Assessment of smoking care by stroke specialists in patients with recent TIA and minor stroke: an international prospective registry-based cohort study.

OBJECTIVES: The objectives are to assess smoking abstinence and its effects on vascular risk and to report tobacco-cessation counselling and pharmacotherapy use in patients who had a recent minor stroke or transient ischaemic attack (TIA). DESIGN AND SETTING: The TIA registry.org project is a prospective, observational registry of patients with TIA and minor stroke that occurred in the previous 7 days with a 5-year follow-up, involving 61 sites with stroke specialists in 21 countries (Europe, Asia, Latin America and Middle East). Of those, 42 sites had 5-year follow-up data on more than 50% of their patients and were included in the present study. PARTICIPANTS: From June 2009 through December 2011, 3847 patients were eligible for the study (80% of the initial cohort). OUTCOMES: Tobacco counselling and smoking-cessation pharmacotherapy use in smoking patients were reported at discharge. Association between 3-month smoking status and risk of a major cardiovascular event (MACE) was analysed with multivariable Cox regression model. RESULTS: Among 3801 patients included, 835 (22%) were smokers. At discharge, only 35.2% have been advised to quit and 12.5% had smoking-cessation pharmacotherapy prescription. At 3 months, 383/835 (46.9%) baseline smokers were continuers. Living alone and alcohol abuse were associated with persistent smoking; high level of education, aphasia and dyslipidaemia with quitting. The adjusted HRs for MACE at 5 years were 1.13 (95% CI 0.90 to 1.43) in former smokers, 1.31 (95% CI 0.93 to 1.84) in quitters and 1.31 (95% CI 0.94 to 1.83) in continuers. Using time-varying analysis, current smoking at the time of MACE non-significantly increased the risk of MACE (HR 1.31 (95% CI 0.97 to 1.78); p=0.080). CONCLUSION: In the TIAregistry.org, smoking-cessation intervention was used in a minority of patients. Surprisingly, in this population in which, at 5 years, other vascular risk factors were well controlled and antithrombotic treatment maintained, smoking cessation non-significantly decreased the risk of MACE.

Underlying Causes of TIA and Minor Ischemic Stroke and Risk of Major Vascular Events.

Importance: The coexistence of underlying causes in patients with transient ischemic attack (TIA) or minor ischemic stroke as well as their associated 5-year risks are not well known. Objective: To apply the ASCOD (atherosclerosis, small vessel disease, cardiac pathology, other cause, or dissection) grading system to assess coexistence of underlying causes of TIA and minor ischemic stroke and the 5-year risk for major vascular events. Design, Setting, and Participants: This international registry cohort (TIAregistry.org) study enrolled 4789 patients from June 1, 2009, to December 31, 2011, with 1- to 5-year follow-up at 61 sites in 21 countries. Eligible patients had a TIA or minor stroke (with modified Rankin Scale score of 0 or 1) within the last 7 days. Among these, 3847 patients completed the 5-year follow-up by December 31, 2016. Data were analyzed from October 1, 2022, to June 15, 2023. Exposure: Five-year follow-up. Main Outcomes and Measures: Estimated 5-year risk of the composite outcome of stroke, acute coronary syndrome, or cardiovascular death. Results: A total of 3847 patients (mean [SD] age, 66.4 [13.2] years; 2295 men [59.7%]) in 42 sites were enrolled and participated in the 5-year follow-up cohort (median percentage of 5-year follow-up per center was 92.3% [IQR, 83.4%-97.8%]). In 998 patients with probable or possible causal atherosclerotic disease, 489 (49.0%) had some form of small vessel disease (SVD), including 110 (11.0%) in whom a lacunar stroke was also probably or possibly causal, and 504 (50.5%) had no SVD; 275 (27.6%) had some cardiac findings, including 225 (22.6%) in whom cardiac pathology was also probably or possibly causal, and 702 (70.3%) had no cardiac findings. Compared with patients with none of the 5 ASCOD categories of disease (n = 484), the 5-year rate of major vascular events was almost 5 times higher (hazard ratio [HR], 4.86 [95% CI, 3.07-7.72]; P < .001) in patients with causal atherosclerosis, 2.5 times higher (HR, 2.57 [95% CI, 1.58-4.20]; P < .001) in patients with causal lacunar stroke or lacunar syndrome, and 4 times higher (HR, 4.01 [95% CI, 2.50-6.44]; P < .001) in patients with causal cardiac pathology. Conclusion and Relevance: The findings of this cohort study suggest that in patients with TIA and minor ischemic stroke, the coexistence of atherosclerosis, SVD, cardiac pathology, dissection, or other causes is substantial, and the 5-year risk of a major vascular event varies considerably across the 5 categories of underlying diseases. These findings further suggest the need for secondary prevention strategies based on pathophysiology rather than a one-size-fits-all approach.

