The Adherence eValuation After Ischemic Stroke Longitudinal (AVAIL) registry: design, rationale, and baseline patient characteristics. Combining Multiple Approaches for the Secondary Prevention of Vascular Events After Stroke: A Quantitative Modeling Study Atherogenic Dyslipidemia and Residual Cardiovascular Risk in Statin-Treated Patients Pioglitazone for secondary prevention after ischemic stroke and transient ischemic attack: rationale and design of the Insulin Resistance Intervention after Stroke Trial. Oxidized Phospholipids on Apolipoprotein B-100 and Recurrent Ischemic Events Following Stroke or Transient Ischemic Attack. A prospective study of plasma fibrinogen levels and the risk of stroke among participants in the bezafibrate infarction prevention study. Update to the AHA/ASA recommendations for the prevention of stroke in patients with stroke and transient ischemic attack. The relationship of fibrinogen and factors VII and VIII to incident cardiovascular disease and death in the elderly: results from the cardiovascular health study. Preventing Recurrence of Thromboembolic Events through Coordinated Treatment in the District of Columbia Discharge educational strategies for reduction of vascular events (DESERVE): design and methods Plasma natriuretic peptide levels and the risk of cardiovascular events and death. Program of rehabilitative exercise and education to avert vascular events after non-disabling stroke or transient ischemic attack (PREVENT Trial): a multi-centred, randomised controlled trial Safety and feasibility of post-stroke care and exercise after minor ischemic stroke or transient ischemic attack: MotiveS & MoveIT. Effect of Low-Dose Aspirin on Functional Outcome From Cerebral Vascular Events in Women Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trial: Rationale and design Lifestyle Factors and Risk of Cerebrovascular Disease in Women: The Copenhagen City Heart Study Empagliflozin and Cerebrovascular Events in Patients With Type 2 Diabetes Mellitus at High Cardiovascular Risk Association of Exhaled Carbon Monoxide With Stroke Incidence and Subclinical Vascular Brain Injury: Framingham Heart Study Safety and efficacy of intensive vs. guideline antiplatelet therapy in high‐risk patients with recent ischemic stroke or transient ischemic attack: rationale and design of the Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) trial (ISRCTN47823388) Lower testosterone levels predict incident stroke and transient ischemic attack in older men. Five-Year Survival After First-Ever Stroke and Related Prognostic Factors in the Perth Community Stroke Study Lipoprotein(a) in patients with acute cerebral ischemia. Kidney Dysfunction Increases Mortality and Incident Events after Young Stroke: The FUTURE Study
BACKGROUND Approximately one third of the 780,000 people in the United States who have a stroke each year have recurrent events . Although efficacious secondary prevention measures are available , levels of adherence to these strategies in patients who have had stroke are largely unknown . Underst and ing medication-taking behavior in this population is an important step to optimizing the appropriate use of proven secondary preventive therapies and reducing the risk of recurrent stroke . METHODS The Adherence eValuation After Ischemic Stroke Longitudinal ( AVAIL ) registry is a prospect i ve study of adherence to stroke prevention medications from hospital discharge to 1 year in patients admitted with stroke or transient ischemic attack . The primary outcomes are medication usage as determined by patient interviews after 3 and 12 months . Potential patient- , provider- , and system-level barriers to persistence of medication use are also collected . Secondary outcomes include the rates of recurrent stroke or transient ischemic attack , vascular events , and rehospitalization and functional status as measured by the modified Rankin score . RESULTS The AVAIL enrolled about 2,900 subjects from 106 hospitals from July 2006 through July 2008 . The 12-month follow-up will be completed in August 2009 . CONCLUSIONS The AVAIL registry will document the current state of adherence and persistence to stroke prevention medications among a nationwide sample of patients . These data will be used to design interventions to improve the quality of care post acute hospitalization and reduce the risks of future stroke and cardiovascular events Background and Purpose — Numerous effective strategies for the secondary prevention of cardiovascular events in high-risk patients have now been established . We sought to calculate the cumulative benefit of combining multiple strategies for preventing recurrent events in patients with a history of ischemic stroke or transient ischemic attack . Methods — A comprehensive literature search was undertaken to identify meta-analyses of r and omized controlled trials reporting on the efficacy of secondary prevention strategies . The baseline incidence of vascular events was modeled from the Life Long After Cerebral Ischemia study . Strategies were combined on a multiplicative scale and cumulative risk reductions were computed over a 5-year interval . Results — The combination of 5 proven strategies applied to survivors of an initial stroke or transient ischemic attack — dietary modification , exercise , aspirin , a statin , and an antihypertensive agent — could result in a cumulative relative risk reduction of 80 % . Given a 5-year major cardiovascular event rate of 24 % , this translates to a number needed to treat of about 5 . Further gains would result from applying multimodality therapy over longer intervals and enriching the base strategy with dual antiplatelet therapy , high-dose statins , and more intensive blood pressure – lowering . Even more benefit would be present in high-risk subgroups with the addition , where appropriate , of carotid endarterectomy , moderate intensity oral anticoagulants , glycemic control , and smoking cessation . Conclusions — At least four-fifths of recurrent