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Objective: Arterial stiffness, cerebral pulsatility, and beat-to-beat blood pressure variability partly mediate the relationship between hypertension and stroke, but it is unknown if these intermediate phenotypes of vascular ageing differ between stroke aetiologies. We therefore aimed to characterize differences in these intermediate cardiovascular phenotypes between patients presenting with strokes of different aetiologies. Methods: In consecutive patients on best medical management 1 month after TIA or nondisabling stroke (Oxford Vascular Study), arterial stiffness (PWV) was measured by applanation tonometry (Sphygmocor), middle cerebral blood flow velocity, and pulsatility index (MCA-PI) were measured by transcranial ultrasound (TCD, DWL Doppler Box), and beat-to-beat BP variability was measured with a Finometer. Differences between patients with large artery (LAS), small vessel (SVD), cardioembolic (CE), or undetermined events were derived, including adjustment for cardiovascular risk factors. Relationships were characterized by mixed linear models. Results: In 909 eligible patients, MCA-PI, PWV, and SBPV were all positively skewed. Mean values were greatest in LAS than CE and lowest in SVD (p < 0.001). However, after adjustment for age, sex, and risk factors, PI was greatest in LAS and lowest in CE stroke, whilst PWV was greatest in SVD and undetermined stroke (p < 0.001). In multivariate linear models, age was more strongly associated with PWV and PI in patients with small vessel stroke than other aetiologies, particularly under the age of 65, but SBPV was only weakly associated with demographic indices in all stroke subtypes. Conclusions: Intermediate cardiovascular phenotypes of vascular ageing had similar demographic associations between stroke aetiologies, but these were particularly strong in patients with small vessel stroke under the age of 65, implying a potential role of these phenotypes in increasing stroke risk in this patient group. [ABSTRACT FROM AUTHOR]

Introduction: TIA and stroke cause cognitive impairment with a typical "vascular" pattern, including prominent frontal/executive deficits. Cognitive impairment is associated with increased delirium risk and the few available data suggest that executive dysfunction is important. We therefore determined the predictive value of both severity and pattern of cognitive deficits for delirium on long-term follow-up after TIA/stroke. Methods: Surviving TIA/stroke participants on October 1, 2013, in the Oxford Vascular Study (OXVASC) were assessed prospectively for delirium during all hospitalizations over the subsequent 6 months. Associations between OXVASC pre-admission mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores, and delirium during hospitalizations on follow-up were determined using logistic regression adjusted for covariates, including demographic factors, history of depression, baseline stroke severity, and admission illness severity. Results: Among 1,565 TIA/stroke survivors, 158 patients (mean/SD age = 79.2/11.5 years) had ≥1 admission and 59 (37%) had ≥1 delirium episode. Mean/SD time between baseline TIA/stroke and admission was 4.7/3.6 years and between most recent OXVASC cognitive testing and admission was 1.7/1.8 years. MMSE and MoCA scores were associated with delirium: odds ratio (OR) = 1.16 (95% CI 1.07–1.27, p < 0.0001 per point decrease in MMSE) and OR = 1.20 (1.11–1.30, p < 0.0001 MoCA) and associations were robust to adjustment for all covariates, including stroke severity: OR = 1.11 (1.01–1.22, p = 0.03, MMSE) and OR = 1.15 (1.05–1.25, p = 0.003, MoCA). All 10 subtests on the MoCA and 4/11 on the MMSE were significantly associated with delirium with highest predictive value for frontal/executive and recall domains. Conclusions: Cognitive impairment of increasing severity after TIA/stroke predisposed to delirium particularly deficits in frontal/executive domains and recall. Long-term risk of delirium should be considered as part of the overall cerebrovascular disease burden. [ABSTRACT FROM AUTHOR]

Background and Purpose: The impact of time-of-day on the cognitive performance of older patients with limited cognitive reserve after a transient ischemic attack (TIA) or stroke, and on short cognitive tests, such as the Montreal Cognitive Assessment (MoCA), is unknown. We retrospectively studied whether morning versus afternoon assessment might affect the classification of patients aged 70 or older as severe (SCI), mild (MCI), and no (NCI) cognitive impairment by the MoCA. Methods: Morning (12 p.m. or earlier) versus afternoon (later than 12 p.m.) proportions of SCI (MoCA score <20), MCI (MoCA score 25-20) and NCI (MoCA score = 26) were compared in a cohort of patients aged = 70, attending a rapidaccess TIA/stroke clinic. Results: Of 278 patients, 113 (40.6%) were tested in the morning and 165 (59.4%) in the afternoon. The proportion with SCI was greater in the afternoon than in the morning (10.9 vs. 1.8%, respectively, p = 0.004), with no difference in age, education, diagnosis, disability, or vascular risk factors. Conclusions: Time-of-day appears to affect cognitive performance of older patients after they undergo TIA and minor stroke. If our cross-sectional findings are confirmed in cross-over studies with repeated testing, timing of assessments should be considered in clinical practice and in research studies. [ABSTRACT FROM AUTHOR]

Background: Stroke is largely preventable, and therefore, a better understanding of risk factors is an essential step in reducing the population stroke rate and resulting disease burden in Arab countries. Summary: We performed 2 separate analyses in 2 similar populations of patients with noncardioembolic ischemic stroke. This first involved 3,635 patients in the Outcomes in Patients with TIA and Cerebrovascular disease (OPTIC) registry (followed for 2 years), with baseline collection of the usual risk factors and 5 socioeconomic variables (unemployment status, residence in rural area, living in fully serviced accommodation, no health-insurance coverage, and low educational level). The second involved patients in the PERFORM trial ( n = 19,100 followed up for 2 years), with baseline collection of the usual risk factors and 1 socioeconomic variable (low educational level). The primary outcome was a composite of nonfatal stroke, nonfatal myocardial infarction, or cardiovascular death. Stroke risk factors were more prevalent in patients in Arab countries. The incidence of major cardiovascular events (MACE; age- and gender-adjusted) was higher in Arab countries (OPTIC, 18.5 vs. 13.3%; PERFORM, 18.4 vs. 9.7%; both p ≤ 0.0001). These results remained significant after adjustment on risk factors and were attenuated in OPTIC after further adjustment on socioeconomic variables (hazard ratio 1.24; 95% CI 0.98-1.55; p = 0.07). Key Messages: Patients with ischemic stroke living in Arab countries had a lower mean socioeconomic status, a much higher prevalence of diabetes mellitus, and a higher rate of MACE compared with patients from non-Arab countries. This finding is partly explained by a higher prevalence of risk factors and also by a high prevalence of poverty and low educational level. [ABSTRACT FROM AUTHOR]

