title: Factors associated with ischemic stroke during aspirin therapy in atrial fibrillation: analysis of 2012 participants in the SPAF I-III clinical trials. The Stroke Prevention in Atrial Fibrillation (SPAF) Investigators. Gender Differences in the Risk of Ischemic Stroke and Peripheral Embolism in Atrial Fibrillation: The AnTicoagulation and Risk factors In Atrial fibrillation (ATRIA) Study Performance of stroke risk scores in older people with atrial fibrillation not taking warfarin: comparative cohort study from BAFTA trial Predictors of major vascular events in patients with a transient ischemic attack or minor ischemic stroke and with nonrheumatic atrial fibrillation. European Atrial Fibrillation Trial (EAFT) Study Group. Transesophageal Echocardiography To Assess Embolic Risk in Patients with Atrial Fibrillation Gender differences in stroke risk of atrial fibrillation patients on oral anticoagulant treatment. Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study.
abstract: 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 Background —Previous studies provide conflicting results about whether women are at higher risk than men for thromboembolism in the setting of atrial fibrillation ( AF ) . We examined data from a large contemporary cohort of AF patients to address this question . Methods and Results —We prospect ively studied 13 559 adults with AF and recorded data on patients ’ clinical characteristics and the occurrence of incident hospitalizations for ischemic stroke , peripheral embolism , and major hemorrhagic events through search ing vali date d computerized data bases and medical record review . We compared event rates by patient sex using multivariable log-linear regression , adjusting for clinical risk factors for stroke , and stratifying by warfarin use . We identified 394  ischemic stroke and peripheral embolic events during 15 494 person-years of follow-up off warfarin . After multivariable analysis , women had higher annual rates of thromboembolism off warfarin than did men ( 3.5 % versus 1.8 % ; adjusted rate ratio [ RR ] , 1.6 ; 95 % CI , 1.3 to 1.9 ) . There was no significant difference by sex in 30-day mortality after thromboembolism ( 23 % for both ) . Warfarin use was associated with significantly lower adjusted thromboembolism rates for both women and men ( RR , 0.4 ; 95 % CI , 0.3 to 0.5 ; and RR , 0.6 ; 95 % CI , 0.5 to 0.8 , respectively ) , with similar annual rates of major hemorrhage ( 1.0 % and 1.1 % , respectively ) . Conclusions —Women are at higher risk than men for AF-related thromboembolism off warfarin . Warfarin therapy appears be as effective in women , if not more so , than in men , with similar rates of major hemorrhage . Female sex is an independent risk factor for thromboembolism and should influence the decision to use anticoagulant therapy in persons with AF Objective To compare the predictive power of the main existing and recently proposed schemes for stratification of risk of stroke in older patients with atrial fibrillation . Design Comparative cohort study of eight risk stratification scores . Setting Trial of thromboprophylaxis in stroke , the Birmingham Atrial Fibrillation in the Aged ( BAFTA ) trial . Participants 665 patients aged 75 or over with atrial fibrillation based in the community who were r and omised to the BAFTA trial and were not taking warfarin throughout or for part of the study period . Main outcome measures Events rates of stroke and thromboembolism . Results 54 ( 8 % ) patients had an ischaemic stroke , four ( 0.6 % ) had a systemic embolism , and 13 ( 2 % ) had a transient ischaemic attack . The distribution of patients classified into the three risk categories ( low , moderate , high ) was similar across three of the risk stratification scores ( revised CHADS2 , NICE , ACC/AHA/ESC ) , with most patients categorised as high risk ( 65 - 69 % , n=460 - 457 ) and the remaining classified as moderate risk . The original CHADS2 ( Congestive heart failure , Hypertension , Age ≥75 years , Diabetes , previous Stroke ) score identified the lowest number as high risk ( 27 % , n=180 ) . The incremental risk scores of CHADS2 , Rietbrock modified CHADS2 , and CHA2DS2-VASc ( CHA2DS2-Vascular disease , Age 65 - 74 years , Sex ) failed to show an increase in risk at the upper range of scores . The predictive accuracy was similar across the tested schemes with C statistic ranging from 0.55 ( original CHADS2 ) to 0.62 ( Rietbrock modified CHADS2 ) , with all except the original CHADS2 predicting better than chance . Bootstrapped paired comparisons provided no evidence of significant differences between the discriminatory ability of the schemes . Conclusions