Abstract 3884: Stroke Subtypes in Hispanic Patients in the NINDS Stroke Genetics Network (SiGN): A Comparison of Two Classification Systems

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Michael Katsnelson ◽  
Tatjana Rundek ◽  
Ralph Sacco ◽  
Hannah Gardener ◽  
Shaneela Malik ◽  
...  

Objectives: Identification of gene variants of stroke subtypes is important for the development of tailored ischemic stroke therapies among various ethnic groups. Valid and reliable determination of ischemic stroke subtype is essential for achieving this goal and to standardize a classification scheme across multi-center studies and different populations. Causative Classification System for Ischemic Stroke (CCS) is a novel computerized subclassification tool developed to improve reliability and accuracy of classifying stroke types. The CCS algorithm relies on both phenotypic and causative stroke variables. A Hispanic subset of the SiGN, an important and distinct target population with greater risk of certain stroke subtypes, was evaluated with Trial of Org 10172 in Acute Stroke Treatment (TOAST) and CCS and the agreement between the two classification systems was analyzed. Methods: Over 6000 subjects at 15 sites across US and Europe were enrolled, with TOAST and CCS locally adjudicated. Blood collection and central data quality control (10% central readjudication) were performed on all participants. A subset of Hispanics was analyzed for the purpose of this study and the agreement between the TOAST and CCS were assessed by kappa statistic. Findings: Hispanics (n=595, 10.9%) compared to non-Hispanics (n=5457) were more likely to be younger (63.7 vs. 64.0), male (55% vs. 46%) and have fewer of the traditional stroke risk factors HTN (54% vs. 64%), Afib (11% vs. 14%), DM(23% vs. 25%), CAD(16% vs. 20%) and smoking(19% vs. 22%). While the TOAST showed no differences between stroke subtypes for Hispanic vs. non-Hispanics, in CCS, Hispanics were classified with more of large vessel (22% vs. 20%), cardioembolic (37% vs. 30%) and small vessel strokes (13% vs. 9%) and fewer with undetermined etiology (28% vs. 40%) as compared to non-Hispanics. TOAST and CCS offered moderate correlation across all stroke types in Hispanics: kappa of 0.66 for large artery atherosclerosis, 0.58 for cardioembolic, and 0.58 for small artery occlusion. Conclusion: CCS offers a more sensitive and accurate system for subphenotyping of strokes in Hispanics who tended to have relatively fewer risk factors and unclassified strokes. Further studies correlating the two classification systems and their relation to genotyping data are warranted.

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Sara Pulit ◽  
Hakan Ay ◽  
Robert D Brown ◽  
Dale M Gamble ◽  
Steven J Kittner ◽  
...  

Stroke subtype classification, applying standard criteria to clinical data, can reduce the heterogeneity of ischemic stroke for genetics studies. To date, most of the replicated genetic loci for ischemic stroke appear subtype-specific. Increasing homogeneity of phenotype comes with a trade-off in sample size, which influences the potential for successful identification of new loci. We estimated genetic associations using the union and intersection of two widely used stroke subtyping systems to assess the influence of sample size and homogeneity on test statistics. Methods: The Stroke Genetics Network (SiGN) study used both the Causative Classification of Stroke (CCS) and the Trial of ORG10172 Acute Stroke Trial (TOAST) classification systems. The CCS generates both a causal and a phenotypic subtype. Using all available data from case-control strata from the a previously performed GWAS, we focused on three main stroke subtypes: cardioembolic (CE), large artery atherosclerosis (LAA), and small artery occlusion (SAO). We estimated genetic associations with the union of the two CCS outputs and TOAST ( eg called CE by at least one method) and the intersection ( eg called CE by all three methods). Our modelling approach included a fixed-effects meta-analysis, i.e. pooling stratum specific estimates from logistic regression models using 10 principle components to account for genetic ancestry responsible for population stratification. Results: The majority of confirmatory findings from SiGN ( PITX2 and ZFHX3 for CE and HDAC9 for LAA) were evident in both models and in both the union and intersection of the subtyping systems. Some findings ( TSPAN2 in LAA) showed up best in the intersection with stronger corresponding p-values and odds ratios whereas other findings (12q24 for SAO) appear stronger in all of the union analyses, but were also evident in intersection analyses. We identify 16 potential novel loci, 6 of which appear in numerous analyses. Conclusion: Both expanding and refining stroke subtypes may help in the identification of additional stroke genetic risk variants and should be considered as complementary to a single classification system. We are pursuing replication of the novel findings.


Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Kathryn M Rexrode ◽  
Braxton D Mitchell ◽  
Kathleen A Ryan ◽  
Steven J Kittner ◽  
Hakan Ay ◽  
...  

Introduction: The relative distribution of stroke risk factors, as well as ischemic stroke subtypes, in women compared with men is not well described. Hypothesis: We hypothesized that the distribution of ischemic stroke risk factors and subtypes would differ by sex, with a later onset in women and greater proportion of comorbidities. Methods: The NINDS Stroke Genetics Network (SiGN) consortium was established to evaluate genetic risk factors for ischemic stroke. A total of 23 separate studies performed Causative Classification of Stroke (CCS) typing using standardized criteria on ischemic stroke cases and contributed data on risk factors. We compared the distribution of ischemic stroke risk factors and CCS phenotypes between men and women with ischemic stroke. Results: Of the 16,228 ischemic strokes in SiGN, 8005 (49.3%) occurred in women. Median age at stroke was older in female than male stroke cases (73 vs. 66 years) (p=<0.0001). Among stroke cases, women were more likely than men cases to have hypertension or atrial fibrillation and less likely to have diabetes or coronary artery disease, or to smoke (p <0.003 for all). The distribution of stroke subtypes also differed by sex, with women less likely than men to have large artery infarction and small artery occlusion, and more likely to have cardioembolic stroke and undetermined stroke due to incomplete work-up (p values all <0.0001; see Table). Results were similar when the distribution of stroke subtypes was examined for those <70 years and ≥70 years, except for cardioembolic stroke remaining more common only among women ≥70. Conclusions: In this large group of carefully phenotyped ischemic strokes, the distribution of ischemic stroke subtypes and risk factor profiles differ significantly by sex. Evaluation of the causes of these differences may highlight areas for improved prevention and risk reduction in both genders.


2019 ◽  
Vol 267 (3) ◽  
pp. 649-658 ◽  
Author(s):  
Petrea Frid ◽  
◽  
Mattias Drake ◽  
A. K. Giese ◽  
J. Wasselius ◽  
...  

Abstract Objective Posterior circulation ischemic stroke (PCiS) constitutes 20–30% of ischemic stroke cases. Detailed information about differences between PCiS and anterior circulation ischemic stroke (ACiS) remains scarce. Such information might guide clinical decision making and prevention strategies. We studied risk factors and ischemic stroke subtypes in PCiS vs. ACiS and lesion location on magnetic resonance imaging (MRI) in PCiS. Methods Out of 3,301 MRIs from 12 sites in the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Genetics Network (SiGN), we included 2,381 cases with acute DWI lesions. The definition of ACiS or PCiS was based on lesion location. We compared the groups using Chi-squared and logistic regression. Results PCiS occurred in 718 (30%) patients and ACiS in 1663 (70%). Diabetes and male sex were more common in PCiS vs. ACiS (diabetes 27% vs. 23%, p < 0.05; male sex 68% vs. 58%, p < 0.001). Both were independently associated with PCiS (diabetes, OR = 1.29; 95% CI 1.04–1.61; male sex, OR = 1.46; 95% CI 1.21–1.78). ACiS more commonly had large artery atherosclerosis (25% vs. 20%, p < 0.01) and cardioembolic mechanisms (17% vs. 11%, p < 0.001) compared to PCiS. Small artery occlusion was more common in PCiS vs. ACiS (20% vs. 14%, p < 0.001). Small artery occlusion accounted for 47% of solitary brainstem infarctions. Conclusion Ischemic stroke subtypes differ between the two phenotypes. Diabetes and male sex have a stronger association with PCiS than ACiS. Definitive MRI-based PCiS diagnosis aids etiological investigation and contributes additional insights into specific risk factors and mechanisms of injury in PCiS.


