eight in patients and out patients with nonrheumatic atrial fibrillation assigned to placebo therapy at 15 U.S. medical centers from 1987 to 1989 in the Stroke Prevention in Atrial Fibrillation study . Patients were followed for a mean of 1.3 years . MEASUREMENTS M-mode and two-dimensional ( 2-D ) echocardiograms performed at study entry and interpreted by local cardiologists . The predictive value of 14 echocardiographic variables for later ischemic stroke or systemic embolism was assessed by multivariate analysis . MAIN RESULTS Left ventricular dysfunction from 2-D echocardiograms ( P = 0.003 ) and the size of the left atrium from M-mode echocardiograms ( P = 0.02 ) were the strongest independent predictors of later thromboembolism . Multivariate analysis of these two independent echocardiographic predictors with the three independent clinical predictors of thromboembolism ( history of hypertension , recent congestive heart failure , previous thromboembolism ) identified 26 % of the cohort with a low risk for thromboembolism ( 1.0 % per year ; 95 % Cl , 0.2 % to 4.0 % ) . Compared with risk stratification using clinical variables alone , echocardiographic results altered thromboembolic risk stratification in 18 % of the entire cohort and in 38 % of those without clinical risk factors . CONCLUSIONS Both left ventricular and left atrial variables are significant predictors of thromboembolism in patients with nonvalvular atrial fibrillation . Our results challenge traditional views of the pathogenesis of ischemic stroke in patients with atrial fibrillation and suggest that st and ard echocardiography contributes to risk stratification , differentiating the one third of patients without clinical risk factors who are at increased risk for stroke from the remainder who may not need antithrombotic prophylaxis Abstract Chronic atrial fibrillation ( AF ) in the presence or absence of rheumatic valvular heart disease is associated with an increased incidence of stroke . 1,2 We reported in a prospect i ve study that at 27-month follow-up , echocardiographic left ventricular ( LV ) hypertrophy in elderly patients with systolic or diastolic hypertension was associated with an increased incidence of new atherothrombotic brain infa rct ion . 3 We also demonstrated in a prospect i ve study that at 3-year follow-up , risk factors for atherothrombotic brain infa rct ion were cigarette smoking , systolic or diastolic hypertension and diabetes mellitus in elderly men and systolic or diastolic hypertension , diabetes mellitus and obesity in elderly women . 4 This report correlates in elderly patients with chronic AF the prevalence of thromboembolic ( TE ) stroke with the presence or absence of rheumatic mitral stenosis , mitral anular calcium , valvular aortic stenosis , systolic or diastolic hypertension , prior myocardial infa rct ion , left atrial enlargement and LV hypertrophy BACKGROUND AND PURPOSE The risk of major vascular events after an initial episode of cerebral ischemia in patients with nonrheumatic atrial fibrillation ( NRAF ) varies from 2 % to 15 % in the first year and is approximately 5 % yearly thereafter . Few studies have reported on risk factors that can be used to identify high-risk subgroups within this patient population . METHODS We studied the predictive value of several easily obtainable clinical characteristics in a group of 375 placebo-treated patients with NRAF and a recent episode of transient or nondisabling cerebral ischemia who were entered in a multicenter clinical trial . The mean follow-up was 1.6 years . RESULTS By means of multivariate modeling , six independent variables were identified : history of previous thromboembolism , ischemic heart disease , enlarged cardiothoracic ratio on chest roentgenogram , systolic blood pressure greater than 160 mm Hg at study entry , NRAF for more than 1 year , and presence of an ischemic lesion on CT scan . These variables could also be used to stratify patients in low- , medium- , and high-risk subgroups for the other two arms of the trial , those treated with anticoagulation and aspirin .  Patients older than 75 years with three or more risk factors seemingly benefited less from both aspirin and anticoagulant treatment . CONCLUSIONS Easily obtainable patient characteristics are helpful in estimating the potential effect of adequate secondary prevention in patients with NRAF who recently suffered a transient ischemic attack or minor ischemic stroke CONTEXT Nonvalvular atrial fibrillation ( AF ) carries an increased risk for stroke , but absolute rates of stroke vary widely within the broad spectrum of AF patients . OBJECTIVE To prospect ively vali date a risk stratification scheme identifying patients with AF with low rates of stroke when given aspirin .  