Risk Of Subsequent Stroke Research Articles

Abstract 11919: Dementia and Stroke Rates Were Lower Among Patients Receiving Long-term Anticoagulation Therapy With Novel Oral Anticoagulants Compared to Warfarin

Introduction: Patients with atrial fibrillation (AF) are at an increased risk of developing dementia, and this risk appears sensitive to quality of warfarin control. Longstanding warfarin use predisposes AF patients to the development of microbleeds if they are over-anticoagulated and microemboli if they are under-anticoagulated. The novel oral anticoagulants (NOACs) offer an alternative to warfarin with a predictable anticoagulant effect, and comparatively favorable intracranial bleeding and thrombosis rates which may lower the risk of dementia. Hypothesis: The use of NOACs will be associated with a lower risk of stroke, TIA, and dementia compared to warfarin. Methods: Patients receiving long-term anticoagulation therapy with either warfarin or a single NOAC for thromboembolism prevention were studied (June 2010-December 2014). NOAC and warfarin patients were matched 1:1 by index date (± 6 months) and propensity score (±0.01). Multivariable Cox hazard regression was performed to evaluate the association of NOAC compared to warfarin use for the composite outcome of dementia, stroke, and TIA. Results: A total of 5,254 (2,627 per group) patients were studied, and those receiving NOACs included: apixaban= 590 (22.5%), dabigatran=583 (22.2%), and rivaroxaban=1,454 (55.3%). Average age was 72.4±10.9 and 59.0% were male. The majority of patients were receiving long-term anticoagulation for AF (warfarin: 96.5% vs. NOAC: 92.7%, p<0.0001). History of a prior stroke/TIA were similar between the groups (warfarin: 10.7% vs. NOAC: 10.8%, p=0.89). Dementia incidence alone was lower in the NOAC group compared to the warfarin group (0.3% vs. 1.6%, p<0.0001). The composite outcome of dementia, stroke, and TIA occurred in 4.7% of warfarin patients and 1.8% of NOAC patients (p<0.0001). After adjustment, patients taking NOACs had a 51% decreased risk of dementia incidence or subsequent stroke or TIA compared to patients taking warfarin (HR=0.49 (0.35, 0.69), p<0.0001). Conclusions: This study shows the use of NOACs in a community setting to be superior to that of warfarin for the composite outcome of dementia, stroke, and TIA among patients receiving long-term oral anticoagulation.

Atrial Fibrillation Monitoring in Cryptogenic Stroke: the Gaps Between Evidence and Practice.

Identifying occult paroxysmal atrial fibrillation as the etiology of cryptogenic stroke has been a top research priority in the past decade. This is because prompt initiation of anticoagulation has significantly decreased subsequent stroke risk. Available evidence suggests that prolonged cardiac monitoring after stroke increases the likelihood of detecting atrial fibrillation. However, further research is required to fill in the gaps in regard to the optimal period of monitoring, candidates for monitoring, etc. Here, we review the current evidence supporting the use of prolonged monitoring for cryptogenic stroke patients and discuss the directions of future research.

National Survey of Neurologists for Transient Ischemic Attack Risk Stratification Consensus and Appropriate Treatment for a Given Level of Risks

Patients with a new transient ischemic attack (TIA) have a 5% subsequent stroke risk within 7 days. The Canadian TIA Score accurately determines the risk of subsequent stroke risk; however, it is unclear if physicians will use this new scale or how it will be used. Our objectives were to assess: (1) anticipated use; (2) component face validity; (3) risk strata for stroke within 7 days; and (4) actions required, for a given risk for subsequent stroke based on the proposed Canadian TIA Score. After a rigorous development process (sample selection, key informant interviews, development of questionnaire following Dillman Tailored Design technique, cognitive interviews, and pilot-testing), a survey questionnaire was administered to a random sample of 300 neurologists selected from all neurologists listed in a national medical directory. The surveys were distributed using a modified Dillman technique. From a total of 265 eligible surveys, we received 140 (52.8%) completed surveys; 7 of 13 components comprising the Canadian TIA Score were rated as "very important" or "important" by survey respondents. Risk categories for subsequent stroke were defined as: minimal risk: less than 1%; low risk: 2%-4.9%; high risk: 5%-10%; critical risk: more than 10% risk of subsequent stroke within 7 days. Most (87.1%) of the neurologists would use a validated Canadian TIA Score. Neurologists appear ready to use a validated Canadian TIA Score in their clinical practice. Risk strata are definable, which may allow physicians to determine immediate actions, based on subsequent stroke risk.