Background: Chronic antiplatelet therapy in the post-acute phase of non-cardioembolic ischemic stroke is limited by the risk of intracranial hemorrhage (ICH) complications. Methods: We developed an ICH risk score based on the PERFORM trial cohort (n = 19,100), which included patients with a noncardioembolic ischemic stroke or transient ischemic attack, and externally validated this score in one contemporary trial of very similar size and inclusion criteria, the PRoFESS trial (n = 20,332 patients). Outcome was ICH over 2 years. A Cox proportional-hazard regression analysis identified risk factors. Discrimination was quantified with c-statistics and calibration was assessed by comparing predicted and observed ICH risk in PERFORM and PRoFESS. Results: ICH occurred within 2 years in 263 (1.4%) patients in PERFORM trial and in 246 (1.2%) patients in PRoFESS trial. A 13-point score based on 9 items (Intracranial-B 2 LEED 3 S score -- low body mass index, blood pressure, lacune, elderly, Asian ethnicity, coronary artery or cerebrovascular disease history, dual antithrombotic agent or oral anticoagulant, gender) was derived from the PERFORM trial. In PERFORM, the observed 2-year ICH risk varied from 0.75% in low-risk (score ≤ 2) to 2.44% in high-risk patients (score ≥ 5) with an acceptable calibration but a low discrimination both in PERFORM (c-statistic 0.64, 95% CI 0.61-0.68) and on external validation in PRoFESS (0.58, 95% CI 0.55--0.62). Conclusion: The Intracranial-B2 LEED3 S score helps identify patients who are at a high risk of bleeding. However, other variables need to be identified to improve the score (e.g., microbleeds) (Clinical Trial Registration Information ISRCTN66157730). [ABSTRACT FROM AUTHOR]

Background: Global stroke epidemiology is changing rapidly. Although age-standardized rates of stroke mortality have decreased worldwide in the past 2 decades, the absolute numbers of people who have a stroke every year, and live with the consequences of stroke or die from their stroke, are increasing. Regular updates on the current level of stroke burden are important for advancing our knowledge on stroke epidemiology and facilitate organization and planning of evidence-based stroke care. Objectives: This study aims to estimate incidence, prevalence, mortality, disability-adjusted life years (DALYs) and years lived with disability (YLDs) and their trends for ischemic stroke (IS) and hemorrhagic stroke (HS) for 188 countries from 1990 to 2013. Methodology: Stroke incidence, prevalence, mortality, DALYs and YLDs were estimated using all available data on mortality and stroke incidence, prevalence and excess mortality. Statistical models and country-level covariate data were employed, and all rates were age-standardized to a global population. All estimates were produced with 95% uncertainty intervals (UIs). Results: In 2013, there were globally almost 25.7 million stroke survivors (71% with IS), 6.5 million deaths from stroke (51% died from IS), 113 million DALYs due to stroke (58% due to IS) and 10.3 million new strokes (67% IS). Over the 1990-2013 period, there was a significant increase in the absolute number of DALYs due to IS, and of deaths from IS and HS, survivors and incident events for both IS and HS. The preponderance of the burden of stroke continued to reside in developing countries, comprising 75.2% of deaths from stroke and 81.0% of stroke-related DALYs. Globally, the proportional contribution of stroke-related DALYs and deaths due to stroke compared to all diseases increased from 1990 (3.54% (95% UI 3.11-4.00) and 9.66% (95% UI 8.47-10.70), respectively) to 2013 (4.62% (95% UI 4.01-5.30) and 11.75% (95% UI 10.45-13.31), respectively), but there was a diverging trend in developed and developing countries with a significant increase in DALYs and deaths in developing countries, and no measurable change in the proportional contribution of DALYs and deaths from stroke in developed countries. Conclusion: Global stroke burden continues to increase globally. More efficient stroke prevention and management strategies are urgently needed to halt and eventually reverse the stroke pandemic, while universal access to organized stroke services should be a priority. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: There is increasing recognition of stroke as an important contributor to childhood morbidity and mortality. Current estimates of global childhood stroke burden and its temporal trends are sparse. Accurate and up-to-date estimates of childhood stroke burden are important for planning research and the resulting evidence-based strategies for stroke prevention and management. Objectives: To estimate the prevalence, mortality and disability-adjusted life years (DALYs) for ischemic stroke (IS), hemorrhagic stroke (HS) and all stroke types combined globally from 1990 to 2013. Methodology: Stroke prevalence, mortality and DALYs were estimated using the Global Burden of Disease 2013 methods. All available data on stroke-related incidence, prevalence, excess mortality and deaths were collected. Statistical models and country-level covariates were employed to produce comprehensive and consistent estimates of prevalence and mortality. Stroke-specific disability weights were used to estimate years lived with disability and DALYs. Means and 95% uncertainty intervals (UIs) were calculated for prevalence, mortality and DALYs. The median of the percent change and 95% UI were determined for the period from 1990 to 2013. Results: In 2013, there were 97,792 (95% UI 90,564-106,016) prevalent cases of childhood IS and 67,621 (95% UI 62,899-72,214) prevalent cases of childhood HS, reflecting an increase of approximately 35% in the absolute numbers of prevalent childhood strokes since 1990. There were 33,069 (95% UI 28,627-38,998) deaths and 2,615,118 (95% UI 2,265,801-3,090,822) DALYs due to childhood stroke in 2013 globally, reflecting an approximately 200% decrease in the absolute numbers of death and DALYs in childhood stroke since 1990. Between 1990 and 2013, there were significant increases in the global prevalence rates of childhood IS, as well as significant decreases in the global death rate and DALYs rate of all strokes in those of age 0-19 years. While prevalence rates for childhood IS and HS decreased significantly in developed countries, a decline was seen only in HS, with no change in prevalence rates of IS, in developing countries. The childhood stroke DALY rates in 2013 were 13.3 (95% UI 10.6-17.1) for IS and 92.7 (95% UI 80.5-109.7) for HS per 100,000. While the prevalence of childhood IS compared to childhood HS was similar globally, the death rate and DALY rate of HS was 6- to 7-fold higher than that of IS. In 2013, the prevalence rate of both childhood IS and HS was significantly higher in developed countries than in developing countries. Conversely, both death and DALY rates for all stroke types were significantly lower in developed countries than in developing countries in 2013. Men showed a trend toward higher childhood stroke death rates (1.5 (1.3-1.8) per 100,000) than women (1.1 (0.9-1.5) per 100,000) and higher childhood stroke DALY rates (120.1 (100.8-143.4) per 100,000) than women (90.9 (74.6-122.4) per 100,000) globally in 2013. Conclusions: Globally, between 1990 and 2013, there was a significant increase in the absolute number of prevalent childhood strokes, while absolute numbers and rates of both deaths and DALYs declined significantly. The gap in childhood stroke burden between developed and developing countries is closing; however, in 2013, childhood stroke burden in terms of absolute numbers of prevalent strokes, deaths and DALYs remained much higher in developing countries. There is an urgent need to address these disparities with both global and country-level initiatives targeting prevention as well as improved access to acute and chronic stroke care. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Recent evidence suggests that stroke is increasing as a cause of morbidity and mortality in younger adults, where it carries particular significance for working individuals. Accurate and up-to-date estimates of stroke burden are important for planning stroke prevention and management in younger adults. Objectives: This study aims to estimate prevalence, mortality and disability-adjusted life years (DALYs) and their trends for total, ischemic stroke (IS) and hemorrhagic stroke (HS) in the world for 1990-2013 in adults aged 20-64 years. Methodology: Stroke prevalence, mortality and DALYs were estimated using the Global Burden of Disease (GBD) 2013 methods. All available data on rates of stroke incidence, excess mortality, prevalence and death were collected. Statistical models were used along with country-level covariates to estimate country-specific stroke burden. Stroke-specific disability weights were used to compute years lived with disability and DALYs. Means and 95% uncertainty intervals (UIs) were calculated for prevalence, mortality and DALYs. The median of the percent change and 95% UI were determined for the period from 1990 to 2013. Results: In 2013, in younger adults aged 20-64 years, the global prevalence of HS was 3,725,085 cases (95% UI 3,548,098-3,871,018) and IS was 7,258,216 cases (95% UI 6,996,272-7,569,403). Globally, between 1990 and 2013, there were significant increases in absolute numbers and prevalence rates of both HS and IS for younger adults. There were 1,483,707 (95% UI 1,340,579-1,658,929) stroke deaths globally among younger adults but the number of deaths from HS (1,047,735 (95% UI 945,087-1,184,192)) was significantly higher than the number of deaths from IS (435,972 (95% UI 354,018-504,656)). There was a 20.1% (95% UI -23.6 to -10.3) decline in the number of total stroke deaths among younger adults in developed countries but a 36.7% (95% UI 26.3-48.5) increase in developing countries. Death rates for all strokes among younger adults declined significantly in developing countries from 47 (95% UI 42.6-51.7) in 1990 to 39 (95% UI 35.0-43.8) in 2013. Death rates for all strokes among younger adults also declined significantly in developed countries from 33.3 (95% UI 29.8-37.0) in 1990 to 23.5 (95% UI 21.1-26.9) in 2013. A significant decrease in HS death rates for younger adults was seen only in developed countries between 1990 and 2013 (19.8 (95% UI 16.9-22.6) and 13.7 (95% UI 12.1-15.9)) per 100,000). No significant change was detected in IS death rates among younger adults. The total DALYs from all strokes in those aged 20-64 years was 51,429,440 (95% UI 46,561,382-57,320,085). Globally, there was a 24.4% (95% UI 16.6-33.8) increase in total DALY numbers for this age group, with a 20% (95% UI 11.7-31.1) and 37.3% (95% UI 23.4-52.2) increase in HS and IS numbers, respectively. Conclusions: Between 1990 and 2013, there were significant increases in prevalent cases, total deaths and DALYs due to HS and IS in younger adults aged 20-64 years. Death and DALY rates declined in both developed and developing countries but a significant increase in absolute numbers of stroke deaths among younger adults was detected in developing countries. Most of the burden of stroke was in developing countries. In 2013, the greatest burden of stroke among younger adults was due to HS. While the trends in declining death and DALY rates in developing countries are encouraging, these regions still fall far behind those of developed regions of the world. A more aggressive approach toward primary prevention and increased access to adequate healthcare services for stroke is required to substantially narrow these disparities. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Accurate information on stroke burden in men and women are important for evidence-based healthcare planning and resource allocation. Previously, limited research suggested that the absolute number of deaths from stroke in women was greater than in men, but the incidence and mortality rates were greater in men. However, sex differences in various metrics of stroke burden on a global scale have not been a subject of comprehensive and comparable assessment for most regions of the world, nor have sex differences in stroke burden been examined for trends over time. Methods: Stroke incidence, prevalence, mortality, disability-adjusted life years (DALYs) and healthy years lost due to disability were estimated as part of the Global Burden of Disease (GBD) 2013 Study. Data inputs included all available information on stroke incidence, prevalence and death and case fatality rates. Analysis was performed separately by sex and 5-year age categories for 188 countries. Statistical models were employed to produce globally comprehensive results over time. All rates were age-standardized to a global population and 95% uncertainty intervals (UIs) were computed. Findings: In 2013, global ischemic stroke (IS) and hemorrhagic stroke (HS) incidence (per 100,000) in men (IS 132.77 (95% UI 125.34-142.77); HS 64.89 (95% UI 59.82-68.85)) exceeded those of women (IS 98.85 (95% UI 92.11-106.62); HS 45.48 (95% UI 42.43-48.53)). IS incidence rates were lower in 2013 compared with 1990 rates for both sexes (1990 male IS incidence 147.40 (95% UI 137.87-157.66); 1990 female IS incidence 113.31 (95% UI 103.52-123.40)), but the only significant change in IS incidence was among women. Changes in global HS incidence were not statistically significant for males (1990 = 65.31 (95% UI 61.63-69.0), 2013 = 64.89 (95% UI 59.82-68.85)), but was significant for females (1990 = 64.892 (95% UI 59.82-68.85), 2013 = 45.48 (95% UI 42.427-48.53)). The number of DALYs related to IS rose from 1990 (male = 16.62 (95% UI 13.27-19.62), female = 17.53 (95% UI 14.08-20.33)) to 2013 (male = 25.22 (95% UI 20.57-29.13), female = 22.21 (95% UI 17.71-25.50)). The number of DALYs associated with HS also rose steadily and was higher than DALYs for IS at each time point (male 1990 = 29.91 (95% UI 25.66-34.54), male 2013 = 37.27 (95% UI 32.29-45.12); female 1990 = 26.05 (95% UI 21.70-30.90), female 2013 = 28.18 (95% UI 23.68-33.80)). Interpretation: Globally, men continue to have a higher incidence of IS than women while significant sex differences in the incidence of HS were not observed. The total health loss due to stroke as measured by DALYs was similar for men and women for both stroke subtypes in 2013, with HS higher than IS. Both IS and HS DALYs show an increasing trend for both men and women since 1990, which is statistically significant only for IS among men. Ongoing monitoring of sex differences in the burden of stroke will be needed to determine if disease rates among men and women continue to diverge. Sex disparities related to stroke will have important clinical and policy implications that can guide funding and resource allocation for national, regional and global health programs. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: World mapping is an important tool to visualize stroke burden and its trends in various regions and countries. Objectives: To show geographic patterns of incidence, prevalence, mortality, disability-adjusted life years (DALYs) and years lived with disability (YLDs) and their trends for ischemic stroke and hemorrhagic stroke in the world for 1990-2013. Methodology: Stroke incidence, prevalence, mortality, DALYs and YLDs were estimated following the general approach of the Global Burden of Disease (GBD) 2010 with several important improvements in methods. Data were updated for mortality (through April 2014) and stroke incidence, prevalence, case fatality and severity through 2013. Death was estimated using an ensemble modeling approach. A new software package, DisMod-MR 2.0, was used as part of a custom modeling process to estimate YLDs. All rates were age-standardized to new GBD estimates of global population. All estimates have been computed with 95% uncertainty intervals. Results: Age-standardized incidence, mortality, prevalence and DALYs/YLDs declined over the period from 1990 to 2013. However, the absolute number of people affected by stroke has substantially increased across all countries in the world over the same time period, suggesting that the global stroke burden continues to increase. There were significant geographical (country and regional) differences in stroke burden in the world, with the majority of the burden borne by low- and middle-income countries. Conclusions: Global burden of stroke has continued to increase in spite of dramatic declines in age-standardized incidence, prevalence, mortality rates and disability. Population growth and aging have played an important role in the observed increase in stroke burden. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Incidence and prevalence studies of neurological disorders play an extremely important role in hypothesis-generation, assessing the burden of disease and planning of health services. However, the assessment of disease estimates is hindered by the poor quality of reporting for such studies. We developed the Standards of Reporting of Neurological Disorders (STROND) guideline in order to improve the quality of reporting of neurological disorders from which prevalence, incidence, and outcomes can be extracted for greater generalisability. Methods: The guideline was developed using a 3-round Delphi technique in order to identify the 'basic minimum items' important for reporting, as well as some additional 'ideal reporting items.' An e-consultation process was then used in order to gauge opinion by external neuroepidemiological experts on the appropriateness of the items included in the checklist. Findings: The resultant 15 items checklist and accompanying recommendations were developed using a similar process and structured in a similar manner to the Strengthening of the Reporting of Observational Studies in Epidemiology checklist for ease of use. This paper presents the STROND checklist with an explanation and elaboration for each item, as well as examples of good reporting from the neuroepidemiological literature. Conclusions: The introduction and use of the STROND checklist should lead to more consistent, transparent and contextualised reporting of descriptive neuroepidemiological studies that should facilitate international comparisons, and lead to more accessible information for multiple stakeholders, ultimately supporting better healthcare decisions for neurological disorders. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Mild cognitive impairment (MCI) is at least as prevalent as dementia after transient ischaemic attack (TIA)/stroke and is increasingly recognised as an important outcome in observational studies and randomised trials. However, there is no consensus on how impairment should be defined, and numerous different criteria exist. Previous studies have shown that different criteria for cognitive impairment impact on prevalence rates in epidemiological studies. However, there are few data on how operational differences within established criteria (e.g. Petersen-MCI) affect measured impairment rates and the performance of short cognitive tests such as the Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA), particularly in cerebrovascular disease. We therefore evaluated the effect of different operational definitions on measured rates of Petersen-MCI and on reliability of short cognitive tests in patients with TIA and stroke. Methods: Consecutive patients underwent the MMSE, MoCA and neuropsychological battery ≥1 year after TIA or stroke in a population-based study. MCI was defined using the Petersen method and subclassified as single or multiple domain, both with (original) and without (modified) subjective memory impairment. Different cut-offs (>1, >1.5 and >2 standard deviations, SD) on a given test relative to published norms were compared together with use of single versus multiple tests to define domain impairment. Results: 91 non-demented subjects completed neuropsychological testing (mean age ± SD 69.7 ± 11.6 years, 54 male, 49 stroke) at a mean of 3.1 ± 1.9 years after the index event. Rates of cognitive impairment ranged from 14/91 (15%) for MCI-original at >2 SD cut-off to 61/91 (67%) MCI-modified at >1 SD cut-off, and the proportion of MCI that was multiple domain varied, e.g. 24/46 (52%) versus only 5/27 (20%) at 1 versus 2 SD cut-off for MCI-modified. Requirement for subjective memory complaint approximately halved estimates [e.g. 17 (19%) vs. 39 (43%) for MCI at 1.5 SD cut-off, single test definition], whereas use of multiple tests versus a single test to define a cognitive domain had less impact. In general, diagnostic accuracy was higher, and optimal cut-offs lower, on MMSE and MoCA for multiple-domain versus single-domain MCI, but the MoCA appeared superior for detecting MCI-modified, whereas the MMSE performed well in detecting MCI-original. Conclusion: Even within established criteria for MCI, differences in operational methodology result in 4-fold variation in MCI estimates. Optimal MMSE and MoCA cut-offs are lower, and reliability more similar, when criteria for MCI are more stringent. Our findings have implications for sample size and adjusted relative risk calculations in randomised trials and for comparisons between studies. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

No abstract available [ABSTRACT FROM AUTHOR]

