Abstract P656: Cardioembolic Risk Factors and Ischemic Stroke a Mendelian Randomization Analysis

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Danyang Tian ◽  
Linjing Zhang ◽  
Zhenhuang Zhuang ◽  
Tao Huang ◽  
Dongsheng Fan

Background: Cardioembolic stroke accounts for a large proportion of ischemic stroke. Observational studies have shown that several risk factors are associated with cardioembolic stroke. However, whether such associations reflect causality remains unknown. Objectives: We aimed to determine whether established and provisional cardioembolic risk factors are causally associated cardioembolic stroke, and whether they have pathways of causal influence on other ischemic stroke subtypes. Methods: Genetic instruments for atrial fibrillation (AF), myocardial infarction (MI), some electrocardiogram (ECG) indices and NT-pro BNP were obtained from large genetic consortiums. Summarized data of ischemic stroke and its subtypes were extracted from the MEGASTROKE consortium. Causal estimates were calculated by applying inverse variance-weighted analysis and other methods. Results: Genetically predicted AF was significantly associated with higher odds of ischemic stroke (OR 1.20, 95% CI 1.16-1.24, P=6.53х10 -30 ) and cardioembolic stroke (OR 1.95, 95% CI 1.85-2.06, P=8.81х10 -125 ). Genetically predicted MI was significantly associated with higher odds of large artery stroke (OR 1.487, 95% CI 1.25-1.77, P=9.53х10 -6 ). Suggestive associations were found between genetically determined resting heart rate and higher odds of ischemic stroke (OR 1.01, 95% CI 1.00-1.02, P=0.005), large artery stroke (OR 1.02, 95% CI 1.00-1.04, P=0.026) and cardioembolic stroke (OR 1.02, 95% CI 1.00-1.04, P=0.028). There was no causal association of P-wave terminal force in the precordial lead V1 (PTFVI), P-wave duration (PWD), N-terminal-pro-brain Natriuretic Peptide (NT-pro BNP) or PR interval with ischemic stroke or any subtypes. Conclusion: Genetic predisposition to AF and heart rate are associated with cardioembolic stroke. No evidence of causality relationship of MI, PTFVI, PWD, NT-pro BNP and PR interval on cardioembolic stroke is found.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Danyang Tian ◽  
Linjing Zhang ◽  
Zhenhuang Zhuang ◽  
Tao Huang ◽  
Dongsheng Fan

AbstractObservational studies have shown that several risk factors are associated with cardioembolic stroke. However, whether such associations reflect causality remains unknown. We aimed to determine whether established and provisional cardioembolic risk factors are causally associated with cardioembolic stroke. Genetic instruments for atrial fibrillation (AF), myocardial infarction (MI), electrocardiogram (ECG) indices and N-terminal pro-brain natriuretic peptide (NT-pro BNP) were obtained from large genetic consortiums. Summarized data of ischemic stroke and its subtypes were extracted from the MEGASTROKE consortium. Causal estimates were calculated by applying inverse-variance weighted analysis, weighted median analysis, simple median analysis and Mendelian randomization (MR)-Egger regression. Genetically predicted AF was significantly associated with higher odds of ischemic stroke (odds ratio (OR): 1.20, 95% confidence intervals (CI): 1.16–1.24, P = 6.53 × 10–30) and cardioembolic stroke (OR: 1.95, 95% CI: 1.85–2.06, P = 8.81 × 10–125). Suggestive associations were found between genetically determined resting heart rate and higher odds of ischemic stroke (OR: 1.01, 95% CI: 1.00–1.02, P = 0.005), large-artery atherosclerotic stroke (OR: 1.02, 95% CI: 1.00–1.04, P = 0.026) and cardioembolic stroke (OR: 1.02, 95% CI: 1.00–1.04, P = 0.028). There was no causal association of P‐wave terminal force in the precordial lead V1 (PTFVI), P-wave duration (PWD), NT-pro BNP or PR interval with ischemic stroke or any subtype.


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.


