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Background: Prevalence of atrial fibrillation (AF) is increasing, due partly to the ageing population. The Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) Trial, published in 2007, provided strong evidence of the effectiveness of warfarin at age≥80 years, but the impact on incidence of AF-related stroke and peripheral embolic vascular events is uncertain.Methods: We studied age-specific incidence and outcome of all AF-related incident strokes and systemic emboli from 2002 to 2012 in the Oxford Vascular Study.Results: Of 3096 acute cerebral or peripheral vascular events, 748 (24.2%) were AF-related. Of the 597 disabling/fatal incident ischaemic strokes, 369 occurred at age ≥80 years, of which 124 (33.6%) were in non-anticoagulated patients with known prior AF. There was no reduction in incident AF-related events after 2007 at all ages (n=231 vs 211; adjusted RR=1.11, 0.91 to 1.36, p=0.29) or at age ≥80 (137 vs 135, RR=1.15, 0.94 to 1.40, p=0.17). Scope for improved prevention at older ages was considerable. Among 208 patients with incident AF-related events at age ≥80 and known prior AF, only 19 (9.1%) were anticoagulated. Of the 189 patients not anticoagulated, 166 (87.8%) had no major disability prior to the event and 167 (88·4%) had a high embolism risk score, of whom 139 (83.2%) were also at low risk of complications. Yet, 125/167 (74.9%) were dead or institutionalised after the event. Potentially preventable embolic events outnumbered warfarin-related intracerebral haemorrhages by about 15-fold (280 vs 19), rising to 50-fold (189 vs 4) at age ≥80 years.Conclusions: We found no reduction in incidence of AF-related vascular events since publication of the BAFTA trial. A third of all disabling/fatal strokes occur in non-anticoagulated patients with known prior AF. [ABSTRACT FROM AUTHOR]

Objectives to measure the number of all transient ischaemic attack (TIAs) and minor strokes managed as outpatients, and hence, the need for 'TIA clinics' in comparison to current estimates of 20,000 TIAs annually in England, based on previous rates of incident-definite events. Subjects all individuals with confirmed or suspected TIA or stroke between 2002 and 2005 in a population-based study of 91,105 individuals in Oxfordshire, UK. Outcome Measures numbers, rates, and risks of recurrent stroke for incident-definite TIA, any probable or definite TIA, stroke, and all referrals of suspected TIA and stroke, stratified according to inpatient versus outpatient management. Results of 1,174 confirmed or suspected events ascertained, 729 (62.1%) were managed as outpatients and 445 (37.9%) as inpatients. Among 757 probable or definite events, 432 (57%) were managed as outpatients. Incident-definite TIAs accounted for only 18% of all referrals to outpatient services. Annual rates per 1,000 population were 2.98 (2.77-3.2) for all referrals to outpatient services and 1.88 (1.71-2.06) for inpatient admissions. Of 73 recurrent strokes within 90 days of initial TIA or stroke, 48 (65.8%) occurred in the outpatient population. Applying these rates to the population of England yields approximately 150,000 new referrals annually to TIA clinics with about 10,000 early recurrent strokes. Conclusion more patients with TIA or stroke are managed as outpatients than inpatients in the UK, and this group has the majority of possibly preventable early recurrent strokes. Current projections of need for TIA clinics in England substantially underestimate the overall requirement for outpatient services. [ABSTRACT FROM AUTHOR]