Effect of atherosclerosis on 5-year risk of major vascular events in patients with transient ischaemic attack or minor ischaemic stroke: an international prospective cohort study.

BACKGROUND: The prevalence of atherosclerosis and the long-term risk of major vascular events in people who have had a transient ischaemic attack or minor ischaemic stroke, regardless of the causal relationship between the index event and atherosclerosis, are not well known. In this analysis, we applied the ASCOD (atherosclerosis, small vessel disease, cardiac pathology, other causes, and dissection) grading system to estimate the 5-year risk of major vascular events according to whether there was a causal relationship between atherosclerosis and the index event (ASCOD grade A1 and A2), no causal relationship (A3), and with or without a causal relationship (A1, A2, and A3). We also aimed to estimate the prevalence of different grades of atherosclerosis and identify associated risk factors. METHODS: We analysed patient data from TIAregistry.org, which is an international, prospective, observational registry of patients with a recent (within the previous 7 days) transient ischaemic attack or minor ischaemic stroke (modified Rankin Scale score of 0-1) from 61 specialised centres in 21 countries in Europe, Asia, the Middle East, and Latin America. Using data from case report forms, we applied the ASCOD grading system to categorise the degree of atherosclerosis in our population (A0: no atherosclerosis; A1 or A2: atherosclerosis with stenosis ipsilateral to the cerebral ischaemic area; A3: atherosclerosis in vascular beds not related to the ischaemic area or ipsilateral plaques without stenosis; and A9: atherosclerosis not assessed). The primary outcome was a composite of non-fatal stroke, non-fatal acute coronary syndrome, or cardiovascular death within 5 years. FINDINGS: Between June 1, 2009, and Dec 29, 2011, 4789 patients were enrolled to TIAregistry.org, of whom 3847 people from 42 centres participated in the 5-year follow-up; 3383 (87·9%) patients had a 5-year follow-up visit (median 92·3% [IQR 83·4-97·8] per centre). 1406 (36·5%) of 3847 patients had no atherosclerosis (ASCOD grade A0), 998 (25·9%) had causal atherosclerosis (grade A1 or A2), and 1108 (28·8%) had atherosclerosis that was unlikely to be causal (grade A3); in 335 (8·7%) patients, atherosclerosis was not assessed (grade A9). The 5-year event rate of the primary composite outcome was 7·7% (95% CI 6·3-9·2; 101 events) in patients categorised with grade A0 atherosclerosis, 19·8% (17·4-22·4; 189 events) in those with grade A1 or A2, and 13·8% (11·8-16·0; 144 events) in patients with grade A3. Compared with patients with grade A0 atherosclerosis, patients categorised as grade A1 or A2 had an increased risk of the primary composite outcome (hazard ratio 2·77, 95% CI 2·18-3·53; p<0·0001), as did patients with grade A3 (1·87, 1·45-2·42; p<0·0001). Except for age, male sex, and multiple infarctions on neuroimaging, most of the risk factors that were identified as being associated with grade A1 or A2 atherosclerosis were modifiable risk factors (ie, hypertension, dyslipidaemia, overweight, smoking cigarettes, and low physical activity; all p values <0·025). INTERPRETATION: In patients with transient ischaemic attack or minor ischaemic stroke, those with atherosclerosis have a much higher risk of major vascular events within 5 years than do those without atherosclerosis. Preventive strategies addressing complications of atherosclerosis should focus on individuals with atherosclerosis rather than grouping together all people who have had a transient ischaemic attack or minor ischaemic stroke (including those without atherosclerosis). FUNDING: AstraZeneca, Sanofi, Bristol Myers Squibb, SOS Attaque Cérébrale Association.

Five-Year Prognosis After TIA or Minor Ischemic Stroke in Asian and Non-Asian Populations.

OBJECTIVE: To determine long-term vascular outcomes of Asian patients who experienced TIA or minor ischemic stroke and to compare the outcomes of Asian patients with those of non-Asian patients, in the context of modern guideline-based prevention strategies. METHODS: This is a subanalysis of the TIAregistry.org project, in which 3,847 patients (882 from Asian and 2,965 from non-Asian countries) with a recent TIA or minor ischemic stroke were assessed and treated by specialists at 42 dedicated units from 14 countries and followed for 5 years. The primary outcome was a composite of cardiovascular death, nonfatal stroke, and nonfatal acute coronary syndrome. RESULTS: No differences were observed in the 5-year risk of the primary outcome (14.0% vs 11.7%; hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.88-1.37; p = 0.41) and stroke (10.7% vs 8.5%; HR, 1.17; 95% CI, 0.90-1.51; p = 0.24) between Asian and non-Asian patients. Asian participants were at higher risk of intracranial hemorrhage (1.8% vs 0.8%; HR, 2.23; 95% CI, 1.09-4.57; p = 0.029). Multivariable analysis showed that the presence of multiple acute infarctions on initial brain imaging was an independent predictor of primary outcome and modified Rankin Scale score of >1 in both Asian (HR, 1.91; 95% CI, 1.11-3.29; p = 0.020) and non-Asian (HR, 1.39; 95% CI, 1.02-1.90; p = 0.037) patients. CONCLUSION: The long-term risk of vascular events in Asian patients was as low as that in non-Asian patients, while Asian participants had a 2.2-fold higher intracranial hemorrhage risk. Multiple acute infarctions were independently associated with future disability in both groups. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that among people who experienced TIA or minor stroke, Asian patients have a similar 5-year risk of cardiovascular death, stroke, and acute coronary syndrome as non-Asian patients.