DESIGN Prospect i ve cohort study with mean duration of follow-up of 2.0 years , conducted between 1993 and 1997 . SETTING Outpatient clinics affiliated with academic medical centers . PATIENTS Patients with AF categorized as " low risk " based on the absence of 4 prespecified thromboembolic risk factors : recent congestive heart failure or left ventricular fractional shortening of 25 % or less , previous thromboembolism , systolic blood pressure greater than 160 mm Hg , or female sex at age older than 75 years . INTERVENTION All participants given aspirin , 325 mg/d . MAIN OUTCOME MEASURES Ischemic stroke ( considered disabling when Rankin score was II or worse 1 - 3 months later ) and systemic embolism ( primary events ) . RESULTS Among 892 participants , the mean ( SD ) age was 67 ( 10 ) years , 78 % were men , and histories of hypertension , diabetes , and ischemic heart disease were present in 46 % , 13 % , and 16 % , respectively . The rate of primary events was 2.2 % per year ( 95 % confidence interval [ CI ] , 1.6%-3.0 % ) , of ischemic stroke was 2.0 % per year ( 95 % CI , 1.5%-2.8 % ) , and of disabling ischemic strokes was 0.8 % per year ( 95 % CI , 0.5%-1.3 % ) . Those with a history of hypertension had a higher rate of primary events ( 3.6 % per year ) than those with no history of hypertension ( 1.1 % per year ) ( P<.001 ) . The rate of disabling ischemic stroke was low in those with and without a history of hypertension ( 1.4 % per year and 0.5 % per year , respectively ) . The rate of major bleeding during aspirin therapy was 0.5 % per year . CONCLUSION Patients with AF who have relatively low rates of ischemic stroke , particularly disabling stroke , during treatment with aspirin can be reliably identified PURPOSE R and omized controlled trials have demonstrated that anticoagulant therapy is very effective at preventing stroke among patients with nonrheumatic atrial fibrillation . However , these trials have reported too few strokes for powerful risk factor analysis . Observational studies may provide additional information . The purpose of this study was to identify risk factors in a larger number of patients with stroke and nonrheumatic atrial fibrillation , using case-control methodology . PATIENTS AND METHODS We identified all patients discharged from one hospital over an 8-year period who met our case definition of nonrheumatic atrial fibrillation and ischemic stroke ( n = 134 ) , and compared them with contemporaneous control subjects who were discharged with nonrheumatic atrial fibrillation without stroke ( n = 131 ) . RESULTS Cases and controls were similar in terms of duration of atrial fibrillation ; proportion with paroxysmal atrial fibrillation ; percentage with a past medical history of angina , myocardial infa rct ion , congestive heart failure , diabetes , or smoking ; and mean left atrial size . In contrast , cases were significantly older than controls ( 78.5 versus 74.8 years , p = 0.002 ) and more likely to have a history of hypertension ( 55 % versus 38 % , p =  
    Output:
    
agent
Few models had addressed the cumulative nature of risk factors where a combination of risk factors would confer a greater risk than either factor alone .
In patients at high risk of stroke , anticoagulation is cost effective , but not for those with a low risk of stroke .
***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: OBJECTIVE This study was performed to characterize the risk of stroke in elderly patients with recurrent intermittent atrial fibrillation ( AF ) . BACKGROUND Although intermittent AF is common , relatively little is known about the attendant risk of stroke . METHODS A longitudinal cohort study was performed comparing 460 participants with intermittent AF with 1,552 with sustained AF treated with aspirin in the Stroke Prevention in Atrial Fibrillation studies and followed for a mean of two years . Independent risk factors for ischemic stroke were identified by multivariate analysis . RESULTS Patients with intermittent AF were , on average , younger ( 66 vs. 70 years , p < 0.001 ) , were more often women ( 37 % vs. 26 % p < 0.001 ) and less often had heart failure ( 11 % vs. 21 % , p < 0.001 ) than those with sustained AF . The annualized rate of ischemic stroke was similar for those with intermittent ( 3.2 % ) and sustained AF ( 3.3 % ) . In patients with intermittent AF , independent predictors of ischemic stroke were advancing age ( relative risk [ RR ] = 2.1 per decade , p < 0.001 ) , hypertension ( RR = 3.4 , p = 0.003 ) and prior stroke ( RR = 4.1 , p = 0.01 ) . Of those with intermittent AF predicted to be high risk ( 24 % ) , the observed stroke rate was 7.8 % per year ( 95 % confidence interval 4.5 to 14 ) . CONCLUSIONS In this large cohort of AF patients given aspirin , those with intermittent AF had stroke rates similar to patients with sustained AF and similar stroke risk factors . Many elderly patients with recurrent intermittent AF have substantial rates of stroke and likely benefit from anticoagulation . High-risk patients with intermittent AF can be identified using the same clinical criteria that apply to patients with sustained AF BACKGROUND AND PURPOSE Nonvalvular atrial fibrillation ( AF ) is a strong , independent risk factor for stroke , but the absolute rate of stroke varies widely among AF patients , importantly influencing the potential benefit of antithrombotic prophylaxis . We explore factors associated with ischemic stroke in AF patients taking aspirin .  