The Association Between Emergency Department Crowding and the Disposition of Patients With Transient Ischemic Attack or Minor Stroke.

Emergency department (ED) crowding has been associated with adverse events, including short-term death and hospitalization among discharged patients. The mechanisms are poorly understood, but may include altered physician decision-making about ED discharge of higher-risk patients. One example is patients with transient ischemic attack (TIA) and minor stroke, who are at high risk of subsequent stroke. While hospitalization is frequently recommended, little consensus exists on which patients require admission. The authors sought to determine the association of ED crowding with the disposition of patients with minor stroke or TIA. This was a retrospective cohort study of prospectively collected data from the Registry of the Canadian Stroke Network at 12 EDs in Ontario, Canada, between 2003 and 2008, linked to administrative health databases. A hierarchical logistic regression model was used to determine the association between crowding at the time the patient was seen in the ED (defined as mean ED length of stay) and patient disposition (admission/discharge), after adjusting for patient and hospital-level variables. The study cohort included 9,759 patients (4,607 with TIA and 5,152 with minor stroke); 49.5% were discharged from the ED. The mean (±SD) age of study patients was 70.78 (±13.40) years, with 52.9% being male, 37.3% arriving by emergency medical services, and 92.3% triaged as emergent or urgent. Greater severity of ED crowding was associated with a lower likelihood of discharge, regardless of ED size. These results suggest that crowding may influence clinical decision-making in the disposition of patients with TIA or minor stroke and that, as crowding worsens, the likelihood of hospitalization increases.

Nursing Assessment of Depression in Stroke Survivors.

Stroke is a leading cause of death and disability worldwide.1,2 Because depression is the second leading cause of disability in the world,3 stroke complicated by depression is doubly disabling. Thirty-one percent of stroke survivors are estimated to be clinically depressed (95% confidence interval 28%–35%).4 Thus, at any given time, between 28% and 35% of stroke survivors are likely to be living with depression. With an annual incidence of 795 000 new or recurrent strokes in the United States,1 we might expect 246 000 will be depressed. Poststroke depression is associated with poorer recovery, reduced health-related quality of life,5 and a higher risk of subsequent stroke and mortality.6,7 We also know that many people hospitalized with stroke have not had their mood assessed by discharge.8 Because depression in chronic illness, including stroke, can be successfully treated, it becomes imperative that we assess for depression for all stroke survivors in our health systems. Indeed, this has become a standard for credentialing stroke care in Australia, the United Kingdom, and the United States.8–12 Nurses are the health professionals most in contact with stroke survivors and their families during an acute episode and are therefore key to assessing the presence of clinical depression. The purpose of this article is to review the screening and diagnostic assessment tools available to health professionals, with emphasis on clinically feasible instruments that can be used by staff nurses. A literature search was conducted in MEDLINE with a secondary search in PsycINFO and CINAHL to ascertain any papers relevant to nursing missed by the MEDLINE search. The search terms included stroke and depression, poststroke depression, assessment, measurement, diagnosis. Sub-collections of systematic reviews, diagnosis, and nursing journals were followed until there were …

Investigation of the composition of arterial plaques based on arterial waveforms and material properties.

Stroke is mainly caused by a narrowing of the carotid artery from a build-up of plaque. The risk of plaque rupture and subsequent stroke is dependent on plaque composition. Advances in imaging modalities offer a non-invasive means to assess the health of blood vessels and detect damage. However, the current diagnosis fails to identify patients with soft lipid plaque that are more susceptible to fissure, resulting in stroke. The aim of this study was to use waveform analysis to identify plaque composition and the risk of rupture. We have investigated pressure and flow by combining an artificial blood flow circuit with tubing containing different materials, to simulate plaques in a blood vessel. We used fat and bone to model lipid and calcification respectively to determine if the composition of plaques can be identified by arterial waveforms. We demonstrate that the arterial plaque models with different percentages of calcification and fat, results in significantly different arterial waveforms. These findings imply that arterial waveform analysis has the potential for further development to identify the vulnerable plaques prone to rupture. These findings could have implications for improved patient prognosis by speed of detection and a more appropriate treatment strategy.