vascular events in patients with cerebrovascular disease might be prevented by application of a comprehensive , multifactorial approach Background and Purpose — Treatment with statins reduces the rate of cardiovascular events in high-risk patients , but residual risk persists . At least part of that risk may be attributable to atherogenic dyslipidemia characterized by low high-density lipoprotein cholesterol ( ⩽40 mg/dL ) and high triglycerides ( triglycerides ≥150 mg/dL ) . Methods — We studied subjects with stroke or transient ischemic attack in the Prevention of Cerebrovascular and Cardiovascular Events of Ischemic Origin With Terutroban  in Patients With a History of Ischemic Stroke or Transient Ischemic Attack ( PERFORM ; n=19 100 ) and Stroke Prevention by Aggressive Reduction in Cholesterol Levels ( SPARCL ; n=4731 ) trials who were treated with a statin and who had high-density lipoprotein cholesterol and triglycerides measurements 3 months after r and omization ( n=10 498 and 2900 , respectively ) . The primary outcome measure for this exploratory analysis was the occurrence of major cardiovascular events ( nonfatal myocardial infa rct ion , nonfatal stroke , or cardiovascular death ) . We also performed a time-varying analysis to account for all available high-density lipoprotein cholesterol and triglyceride measurements . Results — A total of 10 % of subjects in PERFORM and 9 % in SPARCL had atherogenic dyslipidemia after ≥3 months on start statin therapy . After a follow-up of 2.3 years ( PERFORM ) and 4.9 years ( SPARCL ) , a major cardiovascular event occurred in 1123 and 485 patients in the 2 trials , respectively . The risk of major cardiovascular events was higher in subjects with versus those without atherogenic dyslipidemia in both PERFORM ( hazard ratio , 1.36 ; 95 % confidence interval , 1.14–1.63 ) and SPARCL ( hazard ratio , 1.40 ; 95 % confidence interval , 1.06–1.85 ) . The association was attenuated after multivariable adjustment ( hazard ratio , 1.23 ; 95 % confidence interval , 1.03–1.48 in PERFORM and hazard ratio , 1.24 ; 95 % confidence interval , 0.93–1.65 in SPARCL ) . Time-varying analysis confirmed these findings . Conclusions — The presence of atherogenic dyslipidemia was associated with higher residual cardiovascular risk in PERFORM and SPARCL subjects with stroke or transient ischemic attack receiving statin therapy . Specific therapeutic interventions should now be trialed to address this residual risk BACKGROUND Recurrent vascular events remain a major source of morbidity and mortality after stroke or transient ischemic attack ( TIA ) . The IRIS Trial is evaluating an approach to secondary prevention based on the established association between insulin resistance and increased risk for ischemic vascular events . Specifically , IRIS will test the effectiveness of pioglitazone , an insulin-sensitizing drug of the thiazolidinedione class , for reducing the risk for stroke and myocardial infa rct ion ( MI ) among insulin resistant , nondiabetic patients with a recent ischemic stroke or TIA . DESIGN Eligible patients for IRIS must have had insulin resistance defined by a Homeostasis Model Assessment -Insulin Resistance > 3.0 without meeting criteria for diabetes . Within 6 months of the index stroke or TIA , patients were r and omly assigned to pioglitazone ( titrated from 15 to 45 mg/d ) or matching placebo and followed for up to 5 years . The primary outcome is time to stroke or MI . Secondary outcomes include time to stroke alone , acute coronary syndrome , diabetes , cognitive decline , and all-cause mortality .  Enrollment of 3,876 participants from 179 sites in 7 countries was completed in January 2013 . Participant follow-up will continue until July 2015 . SUMMARY The IRIS Trial will determine whether treatment with pioglitazone improves cardiovascular outcomes of nondiabetic , insulin-resistant patients with stroke or TIA . Results are expected in early 2016 BACKGROUND Biomarkers to predict recurrent stroke and targets of therapy to prevent stroke are lacking . OBJECTIVES This study evaluated whether patients with prior cerebrovascular events and elevated levels of oxidized phospholipids on apolipoprotein B-100 ( OxPL-apoB ) , but without prior coronary artery disease ( CAD ) , are at risk for recurrent stroke and CAD events following high-dose statin therapy . METHODS In the SPARCL ( Stroke Prevention by Aggressive Reduction in Cholesterol Levels ) trial , OxPL-apoB levels were measured in 4,385 patients with stroke or transient ischemic attack at baseline and in 3,106 patients at 5 years following r and omization to placebo or 80 mg atorvastatin .  The primary endpoint was the time from r and omization to a second nonfatal or fatal stroke . Secondary endpoints included first major coronary events and any cardiovascular event . RESULTS Patients with recurrent stroke had higher baseline median OxPL-apoB levels than patients without ( 15.5 nmol/l vs. 11.6 nmol/l ; p < 0.0001 ) . After multivariable adjustment , elevated baseline OxPL-apoB predicted recurrent stroke ( hazard ratio [ HR ] : 4.3 ; p < 0.0001 ) , first major coronary events ( HR : 4.0 ; p < 0.0001 ) , and any cardiovascular event ( HR : 4.4 ; p < 0.0001 ) . These comparisons for any endpoint did not differ by treatment , shown as a nonsignificant interaction test . The net reclassification improvement , integrated discrimination improvement , and area under the receiver-operating characteristic curve ( AUC ) were all significantly improved by adding OxPL-apoB to the models , with ΔAUC + 0.0505 ( p < 0.0001 ) for recurrent stroke , ΔAUC + 0.0409 ( p < 0.0001 ) for first major coronary event , and ΔAUC + 0.0791 ( p < 0.0001 ) for any cardiovascular event . CONCLUSIONS Elevated OxPL-apoB levels predicted recurrent stroke and first major coronary events in patients with prior stroke or transient ischemic attack . The lack of statin-OxPL-apoB treatment interaction suggested that OxPLs might be statin-independent therapeutic targets to reduce risk of cardiovascular events . ( Lipitor in the Prevention of Stroke , for Patients Who Have Had a Previous Stroke [ SPARCL ] ; NCT00147602 ) PURPOSE Plasma fibrinogen has emerged as an important predictor of cardiovascular disease , but few data are available on its association with stroke . We sought to determine if plasma fibrinogen is a marker of increased risk or a direct causative risk factor for stroke . SUBJECTS AND METHODS Patients from the Bezafibrate Infa rct ion Prevention Study , a placebo-controlled , r and omized clinical trial of secondary prevention of coronary heart disease by lipid modification with bezafibrate retard ( 400 mg daily ) , were studied .  