Background: Patients with stroke due to spontaneous (non-traumatic) intracerebral haemorrhage (ICH) are at risk of recurrent ICH, ischaemic stroke, and other serious vascular events. We aimed to analyse these risks in population-based studies and compare them with the risks in RESTART, which assessed antiplatelet therapy after ICH.Methods: We pooled individual patient data from two prospective, population-based inception cohort studies of all patients with an incident firs-in-a-lifetime ICH in Oxfordshire, England (Oxford Vascular Study; April 1, 2002, to Sept 28, 2018) and Lothian, Scotland, UK (Lothian Audit of the Treatment of Cerebral Haemorrhage; June 1, 2010, to May 31, 2013). We quantified the absolute and relative risks of recurrent ICH, ischaemic stroke, or any serious vascular event (non-fatal stroke, non-fatal myocardial infarction, or vascular death), stratified by ICH location (lobar vs non-lobar) and comorbid atrial fibrillation (AF). We compared pooled event rates with those after allocation to avoid antiplatelet therapy in RESTART.Findings: Among 674 patients (mean age 74·7 years [SD 12·6], 320 [47%] men) with 1553 person-years of follow-up, 46 recurrent ICHs (event rate 3·2 per 100 patient-years, 95% CI 2·0-5·1) and 25 ischaemic strokes (1·7 per 100 patient-years, 0·8-3·3) were reported. Patients with lobar ICH (n=317) had higher risk of recurrent ICH (5·1 per 100 patient-years, 95% CI 3·6-7·2) than patients with non-lobar ICH (n=355; 1·8 per 100 patient-years, 1·0-3·3; hazard ratio [HR] 3·2, 95% CI 1·6-6·3; p=0·0010), but there was no evidence of a difference in the risk of ischaemic stroke (1·8 per 100 patient-years, 1·0-3·2, vs 1·6 per 100 patient-years, 0·6-4·4; HR 1·1, 95% CI 0·5-2·8). Conversely, there was no evidence of a difference in recurrent ICH rate in patients with AF (n=147; 3·3 per 100 patient-years, 95% CI 1·0-10·7) compared with those without (n=526; 3·2 per 100 patient-years, 2·2-4·7; HR 0·9, 95% CI 0·4-2·1), but the risk of ischaemic stroke was higher with AF (6·3 per 100 patient-years, 3·7-10·9, vs 0·7 per 100 patient-years, 0·1-5·6; HR 8·2, 3·3-20·3; p<0·0001), resulting in patients with AF having a higher risk of all serious vascular events than patients without AF (15·5 per 100 patient-years, 10·0-24·1, vs 6·8 per 100 patient-years, 3·6-12·5; HR 1·78, 95% CI 1·16-2·74; p=0·0090). Only for patients with lobar ICH without comorbid AF was the risk of recurrent ICH greater than the risk of ischaemic stroke (5·2 per 100 patient-years, 95% CI 3·6-7·5, vs 0·9 per 100 patient-years, 0·2-4·8; p=0·00034). Comparing data from the pooled population-based studies with that from patients allocated to not receive antiplatelet therapy in RESTART, there was no evidence of a difference in the rate of recurrent ICH (3·5 per 100 patient-years, 95% CI 1·9-6·0, vs 4·4 per 100 patient-years, 2·6-6·1) or ischaemic stroke (3·4 per 100 patient-years, 1·9-5·9, vs 5·3 per 100 patient-years, 3·3-7·2).Interpretation: The risks of recurrent ICH, ischaemic stroke, and all serious vascular events after ICH differ by ICH location and comorbid AF. These data enable risk stratification of patients in clinical practice and ongoing randomised trials.Funding: UK Medical Research Council, Stroke Association, British Heart Foundation, Wellcome Trust, and the National Institute for Health Research Oxford Biomedical Research Centre. [ABSTRACT FROM AUTHOR]

Background: Lifelong antiplatelet treatment is recommended after ischaemic vascular events, on the basis of trials done mainly in patients younger than 75 years. Upper gastrointestinal bleeding is a serious complication, but had low case fatality in trials of aspirin and is not generally thought to cause long-term disability. Consequently, although co-prescription of proton-pump inhibitors (PPIs) reduces upper gastrointestinal bleeds by 70-90%, uptake is low and guidelines are conflicting. We aimed to assess the risk, time course, and outcomes of bleeding on antiplatelet treatment for secondary prevention in patients of all ages.Methods: We did a prospective population-based cohort study in patients with a first transient ischaemic attack, ischaemic stroke, or myocardial infarction treated with antiplatelet drugs (mainly aspirin based, without routine PPI use) after the event in the Oxford Vascular Study from 2002 to 2012, with follow-up until 2013. We determined type, severity, outcome (disability or death), and time course of bleeding requiring medical attention by face-to-face follow-up for 10 years. We estimated age-specific numbers needed to treat (NNT) to prevent upper gastrointestinal bleeding with routine PPI co-prescription on the basis of Kaplan-Meier risk estimates and relative risk reduction estimates from previous trials.Findings: 3166 patients (1582 [50%] aged ≥75 years) had 405 first bleeding events (n=218 gastrointestinal, n=45 intracranial, and n=142 other) during 13 509 patient-years of follow-up. Of the 314 patients (78%) with bleeds admitted to hospital, 117 (37%) were missed by administrative coding. Risk of non-major bleeding was unrelated to age, but major bleeding increased steeply with age (≥75 years hazard ratio [HR] 3·10, 95% CI 2·27-4·24; p<0·0001), particularly for fatal bleeds (5·53, 2·65-11·54; p<0·0001), and was sustained during long-term follow-up. The same was true of major upper gastrointestinal bleeds (≥75 years HR 4·13, 2·60-6·57; p<0·0001), particularly if disabling or fatal (10·26, 4·37-24·13; p<0·0001). At age 75 years or older, major upper gastrointestinal bleeds were mostly disabling or fatal (45 [62%] of 73 patients vs 101 [47%] of 213 patients with recurrent ischaemic stroke), and outnumbered disabling or fatal intracerebral haemorrhage (n=45 vs n=18), with an absolute risk of 9·15 (95% CI 6·67-12·24) per 1000 patient-years. The estimated NNT for routine PPI use to prevent one disabling or fatal upper gastrointestinal bleed over 5 years fell from 338 for individuals younger than 65 years, to 25 for individuals aged 85 years or older.Interpretation: In patients receiving aspirin-based antiplatelet treatment without routine PPI use, the long-term risk of major bleeding is higher and more sustained in older patients in practice than in the younger patients in previous trials, with a substantial risk of disabling or fatal upper gastrointestinal bleeding. Given that half of the major bleeds in patients aged 75 years or older were upper gastrointestinal, the estimated NNT for routine PPI use to prevent such bleeds is low, and co-prescription should be encouraged.Funding: Wellcome Trust, Wolfson Foundation, British Heart Foundation, Dunhill Medical Trust, National Institute of Health Research (NIHR), and the NIHR Oxford Biomedical Research Centre. [ABSTRACT FROM AUTHOR]