National survey of emergency physicians for transient ischemic attack (TIA) risk stratification consensus and appropriate treatment for a given level of risk.

Five percent of transient ischemic attack (TIA) patients have a subsequent stroke within 7 days. The Canadian TIA Score uses clinical findings to calculate the subsequent stroke risk within 7 days. Our objectives were to assess 1) anticipated use; 2) component face validity; 3) risk strata for stroke within 7 days; and 4) actions required, for a given risk for subsequent stroke. After a rigorous development process, a survey questionnaire was administered to a random sample of 300 emergency physicians selected from those registered in a national medical directory. The surveys were distributed using a modified Dillman technique. From a total of 271 eligible surveys, we received 131 (48.3%) completed surveys; 96.2% of emergency physicians would use a validated Canadian TIA Score; 8 of 13 components comprising the Canadian TIA Score were rated as Very Important or Important by survey respondents. Risk categories for subsequent stroke were defined as minimal-risk: 10% risk of subsequent stroke within 7 days. A validated Canadian TIA Score will likely be used by emergency physicians. Most components of the TIA Score have high face validity. Risk strata are definable, which may allow physicians to determine immediate actions, based on subsequent stroke risk, in the emergency department.

Baseline overall health-related quality of life predicts the 10-year incidence of cardiovascular events in a Chinese population.

To determine the relationship between baseline overall HRQOL as well as domain-specific HRQOL and incident cardiovascular (CV) events over 10years of follow-up in a Chinese general population. We examined the above link using data from a prospective cohort study, conducted between 2002 and 2012 in 11 villages of Beijing. HRQOL was assessed using Chinese 35-item quality of life instrument, and CV risk factors were recorded in either 2002 or 2005. Subjects were followed through the end of the study period, or until they were censored due to an incident CV event [including myocardial infarction (MI) and stroke] or loss to follow-up. A total of 1739 participants were eligible to be included in the current study [female 64.2%, age 57.7 (8.4) years]. There were a total of 190 CV events during the follow-up (14,364 total person-years). Participants in the bottom 20% had 85% increase in risk of CV event [hazard ratio (HR) 1.85; 95% CI 1.14-3.02] compared to those in top 20% of overall HRQOL, after adjusting for sex, age, education, marital status, smoking, alcohol consumption, being physically active, hypertension, diabetes, high cholesterol, and obesity. Among the six HRQOL domains, the independence domain had the largest effect size (fully adjusted HR 2.91; 95% CI 1.67-5.07), followed by physical domain (HR 1.66; 95% CI 1.03-2.67). Other domains did not predict the incidence CV events in this cohort. While overall lower HRQOL predicts subsequent risk of stroke and MI events, this appeared to be driven mainly by the independence domain.

Clopidogrel With Aspirin in Acute Minor Stroke or Transient Ischemic Attack (CHANCE) Trial: One-Year Outcomes.

The Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial showed that the combined treatment of clopidogrel and aspirin decreases the 90-day risk of stroke without increasing hemorrhage in comparison with aspirin alone, but provided insufficient data to establish whether the benefit persisted over a longer period of time beyond the trial termination. We report the 1-year follow-up outcomes of this trial. The trial was a randomized, double-blind, placebo-controlled trial conducted at 114 centers in China. We randomly assigned 5170 patients within 24 hours after onset of minor stroke or high-risk transient ischemic attack to clopidogrel-aspirin therapy (loading dose of 300 mg of clopidogrel on day 1, followed by 75 mg of clopidogrel per day for 90 days, plus 75 mg of aspirin per day for the first 21 days) or to the aspirin-alone group (75 mg/d for 90 days). The primary outcome was stroke event (ischemic or hemorrhagic) during 1-year follow-up. Differences in outcomes between groups were assessed by using the Cox proportional hazards model. Stroke occurred in 275 (10.6%) patients in the clopidogrel-aspirin group, in comparison with 362 (14.0%) patients in the aspirin group (hazard ratio, 0.78; 95% confidence interval, 0.65-0.93; P=0.006). Moderate or severe hemorrhage occurred in 7 (0.3%) patients in the clopidogrel-aspirin group and in 9 (0.4%) patients in the aspirin group (P=0.44). The early benefit of clopidogrel-aspirin treatment in reducing the risk of subsequent stroke persisted for the duration of 1-year of follow-up. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589.