Plasma fibrinogen levels were measured at baseline and yearly thereafter . Stroke , a prospect ively monitored endpoint , was systematic ally assessed regarding stroke type , subtype , and functional outcome . RESULTS Mean baseline fibrinogen levels were significantly higher in patients subsequently having a cerebrovascular event ( 140 strokes , 36 transient ischemic attacks ; mean follow-up , 6.2 years ) than in patients who did not ( 375 vs. 349 mg/dL , P < 0.0001 ) . Fibrinogen levels did not differ significantly by the type , subtype , or severity of the cerebrovascular event . Risk of ischemic stroke increased from 3.3 % in the lowest tertile ( baseline fibrinogen < 314 mg/dL ) to 7.% in the middle tertile ( fibrinogen 314 to 373 mg/dL ) to 10 % in the upper tertile ( fibrinogen > 373 mg/dL , P < 0.001 ) . Adjusting for age , blood pressure , and other covariates , fibrinogen levels in the upper tertile were associated with more than a twofold increase in risk of ischemic stroke compared with in the lowest tertile ( hazard ratio = 2.6 ; 95 % confidence interval : 1.5 to 4.3 ) . We did not find fibrinogen change from baseline to be related to subsequent ischemic stroke events . CONCLUSION Plasma fibrinogen is a strong predictor of , rather than a direct causative factor for , subsequent stroke among patients at increased risk owing to manifest coronary heart disease The American Heart Association/American Stroke Association ( AHA/ASA ) Writing Committee for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack ( TIA ) has review ed the results of recent trials that were published after our previous recommendations were issued.1 Our intention in the present statement is to provide a brief review of the new data , to up date specific recommendations , and to provide the reasons for any modifications . The 2 areas in which major new clinical trials have been published are ( 1 ) the use of specific antiplatelet agents for stroke prevention in patients with a history of noncardioembolic ischemic stroke or TIA and ( 2 ) the use of statins in the prevention of recurrent stroke . Recently published trials have added to the evidence of the benefit of the use of specific antiplatelet agents for stroke prevention in patients with a history of noncardioembolic ischemic stroke or TIA . The secondary prevention guidelines 1 have been up date d to reflect this new evidence . # # # Addition of Clopidogrel to Aspirin for Prevention of Vascular Events The Clopidogrel and Aspirin Versus Aspirin Alone for the Prevention of Atherothrombotic Events ( CHARISMA ) trial2 was a double-blinded study that r and omized 15 603 subjects with cardiovascular disease or multiple risk factors for cardiovascular disease to either clopidogrel 75 mg plus low-dose aspirin ( 75 to 162 mg ) or placebo plus aspirin ( 75 to 162 mg ) . Roughly 35 % of subjects ( n=4320 ) qualified on the basis of the presence of cerebrovascular disease within 5 years of enrollment ; approximately a third experienced TIA . The median follow-up was 28 months . No significant differences were seen in the rates of nonfatal ischemic stroke between the 2 groups ( 1.7 % versus 2.1 % , P = 0.07 ) . The placebo plus aspirin group showed a higher rate of nonfatal stroke than did the clopidogrel group ( 1.9 % versus 2.4 % , P = 0.03 ) . The 2 groups experienced no differences in the rate of intracerebral hemorrhage Little is known about the prospect i ve associations of fibrinogen , factor VII , or factor VIII with  cardiovascular disease ( CVD ) and mortality in the elderly . At baseline in the Cardiovascular Health Study ( 5888 white and African American men and women ; aged > /=65 years ) , we measured  fibrinogen , factor VIII , and factor VII .  We used sex-stratified stepwise Cox survival analysis to determine relative risks ( RRs ) for CVD events and all-cause mortality ( up to 5 years of follow-up ) , both unadjusted and adjusted for CVD risk factors and sub clinical CVD . After adjustment , comparing the fifth quintile to the first , fibrinogen was significantly associated in men with coronary heart disease events ( RR=2.1 ) and stroke or transient ischemic attack ( RR=1.3 ) , and also with mortality within 2.5 years of follow-up ( RR=5.8 ) and later ( RR=1.7 ) . Factor VIII was significantly associated in men with coronary heart disease events ( RR=1.5 ) and mortality ( RR=1.8 ) , and in women with stroke/transient ischemic attack ( RR=1.4 ) . For both factors , values were higher in those who died , whether causes were CVD-related or non-CVD-related , but highest in CVD death . Factor VII exhibited associations with incident angina ( RR=1.44 ) in men and with death in women ( RR , middle quintile compared with first=0.66 ) . However , in general , factor VII was not consistently associated with CVD events in this population . We conclude that , if confirmed in other studies , the measurement of fibrinogen and /or factor VIII may help identify older individuals at higher risk for CVD events and mortality Rationale PROTECT DC examines whether stroke navigators can improve cardiovascular risk factors in urban underserved individuals newly hospitalized for stroke or ischemic attack . Within one-year of hospital discharge , up to one-third of patients no longer adhere to secondary prevention behaviors . Adherence rates are lower in minority-underserved groups , contributing to health disparities . In-hospital programs increase use of stroke prevention therapies but may not be as successful in underserved individuals . In these groups , low literacy , limited healthcare access , and sparse community re sources may reduce adherence . Lay community health workers ( navigators ) improve adherence in other illnesses through education and assisting in overcoming barriers to achieving desired health behaviors and obtaining needed healthcare services . Aims and design PROTECT DC is a Phase II , single-blind , r and omized , controlled trial comparing in-hospital education plus stroke navigators to usual care .  