Prevalence, Characteristics and Risk Factors for Embolic Stroke of Undetermined Source in West and South Asia and North African Population Residing in Qatar.

BACKGROUND AND PURPOSE: Embolic stroke of undetermined source (ESUS) is an important contributor to stroke worldwide. Little is known about ESUS in developing parts of the world such as South Asia, West Asia and North Africa despite the high stroke burden in these areas. The purpose of the study was to characterize the prevalence, demographic, risk factor and clinical aspects of ESUS in patients from South Asia, West Asia and North Africa residing in Qatar. METHODS: Data were retrospectively collected on 3103 stoke patients. Risk factors and clinical features of the ESUS group were compared to all other strokes using Chi-square or student's t-tests. Logistic regression was used to identify factors associated with ESUS. ESUS patients were compared based on ethnicity using Chi-square or one-way ANOVA. RESULTS: 634 patients (30·9%, 95% CI (28·9%-32·9%) met the ESUS criteria. Mean age was 56·3 years ± 13·7 and South Asian ESUS patients were younger than West Asians or North Africans (67·1 ± 13·5 versus 52·1 ± 10·8 versus 53·5 ± 14·2, P = .001). Smoking, diastolic function, prior antiplatelets and wall motion abnormalities were more common in ESUS. Logistic regression showed that South Asian ethnicity (OR 1·50, CI 1·14-1·97, P = ·003), diastolic dysfunction (OR 1·47, CI 1·23-1·75, P = ·005), global (OR 1·79, CI 1·41-2·26, P = ·001) and focal (OR 5·48, CI 3·79-7·92, P = ·001) wall motion abnormalities, predicted ESUS. CONCLUSIONS: ESUS is a major cause of stroke in patients from West Asia, South Asia and North Africa residing in Qatar. The clinical profile and risk factors for ESUS vary based on ethnicity. In South Asians, ESUS occurs at a younger age and is most likely cardiogenic in origin.

Distribution and Temporal Trends From 1993 to 2015 of Ischemic Stroke Subtypes: A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Preventive strategies, together with demographic and socioeconomic changes, might have modified the worldwide distribution of ischemic stroke (IS) subtypes. We investigated those changes by means of a systematic review and meta-analysis. METHODS: We evaluated all population- and hospital-based studies reporting the distribution of IS etiologic subtypes according to the TOAST criteria (Trial of ORG 10172 in Acute Stroke Treatment). Studies were identified by searching articles indexed on PubMed and Scopus from January 1, 1993, to June 30, 2017. Two independent investigators extracted data and checked them for accuracy. Proportions of each etiologic subtype were pooled according to a random effect meta-analytic model weighted by study size; temporal trends were assessed using a mixed-effect meta-regression model. RESULTS: Sixty-five studies including patients from 1993 to 2015 were finally included. Overall, ISs were attributed to cardioembolism (22%; 95% confidence interval [CI], 20-23); large artery atherosclerosis (23%; 95% CI, 21-25); small artery occlusion (22%; 95% CI, 21-24); other determined cause (3%; 95% CI, 3-3); and undetermined cause (26%; 95% CI, 24-28). Cardioembolism was the leading IS etiologic subtype in whites (28%; 95% CI, 26-29) and large artery atherosclerosis in Asians (33%; 95% CI, 31-36). Meta-regression showed an increasing temporal trend for cardioembolism in whites (2.4% annually, P=0.008) and large artery atherosclerosis in Asians (5.7% annually, P<0.001), and a decrease for small artery occlusion in whites (-4.7% annually, P=0.001); there was considerable heterogeneity across all the analyses. CONCLUSIONS: According to our systematic review and meta-analysis, cardioembolism in whites and large artery atherosclerosis in Asians are the leading causes of IS. The heterogeneous distribution of etiologic subtypes of IS may depend on the demographic and socioeconomic characteristics of the different populations. More extensive protocols should be adopted to reduce the persistently relevant proportion of undetermined cause IS.

Association of GGCX gene polymorphism with warfarin dose in atrial fibrillation population in Xinjiang.