Systematic review of rehabilitation programmes initiated within 90 days of a transient ischaemic attack or 'minor' stroke: a protocol.

IntroductionTransient ischaemic attacks (TIAs) and strokes are highly prevalent conditions. Stroke killed 5.7 million people worldwide in 2005 and is estimated to cause 6.5 million deaths globally in 2015. Stroke survivors are often left with considerable disability. Many strokes are preceded by a TIA/‘minor’ stroke in the previous 90 days and therefore the immediate period after a TIA/minor’ stroke is a crucial time to intervene to tackle known vascular risk factors. Although rehabilitation following a TIA/minor stroke is widely recommended, there is a paucity of research that offers an evidence base on which the development or optimisation of interventions can be based, particularly for home-based approaches and non-pharmacological interventions in the acute period following the initial TIA/‘minor’ stroke. This systematic review will investigate the effect of rehabilitation programmes initiated within 90 days of the diagnosis of a TIA or ‘minor’ stroke aimed at reducing the subsequent risk of stroke.Methods/designThis systematic review will be reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses(PRISMA) guidance. Randomised and quasi-randomised controlled trials of rehabilitation programmes initiated within 90 days of a TIA or ‘minor’ stroke will be included. Articles will be identified through a comprehensive search of the following databases, guided by a medical librarian: the Cochrane Library, Web of Science, MEDLINE, Embase, CINAHL and PsycINFO. Two review authors will independently screen articles retrieved from the search for eligibility and extract relevant data on methodological issues. A narrative synthesis will be completed when there is insufficient data to permit a formal meta-analysis.DiscussionThis review will be of value to clinicians and healthcare professionals working in TIA and stroke services as well as to general practitioners/family physicians who care for these patients in the community and to researchers involved in designing and evaluating rehabilitation interventions.Trial registration numberCRD42015016450.

Abstract 11: Compliance With Risk Factor Optimization and Medical Therapy in Patients With Peripheral Vascular Disease (Peripheral Artery and Ischemic Cerebrovascular Disease) Compared to Ischemic Heart Disease.

Background: Cardiovascular disease (CVD) is a systemic process with patients developing atherosclerosis in multiple vascular beds including ischemic heart disease (IHD), ischemic cerebrovascular disease (ICVD) and peripheral artery disease (PAD). PAD and ICVD are associated with increased risk of subsequent myocardial infarction, stroke and death. Medical management and risk factor optimization are recommended for all patients with CVD. Compliance with measures in patients with ICVD and PAD compared to IHD is not known. Methods: In a large national cohort, we identified 1,242,015 patients with cardiovascular disease (CVD) receiving care in 130 Veterans Affairs facilities between 10/1/2013 and 9/30/2014. CVD was defined as the presence of IHD, PAD, or ICVD. We assessed the frequency of compliance with performance measures in patients with IHD (with or without concomitant PAD or ICVD), PAD only, ICVD only, and PAD+ICVD groups. We compared compliance with hypertension control (BP <140/90 mmHg), diabetes control (HbA1C<7.0% among diabetics), and the use of statin therapy between IHD and PAD, ICVD, or PAD+ICVD groups. A composite of all 3 measures (BP control, statin use, HbA1C <7% among diabetics) termed optimal medical therapy (OMT) was also compared between groups. Multivariate logistic regression was performed with IHD group as the referent category. Results (Table): IHD patients comprised 989,380 (79.7%), PAD only 70,404 (5.7%), ICVD only 163,730 (13.2%) and PAD + ICVD 18,501 (1.5%) of the cohort. Compliance with most measures (hypertension control, statin use) as well as OMT was lower for PAD or ICVD patients compared with IHD patients with minimal differences between IHD and PAD +CVD group. Overall, only 32.3%-41.8% received OMT (i.e. met the composite measure). Conclusions: Compliance with OMT was low in all patients. Patients with PAD or ICVD were less likely to receive OMT compared with IHD. Our results suggest potential for improvement in OMT for all CVD patients especially those with PAD and ICVD.