Atherogenic ischemic stroke and transient ischemic attack survivors are recruited from Washington , DC hospitals .  Navigators meet with participants during the index hospitalization , perform home visits , and meet by phone . They focus on stroke education , medication compliance , and overcoming practical barriers to adherence . The interventions are driven by the theories of reasoned action and planned behavior . Study outcomes The primary dependent measure is a summary score of four objective measures of stroke risk factor control : systolic blood pressure , low-density lipoprotein , hemoglobin Hb A1C , and antiplatelet agent pill counts . Secondary outcomes include stroke knowledge , exercise , dietary modification , and smoking cessation . Conclusion PROTECT DC will determine whether a Phase III trial of stroke navigation for urban underserved individuals to improve adherence to secondary stroke prevention behaviors is warranted Rationale Stroke and vascular risk factors disproportionately affect minority population s , with Blacks and Hispanics experiencing a 2.5- and 2.0-fold greater risk compared with whites , respectively . Patients with transient ischemic attacks and mild , nondisabling strokes tend to have short hospital stays , rapid discharges , and inaccurate perceptions of vascular risk . Aim The primary aim of the Discharge Educational Strategies for Reduction of Vascular Events ( DESERVE ) trial is to evaluate the efficacy of a novel community health worker-based multilevel discharge intervention vs. st and ard discharge care on vascular risk reduction among racially/ethnically diverse transient ischemic attack/mild stroke patients at one-year postdischarge . We hypothesize that those r and omized to the discharge intervention will have reduced modifiable vascular risk factors as determined by systolic blood pressure compared with those receiving usual care . Sample size estimates Given 300 subjects per group and alpha of 0.05 , the power to detect a 6 mmHg reduction in systolic blood pressure is 89 % . Design DESERVE trial is a prospect i ve , r and omized , multicenter clinical trial of a novel discharge behavioral intervention .  Patients with transient ischemic attack/mild stroke are r and omized during hospitalization or emergency room visit to intervention or usual care . Intervention begins prior to discharge and continues postdischarge . Study outcomes The primary outcome is difference in systolic blood pressure reduction between groups at 12 months . Secondary outcomes include between-group differences in change in glycated hemoglobin , smoking rates , medication adherence , and recurrent stroke/transient ischemic attack at 12 months . Discussion DESERVE will evaluate whether a novel discharge education strategy leads to improved risk factor control in a racially diverse population BACKGROUND The natriuretic peptides are counterregulatory hormones involved in volume homeostasis and cardiovascular remodeling . The prognostic significance of plasma natriuretic peptide levels in apparently asymptomatic persons has not been established . METHODS We prospect ively studied 3346 persons without heart failure . Using proportional-hazards regression , we examined the relations of plasma B-type natriuretic peptide and N-terminal pro-atrial natriuretic peptide to the risk of death from any cause , a first major cardiovascular event , heart failure , atrial fibrillation , stroke or transient ischemic attack , and coronary heart disease . RESULTS During a mean follow-up of 5.2 years , 119 participants died and 79 had a first cardiovascular event . After adjustment for cardiovascular risk factors , each increment of 1 SD in log B-type natriuretic peptide levels was associated with a 27 percent increase in the risk of death ( P=0.009 ) , a 28 percent increase in the risk of a first cardiovascular event ( P=0.03 ) , a 77 percent increase in the risk of heart failure ( P<0.001 ) , a 66 percent increase in the risk of atrial fibrillation ( P<0.001 ) , and a 53 percent increase in the risk of stroke or transient ischemic attack ( P=0.002 ) . Peptide levels were not significantly associated with the risk of coronary heart disease events . B-type natriuretic peptide values above the 80th percentile ( 20.0 pg per milliliter for men and 23.3 pg per milliliter for women ) were associated with multivariable-adjusted hazard ratios of 1.62 for death ( P=0.02 ) , 1.76 for a first major cardiovascular event ( P=0.03 ) , 1.91 for atrial fibrillation ( P=0.02 ) , 1.99 for stroke or transient ischemic attack ( P=0.02 ) , and 3.07 for heart failure ( P=0.002 ) . Similar results were obtained for N-terminal pro-atrial natriuretic peptide . CONCLUSIONS In this community-based sample , plasma natriuretic peptide levels predicted the risk of death and cardiovascular events after adjustment for traditional risk factors . Excess risk was apparent at natriuretic peptide levels well below current thresholds used to diagnose heart failure Background Despite lack of outward signs , most individuals after non-disabling stroke ( NDS ) and transient ischemic attack ( TIA ) have significant cardiovascular and cerebrovascular disease and are at high risk of a major stroke , hospitalization for other vascular events , or death . Most have multiple modifiable risk factors ( e.g. , hypertension , physical inactivity , hyperlipidaemia , diabetes , tobacco consumption , psychological stress ) . In addition , accelerated rates of depression , cognitive decline , and poor quality of sleep have been reported following TIA , which correlate with poor functional outcomes and reduced quality of life . Thus , NSD and TIA are important warning signs that should not be overlooked . The challenge is not unlike that facing other ' silent ' conditions - to identify a model of care that is effective in changing people 's current behaviors in order to avert further morbidity . Methods / Design A single blind , r and omized controlled trial will be conducted at two sites to compare the effectiveness of a program of rehabilitative exercise and education versus usual care in modifying vascular risk factors in adults after NDS/TIA . 