Cilostazol Versus Aspirin in Ischemic Stroke Patients With High-Risk Cerebral Hemorrhage: Subgroup Analysis of the PICASSO Trial.

Background and Purpose- Although cilostazol has shown less hemorrhagic events than aspirin, only marginal difference was observed in hemorrhagic stroke events among patients at high risk for cerebral hemorrhage. To identify patients who would most benefit from cilostazol, this study analyzed interactions between treatment and subgroups of the PICASSO trial (Prevention of Cardiovascular Events in Asian Ischemic Stroke Patients With High Risk of Cerebral Hemorrhage). Methods- Ischemic stroke patients with a previous intracerebral hemorrhage or multiple microbleeds were randomized to treatment with cilostazol or aspirin and followed up for a mean 1.8 years. Efficacy, defined as the composite of any stroke, myocardial infarction, and vascular death, and safety, defined as the incidence of hemorrhagic stroke, were analyzed in the 2 groups. Interactions between treatment and age, sex, presence of hypertension and diabetes mellitus, index of high-risk cerebral hemorrhage, and white matter lesion burden were analyzed for primary and key secondary outcomes. Changes in vital signs and laboratory results were compared in the 2 groups. Results- Among all 1534 patients enrolled, a significant interaction between treatment group and index of high risk for cerebral hemorrhage on hemorrhagic stroke (P for interaction, 0.03) was observed. Hemorrhagic stroke was less frequent in the cilostazol than in the aspirin group in patients with multiple microbleeds (1 versus 13 events; hazard ratio, 0.08 [95% CI, 0.01-0.61]; P=0.01). A marginal interaction between treatment group and white matter change on any stroke (P for interaction, 0.08) was observed. Cilostazol reduced any stroke significantly in patients with mild (5 versus 16 events; hazard ratio, 0.36 [95% CI, 0.13-0.97]; P=0.04)-to-moderate (16 versus 32 events; hazard ratio, 0.50 [95% CI, 0.29-0.92]; P=0.03) white matter changes. Heart rate and HDL (high-density lipoprotein) cholesterol level were significantly higher in the cilostazol group than in the aspirin group at follow-up. Conclusions- Cilostazol may be more beneficial for ischemic stroke patients with multiple cerebral microbleeds and before white matter changes are extensive. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01013532.

Five-Year Risk of Stroke after TIA or Minor Ischemic Stroke.

BACKGROUND: After a transient ischemic attack (TIA) or minor stroke, the long-term risk of stroke and other vascular events is not well known. In this follow-up to a report on 1-year outcomes from a registry of TIA clinics in 21 countries that enrolled 4789 patients with a TIA or minor ischemic stroke from 2009 through 2011, we examined the 5-year risk of stroke and vascular events. METHODS: We evaluated patients who had had a TIA or minor stroke within 7 days before enrollment in the registry. Among 61 sites that participated in the 1-year outcome study, we selected 42 sites that had follow-up data on more than 50% of their enrolled patients at 5 years. The primary outcome was a composite of stroke, acute coronary syndrome, or death from cardiovascular causes (whichever occurred first), with an emphasis on events that occurred in the second through fifth years. In calculating the cumulative incidence of the primary outcome and secondary outcomes (except death from any cause), we treated death as a competing risk. RESULTS: A total of 3847 patients were included in the 5-year follow-up study; the median percentage of patients with 5-year follow-up data per center was 92.3% (interquartile range, 83.4 to 97.8). The composite primary outcome occurred in 469 patients (estimated cumulative rate, 12.9%; 95% confidence interval [CI], 11.8 to 14.1), with 235 events (50.1%) occurring in the second through fifth years. At 5 years, strokes had occurred in 345 patients (estimated cumulative rate, 9.5%; 95% CI, 8.5 to 10.5), with 149 of these patients (43.2%) having had a stroke during the second through fifth years. Rates of death from any cause, death from cardiovascular causes, intracranial hemorrhage, and major bleeding were 10.6%, 2.7%, 1.1%, and 1.5%, respectively, at 5 years. In multivariable analyses, ipsilateral large-artery atherosclerosis, cardioembolism, and a baseline ABCD2 score for the risk of stroke (range, 0 to 7, with higher scores indicating greater risk) of 4 or more were each associated with an increased risk of subsequent stroke. CONCLUSIONS: In a follow-up to a 1-year study involving patients who had a TIA or minor stroke, the rate of cardiovascular events including stroke in a selected cohort was 6.4% in the first year and 6.4% in the second through fifth years. (Funded by AstraZeneca and others.).