Importance: Some studies have reported increasing stroke incidence at younger ages (<55 years) but have often relied only on administrative data, and more population-based studies of adjudicated stroke are required. An understanding of the drivers of any increase in incidence of young stroke also requires comparisons with stroke trends at older ages and with trends in incidence of other vascular events at younger ages., Objective: To determine temporal changes in incidence of stroke and other major vascular events at younger vs older ages., Design, Setting, and Participants: Prospective population-based incidence study conducted from April 2002 to March 2018 with a mean catchment population of 94 567 in Oxfordshire, England., Exposures: Calendar time, premorbid vascular risk factors, and occupation., Main Outcomes and Measures: Changes in incidence of stroke, transient ischemic attack (TIA), and other major vascular events (myocardial infarction, sudden cardiac death, and peripheral vascular events) stratified by age, sex, diagnostic workup, etiology, and severity., Results: A total of 2429 incident strokes were ascertained (mean age, 73.6 [SD, 14.4] years; 51.3% female). From 2002-2010 to 2010-2018, stroke incidence increased significantly among participants younger than 55 years (incidence rate ratio [IRR], 1.67; 95% CI, 1.31-2.14) but fell significantly among participants aged 55 years or older (IRR, 0.85; 95% CI, 0.78-0.92; P < .001 for difference). The significant increase in incidence at younger than 55 years was independent of sex, stroke severity, pathological subtype, and changes in investigation and was also seen for TIA (IRR, 1.87; 95% CI, 1.36-2.57) but not for myocardial infarction and other major vascular events (IRR, 0.73; 95% CI, 0.58-0.93). Although TIA and stroke at younger than 55 years were significantly associated with diabetes (risk ratio [RR], 3.47; 95% CI, 2.54-4.74), hypertension (RR, 2.52; 95% CI, 2.04-3.12), current smoking (RR, 2.38; 95% CI, 1.92-2.94), and obesity (RR, 1.36; 95% CI, 1.07-1.72), the significant increase in incidence from 2002-2010 to 2010-2018 was still seen in individuals without these risk factors. The increase was greatest in professional/managerial occupations (IRR, 2.52; 95% CI, 1.75-3.62) and least in partially skilled/unskilled occupations (IRR, 1.17; 95% CI, 0.79-1.74). The proportion of TIAs and strokes among those younger than 55 years without known vascular risk factors increased significantly over time (45 [30.4%] vs 115 [42.4%]; absolute difference, 12.0%; 95% CI, 2.6-21.5), especially in patients with cryptogenic events (10 [18.5%] vs 63 [49.2%]; absolute difference, 30.7%; 95% CI, 17.2-44.2; P < .001; P = .002 for heterogeneity)., Conclusions and Relevance: Comparing persons living in Oxfordshire, England, in 2002-2010 vs 2010-2018, there was a significant increase in stroke incidence in those younger than 55 years, but a decrease in those aged 55 years or older. Given the absence of this divergence for other vascular events, further research is needed to understand the causes of this difference.

Background and Purpose: The PROGRESS trial (Perindopril Protection Against Recurrent Stroke Study) conducted in the early 1990s showed that blood pressure (BP) lowering therapy reduced the risks of recurrent stroke by about 50% after spontaneous intracerebral hemorrhage (ICH). However, the ICH subgroup was a minority, and trial cohorts are invariably selective. Therefore, it is unclear whether the impact of BP control on risk of recurrent stroke in ICH observed in PROGRESS would be as great in real-world practice., Methods: We compared BP control (mean BP during study follow-up) and risks of recurrent stroke after first-ever primary ICH in 2 colocated population-based studies before and after the PROGRESS trial (1995–2001) in Oxfordshire: Oxfordshire Community Stroke Project (OCSP; 1981–1986) and OXVASC (Oxford Vascular Study; 2002–2018)., Results: Two hundred seventy-seven patients (753 patient-years of follow-up) with first-ever primary ICH were ascertained in OXVASC and OCSP. Baseline systolic BP was comparable between the 2 studies (mean/SD=183.8/36.5 in OXVASC versus 178.1/38.2 in OCSP, P=0.30) but among one hundred thirty-seven 90-day survivors, mean BP during follow-up was substantially lower in OXVASC versus OCSP (135.2/16.4 versus 157.3/17.8, P<0.0001). Risks of recurrent stroke (per 100 patient-years) decreased from 10.3 (95% CI, 4.7–19.5) in OCSP to 3.1 (1.8–4.8) in OXVASC (P=0.006), predominantly driven by a reduction at younger ages (5-year risk at age <75 years: 35.4% versus 6.9%, P=0.001; hazard ratio, 0.14 [0.04–0.54])., Conclusions: Risks of recurrent stroke after primary ICH have fallen significantly in Oxfordshire over the past 4 decades, coinciding with substantial improvements in BP control during follow-up.