2021 ◽  
Vol 6 (1) ◽  
pp. 6
Author(s):  
Sintija Strautmane ◽  
Kristaps Jurjāns ◽  
Estere Zeltiņa ◽  
Evija Miglāne ◽  
Andrejs Millers

Background and Objectives. Ischemic stroke (IS) is one of the leading causes of disability, morbidity, and mortality worldwide. The goal of the study was to evaluate patient demographics, characteristics, and intrahospital mortality among different ischemic stroke subtypes. Materials and Methods. A retrospective observational non-randomized study was conducted, including only ischemic stroke patients, admitted to Pauls Stradins Clinical university hospital, Riga, Latvia, from January of 2016 until December 2020. Ischemic stroke subtypes were determined according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria as a stroke due to (1) large-artery atherosclerosis (atherothrombotic stroke (AS)), (2) cardioembolism (cardioembolic stroke (CS)), (3) small-vessel occlusion (lacunar stroke (LS)), (4) stroke of other determined etiology (other specified stroke (OSS)), and (5) stroke of undetermined etiology (undetermined stroke (US)). The data between different stroke subtypes were compared. Results. There was a slight female predominance among our study population, as 2673 (56.2%) patients were females. In our study group, the most common IS subtypes were cardioembolic stroke (CS), 2252 (47.4%), and atherothrombotic stroke (AS), 1304 (27.4%). CS patients were significantly more severely disabled on admission, 1828 (81.4%), and on discharge, 378 (16.8%), p < 0.05. Moreover, patients with CS demonstrated the highest rate of comorbidities and risk factors. This was also statistically significant, p < 0.05. Differences between the total patient count with no atrial fibrillation (AF), paroxysmal AF, permanent AF, and different IS subtypes among our study population demonstrated not only statistical significance but also a strong association, Cramer’s V = 0.53. The majority of patients in our study group were treated conservatively, 3389 (71.3%). Reperfusion therapy was significantly more often performed among CS patients, 770 (34.2%), p < 0.05. The overall intrahospital mortality among our study population was 570 (12.0%), with the highest intrahospital mortality rate noted among CS patients, 378 (66.3%), p < 0.05. No statistically significant difference was observed between acute myocardial infarction and adiposity, p > 0.05. Conclusions. In our study, CS and AS were the most common IS subtypes. CS patients were significantly older with slight female predominance. CS patients demonstrated the greatest disability, risk factors, comorbidities, reperfusion therapy, and intrahospital mortality.


2008 ◽  
Vol 65 (11) ◽  
pp. 803-809 ◽  
Author(s):  
Dejana Jovanovic ◽  
Ljiljana Beslac-Bumbasirevic ◽  
Ranko Raicevic ◽  
Jasna Zidverc-Trajkovic ◽  
Marko Ercegovac

Background/Aim. Etiology of ischemic stroke (IS) among young adults varies among countries. The aim of the study was to investigate the causes and risk factors of IS in the young adults of Serbia. Methods. A total of 865 patients with IS, aged 15 to 45 years, were treated throughout the period 1989-2005. Etiologic diagnostic tests were performed on the patient by the patient basis and according to their availability at the time of investigation. The most likely cause of stroke was categorized according to the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria. Results. There were 486 men and 379 women, with 19% of the patients ? 30 years old. Large artery arteriosclerosis and small artery disease were confirmed in 14% of the patients, and embolism and other determined causes in 20%. Undetermined causes made up 32% of the patients, mostly those (26%) with incomplete investigations. Smoking (37%), hypertension (35%) and hyperlipidemia (35%) were the most common risk factors. Rheumatic heart diseases and prosthetic valves were the most common causes of IS. Arterial dissections and coagulation inhibitors deficiency were detected in a small number of patients. Conclusion. Etiology of IS among Serbian young adults shares characteristics of those in both western and less developed countries.