Based on this single trial population , current risk stratification schemes in older people with atrial fibrillation have only limited ability to predict the risk of stroke . Given the systematic undertreatment of older people with anticoagulation , and the relative safety of warfarin versus aspirin in those aged over 70 , there could be a pragmatic rationale for classifying all patients over 75 as “ high risk ” until better tools are available 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 Transesophageal echocardiography visualizes the left atrium and its appendage and is more sensitive than transthoracic echocardiography for diagnosing thrombi of the left atrium and the left atrial appendage and spontaneous echocardiographic contrast of the left atrium [ 1 - 3 ] . The left atrium and especially the left atrial appendage are the presumed sites of thrombus formation and sources of arterial emboli in patients with atrial fibrillation [ 4 ] . Patients with atrial fibrillation and a history of stroke or embolism were shown to have a higher prevalence of thrombi of the left atrium or the left atrial appendage , a higher prevalence of spontaneous echocardiographic contrast , and a larger left atrial appendage than patients with no history of stroke or embolism [ 2 , 5 , 6 ] . However , whether these abnormalities are predictors for stroke or embolism remains controversial [ 7 , 8 ] . Furthermore , no studies have determined whether transesophageal echocardiography helps to assess risk for stroke or embolism in out patients with atrial fibrillation who have no history of stroke or embolism or whether transesophageal echocardiography is useful in the decision to initiate anticoagulation . We therefore performed a prospect i ve , multicenter study of out patients with atrial fibrillation who had not recently had stroke . We sought to determine whether thrombi of the left atrium or the left atrial appendage , spontaneous echocardiographic contrast , and size of the left atrial appendage are associated with stroke or embolism . Our hypothesis was that patients with thrombi of the left atrium or the left atrial appendage , spontaneous echocardiographic contrast , and enlargement of the left atrial appendage have a higher rate of stroke or embolism than do patients without these abnormalities . The baseline clinical and echocardiographic characteristics of our study sample have been reported elsewhere [ 9 ] . Methods Patient Recruitment Our study was conducted in Austria and Slovakia . At the beginning of the study , general practitioners and internists from surrounding participating centers were informed about the study and were asked to refer patients who had constant or intermittent atrial fibrillation . At each patient 's first visit , a cardiologist recorded baseline data , associated illnesses , clinical characteristics ( definitions of which are listed in Appendix 2 ) , and the cause of atrial fibrillation . A 12-lead electrocardiogram was recorded on 2 separate days . We excluded patients with prosthetic valves and those who were already receiving anticoagulation . Current therapy with aspirin was not an exclusion criterion . Patients who had mitral valve stenosis or had recently had stroke were excluded because anticoagulation was indicated for such conditions . For the definition of recent stroke , we chose a cutoff value of 1 year because a previous study reported that the risk for recurrent stroke was increased in patients who had had an ischemic event in the previous year [ 10 ] . Echocardiography For transthoracic echocardiography , 2.5- or 3.5-MHz probes were used . For M-mode measurements , we applied the recommendations of the American Society of Echocardiography [ 11 ] . M-mode measurements were performed on-line and were documented on printouts . Regional wall-motion and valvular abnormalities were recorded . In patients without regional wall-motion abnormalities , left ventricular systolic function was assessed by calculation of left ventricular fractional shortening . For transesophageal echocardiography , biplane 5-MHz probes were used in 64 % of the patients and monoplane 5-MHz probes were used in 36 % . After local anesthesia with lidocaine spray was administered , the probe was introduced into the nonse date d patients , who lay on their left side . The entire study was recorded on S-VHS videotapes . The cardiac chambers and valves were investigated by using all obtainable views [ 12 , 13 ] . Special care was taken to visualize the whole cavity of the left atrium and its appendage from different planes , with the tip of the probe slightly flexed . The size of the left atrial appendage was measured