Prevention of cardiovascular events in Asian patients with ischaemic stroke at high risk of cerebral haemorrhage (PICASSO): a multicentre, randomised controlled trial.

BACKGROUND: The optimal treatment for patients with ischaemic stroke with a high risk of cerebral haemorrhage is unclear. We assessed the efficacy and safety of cilostazol versus aspirin, with and without probucol, in these patients. METHODS: In this randomised, controlled, 2 × 2 factorial trial, we enrolled patients with ischaemic stroke with a history of or imaging findings of intracerebral haemorrhage or two or more microbleeds from 67 centres in three Asian countries. Patients were randomly assigned (1:1:1:1) to receive oral cilostazol (100 mg twice a day), aspirin (100 mg once a day), cilostazol plus probucol (250 mg twice a day), or aspirin plus probucol with centralised blocks stratified by centre. Cilostazol versus aspirin was investigated double-blinded; probucol treatment was open-label, but the outcome assessor was masked to assignment. The co-primary outcomes were incidence of the composite of stroke, myocardial infarction, or vascular death (efficacy) and incidence of haemorrhagic stroke (safety), which were assessed in intention-to-treat and modified intention-to-treat populations. Efficacy was analysed with a non-inferiority test and a superiority test if non-inferiority was satisfied. Safety was assessed with a superiority test only. This trial is registered with ClinicalTrials.gov, NCT01013532. FINDINGS: Between Aug 1, 2009, and Aug 31, 2015, we randomly assigned 1534 patients to one of the four study groups, of whom 1512 were assessed for the co-primary endpoints. During a median follow-up of 1·9 years (IQR 1·0-3·0), the incidence of composite vascular events was 4·27 per 100 person-years in patients who received cilostazol and 5·33 per 100 person-years in patients who received aspirin (HR 0·80, 95% CI 0·57-1·11; non-inferiority p=0·0077; superiority p=0·18). Incidence of cerebral haemorrhage was 0·61 per 100 person-years in patients who received cilostazol and 1·20 per 100 person-years in those who received aspirin (HR 0·51, 97·5% CI 0·20-1·27; superiority p=0·18). The incidence of vascular events was 3·91 per 100 person-years in the probucol group compared with 5·75 per 100 person-years in the non-probucol group (HR 0·69, 95% CI 0·50-0·97; superiority p=0·0316). The incidence of cerebral haemorrhage was 0·72 per 100 person-years in the probucol group and 1·11 per 100 person-years in the non-probucol group (HR 0·65, 97·5% CI 0·27-1·57; p=0·55). Adverse events were similar across the four study groups; the most common events were dizziness, headache, diarrhoea, and constipation. INTERPRETATION: In patients with ischaemic stroke at high risk of cerebral haemorrhage, cilostazol was non-inferior to aspirin for the prevention of cardiovascular events, but did not reduce the risk of haemorrhagic stroke. Addition of probucol to aspirin or cilostazol could be beneficial for reducing the incidence of cardiovascular events. FUNDING: Korea Otsuka Pharmaceutical.

White Matter Hyperintensity Predicts the Risk of Incident Cognitive Decline in Community Dwelling Elderly.

BACKGROUND: Unlike western countries, data on white matter hyperintensity (WMH) in community dwelling elderly in Asian population is very limited. OBJECTIVE: To examine the relation between baseline WMH burden and the risk of incident cognitive decline in a community-based cohort with Chinese-dwelling elderly. METHODS: We prospectively evaluated the incident cognitive decline for 226 participants in the Shanghai Aging Study. Baseline WMH severity was visually rated by the age-related white matter changes (ARWMC) scale based on MRI. Cox proportional hazards regression model was used to estimate the relative risk (RR) of total ARWMC scale, global ARWMC score, presence of lacune and microbleed, for incident cognitive decline by adjusting potential confounders. RESULTS: Forty subjects were identified with incident cognitive decline (new onset 34 mild cognitive impairment and 6 dementia) during a median duration of 6 years follow-up. The incidence of cognitive decline was 3.0 (95% confidence interval [CI] 2.2-4.1) per 100 person-years. Increasing total ARWMC scale [RR1.21 (95% CI 1.06-1.39), p = 0.004)], confluent WMH [RR3.16 (95% CI 1.50-6.64), p = 0.002), and presence of lacunes [RR 2.73 (95% CI 1.21-6.15)] at baseline were independent predictors of incident cognitive decline. CONCLUSION: Our study demonstrated that confluent WMH may increase the risk of incident cognitive decline by 3 folds in community dwelling subjects. Small vessel disease may cause heavy burden of cognitive impairment in the elderly in China.