OBJECTIVE: To study the effects of γ-glutamyl carboxylase (GGCX) rs2592551 polymorphism on warfarin dose in atrial fibrillation patients in Xinjiang region. METHODS: Polymerase chain reaction - restriction fragment length polymorphism and direct sequencing methods were used to detect the rs2592551 genotype in 269 atrial fibrillation patients with warfarin administration. The effects of different genotypes on warfarin dose were statistically analyzed. RESULTS: The rs2592551 polymorphism detection results were 136 cases of wild-type homozygous CC genotype (50.56%), 115 cases of heterozygous CT genotype (42.75%), 18 cases of homozygous TT genotype (6.69%). The allele frequency C was 71.93%, T was 28.07%. The stable warfarin dose average was 2.86 ± 0.61 mg/d in patients with CC genotype, 3.59 ± 0.93 mg/d in patients with CT genotype and 4.06 ± 0.88 mg/d in patients with TT genotype. The warfarin dose in different genotypes were compared, there was statistically significant difference between CC and TT, CC and CT (P <0. 05), but the TT and CT showed no significant difference (P > 0.05). CONCLUSION: In atrial fibrillation population in Xinjiang, patients with CT and TT genotypes in GGCX gene rs259251 loci required for significantly higher warfarin dose than those with CC genotype. Therefore, rs2592551 polymorphism may one of the factors affecting the warfarin dose in patients with atrial fibrillation.

Disparities in stroke type and vascular risk factors between 2 Hispanic populations in Miami and Mexico city.

BACKGROUND: The heterogeneous nature and determinants of stroke among different Hispanic groups was examined by comparing hospitalized Hispanic stroke patients in Miami, where the Hispanic population is largely of Caribbean origin, to a Mestizo population in Mexico City. METHODS: Consecutive Hispanic patients who were admitted with stroke or transient ischemic attack (TIA) and included in the prospective stroke registries of 2 tertiary care teaching hospitals were studied. Demographic factors, stroke subtypes, vascular risk factors, stroke severity, and outcomes were compared. Vascular risk factor definitions were standardized. RESULTS: A total of 928 patients (520 Mexicans and 408 Miami Hispanics) were analyzed. Mexicans were younger, with a greater proportion of women. More cerebral venous thromboses (CVTs) were admitted in Mexico, while TIA and stroke mimics were more commonly admitted in Miami; cardioembolic strokes were more commonly ascertained in Miami, and more cryptogenic strokes in Mexico. Stroke severity was similar for intracerebral hemorrhages, but more severe ischemic strokes and CVTs were included in the Mexican registry. Outcome at 1 and 3 months was similar in both registries after adjusting for age and baseline stroke severity. After adjusting for age and sex, hypertension, dyslipidemia, and atrial fibrillation were more frequent, and diabetes mellitus was less frequent, among Miami Hispanics compared to Mexicans. CONCLUSIONS: We found significant differences in the frequency of hypertension, diabetes, dyslipidemia, and atrial fibrillation in Miami Hispanics and Mexican stroke patients, highlighting the heterogeneity of the Hispanic ethnic group. Future studies are needed to clarify the relative contribution of genetic and environmental disparities amongst Mexican and Caribbean Hispanic stroke patients.

Ischemic stroke in young Asian women: risk factors, subtypes and outcome.

BACKGROUND AND OBJECTIVE: The objective of our study was to describe risk factors, mechanisms and outcome of young Asian women with ischemic stroke. METHODS: Twelve tertiary-care centers in 8 Asian countries participated. Women aged 15-45 years were included if they had an ischemic stroke supported by neuroimaging. Data on age, risk factor history, stroke mechanism and discharge status were collected. RESULTS: A total of 958 subjects were included, their mean age was 34 years. Large-vessel thrombosis comprised 24%, cerebral venous thrombosis 21%, cardioembolism 19% and small-vessel thrombosis 15%. The stroke risk factors included hypertension (29%), diabetes (14%), pregnancy (11%), valvular heart disease (10%) and cigarette smoking (3%). Anemia was found in 42%, and mortality was 4%; at discharge, 17% had modified Rankin score (mRS) >4 and 83% mRS 0-3. CONCLUSION: Unlike among Caucasians, large-vessel thrombosis, cerebral venous thrombosis and cardioembolism are common among young Asian women with stroke. A high proportion are pregnancy-related. More studies are needed.