Introduction: Increasing blood pressure variability has been reported following acute stroke, but there is uncertainty about how best to measure it and about the impact on prognosis following acute ischaemic stroke and transient ischaemic attack., Methods: Enhanced casual blood pressure and ambulatory blood pressure monitoring were completed at baseline (≤48 h post symptom onset). Blood pressure variability was defined by standard deviation and coefficient of variation of systolic, diastolic, mean arterial pressure, and pulse pressure. Modified Rankin scale score ≥3 described poor functional outcome assessed at 1- and 12-months post-stroke. Multivariable logistic regression models incorporating blood pressure variability measurement and other factors were performed, and odds ratio and 95% confidence intervals reported., Results: 232 patients were recruited; 45 were dependent at 1-month, and 37 at 12-months. Dependent patients were more likely to be older, with a higher burden of pre-morbid conditions, and with increased blood pressure variability. Enhanced casual standard deviations of diastolic blood pressure [1.19 (1.02 to 1.39)] and mean arterial pressure [1.20 (1.00 to 1.43)] predicted dependency at 1-month. Predictors of 12-month dependency included: enhanced casual standard deviation of mean arterial pressure [1.21 (1.0-1.46)]; 24 h ambulatory monitor standard deviations of diastolic blood pressure [2.30 (1.08-4.90)] and mean arterial pressure [1.72 (1.09-2.72)], and the coefficient of variation of mean arterial pressure [1.76 (1.05-2.94)]; day-time ambulatory monitor coefficient of variation of systolic blood pressure [1.44 (1.02-2.03)] and mean arterial pressure [1.46 (1.02-2.08)]; and night-time ambulatory standard deviation of diastolic blood pressure [1.65 (1.03 -2.63)], and the coefficient of variation of mean arterial pressure and [1.38 (1.00- 1.90)] and pulse pressure [1.29 (1.00-1.65)]., Conclusion: Increasing blood pressure variability is independently and modestly associated with poor functional outcome at 1- and 12-months following acute stroke., Competing Interests: Declaration of Competing Interest None declared, (Copyright © 2020 Elsevier Inc. All rights reserved.)

Importance: Asymptomatic intracranial stenosis (ICS) is a frequent finding on imaging results, particularly in the assessment of acute stroke. Although the management of symptomatic ICS is informed by randomized trials, to our knowledge there are few data on the prevalence and prognosis of asymptomatic ICS in patients with stroke and transient ischemic attack (TIA)., Objective: To study the age-specific prevalence and prognosis of asymptomatic ICS in a population-based cohort of patients with TIA and minor stroke., Design, Setting, and Participants: All patients (predominantly white) recruited to the Oxford Vascular Study (Oxfordshire, England) between March 1, 2011, and March 1, 2018, with TIA and minor ischemic stroke (National Institutes of Health Stroke Scale score, ≤3), irrespective of age, were included (n = 1579). We determined the age-specific prevalence of 50% or more asymptomatic ICS and the associated stroke risk by face-to-face follow-up to 2018 on standard medical treatment without stenting., Exposures: Patients underwent magnetic resonance angiography of the intracranial and cervicocranial arteries, computed tomography angiography if magnetic resonance angiography was contraindicated, or carotid/transcranial Doppler ultrasonography if computed tomography angiography was contraindicated., Main Outcomes and Measures: The primary outcomes were the prevalence and prognosis of asymptomatic ICS., Results: Of 1368 eligible patients (mean [SD] age, 69.2 [13.9] years; 700 men [51.2%]) with intracranial vascular imaging, 426 ICS were identified in 260 patients (19.0%): 58 (4.2%) with only symptomatic ICS, 155 (11.3%) with only asymptomatic ICS, and 47 (3.4%) with both. The prevalence of any asymptomatic ICS increased from 4.8% for patients younger than 70 years to 34.6% for patients 90 years or older (P for trend < .001; odds ratio per decade, 1.96; 95% CI, 1.69-2.27) and was greater than that of 50% or more asymptomatic carotid bifurcation stenosis (202 [14.8%] vs 105 patients [7.2%]; relative risk, 2.04; 95% CI, 1.63-2.55, P < .001). However, the 155 patients with only asymptomatic ICS had no increase in risk of ischemic stroke compared with those with no ICS (unadjusted HR, 1.03, 95% CI, 0.49-2.17), with 8 first recurrent events (5.2%) during 506 patient-years of follow-up and 3 in the territory of the ICS (annualized risk, 0.59%; 95% CI, 0.12-1.73)., Conclusions and Relevance: The prevalence of asymptomatic ICS increases with age in white patients with TIA and minor stroke and is greater than that of asymptomatic carotid stenosis, but asymptomatic ICS does not increase the short- or medium-term risk of distal recurrent ischemic stroke for patients receiving standard medical treatment.