off-line . A frame that best visualized the left atrial appendage with respect to its orifice , extension , and delineation of borders was selected just before the QRS complex . The length of the left atrial appendage was defined as the distance between the limbus of the left superior pulmonary vein and the apex of the left atrial appendage ; the width of the left atrial appendage was defined as the longest distance between the lateral and ventricular left atrial appendage wall , measured in a line perpendicular to the course of the left atrial appendage curvature ; and the left atrial appendage area was defined as described elsewhere [ 14 ] . For the assessment of intra- and interobserver deviations , left atrial appendage size was measured 1 year after the initial measurement in 20 r and omly selected video recordings by the same observer and in 60 r and omly selected video recordings by three observers from different centers . A thrombus of the left atrium or left atrial appendage was considered definite if at least three of the following five criteria were present : clear borders , echogenicity different from that of surrounding structures , independent mobility , longest diameter greater than 15 mm , and evidence of thrombus in more than one imaging plane [ 15 ] . A second observer from a different center review ed video recordings to confirm diagnosis of thrombus of the left atrium or left atrial appendage . A thrombus was considered probable if only two criteria were present or if the observers disagreed . Spontaneous echocardiographic contrast was diagnosed in the presence of dynamic smoke-like echoes within the left atrium or left atrial appendage with a characteristic swirling motion that was distinct from white noise artifact [ 16 ] . When spontaneous echocardiographic contrast was suspected , the gain setting s were decreased in a stepwise manner to exclude artifact caused by excessive gain . The compression and gain controls were then adjusted to ensure the best possible visualization . Spontaneous echocardiographic contrast was not quantified . A second observer from a different center checked the diagnosis of spontaneous echocardiographic contrast by review ing all video recordings . When the observers disagreed about the presence or absence of spontaneous echocardiographic contrast , the decision made at the time of examination was chosen . This was done because spontaneous echocardiographic contrast was not always visible on review of the video recordings . Outcome Events Primary events were stroke and embolism that extended to viscera or extremities . Stroke was defined as acute onset of a focal neurologic deficit that lasted more than 24 hours and was consistent with a vascular event . Severity and subtypes of stroke were assessed according to established criteria [ 17 ] . Embolism extending to viscera or extremities was defined as a sudden onset of pain that was associated with typical findings on Doppler ultrasonography , angiography , surgery , or autopsy . Secondary events were the need for anticoagulation during follow-up in patients who were primarily receiving aspirin and death not caused by stroke or embolism . Death not caused by stroke or embolism was classified as cardiac or noncardiac on the basis of information from the treating physician and the patient 's family . Follow-up Visits took place 3 , 6 , 12 , 18 , and 24 months after study entry . After a follow-up period of at least 2 years ( ending in February 1994 ) , it was evident that the number of primary outcome events was low . We therefore prolonged the follow-up period and planned further visits , one to be held in 1994 and one to be held in 1995 . Patients who were unwilling or unable to attend the visits were contacted by telephone . Medical records were obtained for patients who had been admitted to a hospital . If a patient had died , an autopsy report or death certificate was obtained . Treatment and Ethical Considerations Although our study was design ed to be observational , we recommended antithrombotic treatment to the patients because of ethical considerations . Because patients with thrombi of the left atrium or left atrial appendage are considered to have a high risk for embolism , we recommended that they receive anticoagulation . The target range for the international normalized ratio was 2.0 to 3.0 , and the treating physicians monitored the ratio [ 5 , 18 ] . We recommended that the remaining patients receive aspirin , 160 mg/d , because preliminary data indicated that aspirin reduces the risk for stroke or embolism in patients with atrial fibrillation [ 19 ] . The institutional review board of the participating