Background: Obstructive sleep apnoea (OSA) is associated with hypertension, nocturnal blood pressure (BP) surges, and increased risk of stroke. It may therefore also be associated with a higher risk of developing leukoaraiosis. Only few data about the prevalence of leukoaraiosis in patients with OSA, and any association between degrees of severity of either condition, exist. Methods: We studied patients who were part of a clinical trial (MOSAIC) in minimally symptomatic OSA. All patients had brain MRI (T2, FLAIR) at baseline. A single observer assessed the images for the presence and severity of leukoaraiosis (ARWMC-score). We related the extent of leukoaraiosis to the severity of OSA (measured by oxygen desaturation index [ODI]) and the presence of other vascular risk factors. Results: 183 patients (156 men, 85.2%; mean age ± SD = 57.7 ± 7.4 years; median oxygen desaturation index = 9.6, interquartile range = 4.6-16.0) took part in the study. Although 135 (74%) patients had some leukoaraiosis, this was generally mild. We confirmed the well-known risk factor associations between leukoaraiosis, increasing age (p < 0.0001) and hypertension (p = 0.003), but we did not find any association between OSA and leukoaraiosis (p = 0.33), despite both conditions being associated with increasing current BP and a history of hypertension. Conclusion: Our data confirm the well-known association between leukoaraiosis, age and increasing BP. However, we found no association between OSA and leukoaraiosis despite some shared risk factor associations. Our findings suggest that OSA is not a strong independent risk factor for leukoaraiosis. Confounding by hypertension may explain any apparent association in previously reported studies of patients with severer OSA. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Stroke patients are at high risk of secondary vascular events. Although in the short term the risk of experiencing a second stroke is high, in the long term patients are more likely to have myocardial infarction. Many stroke patients have also developed polyvascular disease in the form of coronary artery disease and peripheral arterial disease, which is a marker of increased morbidity and mortality in patients with non-cardioembolic ischemic stroke. Despite the high risk of events in these patients, current evidence-based guidelines make very few recommendations that address the need to detect and manage polyvascular disease following a stroke. Optimised Stroke Care for Re-Admission Reduction in Europe (OSCARE) is an initiative that has been set up to address some of these shortcomings. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The prolonged length of stay (PLOS) score has recently been derived and validated in 2 independent national cohorts of acute stroke patients in Israel. The present study aimed to determine the performance of the PLOS score in an independent population-based cohort of stroke patients in a health care system considerably different from that in which the score was derived. Methods: The study was performed on all 434 patients with ischemic stroke or intracerebral hemorrhage hospitalized during the first 5 years of the population-based Oxford Vascular Study (OXVASC) in Oxfordshire, UK. Median (interquartile range) length of stay (LOS) and rates of LOS ≥7 days and LOS ≥30 days by the PLOS score were calculated. Model discrimination was assessed by the c-statistic and goodness of fit was evaluated with the Hosmer-Lemeshow test. Results: Median LOS and rates of LOS ≥7 days increased with the increase in PLOS score among all inpatients and hospital survivors. In the analysis of LOS ≥7 days, the PLOS c-statistic (95% CI) was 0.676 (0.618-0.734) for all inpatients and 0.722 (0.664-0.779) for hospital survivors. Findings were similar for LOS ≥30 days. The Hosmer-Lemeshow showed good calibration. Conclusions: The PLOS score successfully predicted PLOS in the OXVASC population of acute stroke patients. Although the score was originally derived for the prediction of prolonged acute hospitalization, it successfully predicted prolonged total LOS. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and Purpose: The aim of the Synergium was to devise and prioritize new ways of accelerating progress in reducing the risks, effects, and consequences of stroke. Methods: Preliminary work was performed by 7 working groups of stroke leaders followed by a synergium (a forum for working synergistically together) with approximately 100 additional participants. The resulting draft document had further input from contributors outside the synergium. Results: Recommendations of the Synergium are: Basic Science, Drug Development and Technology: There is a need to develop: (1) New systems of working together to break down the prevalent ‘silo’ mentality; (2) New models of vertically integrated basic, clinical, and epidemiological disciplines; and (3) Efficient methods of identifying other relevant areas of science. Stroke Prevention: (1) Establish a global chronic disease prevention initiative with stroke as a major focus. (2) Recognize not only abrupt clinical stroke, but subtle subclinical stroke, the commonest type of cerebrovascular disease, leading to impairments of executive function. (3) Develop, implement and evaluate a population approach for stroke prevention. (4) Develop public health communication strategies using traditional and novel (e.g., social media/marketing) techniques. Acute Stroke Management: Continue the establishment of stroke centers, stroke units, regional systems of emergency stroke care and telestroke networks. Brain Recovery and Rehabilitation: (1) Translate best neuroscience, including animal and human studies, into poststroke recovery research and clinical care. (2) Standardize poststroke rehabilitation based on best evidence. (3) Develop consensus on, then implementation of, standardized clinical and surrogate assessments. (4) Carry out rigorous clinical research to advance stroke recovery. Into the 21st Century: Web, Technology and Communications: (1) Work toward global unrestricted access to stroke-related information. (2) Build centralized electronic archives and registries. Foster Cooperation Among Stakeholders (large stroke organizations, nongovernmental organizations, governments, patient organizations and industry) to enhance stroke care. Educate and energize professionals, patients, the public and policy makers by using a ‘Brain Health’ concept that enables promotion of preventive measures. Conclusions: To accelerate progress in stroke, we must reach beyond the current status scientifically, conceptually, and pragmatically. Advances can be made not only by doing, but ceasing to do. Significant savings in time, money, and effort could result from discontinuing practices driven by unsubstantiated opinion, unproven approaches, and financial gain. Systematic integration of knowledge into programs coupled with careful evaluation can speed the pace of progress. Copyright © 2010 American Heart Association. Inc., S. Karger AG, Basel, and John Wiley & Sons, Inc. [ABSTRACT FROM AUTHOR]