Objective/background: There are few published data on the acute care or long-term costs after acute/critical limb or visceral ischaemia (ACLVI) events. Using data from patients with acute events in a population based incidence study (Oxford Vascular Study), the present study aimed to determine the long-term costs after an ACLVI event., Methods: All patients with first ever incident ACLVI from 2002 to 2012 were included. Analysis was based on follow up until January 2017, with all patients having full 5 year follow up. Multivariate regressions were used to assess baseline and subsequent predictors of total 5 year hospital care costs. Overall costs after an ACLVI event were benchmarked against those after stroke in the same population, during the same period., Results: Among 351 patients with an ACLVI event, mean 5 year total care costs were €35,211 (SD 50,500), of which €6443 (18%) were due to long-term institutionalisation. Costs differed by type of event (acute visceral ischaemia €16,476; acute limb ischaemia €24,437; critical limb ischaemia €46,281; p < 0.001). Results of the multivariate analyses showed that patients with diabetes and those undergoing above knee amputations incurred additional costs of €11,804 (p = 0.014) and €25,692 (p < 0.001), respectively. Five year hospital care costs after an ACLVI event were significantly higher than after stroke (€28,768 vs. €22,623; p = 0.004), but similar after including long-term costs of institutionalisation (€35,211 vs. €35,391; p = 0.957)., Conclusion: Long-term care costs after an ACLVI event are considerable, especially after critical limb ischaemia. Hospital care costs were significantly higher than for stroke over the long term, and were similar after inclusion of costs of institutionalisation., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: reliable delirium risk stratification will aid recognition, anticipation and prevention and will facilitate targeting of resources in clinical practice as well as identification of at-risk patients for research. Delirium risk scores have been derived for acute medicine, but none has been prospectively validated in external cohorts. We therefore aimed to determine the reliability of externally derived risk scores in a consecutive cohort of older acute medicine patients., Methods: consecutive patients aged ≥65 over two 8-week periods (2010, 2012) were screened prospectively for delirium using the Confusion Assessment Method (CAM), and delirium was diagnosed using the DSM IV criteria. The reliability of existing delirium risk scores derived in acute medicine cohorts and simplified for use in routine clinical practice (USA, n = 2; Spain, n = 1; Indonesia, n = 1) was determined by the area under the receiver operating characteristic curve (AUC). Delirium was defined as prevalent (on admission), incident (occurring during admission) and any (prevalent + incident) delirium., Results: among 308 consecutive patients aged ≥65 (mean age/SD = 81/8 years, 164 (54%) female), existing delirium risk scores had AUCs for delirium similar to those reported in their original internal validations ranging from 0.69 to 0.76 for any delirium and 0.73 to 0.83 for incident delirium. All scores performed better than chance but no one score was clearly superior., Conclusions: externally derived delirium risk scores performed well in our independent acute medicine population with reliability unaffected by simplification and might therefore facilitate targeting of multicomponent interventions in routine clinical practice., (© The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society.)

Background: Current abdominal aortic aneurysm (AAA) screening in men age 65 might have limited impact on overall AAA death rates if incidence is moving to older ages. Up-to-date population-based studies of age-specific incidence, risk factors, and outcome of acute AAA are needed to inform screening policy., Methods and Results: In a prospective, population-based study (Oxfordshire, UK, 2002-2014), the incidence and outcome of acute AAA events were determined. Based on population projections and current incidence trends, the impact of screening strategies in the UK was estimated. Over the 12-year period, 103 incident acute AAA events occurred in the study population of 92 728. Incidence/100 000/year was 55 in men ages 65 to 74 years, but increased to 112 at 75 to 85 and 298 at ≥85, with 66.0% of all events occurring at age ≥75 years. Incidence at ages 65 to 74 was highest in male smokers (274), with 96.4% of events in men <75 years occurring in ever-smokers. Extrapolating rates to the UK population, using trial evidence of screening efficacy, the current UK screening program would prevent 5.6% of aneurysm-related deaths (315 200 scans/year: 1426/death prevented, 121/year-of-life saved). Screening only male smokers age 65 and then all men at age 75 would prevent 21.1% of deaths (247 900 scans/year; 297/death prevented, 34/year-of-life saved). By 2030, 91.0% of deaths will occur at age ≥75, 61.6% at ≥85, and 28.6% in women., Conclusions: Given that two thirds of acute AAA occurred at ≥75 years of age, screening older age groups should be considered. Screening nonsmokers at age 65 is likely to have very little impact on AAA event rates., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background and Purpose: Cognitive outcomes in cohorts and trials are often based only on face-to-face clinic assessment. However, cognitive impairment is strongly associated with increased morbidity and mortality, leading to substantial loss to clinic follow-up. In the absence of previous population-based data, we determined the effect of such attrition on measured risk of dementia after transient ischemic attack and stroke., Methods: Patients with transient ischemic attack or stroke prospectively recruited (2002-2007) into the Oxford Vascular (OXVASC) study had baseline clinical/cognitive assessment and follow-up to 2014. Dementia was diagnosed through face-to-face clinic interview, supplemented by home visits and telephone assessment in patients unable to attend clinic and by hand-searching of primary care records in uncontactable patients., Results: Of 1236 patients (mean age/SD, 75.2/12.1 years; 582 men), 527 (43%) died by 5-year follow-up. Follow-up assessment rates (study clinic, home visit, or telephone) of survivors were 947 in 1026 (92%), 857 in 958 (89%), 792 in 915 (87%), and 567 in 673 (84%) at 1, 6, 12 months and 5 years. Dementia developed in 260 patients, of whom 110 (42%; n=50 primary care records, n=49 home visit, and n=11 telephone follow-up) had not been available for face-to-face clinic follow-up at the time of diagnosis. The 5-year cumulative incidence of postevent dementia was 29% (26%-32%) overall but was only 17% (14% to 19%) in clinic assessed versus 45% (39%-51%) in nonclinic-assessed patients (P difference<0.001)., Conclusions: Exclusion of patients unavailable for clinic follow-up reduces the measured risk of postevent dementia. Use of multiple follow-up methods, including home visits, telephone assessments, and consent, to access primary care records substantially increases ascertainment of longer-term dementia outcomes., Competing Interests: Disclosures/ Competing interests: None declared., (© 2015 American Heart Association, Inc.)