centers approved the study . Patients were informed about the background and the procedures of the trial , and informed consent was obtained according to the rules of each center . Statistical Analysis For baseline data , group comparisons were done by analysis of variance for normally distributed data and by the nonparametric Kruskal-Wallis test for data that were not normally distributed . If appropriate , we used the Scheffe post hoc test . The Wilk-Shapiro test was used to check for normality . Contingency table methods , including the chi-square test and the Fisher exact test , were used to analyze categorical data . We used the Cox proportional-hazards model to obtain estimates of relative risk and 95 % CIs for all univariate and multivariate analyses of time-to-event data . All tests were two-sided . The level of significance assumed was an level of 0.05 . We used SAS software ( SAS Institute , Cary , North Carolina ) for analyses . Role of Funding Sources The funding sources had no role in the collection , analysis , or interpretation of the data ; did not review the manuscript at any time ; and were not involved in su bmi tting the paper for publication . Results Patients Patients were recruited between January 1990 and February 1992 . Of the 474 The efficacy of adjusted-dose oral anticoagulant treatment ( OAT ) in the prevention of stroke in atrial fibrillation ( AF ) is well documented . Available data show that AF patients are widely heterogeneous in terms of ischaemic stroke risk . The role of female gender as a predictor of stroke risk is inconsistent , in particular it is unclear if warfarin treatment is able to prevent stroke equally in both sexes . We performed a prospect i ve study on 780 AF patients on OAT , followed by an Anticoagulation Clinic , to evaluate if female gender is a risk factor for stroke among patients on OAT  and if the quality of anticoagulation is different between genders . No difference was found in relation to the quality of anticoagulation between genders ( p=0.5 ) . During follow-up 33 patients had major bleedings ( rate 1.37 x 100 pt/yrs ) but no difference was found between genders in bleeding risk . Forty patients had ischaemic events [ rate 1.66 x 100 pt/yrs ; males rate 1.2 x 100 pt/yrs ; females rate 2.43 x 100 pt/yrs ; p=0.042 ; relative risk ( RR ) of females vs. males 2.0 ( 95 % confidence interval [ CI ] 1.3 - 3.1 ) ; p= 0.004 ] . The higher rate of ischaemic events in females with respect to males was confirmed at Cox regression analysis after correction for age ( p=0.009 ) . In addition , strokes occurring in females were more disabling , and RR for severe and fatal stroke , defined according to Modified Rankin scale , of females vs. males was 3.1 ( 95 % CI 1.3 - 6.5 ; p=0.001 ) . In conclusion , our data show a higher risk of stroke in anticoagulated AF females with respect to males , despite a similar quality of anticoagulation AIMS We aim ed to investigate the prevalence and incidence of atrial fibrillation ( AF )  in a large European population -based study . METHODS AND RESULTS The study is part of the Rotterdam study , a population -based prospect i ve cohort study among subjects aged 55 years and above . The prevalence at baseline was assessed in 6808 participants .  Incidence of AF was investigated during a mean follow-up period of 6.9 years in 6432 persons . We identified 376 prevalent and 437 incident cases . Overall prevalence was 5.5 % , rising from 0.7 % in the age group 55 - 59 years to 17.8 % in those aged 85 years and above . The overall incidence rate was 9.9/1000 person-years . The incidence rate in the age group 55 - 59 years was 1.1/1000 person-years , rose to 20.7/1000 person-years in the age group 80 - 84 years and stabilized in those aged 85 years and above . Prevalence and incidence were higher in men than in women . The lifetime risk to develop AF at the age of 55 years was 23.8 % in men and 22.2 % in women . CONCLUSION In this prospect i ve study in a European population , the prevalence and incidence of AF increased with age and were higher in men than in women . The high lifetime risk to develop AF was similar to North American epidemiological data
target: Women with AF are at increased risk of stroke , particularly elderly women .
background: BACKGROUND Atrial fibrillation ( AF ) increases the risk of stroke , but this risk is not homogenous .
  Many risk factors contribute to stroke risk however , the evidence for female sex as a risk factor is less well-established .
  AIM To perform a systematic review and meta- analysis of the available evidence to establish if female sex is a risk factor for stroke/thromboembolism among patients with AF .