250 adults within 90 days of being diagnosed with NDS/TIA will be r and omly allocated to a 12-week program of exercise and education ( PREVENT ) or to an outpatient clinic assessment and discussion of secondary prevention recommendations with return clinic visits as indicated ( USUAL CARE ) . Primary outcome measures will include blood pressure , waist circumference , 12-hour fasting lipid profile , and 12-hour fasting glucose/hemoglobin A1c . Secondary measures will include exercise capacity , walking endurance , physical activity , cognitive function , depression , goal attainment and health-related quality of life . Outcome assessment will be conducted at baseline , post-intervention , and 6- and 12-month follow-ups . Direct health care costs incurred over one year by PREVENT versus USUAL CARE participants will also be compared . Ethical approval for the trial has been obtained from the relevant Human Research Ethics Boards . Discussion Whether timely delivery of an adapted cardiac rehabilitation model is effective in attaining and maintaining vascular risk reduction targets in adults after NDS/TIA is not yet known . We anticipate that the findings of this trial will make a meaningful contribution to the knowledge base regarding secondary stroke prevention . Trial registration This trial is registered with the Clinical Trials.gov Registry ( NCT00885456 ) BACKGROUND Despite the beneficial effect of cardiac rehabilitation after myocardial infa rct ion , a rehabilitation program to improve cardiorespiratory fitness and influence secondary prevention has not been implemented for ischemic stroke and transient ischemic attack ( TIA ) . OBJECTIVE To investigate the safety and feasibility of a post-stroke care including an exercise program after minor ischemic stroke or TIA . METHODS In a r and omised controlled trial , 20 patients with a recent minor stroke or TIA without cardiac contraindications were r and omly assigned to one of the two interventions ; post-stroke care without exercise or post-stroke care with exercise . Patients were evaluated at baseline , 6 and 12 months . RESULTS Eighteen patients completed the intervention . In none of the patients cardiopulmonary contraindications for the maximal exercise test and exercise program were found . No cardiovascular events occurred during the maximal exercise tests and exercise program . After one year , significantly more patients in the post-stroke care with exercise group achieved the composite endpoint of optimal medical therapy . CONCLUSIONS Post-stroke care including an exercise program is safe and feasible in the acute phase after minor stroke or TIA and might be a way to increase effectiveness of secondary stroke prevention . We are currently conducting a larger trial to vali date these results Background and Purpose — Although aspirin is effective in prevention of stroke , fewer studies have examined the impact of aspirin on stroke morbidity . Methods — The Women ’s Health Study is a completed r and omized , placebo-controlled trial design ed to test the effect of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer , which enrolled 39 876 women . We used multinomial logistic regression to evaluate the relationship between r and omized aspirin assignment and functional outcomes from stroke . Possible functional outcomes were neither stroke nor transient ischemic attack ( TIA ) , modified Rankin scale ( mRS ) score 0 to 1 , 2 to 3 , and 4 to 6 . Results — After a mean of 9.9 years of follow-up , 460 confirmed strokes ( 366 ischemic , 90 hemorrhagic , and 4 unknown type ) and 405 confirmed TIAs occurred . With regard to total and ischemic stroke , women who were r and omized to aspirin had a nonsignificant decrease in risk of any outcome compared to women not r and omized to aspirin . This decrease in risk only reached statistical significance for those experiencing TIA compared to participants without stroke or TIA ( odds ratio=0.77 ; 95 % confidence interval , 0.63–0.94 ) . For hemorrhagic stroke , a nonsignificant increase in the risk of achieving an mRS score 2 to 3 or 4 to 6 compared with no stroke or TIA was observed for the women r and omized to aspirin compared to those r and omized to placebo . Conclusions — Results from this large r and omized clinical trial provide evidence that 100 mg of aspirin every other day may reduce the risk of ischemic cerebral vascular events but does not have differential effects on functional outcomes from stroke Background Ischemic stroke and other vascular outcomes occur in 10–20 % of patients in the three-months following a transient ischemic attack or minor ischemic stroke , and many are disabling . The highest risk period for these outcomes is the early hours and days immediately following the ischemic event . Aspirin is the most common antithrombotic treatment used for these patients . Aim The aim of POINT is to determine whether clopidogrel plus aspirin taken < 12 h after transient ischemic attack or minor ischemic stroke symptom onset is more effective in preventing major ischemic vascular events at 90 days in the high-risk , and acceptably safe , compared with