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 9 (1) ◽  
Author(s):  
Fan Yu ◽  
Xiaolu Liu ◽  
Qiong Yang ◽  
Yu Fu ◽  
Dongsheng Fan

Abstract Acute ischemic stroke (AIS) has a high risk of recurrence, particularly in the early stage. The purpose of this study was to assess the frequency and risk factors of in-hospital recurrence in patients with AIS in China. A retrospective analysis was performed of all of the patients with new-onset AIS who were hospitalized in the past three years. Recurrence was defined as a new stroke event, with an interval between the primary and recurrent events greater than 24 hours; other potential causes of neurological deterioration were excluded. The risk factors for recurrence were analyzed using univariate and logistic regression analyses. A total of 1,021 patients were included in this study with a median length of stay of 14 days (interquartile range,11–18). In-hospital recurrence occurred in 58 cases (5.68%), primarily during the first five days of hospitalization. In-hospital recurrence significantly prolonged the hospital stay (P < 0.001), and the in-hospital mortality was also significantly increased (P = 0.006). The independent risk factors for in-hospital recurrence included large artery atherosclerosis, urinary or respiratory infection and abnormal blood glucose, whereas recurrence was less likely to occur in the patients with aphasia. Our study showed that the patients with AIS had a high rate of in-hospital recurrence, and the recurrence mainly occurred in the first five days of the hospital stay. In-hospital recurrence resulted in a prolonged hospital stay and a higher in-hospital mortality rate.


2021 ◽  
pp. 174749302110059
Author(s):  
Yiu Ming Bonaventure Ip ◽  
Lisa Au ◽  
Yin Yan Anne Chan ◽  
Florence Fan ◽  
Hing Lung Ip ◽  
...  

Background: Depicting the time trends of ischemic stroke subtypes may inform healthcare resource allocation on etiology-based stroke prevention and treatment. Aim: To reveal the evolving ischemic stroke subtypes from 2004 to 2018. Methods: We determined the stroke etiology of consecutive first-ever transient ischemic attack or ischemic stroke patients admitted to a regional hospital in Hong Kong from 2004 to 2018. We analyzed the age-standardized incidences and the 2-year recurrence rate of major ischemic stroke subtypes. Results: Among 6940 patients admitted from 2004 to 2018, age-standardized incidence of ischemic stroke declined from 187.0 to 127.4 per 100,000 population (p<0.001), driven by the decrease in large artery disease (43.0 to 9.67 per 100,000 population (p<0.001)) and small vessel disease (71.9 to 45.7 per 100,000 population (p<0.001)). Age-standardized incidence of cardioembolic stroke did not change significantly (p=0.2). Proportion of cardioembolic stroke increased from 20.4% in 2004-2006 to 29.3% in 2016-2018 (p<0.001). 2-year recurrence rate of intracranial atherothrombotic stroke reduced from 19.3% to 5.1% (p<0.001) with increased prescriptions of statin (p<0.001) and dual anti-platelet therapy (<0.001). In parallel with increased anticoagulation use across the study period (p<0.001), the 2-year recurrence of AF-related stroke reduced from 18.9% to 6% (p<0.001). Conclusion: Etiology-based risk factor control might have led to the diminishing stroke incidences related to atherosclerosis. To tackle the surge of AF-related strokes, arrhythmia screening, anticoagulation usage and mechanical thrombectomy service should be reinforced. Comparable preventive strategies might alleviate the enormous stroke burden in mainland China.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Fred S Sarfo ◽  
Bruce Ovbiagele ◽  
Onoja M Akpa ◽  
Rufus Akinyemi ◽  
Albert Akpalu ◽  
...  

Background: The risk factors associated with the occurrence of the distinct pathophysiologic subtypes of ischemic stroke are unknown among indigenous Africans. Objective: To identify and quantify the contributions of risk factors for occurrence of ischemic stroke and its etiologic subtypes among West Africans. Methods: The Stroke Investigative Research and Educational Network (SIREN) is a multicenter, case-control study involving 15 sites in Nigeria and Ghana. Cases included adults aged >18 years with CT/MRI confirmed stroke and ischemic strokes were etiologically subtyped using the TOAST protocol. Controls were age-and-gender matched stroke-free adults recruited from the communities in catchment areas of cases. Comprehensive evaluation for vascular, lifestyle and psychosocial factors was performed using standard instruments. We used conditional logistic regression to estimate odds ratios (OR) with 95% CIs. Results: There were 1,721 ischemic stroke cases with a mean age of 62.19 ± 14.03 vs 60.86 ± 13.71 for controls. Using the TOAST etiologic scheme, 867 (50.3%) were small vessel occlusions, 425(24.7%) were large-artery atherosclerotic, 181(10.5%) were cardio-embolic, 204(11.9%) were undetermined and 44(2.6%) were of other determined etiology. The 7 dominant risk factors for ischemic strokes aOR (95%CI) were hypertension 10.76(7.15-16.20), dyslipidemia 5.30(3.86-7.29), diabetes 3.61(2.72-4.80), psychosocial stress 1.68(1.20-2.35), cardiac disease 1.94 (1.25-3.02), meat consumption 2.02(1.54-2.65), green vegetable consumption 0.44(0.33-0.59). Hypertension, dyslipidemia, diabetes, meat consumption and green vegetable intake were confluent factors shared by small-vessel, large-vessel and cardio-embolic ischemic stroke subtypes. Conclusion: We provide empiric evidence of risk factors to be targeted for stroke prevention. Our findings open a vista into future studies aimed at elucidating the genetic factors linked with pathophysiologic subtypes of stroke among Africans.