No evidence that frailty modifies the positive impact of antihypertensive treatment in very elderly people: an investigation of the impact of frailty upon treatment effect in the HYpertension in the Very Elderly Trial (HYVET) study, a double-blind, placebo-controlled study of antihypertensives in people with hypertension aged 80 and over.

BackgroundTreatment for hypertension with antihypertensive medication has been shown to reduce stroke, cardiovascular events, and mortality in older adults, but there is concern that such treatment may not be appropriate in frailer older adults. To investigate whether there is an interaction between effect of treatment for hypertension and frailty in older adults, we calculated the frailty index (FI) for all available participants from the HYpertension in the Very Elderly Trial (HYVET) study, a double-blind, placebo-controlled study of antihypertensives in people with hypertension aged 80 and over, and obtained frailty adjusted estimates of the effect of treatment with antihypertensive medication on risk of stroke, cardiovascular events, and mortality.MethodsParticipants in HYVET were randomised 1:1 to active treatment with indapamide sustained release 1.5 mg ± perindopril 2 to 4 mg or to matching placebo. Data relating to blood pressure, comorbidities, cognitive function, depression, and quality of life were collected at entry into the study and at subsequent follow-up visits. The FI was calculated at entry, based on 60 potential deficits. The distribution of FI was similar to that seen in population studies of adults aged 80 years and above (median FI, 0.17; IQR, 0.11–0.24). Cox regression was used to assess the impact of FI at entry to the study on subsequent risk of stroke, total mortality, and cardiovascular events. Models were stratified by region of recruitment and adjusted for sex and age at entry. Extending these models to include a term for a possible interaction between treatment for hypertension and FI provided a formula for the treatment effect as a function of FI. For all three models, the point estimates of the hazard ratios for the treatment effect decreased as FI increased, although to varying degrees and with varying certainty.ResultsWe found no evidence of an interaction between effect of treatment for hypertension and frailty as measured by the FI. Both the frailer and the fitter older adults with hypertension appeared to gain from treatment.ConclusionsFurther work to examine whether antihypertensive treatment modifies frailty as measured by the FI should be explored.Trial registrationClinicalTrials.gov NCT00122811 (July 2005)Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-015-0328-1) contains supplementary material, which is available to authorized users.

(156) - Percutaneous Driveline Infection Does Not Increase Subsequent Risk of Stroke and Pump Thrombus During Support With a Left Ventricular Assist Device

(156) - Percutaneous Driveline Infection Does Not Increase Subsequent Risk of Stroke and Pump Thrombus During Support With a Left Ventricular Assist Device

China Angioplasty and Stenting for Symptomatic Intracranial Severe Stenosis (CASSISS): A new, prospective, multicenter, randomized controlled trial in China.

Patients with symptomatic stenosis of intradural arteries are at high risk for subsequent stroke. Since the SAMMPRIS trial, stenting is no longer recommended as primary treatment; however, the results of this trial, its inclusion criteria and its center selection received significant criticism and did not appear to reflect our experience regarding natural history nor treatment complications rate. As intracranial atherosclerosis (ICAS) is the most common cause for stroke in Asian countries, we are hereby proposing a refined prospective, randomized, multicenter study in an Asian population with strictly defined patient and participating center inclusion criteria. The China Angioplasty and Stenting for Symptomatic Intracranial Severe Stenosis (CASSISS) trial is an ongoing, government-funded, prospective, multicenter, randomized trial. It recruits patients with recent TIA or stroke caused by 70%-99% stenosis of a major intracranial artery. Patients with previous stroke related to perforator ischemia will not be included. Only high-volume centers with a proven track record will enroll patients as determined by a lead-in phase. Patients will be randomized (1:1) to best medical therapy alone or medical therapy plus stenting. Primary endpoints are any stroke or death within 30 days after enrollment or after any revascularization procedure of the qualifying lesion during follow-up, or stroke in the territory of the symptomatic intracranial artery beyond 30 days. The CASSISS trial will be conducted in eight sites in China with core imaging lab review at a North American site and aims to have a sample size of 380 participants (stenting, 190; medical therapy, 190). Recruitment is expected to be finished by December 2016. Patients will be followed for at least three years. The trial is scheduled to complete in 2019. In the proposed trial, certain shortcomings of SAMMPRIS including patient and participating center selection will be addressed. The present manuscript outlines the rationale and design of the study. We estimate that this trial will allow for a critical reappraisal of the role of intracranial stenting for selected patients in high-volume centers.