aspirin alone . Design POINT is a prospect i ve , r and omized , double-blind , multicenter trial in patients with transient ischemic attack or minor ischemic stroke . Subjects are r and omized to clopidogrel  ( 600 mg loading dose followed by 75 mg/day )  or matching placebo  , and all will receive  open-label aspirin 50–325 mg/day , with a dose of 162 mg daily for five-days followed by 81 mg daily strongly recommended . Study Outcomes The primary efficacy outcome is the composite of new ischemic vascular events — ischemic stroke , myocardial infa rct ion , or ischemic vascular death — by 90 days . The primary safety outcome is major hemorrhage , which includes symptomatic intracranial hemorrhage . Discussion Aspirin is the most common antithrombotic given to patients with a stroke or transient ischemic attack , as it reduces the risk of subsequent stroke . This trial expects to determine whether more aggressive antithrombotic therapy with clopidogrel plus aspirin , initiated acutely , is more effective than aspirin alone Background and Purpose The purpose of the present analysis was to determine how lifestyle influences the risk of cerebrovascular disease in women participating in the Copenhagen City Heart Study . Methods A r and om sample of a white , lower and middle-class , urban population selected in 1976 was invited to two cardiovascular examinations at 5-year intervals . The present analysis was based on 7060 women invited to an initial examination from 1976 through 1978 , aged 35 years or more , and without previous stroke or transient ischemic attack . At the initial examination , potential risk factors were recorded . The 265 first cases of stroke and transient ischemic attack were ascertained at a second examination 5 years later and through hospital records and death certificates through 1988 . The Cox regression model was used to estimate the influence of the factors recorded on the risk of cerebrovascular disease . Results The relative risks of cigarette smoking and lack of physical activity were 1.4 and 1.45 ; 95 % confidence limits , 1.02 to 1.94 and 1.01 to 2.08 , respectively ) . The relative risk of daily consumption of tranquilizers  was 1.25 ( 95 % confidence limits , 0.96 to 1.62 ) . No significant influence was found for number of cigarettes , body mass index , or alcohol intake . In postmenopausal women , there was a statistically significant interaction ( P < .041 ) between smoking and hormone replacement therapy .  Smokers receiving this therapy had a 28 % lower risk of cerebrovascular disease than smokers not receiving it . Conclusions The statistically significant and equally potent effects on the risk of cerebrovascular disease were found for cigarette smoking and lack of physical activity . The risk associated with smoking seemed to be influenced by hormonal replacement therapy Background and Purpose — In the EMPA-REG OUTCOME trial ( Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients ) , empagliflozin added to st and ard of care in patients with type 2 diabetes mellitus and high cardiovascular risk reduced the risk of 3-point major adverse cardiovascular events , driven by a reduction in cardiovascular mortality , with no significant difference between empagliflozin and placebo in risk of myocardial infa rct ion or stroke . In a modified intent-to-treat analysis , the hazard ratio for stroke was 1.18 ( 95 % confidence interval , 0.89–1.56 ; P=0.26 ) . We further investigated cerebrovascular events . Methods — Patients were r and omized to empagliflozin 10 mg , empagliflozin 25 mg , or placebo ; 7020 patients were treated . Median observation time was 3.1 years . Results — The numeric difference in stroke  between empagliflozin and placebo in the modified intent-to-treat analysis was primarily because of 18 patients in the empagliflozin group with a first event > 90 days after last intake of study drug ( versus 3 on placebo ) . In a sensitivity analysis based on events during treatment or ⩽90 days after last dose of drug , the hazard ratio for stroke with empagliflozin versus placebo was 1.08 ( 95 % confidence interval , 0.81–1.45 ; P=0.60 ) . There were no differences in risk of recurrent , fatal , or disabling strokes , or transient ischemic attack , with empagliflozin versus placebo . Patients with the largest increases in hematocrit or largest decreases in systolic blood pressure did not have an increased risk of stroke . Conclusions — In patients with type 2 diabetes mellitus and high cardiovascular risk , there was no significant difference in the risk of cerebrovascular events with empagliflozin versus placebo . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01131676 Background and Purpose — Exhaled carbon monoxide ( CO ) is associated with cardiometabolic traits , sub clinical atherosclerosis , and cardiovascular disease , but its specific relations with stroke are unexplored . We related exhaled CO to magnetic resonance imaging measures of sub clinical cerebrovascular disease cross-sectionally and to incident stroke/transient ischemic attack prospect ively in the Framingham Offspring study . Methods — We measured exhaled CO in 3313 participants ( age 59±10 years ; 53 % women ) , and brain magnetic resonance imaging was available in 1982 individuals ( age 58±10 years ; 54 % women ) . Participants were analyzed according to tertiles of exhaled CO concentration . Results — In age- and sex-adjusted models , the highest tertile of exhaled CO was associated with lower total cerebral brain volumes , higher white-matter hyperintensity volumes , and greater prevalence of silent cerebral infa rcts ( P<0.05 for all ) . The results for total cerebral brain volume and white-matter hyperintensity volume were consistent after removing smokers from the sample , and the association with white-matter hyperintensity volume persisted after multivariable adjustment ( P=0.04 ) . In prospect i ve analyses ( mean follow-up 12.9 years ) , higher exhaled CO was associated with 67 % ( second tertile ) and 97 % ( top tertile ) increased incidence of stroke/transient ischemic attack relative to the first tertile that served as referent ( P<0.01 for both ) . These results were consistent in nonsmokers and were partially attenuated upon adjustment for vascular risk factors . Conclusions — In this large , community-based sample of individuals without clinical stroke/transient ischemic attack at baseline , higher exhaled CO was associated with a greater burden of sub clinical cerebrovascular disease cross-sectionally and with increased risk of stroke/transient ischemic attack prospect ively . Further investigation is necessary to explore the biological mechanisms linking elevated CO with stroke Rationale The risk of recurrence following a stroke or transient ischemic attack is high , especially immediately after the event . Hypothesis Because two antiplatelet agents are superior to one in patients with non-cardioembolic events , more intensive treatment might be even more effective . Sample size estimates The sample size of 4100 patients will allow a shift to less recurrence , and less severe recurrence , to be detected ( odds ratio 0·68 ) with 90 % power at 5 % significance . Methods and design Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke ( IS RCT N47823388 ) is comparing the safety and efficacy of intensive ( combined aspirin , clopidogrel , and dipyridamole ) vs. guideline antiplatelet therapy , both given for one-month . This international collaborative parallel-group prospect i ve r and omized open-label blinded-end-point phase III trial plans to recruit 4100 patients with acute ischemic stroke or transient ischemic attack . R and omization and data collection are performed over a secure Internet site with real-time data validation and concealment of allocation . Outcomes , serious adverse events , and neuroimaging are adjudicated central ly with blinding to treatment allocation . Study outcome The primary outcome is stroke recurrence and its severity ( ‘ ordinal recurrence ’ based on modified Rankin Scale ) at 90 days , with masked assessment central ly by telephone . Secondary outcomes include vascular events , functional measures ( disability , mood , cognition , quality of life ) , and safety ( bleeding , death , serious adverse events ) . Discussion The trial has recruited more than 50 % of its target sample size ( latest number : 2399 ) and is running in 104 sites in 4 countries . One-third of patients presented with a transient ischemic attack CONTEXT Lower circulating testosterone concentrations are associated with metabolic syndrome , type 2 diabetes , carotid intima-media thickness , and aortic and lower limb arterial disease in men . However , it is unclear whether lower testosterone levels predict major cardiovascular events . OBJECTIVE We examined whether lower serum testosterone was an independently significant risk factor for symptomatic cerebrovascular events  in older men . DESIGN This was a prospect i ve observational study with median follow-up of 3.5 yr . SETTING Community-dwelling , stroke-free older men were studied . PARTICIPANTS A total of 3443 men at least 70 yr of age participated in the study . MAIN OUTCOME MEASURES  Baseline serum total testosterone , SHBG , and LH were assayed . Free testosterone  was calculated using mass action equations . Incident stroke or transient ischemic attack ( TIA ) was recorded . RESULTS A first stroke or TIA occurred in 119 men ( 3.5 % ) .  Total and free testosterone concentrations in the lowest quartiles ( < 11.7 nmol/liter and < 222 pmol/liter ) were associated with reduced event-free survival ( P = 0.014 and P = 0.01 , respectively ) . After adjustment including age , waist-hip ratio , waist circumference , smoking , hypertension , dyslipidemia , and medical comorbidity , lower total testosterone predicted increased incidence of stroke or TIA ( hazard ratio = 1.99 ; 95 % confidence interval , 1.33 - 2.99 ) . Lower free testosterone was also associated ( hazard ratio = 1.69 ; 95 % confidence interval , 1.15 - 2.48 ) , whereas SHBG and LH were not independently associated with incident stroke or TIA . CONCLUSIONS In older men , lower total testosterone levels predict increased incidence of stroke or TIA after adjusting for conventional risk factors for cardiovascular disease . Men with low-normal testosterone levels had increased risk . Further studies are warranted to determine whether interventions that raise circulating testosterone levels might prevent cerebrovascular disease in men Background and Purpose Few community-based studies have examined the long-term survival and prognostic factors for death within 5 years after an acute first-ever stroke . This study aim ed to determine the absolute and relative survival and the independent baseline prognostic factors for death over the next 5 years among all individuals and among 30-day survivors after a first-ever stroke in a population of Perth , Western Australia . Methods Between February 1989 and August 1990 , all individuals with a suspected acute stroke or transient ischemic attack of the brain who were resident in a geographically defined region of Perth , Western Australia , with a population of 138 708 people , were registered prospect ively  and assessed according to st and ardized diagnostic criteria . Patients were followed up prospect ively at 4 months , 12 months , and 5 years after the index event . Results Three hundred seventy patients with first-ever stroke were registered , and 362 ( 98 % ) were followed up at 5 years , by which time 210 ( 58 % ) had died . In the first year after stroke the risk of death was 36.5 % ( 95 % CI , 31.5 % to 41.4 % ) , which was 10-fold ( 95 % CI , 8.3 % to 11.7 % ) higher than that expected among the general population of the same age and sex . The most common cause of death was the index stroke ( 64 % ) . Between 1 and 5 years after stroke , the annual risk of death was approximately 10 % per year , which was approximately 2-fold greater than expected , and the