2021 ◽  
Vol 15 (2) ◽  
pp. 216-222
Author(s):  
Wafik Mahmoud El-Sheik ◽  
Aktham Ismail El-Emam ◽  
Ahmed Abd El-Galil Abd El-Rahman ◽  
Gelan Mahmoud Salim

ABSTRACT. Various mechanisms contribute to dementia after first ischemic stroke as lesions on strategic areas of cognition and stroke premorbidity. Objectives: Assessing clinical and neuroimaging predictors of dementia after first ischemic stroke and its relation to stroke location, subtypes and severity. Methods: Eighty first ischemic stroke patients were included. Forty patients with dementia after first stroke and forty patients without dementia according to DSM-IV diagnostic criteria of vascular dementia. All patients were subjected to general and neurological assessment, National Institute Health Stroke Scale (NIHSS) for stroke severity, Montreal Cognitive Assessment (MoCA) scale for cognition assessment, MRI brain and Trial of Org 10172 in acute stroke treatment (TOAST) classification for stroke subtypes. Results: Left hemispheric ischemic stroke, strategic infarctions, diabetes mellitus and stroke of anterior circulation were found to be independent risk factors for dementia after first ischemic stroke (OR=3.09, 95%CI 1.67-10.3, OR=2.33, 95%CI 1.87-8.77, OR=1.88, 95%CI 1.44-4.55, OR=1.86, 95%CI 1.45-6.54, respectively). Hypertension, dyslipidemia, smoking, ischemic heart disease, high NIHSS score and large vessel infarction were significantly higher among post stroke dementia patients. However, on binary logistic regression, they did not reach to be independent risk factors. Conclusion: Stroke location (left stroke, strategic infarction, anterior circulation stroke) and diabetes mellitus could be predictors of dementia after first ischemic stroke, but stroke severity, stroke subtypes, hypertension, dyslipidemia, smoking and ischemic heart could not.


Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Chrysi Bogiatzi ◽  
Daniel G Hackam ◽  
Ian A McLeod ◽  
David J Spence

Introduction: In Canada, major stroke hospital admission decreased by 27.6% and stroke mortality decreased by 28.2% between 1994 and 2004. However, there are no regional data on rates of incident minor stroke/TIA. We hypothesized that there has been a decrease in minor stroke/TIA over time due to better management of cerebrovascular risk factors. Methods: We included patients who diagnosed with a minor stroke/TIA in the regional Urgent TIA Clinic in London, Ontario, Canada from 2002 to 2012. We used a valid and reliable classification system for subtypes of ischemic stroke (SPARKLE) to categorize patients into five etiological stroke subtypes. Secular trends of minor stroke/TIA and the five ischemic stroke subtypes, represented with Lattice Plots, were analyzed using Poisson regression analysis with spline trend function. Results: Between 2002 and 2012, we identified 3,445 eligible patients. There was no decrease in minor stroke/TIA during the study period (348 patients in 2002 versus 261 patients in 2012, p=0.65 for trend). However, there was a significant increase in cardioembolic stroke/TIA, with a corresponding decrease in all other ischemic stroke subtypes. Patients in 2012 were one year younger compared to patients in 2002 (p=0.04). Discussion: Stroke mortality and major stroke incidence have decreased over time, but numbers of patients who experience a first-ever minor stroke/TIA have remained constant. With more intensive medical therapy there may have been a shift from major to minor stroke occurrence, given that more recent patients are younger than patients presenting in previous years. Further investigation is required to identify prevailing stroke risk factors in this population to decrease the burden and incidence of stroke/TIA.