Abstract W P172: Baseline Quality of Life and Risk of Stroke in the Antihypertensive and Lipid Lowering to Prevent Heart Attack (ALLHAT) Trial

Background: Quality of Life (QoL) is an integrative health status measure that may predict medical outcomes. No prospective study assessed relationship between QoL, subsequent stroke risk, and post-stroke outcome. Objective: Determine how baseline QoL predicted non-fatal stroke, as well as the impact of stroke risk factors on QoL in ALLHAT using visual analogue scale (VAS) – a validated QoL tool. Methods: ALLHAT randomized hypertensive patients to Chlorthalidone (C), Amlodipine (A) or Lisinopril (L), and used VAS to measure global QoL (0.00 -1.00) at baseline, 2, 4, and 6 yrs. QoL values underwent statistical Torrance transformation (TQoL). Mean QoL and TQoL pre (baseline) and post non-fatal stroke were analyzed. Hazard ratios (HR) and Kaplan-Meier curves for each quartile of baseline QoL were calculated. Baseline QOL, TQoL, and stroke risk factors were used in a multiple linear regression model to predict post-stroke QoL. QoL changes were examined by study arm, age, gender, and race. Results: 28,534 (86%) participants completed at least one VAS. Of the 1,517 strokes; 22% (n=322) were fatal. QoL and TQoL results were similar. Patients who experienced in-trial stroke in C and A arms had lower baseline QoL than those who did not (HR =.71 vs .74, p<0.001and .71 vs .74, p=0.004, respectively), but not in L (HR=.73 vs .74, p=0.24). A 10% increment in baseline QoL or TQoL was associated with 5% and 7% reduction in the risk of stroke respectively (adjusted HR; 95% CI = .95; .91 -.99) and .93; .89 –.98). In risk factor adjusted models, lowest baseline QoL quartile had a 20% higher stroke risk (HR =1.20; 95% CI: 1.00-1.44) than highest quartile. QoL worsened post stroke, dropping most in elderly >75 yrs (-.08 units, p<0.0001), compared to groups 55-64 (-.04, p<0.05) and 65-75 yrs, (-.07, p <0.0001), and in A arm (-.09 units, p<0.0001) compared with C (-.05, p=0.0006) and L (-.07, p< 0.0001), but did not differ by gender or race. In a multiple linear regression model, baseline QoL predicted post-stroke QoL. Conclusions: Lower baseline QoL was associated with higher stroke risk. Qol was lower post stroke. Baseline QoL was the only factor predicting post stroke QoL, and QoL change increased with age. Investigation of factors determining QoL may be fertile ground for stroke risk reduction.

Abstract W P166: Transient Ischemic Attacks In Post-menopausal Women With History Of Migraines Have Lower Risk For Subsequent Ischemic Strokes