METHODS We performed multivariate logistic regression analysis of 2012 participants given aspirin alone or in combination with low , inefficacious doses of warfarin in the Stroke Prevention in Atrial Fibrillation I-III trials followed for a mean of 2.0 years , during which 130 ischemic strokes were observed . RESULTS Age ( relative risk [RR]=1.8 per decade , P<0.001 ) , female sex ( RR=1.6 , P=0.01 ) , history of hypertension ( RR=2.0 , P<0.001 ) , systolic blood pressure > 160 mm Hg ( RR=2.3 , P<0.001 ) , and prior stroke or transient ischemic attack ( RR=2.9 , P<0.001 ) were independently associated with increased stroke risk . Regular consumption of > /=14 alcohol-containing drinks per week was associated with reduced stroke risk ( adjusted RR=0.4 , P=0.04 ) . Among SPAF III participants , estrogen hormone replacement therapy was associated with a higher risk of ischemic stroke ( adjusted RR=3.2 , P=0.007 ) . With the use of these variables , a risk stratification scheme for primary prevention separated participants into those with high ( 7.1%/y , 22 % of the cohort ) , moderate ( 2.6%/y , 37 % of the cohort ) , and low ( 0.9%/y , 41 % of the cohort ) rates of stroke . Ischemic strokes in low-risk participants were less often disabling ( P<0.001 ) . CONCLUSIONS Patients with AF who have high and low rates of stroke during treatment with  aspirin can be identified . However , validation of our risk stratification scheme is necessary before it can be applied with confidence to clinical management . Postmenopausal estrogen replacement therapy and moderate alcohol consumption may additionally modify the risk of stroke in AF , but these findings require confirmation In a prospect i ve study of 312 older patients with chronic atrial fibrillation , at 36-month follow-up evaluation , new thromboembolic stroke developed in 162 of 312 patients ( 52 % ) . Significant independent risk factors for new thromboembolic stroke were prior stroke ( risk ratio = 1.6 ) , rheumatic mitral stenosis ( risk ratio = 2.0 ) , left ventricular ( LV ) hypertrophy ( risk ratio = 2.8 ) , abnormal LV ejection fraction ( risk ratio = 1.8 ) , serum total cholesterol ( risk ratio = 1.005 ) , and serum high-density lipoprotein cholesterol ( risk ratio = 0.96 ) OBJECTIVE To identify echocardiographic predictors of arterial thromboembolism in patients with nonrheumatic atrial fibrillation and to determine whether these add to clinical variables for risk stratification . DESIGN Cohort study of patients assigned to placebo in a r and omized clinical trial . SETTING Five hundred sixty-eight in patients and out patients with nonrheumatic atrial fibrillation assigned to placebo therapy at 15 U.S. medical centers from 1987 to 1989 in the Stroke Prevention in Atrial Fibrillation study . Patients were followed for a mean of 1.3 years . MEASUREMENTS M-mode and two-dimensional ( 2-D ) echocardiograms performed at study entry and interpreted by local cardiologists . The predictive value of 14 echocardiographic variables for later ischemic stroke or systemic embolism was assessed by multivariate analysis . MAIN RESULTS Left ventricular dysfunction from 2-D echocardiograms ( P = 0.003 ) and the size of the left atrium from M-mode echocardiograms ( P = 0.02 ) were the strongest independent predictors of later thromboembolism . Multivariate analysis of these two independent echocardiographic predictors with the three independent clinical predictors of thromboembolism ( history of hypertension , recent congestive heart failure , previous thromboembolism ) identified 26 % of the cohort with a low risk for thromboembolism ( 1.0 % per year ; 95 % Cl , 0.2 % to 4.0 % ) . Compared with risk stratification using clinical variables alone , echocardiographic results altered thromboembolic risk stratification in 18 % of the entire cohort and in 38 % of those without clinical risk factors . CONCLUSIONS Both left ventricular and left atrial variables are significant predictors of thromboembolism in patients with nonvalvular atrial fibrillation . Our results challenge traditional views of the pathogenesis of ischemic stroke in patients with atrial fibrillation and suggest that st and ard echocardiography contributes to risk stratification , differentiating the one third of patients without clinical risk factors who are at increased risk for stroke from the remainder who may not need antithrombotic prophylaxis Abstract Chronic atrial fibrillation ( AF ) in the presence or absence of rheumatic valvular heart disease is associated with an increased incidence of stroke . 1,2 We reported in a prospect i ve study that at 27-month follow-up , echocardiographic left ventricular ( LV ) hypertrophy in elderly patients with systolic or diastolic hypertension was associated with an increased incidence of new atherothrombotic brain infa rct ion . 3 We also demonstrated in a prospect i ve study that at 3-year follow-up , risk factors for atherothrombotic brain infa rct ion were cigarette smoking , systolic or diastolic hypertension and diabetes mellitus in elderly men and systolic or diastolic hypertension , diabetes mellitus and obesity in elderly women . 