Objective: To evaluate the 5-year impact of stroke and TIA on utility and quality-adjusted survival., Methods: TIA and stroke patients from a UK population-based study (Oxford Vascular Study) were recruited from 2002 to 2007, and followed up until 2012. Quality of life was assessed over 5 years using the EQ-5D (EuroQol-5 Dimensions), with responses converted into utilities ranging from -0.59 (worse than death) to 1 (perfect health), using UK population valuations. Utilities for stroke and TIA patients were compared with those in matched controls obtained from the 2006 Health Survey for England. Five-year quality-adjusted life years were estimated by combining utility and survival information., Results: Four hundred forty TIA and 748 stroke patients were ascertained and included. Utility remained constant at approximately 0.78 over the 5 years after TIA. Utility improved from 0.64 one month after stroke to 0.70 at 6 months (p = 0.006), remaining at approximately 0.70 thereafter. Matched controls had considerably higher utility levels than stroke/TIA patients (0.85, p < 0.001). Event severity and recurrent stroke were significant predictors of decreased long-term utility. Five-year quality-adjusted life expectancy was 3.32 (95% confidence interval: 3.22-3.48) quality-adjusted life years after TIA and 2.21 (2.15-2.37) after stroke, varying considerably by severity (minor: 2.94; moderate: 1.65; and severe: 0.70)., Conclusion: Quality-adjusted survival is low over the 5 years after stroke and TIA, with severity and recurrent stroke being major predictors. There remains considerable scope for improvements in acute treatment and secondary prevention to improve the quality of life after TIA and stroke.

Background and Purpose: Long-term outcome information after transient ischemic attack (TIA) and stroke is required to help plan and allocate care services. We evaluated the impact of TIA and stroke on disability and institutionalization over 5 years using data from a population-based study., Methods: Patients from a UK population-based cohort study (Oxford Vascular Study) were recruited from 2002 to 2007 and followed up to 2012. Patients were followed up at 1, 6, 12, 24, and 60 months postevent and assessed using the modified Rankin scale. A multivariate regression analysis was performed to assess the predictors of disability postevent., Results: A total of 748 index stroke and 440 TIA cases were studied. For patients with TIA, disability levels increased from 14% (63 of 440) premorbidly to 23% (60 of 256) at 5 years (P=0.002), with occurrence of subsequent stroke being a major predictor of disability. For stroke survivors, the proportion disabled (modified Rankin scale >2) increased from 21% (154 of 748) premorbidly to 43% (273 of 634) at 1 month (P<0.001), with 39% (132 of 339) of survivors disabled 5 years after stroke. Five years postevent, 70% (483 of 690) of patients with stroke and 48% (179 of 375) of patients with TIA were either dead or disabled. The 5-year risk of care home institutionalization was 11% after TIA and 19% after stroke. The average 5-year cost per institutionalized patient was $99,831 (SD, 67 020) for TIA and $125,359 (SD, 91 121) for stroke., Conclusions: Our results show that 70% of patients with stroke are either dead or disabled 5 years after the event. Thus, there remains considerable scope for improvements in acute treatment and secondary prevention to reduce postevent disability and institutionalization.

Background: Leukoaraiosis is associated with an increased risk of stroke, but the underlying mechanism remains uncertain, as do the associations with other risk factors, such as carotid disease. We aimed to determine the role of carotid disease and of other clinical variables in the development of leukoaraiosis and to define their contributions to the associated increased risk of stroke., Methods and Results: We prospectively studied a large cohort of consecutive patients with transient ischemic attack (TIA) and minor stroke who attended a TIA clinic between 2002 and 2009. Detailed clinical data were obtained, and patients underwent magnetic resonance brain and vascular imaging. We assessed the severity of leukoaraiosis with use of the ARWMC (Age Related White Matter Changes) score: 671 patients (374 [56%] men; mean [SD] age 71 [11] years) were studied, of whom 415 (62%) had leukoaraiosis. In a multivariate analysis, leukoaraiosis was associated with increasing age (P<0.0001) and hypertension (P=0.01), as well as the presence of acute (P<0.0001) and chronic (P=0.014) infarction on magnetic resonance imaging. In the univariate analysis, a current and past diagnosis of stroke versus TIA also showed a strong association. Carotid disease was not associated with leukoaraiosis, even in the presence of a flow-limiting (>70%) stenosis or occlusion, and the risk factor profiles for leukoaraiosis and carotid disease differed., Conclusions: The association with more severe ischemic events (stroke versus TIA) and infarction on imaging is consistent with leukoaraiosis being a marker of increased cerebral susceptibility to ischemia. In contrast, the presence, severity of, and risk factors for atheromatous disease showed no association with leukoaraiosis, suggesting that these are two unrelated disease processes.