Converting MMSE to MoCA and MoCA 5-minute protocol in an educationally heterogeneous sample with stroke or transient ischemic attack.

BACKGROUND: The Montreal Cognitive Assessment (MoCA) is psychometrically superior over the Mini-mental State Examination (MMSE) for cognitive screening in stroke or transient ischemic attack (TIA). It is free for clinical and research use. The objective of this study is to convert scores from the MMSE to MoCA and MoCA-5-minute protocol (MoCA-5 min) and to examine the ability of the converted scores in detecting cognitive impairment after stroke or TIA. METHODS: A total of 904 patients were randomly divided into training (n = 623) and validation (n = 281) samples matched for demography and cognition. MMSE scores were converted to MoCA and MoCA-5 min using (1) equipercentile method with log-linear smoothing and (2) Poisson regression adjusting for age and education. Receiver operating characteristics curve analysis was used to examine the ability of the converted scores in differentiating patients with cognitive impairment. RESULTS: The mean education was 5.8 (SD = 4.6; ranged 0-20) years. The entire spectrum of MMSE scores was converted to MoCA and MoCA-5 min using equipercentile method. Relationship between MMSE and MoCA scores was confounded by age and education, and a conversion equation with adjustment for age and education was derived. In the validation sample, the converted scores differentiated cognitively impaired patients with area under receiver operating characteristics curve 0.826 to 0.859. CONCLUSION: We provided 2 methods to convert scores from the MMSE to MoCA and MoCA-5 min based on a large sample of patients with stroke or TIA having a wide range of education and cognitive levels. The converted scores differentiated patients with cognitive impairment after stroke or TIA with high accuracy.

Long-Term Evolutionary Change in the Lumen of Intracranial Atherosclerotic Stenosis Following Angioplasty and Stenting.

BACKGROUND: Angioplasty and stenting is a recognized treatment option for patients with intracranial atherosclerosis. OBJECTIVE: To evaluate the long-term evolutionary luminal changes of intracranial atherosclerosis after angioplasty and stenting. METHODS: This was a retrospective study with patient consent. Eighty-two patients presenting with acute and minor cerebral ischemia due to stenosis ≥70%, who had received medical therapy with or without stenting (Wingspan), were invited. Luminal imaging was provided using 3-dimensional rotational angiography (3-DRA) at baseline and 12 mo, and cone-beam computed tomography angiography with intravenous contrast (CBCT) was provided at follow-up (median 82.4 mo [interquartile range 61.9-96.9 mo]). RESULTS: Thirty-six patients in the stenting group and 26 patients in the medical group were recruited and completed the study. There was no statistically significant difference in demographics between the 2 patient groups. The luminal gain at 12 or 80 mo as compared to baseline in the stenting group was significantly greater than that in the medical group (12 mo: median gain 30% vs 7.2%, P < .001; 80 mo: median gain 42.9% vs 7.2%, P < .0001). Luminal loss or unchanged lumen was correlated with recurrent ischemic event. The differences in the stenosis degree assessment between CBCT and 3-DRA in the same 10 patients with or without stenting were 1.2 ± 0.6% or 0.2 ± 0.06%, respectively. There was a correlation between recurrent ischemic events and luminal loss. CONCLUSION: Arterial lumen after angioplasty and stenting can probably be well maintained and delayed luminal gain does occur, long-term luminal loss is associated with recurrent ischemic events, CBCT might be useful as a less-invasive means for long-term assessment.

Discrepant relationships between admission blood pressure and mortality in different stroke subtypes.

The relationship between blood pressure(BP) and clinical outcome in patients with acute stroke is still controversial. The present study aimed to elucidate the impact of admission blood pressure on mortality in patients with acute stroke of different subtypes. Data were from ChinaQUEST (QUality Evaluation of Stroke Care and Treatment), a multicenter, prospective hospital registry study in 37 cities across China. A total of 6427 patients were admitted within 24h of onset and after following up for 12months, 5501 were included in the final analysis. Multivariate Cox regression model were used in data analysis. A "U-curve shaped" relationship was observed between admission systolic or diastolic BP and mortality at 12months in the overall study population. Compared to first quartile, the Hazard ratio (HR) for the systolic BP of top quartile was 1.444 (95%CI 1.854-1.636), while the HR was 0.692 (95%CI 0.802-0.930) for the second quartile. Similar associations were observed when we applied admission diastolic BP. In subgroup analysis, the U-shaped effect was remained only in patients with intracranial hemorrhage (ICH). The HR for the systolic BP of top quartile was 2.274 (95%CI 1.878-2.755), while the HR was 0.751 (95%CI 0.571-0.986) for the second quartile. Moreover, admission diastolic BP of top quartile was significantly associated with elevated risk of death for patients with ischemic stroke caused by small vessel diseases (LACI)(HR 1.470; CI 1.040-2.078). In addition, we found a heterogeneity of the admission BP distribution among different subtypes, which may explain the "U-curve" effect.