The effects of cardiopulmonary bypass on the number of cerebral microemboli and the incidence of cognitive dysfunction after coronary artery bypass graft surgery.

BACKGROUND: Postoperative cognitive dysfunction (POCD) can be a debilitating complication after coronary artery bypass graft (CABG) surgery. Cerebral microemboli during cardiopulmonary bypass (CPB) are believed to be an important etiologic factor of POCD. In this study, we examined whether avoidance of CPB with "off-pump" surgery reduces the number of cerebral microemboli and the incidence of POCD after CABG surgery in Chinese population. METHODS: Two hundred twenty-seven patients were enrolled in this prospective cohort study. Fifty-nine patients underwent CABG surgery with CPB and 168 underwent off-pump surgery. Cerebral microemboli were measured continuously with bilateral transcranial Doppler ultrasonography of the middle cerebral arteries. A neuropsychological test battery that included seven tests with nine subscales was administered at baseline, as well as at 1 wk and 3 mo after surgery. POCD was defined using the international study of POCD1 definition. RESULTS: The median total number of cerebral microemboli for the case was 430 (range: 155-2088) in patients undergoing surgery with CPB and 2 (0-66) in the off-pump patients (P < 0.001). There were no differences in the incidence of POCD between the patients having surgery with or without CPB either at 1 wk (55.2% or 32 of 58 patients [95% confidence interval: 41.5%-68.3%] vs 47.0% or 78 of 166 patients [39.2%-54.9%], P = 0.283) or 3 mo (6.4% or 3 of 47 patients [1.3%-17.5%] vs 13.1% or 16 of 122 of patients [7.7%-20.4%], P = 0.214) after surgery. Increasing age and shorter duration of postoperative hospital stay were independently associated with cognitive dysfunction at 1 wk after surgery. Increasing age and a history of diabetes mellitus were independently associated with cognitive dysfunction 3 mo after surgery. CPB or cerebral microemboli were not significantly related to the occurrence of POCD. CONCLUSIONS: In Chinese population, avoidance of CPB during CABG surgery significantly decreased the number of cerebral microemboli, but it did not decrease the incidence of POCD at either 1 wk or 3 mo after CABG. Neither CPB nor cerebral microemboli was independently associated with the risk of POCD.

MTAP gene is associated with ischemic stroke in Chinese Hans.

Common pathogenic mechanisms may be involved in the prevalence of ischemic stroke and coronary heart disease. Recently, genome-wide association (GWA) studies identified a chromosome region (9p21) that confers the risk of coronary heart disease. In a hospital-based case-control study conducted in Chinese Hans, we tested the hypothesis that the methylthioadenosine phosphorylase (MTAP) gene on chromosome region 9p21 is involved in the aetiology of ischemic stroke using a tagging single nucleotide polymorphism (tSNP) strategy. We observed significant association of rs10118757 in the MTAP gene with ischemic stroke. The G allele of rs10118757 was associated with an increased risk of stroke, with a per-allele OR of 1.31(95% CI, 1.04-1.65, p=0.025). The association remains after controlling for confounding factors including age, gender, body mass index, smoking, alcohol drinking, hypertension, diabetes, and hyperlipidaemia (OR=1.38, 95 CI, 1.02-1.88, p=0.039). In addition, the GA+GG genotype of rs10118757 was associated with the increased risk of an undetermined subtype of ischemic stroke (OR=2.14, 95 CI, 1.35-3.38, p=0.001). Further, we also observed the combined effects of rs10118757 with alcohol drinking and hypertension, which increased the risk of ischemic stroke. Our observations support the hypothesis that the MTAP gene may be involved in the prevalence of ischemic stroke in Chinese Hans.

Right-to-left shunts may be not uncommon cause of TIA in Japan.