4 This report correlates in elderly patients with chronic AF the prevalence of thromboembolic ( TE ) stroke with the presence or absence of rheumatic mitral stenosis , mitral anular calcium , valvular aortic stenosis , systolic or diastolic hypertension , prior myocardial infa rct ion , left atrial enlargement and LV hypertrophy BACKGROUND AND PURPOSE The risk of major vascular events after an initial episode of cerebral ischemia in patients with nonrheumatic atrial fibrillation ( NRAF ) varies from 2 % to 15 % in the first year and is approximately 5 % yearly thereafter . Few studies have reported on risk factors that can be used to identify high-risk subgroups within this patient population . METHODS We studied the predictive value of several easily obtainable clinical characteristics in a group of 375 placebo-treated patients with NRAF and a recent episode of transient or nondisabling cerebral ischemia who were entered in a multicenter clinical trial . The mean follow-up was 1.6 years . RESULTS By means of multivariate modeling , six independent variables were identified : history of previous thromboembolism , ischemic heart disease , enlarged cardiothoracic ratio on chest roentgenogram , systolic blood pressure greater than 160 mm Hg at study entry , NRAF for more than 1 year , and presence of an ischemic lesion on CT scan . These variables could also be used to stratify patients in low- , medium- , and high-risk subgroups for the other two arms of the trial , those treated with anticoagulation and aspirin .  Patients older than 75 years with three or more risk factors seemingly benefited less from both aspirin and anticoagulant treatment . CONCLUSIONS Easily obtainable patient characteristics are helpful in estimating the potential effect of adequate secondary prevention in patients with NRAF who recently suffered a transient ischemic attack or minor ischemic stroke CONTEXT Nonvalvular atrial fibrillation ( AF ) carries an increased risk for stroke , but absolute rates of stroke vary widely within the broad spectrum of AF patients . OBJECTIVE To prospect ively vali date a risk stratification scheme identifying patients with AF with low rates of stroke when given aspirin .  DESIGN Prospect i ve cohort study with mean duration of follow-up of 2.0 years , conducted between 1993 and 1997 . SETTING Outpatient clinics affiliated with academic medical centers . PATIENTS Patients with AF categorized as " low risk " based on the absence of 4 prespecified thromboembolic risk factors : recent congestive heart failure or left ventricular fractional shortening of 25 % or less , previous thromboembolism , systolic blood pressure greater than 160 mm Hg , or female sex at age older than 75 years . INTERVENTION All participants given aspirin , 325 mg/d . MAIN OUTCOME MEASURES Ischemic stroke ( considered disabling when Rankin score was II or worse 1 - 3 months later ) and systemic embolism ( primary events ) . RESULTS Among 892 participants , the mean ( SD ) age was 67 ( 10 ) years , 78 % were men , and histories of hypertension , diabetes , and ischemic heart disease were present in 46 % , 13 % , and 16 % , respectively . The rate of primary events was 2.2 % per year ( 95 % confidence interval [ CI ] , 1.6%-3.0 % ) , of ischemic stroke was 2.0 % per year ( 95 % CI , 1.5%-2.8 % ) , and of disabling ischemic strokes was 0.8 % per year ( 95 % CI , 0.5%-1.3 % ) . Those with a history of hypertension had a higher rate of primary events ( 3.6 % per year ) than those with no history of hypertension ( 1.1 % per year ) ( P<.001 ) . The rate of disabling ischemic stroke was low in those with and without a history of hypertension ( 1.4 % per year and 0.5 % per year , respectively ) . The rate of major bleeding during aspirin therapy was 0.5 % per year . CONCLUSION Patients with AF who have relatively low rates of ischemic stroke , particularly disabling stroke , during treatment with aspirin can be reliably identified PURPOSE R and omized controlled trials have demonstrated that anticoagulant therapy is very effective at preventing stroke among patients with nonrheumatic atrial fibrillation . However , these trials have reported too few strokes for powerful risk factor analysis . Observational studies may provide additional information . The purpose of this study was to identify risk factors in a larger number of patients with stroke and nonrheumatic atrial fibrillation , using case-control methodology . PATIENTS AND METHODS We identified all patients discharged from one hospital over an 8-year period who met our case definition of nonrheumatic atrial fibrillation and ischemic stroke ( n = 134 ) , and compared them with contemporaneous control subjects who were discharged with nonrheumatic atrial fibrillation without stroke ( n = 131 ) . RESULTS Cases and controls were similar in terms of duration of atrial fibrillation ; proportion with paroxysmal atrial fibrillation ; percentage with a past medical history of angina , myocardial infa rct ion , congestive heart failure , diabetes , or smoking ; and mean left atrial size . In contrast , cases were significantly older than controls ( 78.5 versus 74.8 years , p = 0.002 ) and more likely to have a history of hypertension ( 55 % versus 38 % , p =  
    Output:
    