Background: TIAs and migraines have both been found to increase the risk of ischemic strokes. The risk for ischemic strokes may be further increased in patients with both of these risk factors. Objective: To compare the risk of ischemic strokes in women with and without a history of migraine following a TIA. Methods: The Observational Study (OS) of the Women’s Health Initiative (WHI) was the observational component of the WHI Study. We analyzed the 93,676 women aged 50-79 years, who participated in the OS over a period of 12±1 years. We determined the risk of incident ischemic stroke following TIAs in women with and without history of migraine. A logistic regression analysis was used to determine the differential risk of ischemic stroke in women with and without history of migraine after adjusting for potential confounders. Results: A total of 133 of the 93676 women without history of migraine and 20 women with history of migraine from the same population developed ischemic strokes. Logistic regression analysis demonstrated that women without history of migraine had a higher odds of developing ischemic stroke [OR 1.9 (95%CI 1.5-2.5) p<.0001] compared with women without TIA after adjustments were made for age, systolic blood pressure, alcohol intake, carotid endarterectomy, DVT, pulmonary embolism, bleeding problems, oral contraceptive use, and hormone replacement therapy. There was not a higher risk of subsequent ischemic stroke among women with migraine history after TIA [OR 1.5 (95%CI 0.7-3.3); p =0.3] Conclusions: The risk of ischemic stroke is lower following TIA in women with migraine history (compared with those without migraine) suggesting potentially different pathophysiology in such women.

Abstract 134: Relative MTT Predicts Subsequent Stroke in Symptomatic Carotid Occlusion

Relative mean transit time (MTT) is readily obtainable from dynamic susceptibility contrast MRI of the brain. While it has received much attention in acute ischemic stroke as a possible means to identify patients for reperfusion therapies, little has been done to determine if it has clinical significance outside the acute setting. To determine if relative MTT could be used to identify patients who are at high risk for subsequent stroke, we analyzed data from the St. Louis Carotid Occlusion Study. This prospective study was carried out from 1992-1997 to determine if PET measurement of oxygen extraction fraction could identify medically treated patients with recently symptomatic carotid artery occlusion at high risk for subsequent stroke. Sixty-eight of the participants in the study had quantitative PET measurements of cerebral blood flow (CBF) and cerebral blood volume (CBV). From these we calculated the MTT (CBV/CBF) in each middle cerebral artery territory and determined the MTT ratio of the ipsilateral to the contralateral hemisphere (I/C MTT ratio). Nine of the 68 participants had a subsequent ipsilateral ischemic stroke during mean follow-up of 2.6 years (range .5 - 5 years). The I/C MTT ratio was significantly associated with subsequent stroke as a continuous variable by Cox regression analysis (HR 65, 95%CI 7-613, p < .001). The maximum combination of sensitivity (.778) and specificity (.763) was obtained with a cutpoint of ≥ 1.387 which identified 7/9 subsequent strokes (PPV .333, NPV .957). Relative MTT shows great promise as a means to identify patients with large artery disease who are at high risk for subsequent stoke. These results need to be confirmed using MRI in a cohort receiving contemporary medical management.

Abstract 209: Intracranial Wall Irregularity and Recurrent Stroke: the SPS3 Trial

Background and Purpose: Intracranial atherosclerosis is an important cause of ischemic stroke and even mild stenosis or subtle wall changes may be a marker for subsequent stroke risk. We tested whether any arterial wall irregularity was predictive of recurrent stroke in participants of the Secondary Prevention of Small Subcortical Strokes (SPS3) trial. Methods: SPS3 was a randomized trial investigating optimal blood pressure target and antiplatelet regimen in patients with recent, symptomatic, MRI-confirmed lacunar stroke patients. Magnetic resonance angiography (MRA) proximate to study entry was adequate and available for 2169 of 3020 study patients. Seven intracranial arteries (basilar [BA], vertebral [VA], internal carotid [ICA], and middle cerebral artery [MCA]) were assessed on time-of-flight MRA for wall irregularities including stenosis and changes of arterial diameter. Cox Proportional Hazards models adjusted for assigned treatments and clinical risk factors were used to estimate risk for recurrent stroke associated with any wall irregularity overall and in specific arteries. Results: Mean age of the 2169 patients was 63 yr with 63% male; hypertension, diabetes, and prior lacunar stroke were present in 75%, 36%, and 10%, respectively. Wall irregularities in ≥1 artery (325 one artery, 250 > 1 artery) were observed in 575 patients (27%). Recurrent stroke occurred in 195 patients during mean follow-up of 3.5 years (annualized rate 2.5% per patient-year). Patients with at least one wall irregularity had an increased risk of recurrent stroke (adjusted HR 1.4, 95% CI 1.0-1.9). There was no interaction between either randomized treatment arm (antiplatelet therapy or blood pressure control target) and wall irregularities. Irregularity by any individual artery (BA, n = 115, 14 strokes; VA, n = 150, 17 strokes; ICA, n = 268, 31 strokes; or MCA, n = 316, 37 strokes) was not predictive of recurrent stroke (each p >0.1). Conclusion: In this large well characterized cohort of lacunar stroke patients, any wall irregularity in at least one artery was associated with recurrent stroke independent of clinical risk factors and assigned treatment groups.