Brain microbleeds, anticoagulation, and hemorrhage risk: Meta-analysis in stroke patients with AF.

OBJECTIVES: To assess the association between cerebral microbleeds (CMBs) and future spontaneous intracerebral hemorrhage (ICH) risk in ischemic stroke patients with nonvalvular atrial fibrillation (AF) taking oral anticoagulants. METHODS: This was a meta-analysis of cohort studies with >50 patients with recent ischemic stroke and documented AF, brain MRI at baseline, long-term oral anticoagulation treatment, and ≥6 months of follow-up. Authors provided summary-level data on stroke outcomes stratified by CMB status. We estimated pooled annualized ICH and ischemic stroke rates from Poisson regression. We calculated odds ratios (ORs) of ICH by CMB presence/absence, ≥5 CMBs, and CMB topography (strictly lobar, mixed, and strictly deep) using random-effects models. RESULTS: We established an international collaboration and pooled data from 8 centers including 1,552 patients. The crude CMB prevalence was 30% and 7% for ≥5 CMBs. Baseline CMB presence (vs no CMB) was associated with ICH during follow-up (OR 2.68, 95% confidence interval [CI] 1.19-6.01, p = 0.017). Presence of ≥5 CMB was related to higher future ICH risk (OR 5.50, 95% CI 2.07-14.66, p = 0.001). The pooled annual ICH incidence increased from 0.30% (95% CI 0.04-0.55) among CMB-negative patients to 0.81% (95% CI 0.17-1.45) in CMB-positive patients (p = 0.01) and 2.48% (95% CI 1.2-6.2) in patients with ≥5 CMBs (p = 0.001). There was no association between CMBs and recurrent ischemic stroke. CONCLUSIONS: The presence of CMB on MRI and the dichotomized cutoff of ≥5 CMBs might identify subgroups of ischemic stroke patients with AF with high ICH risk and after further validation could help in risk stratification, in anticoagulation decisions, and in guiding randomized trials and ongoing large observational studies.

Differences in Characteristics and Outcomes Between Asian and Non-Asian Patients in the TIAregistry.org.

BACKGROUND AND PURPOSE: This study provides the contemporary causes and prognosis of transient ischemic attack (TIA) and minor stroke in Asians and the direct comparisons with non-Asians. METHODS: The TIAregistry.org enrolled 4789 patients (1149 Asians and 3640 non-Asians) with a TIA or minor ischemic stroke within 7 days of onset. Every participating facility had systems dedicated to urgent intervention of TIA/stroke patients by specialists. The primary outcome was a composite of cardiovascular death, nonfatal stroke, and nonfatal acute coronary syndrome. RESULTS: Approximately 80% of patients were evaluated within 24 hours of symptom onset. At 1 year, there were no differences in the rates of composite cardiovascular events (6.8% versus 6.0%; P=0.38) and stroke (6.0% versus 4.8%; P=0.11) between Asians and non-Asians. Asians had a lower risk of cerebrovascular disease (stroke or TIA) than non-Asians (adjusted hazard ratio, 0.79; 95% confidence interval, 0.63-0.98; P=0.03); the difference was primarily driven by a lower rate of TIA in Asians (4.2% versus 8.3%; P<0.001). Moderately severe bleeding was more frequent in Asians (0.8% versus 0.3%; P=0.02). In multivariable analysis, multiple acute infarcts (P=0.005) and alcohol consumption (P=0.02) were independent predictors of stroke recurrence in Asians, whereas intracranial stenosis (P<0.001), ABCD2 score (P<0.001), atrial fibrillation (P=0.008), extracranial stenosis (P=0.03), and previous stroke or TIA (P=0.03) were independent predictors in non-Asians. CONCLUSIONS: The short-term stroke risk after a TIA or minor stroke was lower than expected when urgent evidence-based care was delivered, irrespective of race/ethnicity or region. However, the predictors of stroke were different for Asians and non-Asians.

Cortical Microinfarcts in Patients with Middle Cerebral Artery Stenosis.