BACKGROUND AND PURPOSE: Although 30% to 60% of transient ischemic attacks (TIAs) have embolic sources, the etiology of the remaining TIAs is unknown. Right-to-left shunt (RLS) is one of the most important etiologies of cryptogenic stroke. The aim of this study was to determine whether RLS is related to transient ischemic attack (TIA) of unknown etiology. METHODS: We performed transesophageal echocardiography (TEE) and/or transcranial Doppler (TCD) studies for consecutive TIA patients in order to detect RLS from April 2004 to December 2006. TIA patients were divided into three groups, as follows: 1) Cardioembolic TIA, with a patent cardioembolic source, 2) thrombotic TIA, with an atherothrombotic and/or lacunar mechanism, and 3) undetermined TIA, without identified cause of TIA. We compared the characteristics and presence of RLS among these three groups. RESULTS: We enrolled 124 TIA patients (age: 67+/-13 years old, 80 men). There were 13 patients with Cardioembolic TIA, 25 with Thrombotic TIA, and 86 with Undetermined TIA. TEE and/or TCD were able to detect RLS in 61 of the 124 (49%) patients. RLS was frequent in patients with Undetermined TIA compared with those in the other TIA groups (60% in the Undetermined TIA group, 28% in the Thrombotic TIA group, and 15% in the Cardioembolic TIA group; p<0.001). Smoking and previous history of TIA were frequent in the Thrombotic TIA group (p=0.030 and p=0.016, respectively). CONCLUSION: RLS may play an important role in the etiology of TIA of undetermined cause.

Differences in stroke subtypes between black and white patients with stroke: the South London Ethnicity and Stroke Study.

BACKGROUND: Determining whether the distribution of stroke subtypes differs between ethnic groups is important in understanding the mechanisms of the increased stroke incidence in black patients. METHODS AND RESULTS: In this study, 600 black and 600 white patients with stroke were prospectively and consecutively recruited to determine differences in stroke subtypes. The pathophysiological Trial of Org 10172 (TOAST) classification was used and compared with a clinical (Oxfordshire Community Stroke Project) subtype classification. Stroke subtypes were determined by one investigator by review of original imaging. Black patients with stroke were significantly younger and had higher prevalences of hypertension, diabetes, and obesity. They were less likely to be smokers and had lower prevalences of myocardial infarction and atrial fibrillation. In the black patients, 33% of stroke was due to cerebral small vessel disease compared with 14% in the white stroke cohort (odds ratio, 2.94; 95% confidence interval, 1.97 to 4.39; P<0.001, controlling for age, gender, cardiovascular risk factors, and social class). The black stroke cohort had less large vessel atherosclerosis (odds ratio, 0.49; 95% confidence interval, 0.29 to 0.82; P=0.007) and cardioembolic disease (odds ratio, 0.54; 95% confidence interval, 0.37 to 0.80; P=0.002). Using a classification based on clinical syndrome alone gave a higher estimate of the frequency of small vessel disease stroke, particularly in white patients. CONCLUSIONS: A relative excess of small vessel disease was observed in black patients with stroke compared with an excess of extracranial atherosclerosis and cardioembolic stroke in white patients with stroke that was independent of conventional risk factors and social class. Whether these excesses are due to differences in genetic susceptibility or as-yet undetermined differences in environmental risk remains to be determined.

Ethnic variations in risk factor profile, pattern and recurrence of non-cardioembolic ischemic stroke.

BACKGROUND: Ischemic stroke is influenced by ethnic and geographical variations. The aim of this study was to identify the risk factor profiles, subtypes and recurrence of non-cardioembolic ischemic stroke for the two largest subpopulations, the Arab and South Asians, at the only stroke-admitting hospital in Qatar. METHODS: Data on stroke patients admitted to Hamad Medical Corporation from January through December 2001 were reviewed in January 2005. Only patients with non-cardioembolic ischemic stroke and complete work-up were included. RESULTS: A total of 303 patients with ischemic non-cardioembolic stroke fit the entry criteria. Sixty seven percent of the overall patient population (sex ratio 2:6, M/F) was of Arab origin, and 32% were South Asians. Hypertension was the most commonly encountered risk factor followed by dyslipidemia, diabetes mellitus, and obesity. Significant differences between the Arab and South Asian subgroup of patients were observed with respect to number of risk factors and occurrence of obesity and diabetes. Carotid artery stenotic lesions, ventricular wall motion abnormalities and stroke recurrence were observed with a higher frequency in the Arab subgroup of patients compared with the South Asians. The majority of strokes were lacunar hemispheric strokes (68%), followed by lacunar brainstem strokes (15%) and large-vessel hemispheric infarctions (10%). Patients with a previous history of stroke had a higher frequency of carotid artery stenosis (p = 0.05) and risk of stroke recurrence (p = 0.04). CONCLUSIONS: Unlike in other studies originating from the Arabian Gulf, lacunar stroke is the most common subtype of non-cardioembolic ischemic stroke in both the Arabs and South Asians in Qatar. Significant ethnic differences in age of occurrence, risk factor profile, and cardiovascular variables were observed.