Alcohol consumption at midlife and risk of stroke during 43 years of follow-up: cohort and twin analyses.

Although alcohol-stroke association is well known, the age-varying effect of alcohol drinking at midlife on subsequent stroke risk across older adulthood has not been examined. The effect of genetic/early-life factors is also unknown. We used cohort and twin analyses of data with 43 years of follow-up for stroke incidence to help address these gaps. All 11 644 members of the population-based Swedish Twin Registry born 1886 to 1925 with alcohol data aged ≤60 years were included. The interaction of midlife alcohol consumption by age at stroke was evaluated in Cox-regression and analyses of monozygotic twins were used. Covariates were baseline age, sex, cardiovascular diseases, diabetes mellitus, stress reactivity, depression, body mass index, smoking, and exercise. Altogether 29% participants developed stroke. Compared with very-light drinkers (<0.5 drink/d), heavy drinkers (>2 drinks/d) had greater risk of stroke (hazard ratio, 1.34; P=0.02) and the effect for nondrinkers approached significance (hazard ratio, 1.11; P=0.08). Age increased stroke risk for nondrinkers (P=0.012) and decreased it for heavy drinkers (P=0.040). Midlife heavy drinkers were at high risk from baseline until the age of 75 years when hypertension and diabetes mellitus grew to being the more relevant risk factors. In analyses of monozygotic twin-pairs, heavy drinking shortened time to stroke by 5 years (P=0.04). Stroke-risk associated with heavy drinking (>2 drinks/d) in midlife seems to predominate over well-known risk factors, hypertension and diabetes, until the age of ≈75 years and may shorten time to stroke by 5 years above and beyond covariates and genetic/early-life factors. Alcohol consumption should be considered an age-varying risk factor for stroke.

Association between incident cancer and subsequent stroke.

A study was undertaken to examine the association between incident cancer and the subsequent risk of stroke. Using the Surveillance, Epidemiology, and End Results-Medicare linked database, we identified patients with a new primary diagnosis of breast, colorectal, lung, pancreatic, or prostate cancer from 2001 through 2007. These patients were individually matched by age, sex, race, registry, and medical comorbidities to a group of Medicare enrollees without cancer, and each pair was followed through 2009. Validated diagnosis codes were used to identify a primary outcome of stroke. Cumulative incidence rates were calculated using competing risk survival statistics. Among 327,389 pairs of cancer patients and matched controls, the 3-month cumulative incidence of stroke was generally higher in patients with cancer. Cumulative incidence rates were 5.1% (95% confidence interval [CI] = 4.9-5.2%) in patients with lung cancer compared to 1.2% (95% CI = 1.2-1.3%) in controls (p < 0.001), 3.4% (95% CI = 3.1-3.6%) in patients with pancreatic cancer compared to 1.3% (95% CI = 1.1-1.5%) in controls (p < 0.001), 3.3% (95% CI = 3.2-3.4%) in patients with colorectal cancer compared to 1.3% (95% CI = 1.2-1.4%) in controls (p < 0.001), 1.5% (95% CI = 1.4-1.6%) in patients with breast cancer compared to 1.1% (95% CI = 1.0-1.2%) in controls (p < 0.001), and 1.2% (95% CI = 1.1-1.3%) in patients with prostate cancer compared to 1.1% (95% CI = 1.0-1.2%) in controls (p = 0.085). Excess risks attenuated over time and were generally no longer present beyond 1 year. Incident cancer is associated with an increased short-term risk of stroke. This risk appears highest with lung, pancreatic, and colorectal cancers.