most common cause of death was cardiovascular disease ( 41 % ) . The independent baseline factors among 30-day survivors that predicted death over 5 years were intermittent claudication ( hazard ratio [ HR ] , 1.9 ; 95 % CI , 1.2 to 2.9 ) , urinary incontinence ( HR , 2.0 ; 95 % CI , 1.3 to 3.0 ) , previous transient ischemic attack ( HR , 2.4 ; 95 % CI , 1.4 to 4.1 ) , and prestroke Barthel Index < 20/20 ( HR , 2.0 ; 95 % CI , 1.2 to 3.2 ) . Conclusions One-year survivors of first-ever stroke continue to die over the next 4 years at a rate of approximately 10 % per year , which is twice the rate expected among the general population of the same age and sex . The most common cause of death is cardiovascular disease . Long-term survival after stroke may be improved by early , active , and sustained implementation of effective strategies for preventing subsequent cardiovascular events BACKGROUND AND PURPOSE In several cross-sectional studies , a high serum lipoprotein(a ) [ Lp(a ) ] level was found to be an independent risk factor for cerebral infa rct ion . In a recent prospect i ve study , however , no association was found between Lp(a ) levels at baseline and future risk of stroke . Whether Lp(a ) is a prognostic factor in a high-risk population of patients with acute ischemic stroke remains unclear . METHODS We assessed  Lp(a ) level  on admission to study its relationship with cardiovascular risk profile , stroke severity , and prognosis in 151 consecutive patients with acute cerebral ischemia . The mean follow-up period was 2.5 + /- 1.2 years .  Lp(a )  was measured by means of a solid-phase two-site immunoradiometric assay . RESULTS Increased Lp(a ) levels were found in 53 ( 35 % ) of the patients with cerebral ischemia . Median ( 5th and 95th percentile ) values of Lp(a ) were 191 ( 12 and 1539 ) mg/L and 197 ( 10 and 1255 ) mg/L for patients with transient ischemic attack and patients with ischemic stroke , respectively . No relationship was found between Lp(a ) levels and stroke severity ( P=.68 ) or the occurrence of vascular events during follow-up ( P log rank=0.81 ) . CONCLUSIONS We conclude that Lp(a ) is increased in about one third of patients with acute cerebral ischemia , but it does not appear to be associated with the cardiovascular risk profile , stroke characteristics , or the prognosis of such patients Background : In about 30 % of young stroke patients , no cause can be identified . In elderly patients , kidney dysfunction has been suggested as a contributing risk factor for mortality as well as stroke . There are hypotheses that novel non-traditional risk factors , like chronic inflammation and oxidative stress , are involved in chronic kidney disease , affecting the cerebral microvasculature that would in turn lead to stroke . Our objective is to investigate the influence of kidney dysfunction on long-term mortality and incident vascular events after stroke in young adults aged 18 through 50 and if this relationship would be independent of other cardiovascular risk factors . Methods : We prospect ively included 460 young stroke patients with an ischemic stroke or transient ischemic attack admitted to our department between January 1 , 1980 and November 1 , 2010 . Follow-up was done between 2014 and 2015 . Estimated glomerular filtration rate ( eGFR ) was calculated from baseline creatinine levels and was divided in 3 subgroups : eGFR < 60 , 60 - 120 and > 120 ml/min/1.73 m2 . Cox proportional hazard models were used to determine the effect of kidney dysfunction on mortality and incident vascular events , adjusting for cardiovascular risk factors . Results : An eGFR < 60 ( HR 4.6 ; 95 % CI 2.6 - 8.2 ) was associated with an increased risk of death and an increased risk of incident stroke ( HR 4.1 ; 95 % CI 1.9 - 9.0 ) independent of cardiovascular risk factors , but it was not associated with other vascular events . The point estimate for the 15-year cumulative mortality was 70 % ( 95 % CI 46 - 94 ) for patients with a low eGFR , 24 % ( 95 % CI 18 - 30 ) for patients with a normal eGFR and 30 % ( 95 % CI 12 - 48 ) for patients with a high eGFR . The point estimate for the 15-year cumulative risk of incident stroke was 45 % ( 95 % CI 16 - 74 ) for patients with a low eGFR , 13 % ( 95 % CI 9 - 17 ) for patients with a normal eGFR and 8 % ( 95 % CI 0 - 18 ) for patients with a high eGFR . Conclusions : Kidney dysfunction is related to long-term mortality and stroke recurrence , but not to incident cardiovascular disease , on average 11 years after young stroke . This warrants a more intensive follow-up of young stroke patients with signs of kidney dysfunction in the early phase . In addition , the clear association between kidney dysfunction and incident stroke seen in our young stroke population might be a first step in the recognition of kidney dysfunction as a new risk factor for the development of stroke at young age . Also , it can lead to new insights in the etiological differences between cardiovascular and cerebrovascular disease
No significant effect was found on cardiovascular events , mortality , diastolic blood pressure , or cholesterol .
Conclusions — We found that lifestyle interventions are effective in lowering systolic blood pressure .
About other end points , this systematic review found no effect of lifestyle interventions on cardiovascular event rate mortality , diastolic blood pressure , or total cholesterol
Background and Purpose — Patients with a transient ischemic attack or ischemic stroke have an increased risk of subsequent cardiovascular events .
The purpose of this systematic review and meta- analysis was to determine whether lifestyle interventions focusing on behaviorally modifiable risk factors with or without an exercise program are effective in terms of ( 1 ) preventing recurrent cardiovascular events , ( 2 ) reducing mortality , and ( 3 ) improving modifiable risk factors associated with cardiovascular disease in patients after a transient ischemic attack or ischemic stroke .