BACKGROUND: Cortical microinfarcts (CMIs) have been correlated to cognitive decline and dementia. It was previously considered only visible on microscope, but was recently reported to be visible on 3.0 Tesla magnetic resonance imaging (MRI) and linked to presence of intracranial stenosis. We aimed to investigate CMIs on 3.0 Tesla MRI in patients with M1 middle cerebral artery (MCA-M1) stenosis. METHODS: Patients with a recent non-cardioembolic ischemic stroke or transient ischemic attack and an atherosclerotic MCA-M1 stenosis were recruited. The severity of MCA stenosis was defined as moderate (50%-69%) or severe (70%-99% or focal flow void) on time-of-flight MR angiography (MRA). The distal to proximal signal intensity ratio (SIR) of MCA stenosis was measured on time-of-flight MRA to represent its hemodynamic significance. The presence of CMI(s) in the ipsilateral hemisphere was assessed on axial T1- or T2-weighted images and T2-weighted fluid-attenuated inversion-recovery images. RESULTS: Overall, 86 patients (mean age: 62.8 years; 77.9% males) were analyzed, 66 (76.7%) and 20 (23.3%), respectively, having moderate and severe MCA-M1 stenoses. The median SIR was .91. Forty-five (52.3%) patients had ipsilateral CMI(s). Multivariate logistic regression showed a history of dyslipidemia (odds ratio [OR] = 6.83, P = .008), and an SIR lower than the median (OR = 4.73, P = .014) were independently associated with presence of CMI(s) in ipsilateral hemisphere to an MCA-M1 stenosis. CONCLUSIONS: Patients with stroke and intracranial stenosis had a high burden of CMI. Except for a history of dyslipidemia, the hemodynamic significance of the arterial stenosis may contribute to the presence of ipsilateral CMI(s) in these patients, which warrants further investigation in prospective, longitudinal studies.

Symptomatic Patients Remain at Substantial Risk of Arterial Disease Complications Before and After Endarterectomy or Stenting.

BACKGROUND AND PURPOSE: After carotid endarterectomy (CEA) or carotid artery stenting (CAS) in patients with transient ischemic attack or minor ischemic stroke, recurrent stroke risk falls to a low rate on modern medical treatment. METHODS: We used data from 4583 patients with recent transient ischemic attack or minor stroke enrolled in the TIAregistry.org to perform a nested case-control analysis to evaluate pre- and post-CEA/CAS risk. Cases were defined as patients with a CEA/CAS during the 1-year follow-up period. For each case, 2 controls with a follow-up time greater than the time from qualifying event to CEA/CAS were randomly selected, matched by age and sex. Primary outcome was defined as major vascular events (MVE, including stroke, cardiovascular death, and myocardial infarction). RESULTS: The median delay from symptom onset of qualifying event to CEA/CAS was 11 days (interquartile range, 6-23). Overall, patients with CEA/CAS had a higher 1-year risk of MVE than other patients (14.8% versus 5.8%; adjusted hazard ratio, 2.40; 95% confidence interval, 1.61-3.60; P<0.001). During the matched preprocedural period, MVE occurred in 14 (7.5%) cases and in 13 (3.5%) controls, with an adjusted odds ratio =2.46 (95% confidence interval, 1.07-5.64; P=0.03). In the postprocedural period, the risk of MVE was also higher in cases than in controls (adjusted P<0.03). CONCLUSIONS: Patients with CEA/CAS had a higher 12-month risk of MVE, as well as during pre- and postprocedural periods. These results suggest that patients in whom CEA/CAS is anticipated are likely to be an informative population for inclusion in studies testing new antithrombotic strategies started soon after symptom onset.

Sex Differences Do Not Exist in Outcomes among Stroke Patients with Intracranial Atherosclerosis in China: Subgroup Analysis from the Chinese Intracranial Atherosclerosis Study.

BACKGROUND: To date, sex difference in outcomes among patients with intracranial atherosclerosis (ICAS) has rarely been discussed in China as well as in the world. This study aimed to estimate the sex difference in outcomes among patients with ICAS in Chinese cerebral ischemia patients. METHODS: We analyzed 1,335 men and women with ICAS who were enrolled in the Chinese Intracranial Atherosclerosis study. They were followed-up for ischemic stroke recurrence, any cause of death, cerebral vascular events (including transient ischemic attack, ischemic and hemorrhagic stroke), combined end points (including cerebral vascular events, angina or myocardial infarction, pulmonary embolism, peripheral vascular events), and unfavorable outcome (modified Rankin scale score of 3-6) at 1 year. RESULTS: During the follow-up period, 59 (13.44%) combined end points were documented in women and 107 (11.94%) in men. Of the combined end points, 47 were recurrent ischemic stroke events (14 in women and 33 in men), and 51 other causes of deaths (24 in women and 27 in men). There were 349 unfavorable end points (117 in women and 232 in men). The cumulative probability of death was higher in women, but after adjusting for age, diabetes mellitus, hypertension, family history of stroke, current smoker, heavy drinking, hyperhomocysteinemia, and heart disease, there was no significant difference. There was also a lack of difference in 1-year ischemic stroke recurrence, cerebral vascular events, combined end points, and unfavorable outcome between women and men at 1 year. CONCLUSIONS: These results suggest no sex difference in outcome among patients with ICAS in Chinese cerebral ischemia patients.