Background and Purpose: The aim of the Synergium was to devise and prioritize new ways of accelerating progress in reducing the risks, effects, and consequences of stroke. Methods: Preliminary work was performed by 7 working groups of stroke leaders followed by a synergium (a forum for working synergistically together) with approximately 100 additional participants. The resulting draft document had further input from contributors outside the synergium. Results: Recommendations of the Synergium are: Basic Science, Drug Development and Technology: There is a need to develop: (1) New systems of working together to break down the prevalent 'silo' mentality; (2) New models of vertically integrated basic, clinical, and epidemiological disciplines; and (3) Efficient methods of identifying other relevant areas of science. Stroke Prevention: (1) Establish a global chronic disease prevention initiative with stroke as a major focus. (2) Recognize not only abrupt clinical stroke, but subtle subclinical stroke, the commonest type of cerebrovascular disease, leading to impairments of executive function. (3) Develop, implement and evaluate a population approach for stroke prevention. (4) Develop public health communication strategies using traditional and novel (e.g., social media/marketing) techniques. Acute Stroke Management: Continue the establishment of stroke centers, stroke units, regional systems of emergency stroke care and telestroke networks. Brain Recovery and Rehabilitation: (1) Translate best neuroscience, including animal and human studies, into poststroke recovery research and clinical care. (2) Standardize poststroke rehabilitation based on best evidence. (3) Develop consensus on, then implementation of, standardized clinical and surrogate assessments. (4) Carry out rigorous clinical research to advance stroke recovery. Into the 21st Century: Web, Technology and Communications: (1) Work toward global unrestricted access to stroke-related information. (2) Build centralized electronic archives and registries. Foster Cooperation Among Stakeholders (large stroke organizations, nongovernmental organizations, governments, patient organizations and industry) to enhance stroke care. Educate and energize professionals, patients, the public and policy makers by using a 'Brain Health' concept that enables promotion of preventive measures. Conclusions: To accelerate progress in stroke, we must reach beyond the current status scientifically, conceptually, and pragmatically. Advances can be made not only by doing, but ceasing to do. Significant savings in time, money, and effort could result from discontinuing practices driven by unsubstantiated opinion, unproven approaches, and financial gain. Systematic integration of knowledge into programs coupled with careful evaluation can speed the pace of progress. Copyright © 2010 American Heart Association. Inc., [ABSTRACT FROM AUTHOR]

Background: Aspirin plus clopidogrel (A+C) may be more effective than aspirin only (AO) acutely after TIA and minor stroke, but the risk of bleeding in the acute phase is uncertain. We determined this risk, focusing particularly on aspirin-naïve patients. Methods: We studied consecutive referrals to the EXPRESS study clinic from 1/4/02 to 31/3/08. A 30- to 90-day course of A+C was given to patients presenting acutely. Bleeding events were identified by face-to-face follow-up, diagnostic coding, and blood transfusion data. Unpublished data from the FASTER pilot trial were also studied. Results: Among 633 EXPRESS patients treated with aspirin (+/– clopidogrel), there were 12 spontaneous bleeds (6 minor, 6 major/life-threatening) within 90 days after assessment, with a higher risk for A+C vs. AO (8/247 vs. 4/386, p = 0.047 overall; 5/247 vs. 1/386, p = 0.03 for major/life-threatening bleeds). The excess of major/life-threatening bleeds on A+C vs. AO was seen in aspirin-naïve patients, (4/137 vs. 0/273, p = 0.01), but not in prior-aspirin patients (1/110 vs. 1/113, p = 0.98). All symptomatic bleeds in the FASTER pilot also occurred in aspirin-naïve patients randomized to A+C (6/104 vs. 0/94, p = 0.03). In a pooled analysis, major/life-threatening bleeding on A+C occurred in 9/241 aspirin-naïve patients (90-day risk = 4.8%, 1.6–8.0) versus 1/204 prior-aspirin patients (p = 0.009). Conclusion: Although based on relatively few outcomes, the high risk of major bleeding on A+C acutely after TIA or minor stroke in aspirin-naïve patients is a cause for concern. The potential risk to patients is sufficient to mandate detailed monitoring of bleeding risk in ongoing trials and stratify results by whether patients were aspirin-naïve. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The early risk of recurrence after transient ischaemic attack (TIA) or minor stroke is high, ranging from 11% at 7 days in population-based studies, where patients are seen non-urgently, to 3% at 7 days in studies where patients are seen urgently in specialist services. In long-term (up to 10 years) studies of vascular risks after TIA and stroke, the risk of stroke is highest early after the event, and then falls, whereas the risk of coronary events is constant over the follow-up period at around 2% per year. In contrast to the early risk after TIA and stroke, the long-term risks are more dependent on the underlying vascular risk factors than the characteristics of the event itself. Stroke is also associated with an increased risk of dementia. Prevalence of post-stroke dementia varies between studies but is around 28% at 3 months in hospital-based studies where pre-stroke dementia was not excluded and 18% in hospital-based studies excluding pre-stroke dementia. Risk factors for post-stroke dementia include low education, prior or recurrent stroke, and older age. In conclusion, available data suggest that the risk of recurrent vascular events is considerable after TIA and stroke, even in the longer term, and that there is also a high risk of dementia after stroke. However, more studies are required to determine medium- and long-term outcomes in the current era of aggressive secondary preventive therapy. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Several studies have shown serum urate to be an independent risk factor for vascular disease, but others have not, although a stronger association in women than in men has been a consistent finding. Studies of stroke patients have shown possible associations between urate level and stroke severity, but there have been no large cohort studies of the effect of urate on the long-term risk of future vascular events in patients with a transient ischaemic attack (TIA) or stroke. We studied this relationship in 2 independent cohorts. Methods: Individual data on 15,483 patient-years of follow-up from the UK-TIA trial (13,182 patient-years) and the Oxford TIA study (2,301 patient-years) were analyzed. Hazard ratios (per unit increase of baseline urate in mg/dl) for the risks of stroke and acute coronary events (ACE) were obtained from Cox models stratified by study, with and without adjustment for potential confounders. Potential interactions between urate and baseline characteristics were also assessed. Results: Linear associations between urate and risk of ACE were found in both studies: pooled age- and sex-adjusted hazard ratio = 1.17, 95% CI 1.06–1.30, per unit increase of urate (p = 0.003). Sex, body mass index and previous myocardial infarction or angina were effect modifiers, but only the effect of sex remained after adjustment for other risk factors (p = 0.002), with a 5th:1st quintile hazard ratio of 4.23 (1.97–9.07, p < 0.0001) in women and 1.09 (0.70–1.71, p = 0.69) in men. These findings were consistent across the 2 studies. No associations were found between urate level and either risk or severity of stroke. Conclusions: High urate levels were independent predictors of long-term risk of ACE in women who had a TIA or stroke, but not in men, in 2 independent studies. Urate levels could be useful in identifying women at high risk of coronary events in routine practice. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: Inflammatory stenoses of cerebral arteries cause stroke in patients with florid vasculitis. However, diagnosis is often difficult even with digital subtraction angiography (DSA) and biopsy. The purpose of this study was to establish the value of contrast-enhanced MRI, proven to be sensitive to extradural arteritis, for the identification of intracranial vessel wall inflammation. Patients and Methods: Twenty-seven patients with a diagnosis of cerebral vasculitis affecting large brain vessels were retrieved from the files: 8 children (2–10 years, 7 female, 1 male) and 19 adults (16–76 years, 10 female, 9 male). Diagnosis was based on histological or serological proof of vasculitis or on clinical and imaging criteria. All MRI examinations included diffusion-weighted imaging, time-of-flight magnetic resonance angiography (TOF-MRA) and contrast-enhanced scans. MRI scans were assessed for the presence of ischemic brain lesions, arterial stenoses, vessel wall thickening and contrast uptake. Results: Ischemic changes of the brain tissue were seen in 24/27 patients and restricted diffusion suggestive of recent ischemia in 17/27; 25/27 patients had uni- or multifocal stenoses of intracranial arteries on TOF-MRA and 5/6 had stenoses on DSA. Vessel wall thickening was identified in 25/27, wall enhancement in 23/27 patients. Conclusion: Wall thickening and intramural contrast uptake are frequent findings in patients with active cerebral vasculitis affecting large brain arteries. Further prospective studies are required to determine the specificity of this finding. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

There is still considerable uncertainty about the place of carotid stenting in patients with recently symptomatic carotid bifurcation stenosis. Most reviews of carotid endarterectomy versus carotid stenting concentrate on technical aspects and advances in stenting, but the techniques involved in both carotid endarterectomy and stenting are evolving. In addition to reviewing the results of the various randomised controlled trials of carotid endarterectomy versus stenting for symptomatic carotid stenosis, this review considers recent advances and current best practice for endarterectomy. Ongoing randomized trials will determine whether or not the procedural risk of stroke and death is definitely lower with endarterectomy than with stenting, but the key issue that remains to be determined reliably is how the procedural risks of stenting vary with patient characteristics – perhaps the most important question being not whether endarterectomy is better than stenting or vice versa, but for whom is one technique likely to be better than the other. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: It has been suggested that scores for risk stratification of TIA patients might not identify patients with carotid stenosis or atrial fibrillation (AF) and that this might undermine the usefulness of such scores. Methods: In patients with TIA in the Oxford Vascular Study, we studied the associations between ABCD and ABCD2 scores, the presence of ≥50% ipsilateral carotid stenosis or AF, and the risk of stroke at 7 days. Results: Among 285 TIA patients (from 559 referrals of possible TIA), 69 (24.2%) had either ≥50% carotid stenosis (n = 29) or AF (n = 42), or both (n = 2). Although the ABCD and ABCD2 scores were highly predictive of stroke at 7 days (p < 0.0001), there was no clear relationship between either score and the prevalence of ≥50% carotid stenosis or AF. However, the scores did predict the 7-day stroke risk in patients with these pathologies: ABCD score (trend – p = 0.05); ABCD2 (trend – p = 0.03). Five of the 6 patients with AF or symptomatic stenosis who had a stroke within 7 days of their TIA had an ABCD score of ≥5 and all 6 had an ABCD2 score of ≥4. Conclusions: The ABCD and ABCD2 risk scores appear to identify patients with ≥50% carotid stenosis or AF who are at high risk of stroke. However, these findings should be interpreted with caution due to the small number of outcomes among these subgroups, and further validations are necessary. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The basic principles of stroke prevention are the same in patients with diabetes and/or the metabolic syndrome as in those without. Blood-pressure lowering is highly effective in both primary and secondary prevention of stroke in diabetics, and there is no evidence to suggest that the benefits of lipid-lowering therapy are any less. Antiplatelet agents are effective in secondary prevention and may be indicated in asymptomatic diabetic patients, who have a substantially increased risk of acute vascular events. Uncertainty over optimal management of patients with diabetes, and possibly of those with metabolic syndrome, relates more to the thresholds for initiation of treatment. The decision to initiate treatment should depend on the balance between the absolute risk of potentially preventable events and the risks of any complications of treatment. The absolute risks of ischaemic stroke and acute coronary events are significantly increased in diabetics in population-based cohort studies and the recommended thresholds for instigating blood pressure lowering and lipid lowering are therefore lower than in the general population. Optimization of strategies to prevent vascular complications must be a priority, given the rapid rises in the incidence and prevalence of type 2 diabetes and the metabolic syndrome in most populations across the globe. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: To identify new treatments to prevent stroke, it is important that we have reliable data on potential novel risk factors. Methods: We studied seven novel vascular risk factors [apo-lipoprotein (b), C-reactive protein, Chlamydia pneumoniae, fibrin-D dimer, fibrinogen, Helicobacter pylori and lipoprotein (a)] and compared the amount of published data on their relations with ischaemic stroke versus acute coronary events by systematic review of all studies published up to 2003. Results: From a total of 22,875 abstracts reviewed, 266 eligible studies were identified (167 case-control studies and 99 cohort studies). Two hundred and eleven (79%) studies included coronary events as an outcome for the purpose of a risk factor analysis. In 186 (70%) studies, coronary events were the only outcome that was analysed. Only 73 (27%) studies included stroke or TIA as an outcome event, and only 45 studies (17%) reported risk factor analyses for ischaemic stroke separately. These results were qualitatively consistent across the risk factors studied and the relative lack of data on risk factors for stroke was even greater in prospective cohort studies. Conclusion: Data on novel risk factors for stroke are lacking compared with the equivalent data for acute coronary events, and there are very few data on specific subtypes of ischaemic stroke. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Comments on the risks associated with carotid endarterectomy after a transient ischaemic attack or cerebral infarction. Operative risks in neurologically stable patients undergoing endarterectomy after stroke; Findings of randomised controlled trials concerning the potential of endarterectomy in reducing the risk of stroke; Need for patients with stenosis to undergo surgery to prevent ipsilateral stroke.