Background and Purpose: Reliable comparisons of stroke incidence are important. To determine the impact of systematic assessment of patients referred with transient ischemic attack on the measured incidence and severity of stroke, we compared 2 population-based studies., Methods: Patients with first-ever stroke ascertained during 2006 through 2010 from the Dijon Stroke Registry and the Oxford Vascular (OXVASC) Study were studied. Both studies comply with the criteria for ideal incidence studies, but the OXVASC Study also systematically assessed all patients referred with transient ischemic attack. Stroke severity was measured by the National Institutes of Health Stroke Scale., Results: Among 902 incident strokes in Dijon and 748 cases in the OXVASC Study, age and gender distribution were comparable, but severity was lower in the OXVASC Study (median National Institutes of Health Stroke Scale, 2 versus 6; P<0.001). Although overall incidence of ischemic stroke was higher in the OXVASC Study (157 versus 98 of 100 000/y; incidence rate ratio, 1.59; 95% confidence interval, 1.24-2.05; P<0.001), this was accounted for by a 3-fold excess incidence of stroke with National Institutes of Health Stroke Scale ≤2 in the OXVASC Study (90 versus 29/100 000/y; P<0.001), with no difference in incidence of more severe ischemic stroke (incidence rate ratio, 0.95; 95% confidence interval, 0.68-1.33). Of all 660 incident ischemic strokes in the OXVASC Study, 375 (56.8%) cases had an National Institutes of Health Stroke Scale ≤2, of which 232 had been ascertained in the transient ischemic attack clinic. Of these 232 minor strokes, only 71 cases had a diagnosis of definite stroke documented in the medical records by the referring physician., Conclusions: Reliance on routine clinical coding underestimates the incidence of minor stroke. To improve comparability of incidence studies, researchers should assess patients referred with transient ischemic attack, and all studies should stratify incidence rates by stroke severity.

Background: Acute aortic dissection is a preventable life-threatening condition. However, there have been no prospective population-based studies of incidence or outcome to inform an understanding of risk factors, strategies for prevention, or projections for future clinical service provision., Methods and Results: We prospectively determined incidence and outcomes of all acute aortic dissections in a population of 92 728 in Oxfordshire, United Kingdom, from 2002 to 2012. Among 155 patients with 174 acute aortic events, 54 patients had 59 thoracoabdominal aortic dissections (52 incident events: 6/100 000, 95% confidence interval, 4-7; 37 Stanford type A, 15 Stanford type B; 31 men, mean age=72.0 years). Among patients with type A incident events, 18 (48.6%) died before hospital assessment (61.1% women). The 30-day fatality rate was 47.4% for patients with type A dissections who survived to hospital admission and 13.3% for patients with type B dissections, although subsequent 5-year survival rates were high (85.7% for type A; 83.3% for type B). Even though 67.3% of patients were on antihypertensive drugs, 46.0% of all patients had at least 1 systolic BP ≥180 mm Hg in their primary care records over the preceding 5 years, and the proportion of blood pressures in the hypertensive range (>140/90 mm Hg) averaged 56.0%. Premorbid blood pressure was higher in patients with type A dissections that were immediately fatal than in those who survived to admission (mean/standard deviation pre-event systolic blood pressure=151.2/19.3 versus 137.9/17.9; P<0.001)., Conclusions: Uncontrolled hypertension remains the most significant treatable risk factor for acute aortic dissection. Prospective population-based ascertainment showed that hospital-based registries will underestimate not only incidence and case fatality, but also the association with premorbid hypertension.

Background and Purpose: Most guidelines now recommend that patients with minor stroke or high-risk transient ischemic attack (TIA) are assessed within 24 hours of their event, but the feasibility of this depends on patients' behavior. We studied behavior immediately after TIA and minor stroke according to clinical characteristics, patients' perception of the nature of the event, and their predicted stroke risk., Methods: In a population-based study in Oxfordshire, UK, with face-to-face interview of 1000 consecutive patients with TIA and minor stroke (National Institutes of Health Stroke Scale < or =5) from 2002 to 2007 (Oxford Vascular Study), we studied delay in seeking medical attention and identified patients who did not seek attention after an initial event and only presented after a recurrent stroke., Results: Of 1000 patients (459 TIAs, 541 minor strokes), 300 (67%) with TIA and 400 (74%) with minor stroke sought medical attention within 24 hours and 208 (47%) and 234 (46%), respectively, sought attention within 3 hours. Most patients (77%) first sought attention through their primary care physician. In patients with TIA, incorrect recognition of symptoms, absence of motor or speech symptoms, shorter duration of event, lower ABCD(2) score, no history of stroke or atrial fibrillation, and weekend presentation were associated with significantly longer delays. However, age, sex, social class, and educational level were all unrelated to either correct recognition of symptoms or to delay in seeking attention. Of 129 patients with TIA or minor stroke who had a recurrent stroke within 90 days, 41 (31%) did not seek medical attention after their initial event. These patients were more likely to have had a TIA (P=0.003), shorter duration of event (P=0.02), and a history of TIA (P=0.09) and less likely to have had motor (P=0.004) or speech symptoms (P=0.04) compared with those patients who sought medical attention for their initial event., Conclusions: Approximately 70% of patients do not correctly recognize their TIA or minor stroke, 30% delay seeking medical attention for >24 hours, regardless of age, sex, social class, or educational level, and approximately 30% of early recurrent strokes occur before seeking attention. Without more effective public education of all demographic groups, the full potential of acute prevention will not be realized.