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.


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 ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
JUN LEE ◽  
Na-Young Kim

Background The relationship between stroke and non-atrial fibrillation cardiac arrhythmias remains unclear. Frequent premature ventricular contractions (PVCs) are associated with impaired ventricular relaxation and may increase the risk of clot formation and subsequent embolization. This study investigated the relationship between frequency of PVCs and etiologic subtypes of ischemic stroke. Methods Consecutive ischemic stroke patients admitted within 7 days of onset who underwent 24-hour Holter monitoring were enrolled (n=451). Subtypes of ischemic stroke were defined according to the SSS-TOAST classification as Large artery atherosclerosis (LAD), cardioembolic stroke (CE), small vessel occlusion (SVO), other causes (OC), and cryptogenic stroke (CS). Risk factors, demographic information, and 24-hour Holter recordings were compared between the subtypes of ischemic stroke. Results There were 182 women and 269 men (191 LAD, 90 CE, 93 SVO, 13 OC, 64 CS), with a mean age of 66 years (median 68). PVCs were seen in 305 patients (67.5%) on 24-hour Holter monitoring (median 3, IQR 0-48). CE had a higher median number of PVCs (median 24, IQR 0-258) than LAD (median 2, p=0.01), SVO (median 1, p<0.001), OC (median 0, p=0.013), and CS (median 4, p=0.2). The proportions of frequent PVCs (>50 in a 24-hour Holter monitoring) were higher in CE (43.3%) compared with the other groups (20.9% in LAD, 15.1% in SVO, 15.4% in OC, and 23.4% in CS; p<0.001). Compared with the SVO, the upper 3 quartiles of PVCs were associated with CE (OR 2.93; 95% CI, 1.69 to 5.06) and CS (OR 1.86; 95% CI, 1.07 to 3.2) in ordinal logistic regression analysis after adjustment for traditional risk factors. Conclusions The number of PVCs detected by 24-hour Holter monitoring is associated with CE and CS. The presence of high frequency of PVC may help in stratifying patients with different stroke subtypes, particularly embolic stroke. The role of these arrhythmias as a risk marker for ischemic stroke deserves further investigation.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Tyler P Behymer ◽  
Achala Vagal ◽  
Heidi Sucharew ◽  
Vineeth Yeluru ◽  
Arjun Minhas ◽  
...  

Introduction: Cryptogenic stroke is defined as not attributable to an identified source despite standard evaluation. The absence of small vessel or large artery disease in such evaluation suggests that cryptogenic stroke may be largely cardioembolic. We hypothesized that cryptogenic stroke would be similar to cardioembolic stroke in clinical and imaging characteristics. Methods: The Greater Cincinnati/Northern Kentucky Stroke Study (GCNKSS) is a population-based study that tracks the regional incidence of stroke. A convenient subsample from the 2010 GCNKSS ischemic stroke cohort (N= 368) was selected for detailed neuroimaging analysis. The study physician subtyped cases based on clinical, radiographic and laboratory findings (carotid ultrasound, echocardiography, vascular imaging). Subtypes included cryptogenic, cardioembolic, large-vessel, small-vessel, undetermined, and other. Three radiologists performed imaging analysis including number of acute infarcts, location and white matter hyperintensity (WMH). Infarct volume was segmented using manual tracing. Results: Of 368 ischemic stroke cases with imaging data, subtypes were 26.4% cryptogenic, 16.3% large vessel, 15.5% small vessel, 24.7% cardioembolic, 5.4% undetermined, and 11.7% other. Compared to cardioembolic, cryptogenic stroke patients were younger, had less hypertension, higher alcohol use, smaller infarct volume and differed in location of stroke. Cryptogenic stroke had more clinical and radiological features in common with large and small-vessel stroke (Table). Undetermined and other had no significant differences to cryptogenic. Conclusion: Contrary to our hypothesis, cryptogenic stroke was different from cardioembolic stroke and appeared more similar to large vessel stroke in clinical and radiological characteristics. Further testing on a larger sample size to evaluate the impact of cardiac event monitoring on subtype distribution is needed.


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