Background: Family history (FHx) of stroke is perceived to be an important risk factor for ischaemic stroke. However, there are several intermediate phenotypes that are often involved in the aetiology of ischaemic stroke and that have a substantial genetic component themselves. We studied FHx of ischaemic heart disease (IHD), hypertension (HTN) and diabetes mellitus (DM) as risk factors for ischaemic stroke. Methods: We performed a systematic review of case-control and cohort studies reporting on FHxIHD, FHxHTN or FHxDM as risk factors for stroke using bibliographic databases, and by hand searching reference lists and journals. Odds ratios of FHx as a risk factor for stroke were calculated within individual studies. We included unpublished data from two Oxfordshire population-based studies to assess effects on subtypes of ischaemic stroke. Results: We identified 54 studies that investigated the odds of stroke conferred by a positive FHx, 24 of which reported data on FHx of one or more intermediate phenotypes in addition to FHx of stroke. Most studies reported an increased frequency of FHxIHD and FHxHTN in stroke patients versus controls. The association was significant in 6 out of 14 studies for FHxIHD and 4 out of 11 studies for FHxHTN. In contrast, FHxDM was not associated with stroke. FHxIHD was particularly associated with large vessel strokes (OR 1.72, CI 1.3–2.2, p = 0.00004). Conclusions: FHxIHD and FHxHTN are both risk factors for stroke. It is likely that the apparent heritability of stroke is partly accounted for by heritability of HTN and large vessel atherosclerosis. Analyses of heritability of stroke and candidate gene studies should be adjusted accordingly.Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Patients with recently symptomatic carotid stenosis require effective medical treatment, and some require surgical removal of the carotid plaque. Randomized controlled trials have shown that endarterectomy reduces the overall risk of stroke in patients with severe carotid stenosis and, to a lesser extent, in patients with moderate stenosis. However, operating on all patients is not necessarily the most effective approach. The effectiveness of endarterectomy could be improved by selecting patients more rigorously. To do this, we first need to use data from existing randomized controlled trials to precisely determine the overall effect of surgery for different degrees of stenosis, identify subgroups in which benefit is increased, and use risk modeling to identify individuals at particularly high risk of stroke without surgery. Such an approach will also be useful in targeting angioplasty and stenting in patients in whom endarterectomy is not possible.Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Rupture of atherosclerotic plaque is the main cause of acute coronary syndromes and carotid territory ischaemic stroke. Haemodynamic stress is important in early plaque formation and may affect the stability of mature plaques. There is some evidence that macrophage infiltration and plaque rupture tend to localise to the proximal (upstream) part of the plaque where shear stress is highest. However, previous studies have been too small to assess this reliably. We studied the site of ulceration in a large number of carotid plaques. Methods: We studied angiograms of 3,007 symptomatic carotid stenoses, and the pathological appearance of 119 carotid plaques (77 asymptomatic), to identify the presence and position of plaque ulceration. Results: Angiographic ulceration, which was present in 421 patients (14%), was more likely to be proximal than distal to the point of maximum stenosis (OR = 16.6, 95% CI = 11.6-26.9, p < 0.001). This trend increased with severity of stenosis (p = 0.002). Pathological examination of the 119 carotid plaques also showed that ulceration was more likely to occur proximal to the point of maximum stenosis (OR = 6.1, 95% CI = 2.8-13.6, p < 0.001). Conclusions: Ulceration of carotid plaques, visible on angiography or on pathological examination, is seen most often in the proximal (upstream) part where shear stress is highest. [ABSTRACT FROM AUTHOR]

Stroke is a considerable clinical, social and economic burden. In recent clinical trials, a number of strategies have been shown to reduce the risk of stroke and transient ischaemic attack (TIA) in both primary and secondary prevention settings. Whether these treatments are leading to a significant reduction in the incidence of first and recurrent stroke in the clinic, however, remains unclear due to a paucity of high-quality epidemiological data. A similar lack of reliable epidemiological studies has undermined our understanding of the relationship between many potentially important vascular risk factors and stroke risk. Improvement in our knowledge of stroke epidemiology is a prerequisite for the planning of stroke services, the effective application of current stroke prevention strategies, the development of new strategies, and our understanding of the mechanisms of stroke. Future studies must take into account the clinical and pathological heterogeneity of TIA and stroke, and must be powered to allow subtype differences in risk factor relationships and prognosis to be determined reliably. In many cases, this will require meta-analysis of detailed individual patient data from multiple independent studies.Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Stability of atheromatous plaques is influenced by local mechanical and haemodynamic factors, such as plaque motion and shear stress. However, although blood vessel anatomy is an important determinant of haemodynamics, particularly at bifurcations, there have been no previous clinical studies of the association between arterial anatomy and plaque ulceration. We therefore studied arterial anatomy and plaque ulceration using angiograms of 4,627 carotid bifurcations with atheromatous disease from the European Carotid Surgery Trial (ECST). We studied the vessel diameter and area ratios that have been shown in flow models to affect local haemodynamics and shear stress, and which are known to vary widely between and within individuals (internal to common, external to common, external to internal carotid artery and outflow/inflow area). Angiographic plaque surface morphology was defined as ulcerated or not ulcerated. To avoid any potential bias due to selective inclusion of patients in the ECST, we studied the contralateral, and usually asymptomatic, as well as the symptomatic carotid artery. To correct for the effects of systemic factors that might influence plaque stability, we also studied the relationship between the degree of asymmetry of bifurcation anatomy within individuals and the presence of plaque ulceration. Despite considerable inter-individual variation in carotid anatomy, we found no association between the prevalence of angiographic plaque ulceration and any of the anatomical parameters studied in either symptomatic or contralateral carotid arteries. There were also no associations between ipsilateral bifurcation anatomy and plaque ulceration in individuals with unilateral plaque ulceration. Carotid arterial anatomy does not appear to be an important determinant of plaque stability. Other factors that influence local haemodynamics, such as the anatomy and composition of the plaque itself may be more important. [ABSTRACT FROM AUTHOR]