We studied the effect of prophylactic aspirin (ASA) ingestion on platelet function in 463 patients with stroke, transient ischemic attack (TIA) or acute coronary disease (ACD), using the Platelet Function Analyzer-100 (PFA-100). We correlated ASA responsiveness with haplotypes of seven candidate genes, selected for their documented role in platelet function, namely, the genes for integrins alpha2beta1and alphaIIbbeta3 (ITGA2, ITGA2B, and ITGB3), platelet glycoproteins Ibalpha and VI (GPIBA and GP6), the purinergic receptor P2Y1 (P2RY1), and prostaglandin H synthase 1 (PTGS1 = COX1). Non-responsiveness to ASA was defined as the failure of prior ASA ingestion to prolong the PFA-100 closure time (CT) when blood was perfused through cartridges coated with collagen plus epinephrine (CEPI-CT). ASA non-responsiveness was observed in 114 of 463 patients (24.6 %), but was not associated with haplotypes of any of the seven candidate genes. There was also no association between any haplotypes and the CT when blood was perfused through cartridges coated with collagen plus ADP (CADP-CT). The ASA non-responsive cohort had significantly increased whole blood platelet counts (p = 0.03) and plasma von Willebrand Factor antigen levels (p < 0.001), which likely contributes to resistance to the inhibitory effects of ASA in the PFA-100.

Objective: To assess the influence of general practice opening hours on healthcare seeking behaviour after transient ischaemic attack (TIA) and minor stroke and feasibility of clinical assessment within 24 hours of symptom onset., Design: Population based prospective incidence study (Oxford vascular study)., Setting: Nine general practices in Oxfordshire., Participants: 91 000 patients followed from 1 April 2002 to 31 March 2006., Main Outcome Measures: Events that occurred overnight and at weekends (out of hours) and events that occurred during surgery hours., Results: Among 359 patients with TIA and 434 with minor stroke, the median (interquartile range) time to call a general practitioner after an event during surgery hours was 4.0 (1.0-45.5) hours, and 68% of patients with events during surgery hours called within 24 hours of onset of symptoms. Median (interquartile range) time to call a general practitioner after events out of hours was 24.8 (9.0-54.5) hours for patients who waited to contact their registered practice compared with 1.0 (0.3-2.6) hour in those who used an emergency general practitioner service (P<0.001). In patients with events out of hours who waited to see their own general practitioner, seeking attention within 24 hours was considerably less likely for events at weekends than weekdays (odds ratio 0.10, 95% confidence interval 0.05 to 0.21): 70% with events Monday to Friday, 33% on Sundays, and none on Saturdays. Thirteen patients who had events out of hours and did not seek emergency care had a recurrent stroke before they sought medical attention. A primary care centre open 8 am-8 pm seven days a week would have offered cover to 73 patients who waited until surgery hours to call their general practitioner, reducing median delay from 50.1 hours to 4.0 hours in that group and increasing those calling within 24 hours from 34% to 68%., Conclusions: General practitioners' opening hours influence patients' healthcare seeking behaviour after TIA and minor stroke. Current opening hours can increase delay in assessment. Improved access to primary care and public education about the need for emergency care are required if the relevant targets in the national stroke strategy are to be met.

Background and Purpose: Stroke mortality appears to be declining more rapidly in the UK than in many other Western countries. To understand this apparent decline better, we studied trends in mortality in the UK using more detailed data than are routinely available., Methods: Analysis of datasets that include both the underlying cause and all other mentioned causes of death (together, termed "all mentions"): the Oxford Record Linkage Study from 1979 to 2004 and English national data from 1996 to 2004., Results: Mortality rates based on underlying cause and based on all mentions showed similar downward trends. Mortality based on underlying cause alone misses about one quarter of all stroke-related deaths. Changes during the period in the national rules for selecting the underlying cause of death had a significant but fairly small effect on the trend. Overall, mortality fell by an average annual rate of 2.3% (95% confidence interval 2.1% to 2.5%) for stroke excluding subarachnoid hemorrhage; and by 2.1% (1.7% to 2.6%) per annum for subarachnoid hemorrhage. Coding of stroke as hemorrhagic, occlusive, or unspecified varied substantially across the study period. As a result, rates for hemorrhagic and occlusive stroke, affected by artifact, seemed to fall substantially in the first part of the study period and then leveled off., Conclusions: Studies of stroke mortality should include all mentions as well as the certified underlying cause, otherwise the burden of stroke will be underestimated. Studies of stroke mortality that include strokes specified as hemorrhagic or occlusive, without also considering stroke overall, are likely to be misleading. Stroke mortality in the Oxford region halved between 1979 and 2004.