2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Salim Harris ◽  
Saleha Sungkar ◽  
Al Rasyid ◽  
Mohammad Kurniawan ◽  
Taufik Mesiano ◽  
...  

Background and Purpose. Stroke is a leading cause of death and disability, with ischemic stroke as the highest prevalent cases in Indonesia. Ischemic stroke can be classified further into five subtypes according to TOAST classification. Numerous studies have revealed that stroke risk factor has variable correlation with different stroke subtype. Currently, there is no data regarding this phenomenon in Indonesia. The aim of study is to identify characteristic of ischemic stroke subtypes and the risk factors in TOAST classification. Methods. A retrospective, cross-sectional study of patients diagnosed with ischemic stroke at Cipto Mangunkusumo Hospital from January till December 2016. Demographic data, ischemic stroke subtypes, risk factors, and other relevant data were documented. Bivariate and multivariate analysis was done using SPSS 23. Results. 235 recorded data patients were included. Large artery atherosclerosis (LAA) was the most prevalent stroke subtypes at 59,6%, followed with small vessel disease (SVD) at 26,7%, undetermined etiology at 9,8%, cardioembolism (CE) at 2,1%, and other determined etiology at 0,9%. Hypertension was the most common vascular risk factor. However, it was only significant in SVD (p=0,023) and undetermined etiology subtypes (p<0,001). Significant risk factor in LAA was diabetes (55%; p=0,016) while in CE subtypes was atrial fibrillation (60%;p<0,001). In multivariate analyses, hypertension (OR 3; 95% CI 1,12-8,05) was the only variable that was related to SVD while in CE it was atrial fibrillation (OR 113,5; 95% CI 13,6-946,5). Conclusion. LAA was the most common stroke ischemic subtypes. Associated risk factor in LAA was diabetes while in SVD and undetermined etiology subtypes it was hypertension. Atrial fibrillation was associated with cardioembolism.


Hypertension ◽  
2021 ◽  
Vol 77 (4) ◽  
pp. 1391-1398
Author(s):  
Clinton B. Wright ◽  
Alexander P. Auchus ◽  
Alan Lerner ◽  
Walter T. Ambrosius ◽  
Hakan Ay ◽  
...  

In the SPRINT (Systolic Blood Pressure Intervention Trial), the number of strokes did not differ significantly by treatment group. However, stroke subtypes have heterogeneous causes that could respond differently to intensive blood pressure control. SPRINT participants (N=9361) were randomized to target systolic blood pressures of <120 mm Hg (intensive treatment) compared with <140 mm Hg (standard treatment). We compared incident hemorrhage, cardiac embolism, large- and small-vessel infarctions across treatment arms. Participants randomized to the intensive arm had mean systolic blood pressures of 121.4 mm Hg in the intensive arm (N=4678) and 136.2 mm Hg in the standard arm (N=4683) at one year. Sixty-nine strokes occurred in the intensive arm and 78 in the standard arm when SPRINT was stopped. The breakdown of stroke subtypes across treatment arms included hemorrhagic (intensive treatment, n=6, standard treatment, n=7) and ischemic stroke subtypes (large artery atherosclerosis: intensive treatment n=11, standard treatment, n=13; cardiac embolism: intensive treatment n=11, standard treatment n=15; small artery occlusion: intensive treatment n=8, standard treatment n=8; other ischemic stroke: intensive treatment n=3, standard treatment n=1). Fewer strokes occurred among participants without prior cardiovascular disease in the intensive (n=43) than the standard arm (n=61), but the difference did not reach predefined statistical significance level of 0.05 ( P =0.09). The interaction between baseline cardiovascular risk factor status and treatment arm on stroke risk did not reach significance ( P =0.05). Similar numbers of stroke subtypes occurred in the intensive BP control and standard control arms of SPRINT.


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