Early-onset and delayed-onset poststroke dementia - revisiting the mechanisms.

Incident stroke has long been recognized to cause dementia shortly after the event. Patients who survive stroke without early-onset poststroke dementia (PSD) are at a high risk of developing dementia months to years after the initial stroke incident, which has generated enthusiasm for exploring treatments to prevent delayed-onset PSD in survivors of stroke. However, results from clinical trials completed in the past 10-15 years have been disappointing. In light of these results, the present Review revisits the mechanisms of both early-onset and delayed-onset PSD and proposes preventive strategies and directions for future clinical trials. Early-onset PSD results from a complex interplay between stroke lesion features and brain resilience, whereas delayed-onset PSD is associated mainly with the presence of severe sporadic small vessel disease (SVD), and to a lesser extent with Alzheimer disease pathology or recurrent stroke. As well as preventing stroke and delivering acute stroke treatments to reduce initial brain damage, measures to increase brain resilience could also reduce the risk of developing dementia if an incident stroke occurs. Future efforts to prevent delayed-onset PSD should focus on the study of sporadic SVD and on evaluating whether other strategies, in addition to conventional secondary stroke prevention, are effective in dementia prevention in this high-risk group.

Obesity is associated with better survival and functional outcome after acute intracerebral hemorrhage.

OBJECTIVE: To evaluate the association of obesity measured by body mass index (BMI) with mortality and functional outcome in patients with acute intracerebral hemorrhage (ICH). METHODS: Data were from 1571 patients with ICH enrolled in a national, multi-centre, prospective, hospital-based register: the ChinaQUEST (Quality Evaluation of Stroke Care and Treatment) study. The outcomes included all-cause mortality at 12months, and death or high dependency at 3 and 12months. High dependency was defined as a modified Rankin Scale score of 3-5. RESULTS: Of 1571 patients with ICH, 109 were underweight (BMI<18.5kg/m2), 657 were normal-weight (BMI 18.5-23kg/m2), 341 were overweight (BMI 23-25kg/m2) and 464 were obese (BMI≥25kg/m2). Compared with normal-weight patients, obese patients had significantly decreased risks of death at 12months (HR: 0.71, 95% CI: 0.56-0.91) and death or high dependency at 3 and 12months (OR: 0.71, 95% CI: 0.53-0.95; OR: 0.69, 95% CI: 0.51-0.94) after adjusting for baseline characteristics. Neither underweight nor overweight was associated with these three outcomes significantly. CONCLUSIONS: In patients with acute ICH, being obese is associated with a decreased mortality and better functional recovery. Further interventional studies are needed to guide the weight management strategy for patients with ICH.

Neuropsychiatric Symptom Clusters in Stroke and Transient Ischemic Attack by Cognitive Status and Stroke Subtype: Frequency and Relationships with Vascular Lesions, Brain Atrophy and Amyloid.

BACKGROUND: The objectives of this study are 1) to examine the frequencies of neuropsychiatric symptom clusters in patients with stroke or transient ischemic attack (TIA) by cognitive level and stroke subtype; and 2) to evaluate effect of demographic, clinical, and neuroimaging measures of chronic brain changes and amyloid upon neuropsychiatric symptom clusters. METHODS: Hospital-based, cross-sectional study. 518 patients were administered the Neuropsychiatric Inventory (NPI) 3-6 months post index admission. NPI symptoms were classified into four symptom clusters (Behavioral Problems, Psychosis, Mood Disturbance & Euphoria) derived from a confirmatory factor analysis of the 12 NPI items. Multivariable logistic regression was used to determine independent associations between demographic, clinical and neuroimaging measures of chronic brain changes (white matter changes, old infarcts, whole brain atrophy, medial temporal lobe atrophy [MTLA] and frontal lobe atrophy [FLA]) with the presence of NPI symptoms and all symptom clusters except euphoria. 11C-Pittsburg Compound B Positron Emission Tomography (11C-PiB PET) was performed in 24 patients to measure amyloid retention for Alzheimer's Disease (AD) pathology. RESULTS: 50.6% of the whole sample, including 28.7% cognitively normal and 66.7% of patients with mild cognitive symptoms, had ≥1 NPI symptoms. Frequencies of symptom clusters were largely similar between stroke subtypes. Compared to patients with cardioembolic stroke and intracranial haemorrhage, those with TIA had less frequent mood disturbance. Stroke severity at admission and MTLA were the most robust correlates of symptoms. FLA was associated with behavioral problems cluster only. Frequency of symptom clusters did not differ between patients with and without significant amyloid retention. CONCLUSION: Frequency of neuropsychiatric symptoms increased with level of cognitive impairment but was largely similar between stroke subtypes. Stroke severity and MTLA were associated with neuropsychiatric symptoms. AD pathology appeared to be unrelated to neuropsychiatric manifestations but further studies with larger sample size are required to substantiate this finding.