Ischemic stroke subtype incidence among whites, blacks, and Hispanics: the Northern Manhattan Study.

BACKGROUND: Stroke incidence is greater in blacks than in whites; data on Hispanics are limited. Comparing subtype-specific ischemic stroke incidence rates may help to explain race-ethnic differences in stroke risk. The aim of this population-based study was to determine ischemic stroke subtype incidence rates for whites, blacks, and Hispanics living in one community. METHODS AND RESULTS: A comprehensive stroke surveillance system incorporating multiple overlapping strategies was used to identify all cases of first ischemic stroke occurring between July 1, 1993, and June 30, 1997, in northern Manhattan. Ischemic stroke subtypes were determined according to a modified NINDS scheme, and age-adjusted, race-specific incidence rates calculated. The annual age-adjusted incidence of first ischemic stroke per 100,000 was 88 (95% CI, 75 to 101) in whites, 149 (95% CI, 132 to 165) in Hispanics, and 191 (95% CI, 160 to 221) in blacks. Among blacks compared with whites, the relative rate of intracranial atherosclerotic stroke was 5.85 (95% CI, 1.82 to 18.73); extracranial atherosclerotic stroke, 3.18 (95% CI, 1.42 to 7.13); lacunar stroke, 3.09 (95% CI, 1.86 to 5.11); and cardioembolic stroke, 1.58 (95% CI, 0.99 to 2.52). Among Hispanics compared with whites, the relative rate of intracranial atherosclerotic stroke was 5.00 (95% CI, 1.69 to 14.76); extracranial atherosclerotic stroke, 1.71 (95% CI, 0.80 to 3.63); lacunar stroke, 2.32 (95% CI, 1.48 to 3.63); and cardioembolic stroke, 1.42 (95% CI, 0.97 to 2.09). CONCLUSIONS: The high ischemic stroke incidence among blacks and Hispanics compared with whites is due to higher rates of all ischemic stroke subtypes.

Southern Buenos Aires stroke project.

BACKGROUND: Ethnic differences and vascular risk factors are the major determinants of stroke subtypes. Nevertheless, specific data from undeveloped countries is difficult to obtain. Natives from South America may have a higher frequency of penetrating small vessel disease and hemorrhagic stroke. However, there are few studies in South America supporting these findings. OBJECTIVE: We analyze demographic, ethnic, risk factors, clinical characteristics, and stroke subtypes in all patients with acute stroke admitted to our hospital. METHODS: We studied all consecutive acute stroke patients admitted to the Ramos Mejia Hospital in Buenos Aires from 1997 to 1999. Our hospital serves a determined population of Southern Buenos Aires. Data were collected prospectively on patients' admission in a form especially designed for this study including vascular risk factors, clinical features, epidemiological characteristics, and neuroradiological findings. Stroke subtypes were determined according to the TOAST classification. RESULTS: Among 361 acute stroke patients, 31% had hemorrhagic stroke. It was more frequent among Natives (34%) than Caucasians (27%) (P<0.002). Ischemic stroke subtypes were as follows: 105 (42%) patients had lacunar, 31 (12%) atherosclerotic stroke, 53 (21%) cardioembolic infarction, and 16 (6%) other causes of stroke. Forty-five (18%) patients were classified as undetermined. Small vessel disease was higher among Caucasians (35%) than Natives (24%). CONCLUSIONS: Penetrating artery disease (42%) and intracranial hemorrhage (31%) were the most common stroke subtypes, being more frequent than reported in the literature. Natives had significantly higher frequency of hemorrhagic stroke than Caucasians.