Abstract TP216: Identifying Common Genetic Variants Associated With Fatal Stroke in Incident Ischemic Stroke Patients

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Vida Abedi ◽  
Jiang Li ◽  
Ayesha Khan ◽  
Aniket Mishra ◽  
Stéphanie Debette ◽  
...  

Introduction: There is an unmet need to understand the genetic factors associated with stroke outcome. The purpose of this study is to identify the common genetic variants, if any, associated with incident of ischemic stroke in a community-based population and to determine if any genetic risk can be enriched in fatal stroke patients. Methods: Cases and controls of ischemic stroke were identified by leveraging the comprehensive Electronic Health Record, and endophenotypes, e.g. the fatal or nonfatal stroke was defined by those dying within one month (fatal incidence) or surviving to 12 months (nonfatal incidence) of their first-ever stroke incident. The GWAS was carried out in a nested case-control design by considering all patients with age >79 and without any stroke-related diagnostic codes as low-risk control. A linear mixed regression model (SAIGE) with saddlepoint approximation, adjusted for covariates was conducted to account for the relatedness and case-control imbalance. Results: No genome-wide significant association was identified for ischemic stroke (n=1,179) versus control (n=7,489). When stratifying stroke patients by the fatality (n=61/1,118), rs80094021 (MAF = 0.038; OR=3.332±0.635; p=9.04E-11) and SNPs in LD with, located at an intronic region of TIAM1, were the top associated signal. All these SNPs served as eQTL for TIAM1(β=0.144, p=5.8E-13, eQTLGen). Rs79694970, the second top SNP (MAF = 0.020; OR=4.179±0.931; p=9.27E-09), is located near GPD1L and functions as eQTL for GPD1L(β=-0.279, p=6.1E-28). GPD1L plays a role in the DPD1L-dependent SCN5A phosphorylation pathway, thereby regulating cardiac sodium current. Dysfunction of sodium current can cause fatal ventricular arrhythmia. According to PheWAS data from UK Biobank, rs80094021 showed a moderate association with high cholesterol (p=0.0045), coronary atherosclerosis (p=0.0075), and angina (p=0.012), with the same direction for the minor allele which increased the risk for fatal stroke. rs79694970 were associated with ischemic stroke (large artery atherosclerosis) with p=0.0016. Conclusion: Through stratification of ischemic stroke by fatality some genetic risk factors and genes with biological relevant to the pathogenesis of stroke could be identified.

2005 ◽  
Vol 12 (8) ◽  
pp. 614-618 ◽  
Author(s):  
M. Linnebank ◽  
M. Montenarh ◽  
H. Kolsch ◽  
A. Linnebank ◽  
K. Schnez ◽  
...  

2017 ◽  
Vol 378 ◽  
pp. 146-151 ◽  
Author(s):  
Carmen Rosa Hernández-Socorro ◽  
Francisco Javier Rodríguez-Esparragón ◽  
Jennifer Celli ◽  
Juan Carlos López-Fernández

2021 ◽  
pp. neurintsurg-2021-017597
Author(s):  
Jeong-Min Kim ◽  
Jun-Soo Byun ◽  
Jiah Kim ◽  
Moo-Seok Park ◽  
Soon Auck Hong ◽  
...  

BackgroundWe investigated the microRNA expression pattern from thrombus retrieved by mechanical thrombectomy in acute stroke patients to understand the stroke mechanism.MethodsThis study included acute ischemic stroke patients who had undergone intra-arterial thrombectomy at Chung-Ang University Hospital in Seoul, Korea between February 2016 and March 2019. The thrombus was retrieved and stored at −70℃ after obtaining informed consent. MicroRNA microarray analysis was performed for the patients with identified stroke mechanisms including (1) large artery atherosclerosis, (2) cardioembolism with atrial fibrillation, and (3) cardioembolism with valvular heart disease. The microRNAs derived from microarray analysis were validated by quantitative real-time polymerase chain reaction (qRT-PCR) from different patient populations. The correlation analysis was performed between microRNA levels and laboratory data to understand the functional relevance of the altered microRNA.ResultsIn total, 55 thrombi were obtained from 74 patients, and the microRNAs were analyzed in 45 samples. Microarray analysis of 2578 microRNAs revealed that 50 microRNAs were significantly altered among the three groups. Validation using qRT-PCR showed that miR-378f and miR-450b-5p were significantly elevated among the cardioembolic thrombi; both microRNAs were inversely correlated with the ejection fraction from echocardiography. Thrombi from patients with early neurological deterioration exhibited higher levels of miR-93-5p and lower levels of miR-629-5p than those from neurologically stable patients.ConclusionsThe microRNA expression pattern can provide information regarding the mechanism of stroke by reflecting the underlying pathological status of the organ from which the thrombus was derived.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Ting Ye ◽  
Yi Dong ◽  
Shengyan Huang

Background: The dysphagia screening in acute ischemic stroke plays an important role in patients with risk of dysphagia. The aim of this hospital-based case-control study is to explore if V-VST, as a new nurse-driven dysphagia screening tool for AIS patients, might help to reduce the rate of post-stroke pneumonia and early withdraw of feeding tube. Methods: 1598 acute ischemic stroke patients were enrolled in this study. The standard protocol in AIS patients were assessed by WST (before intervention and plus with V-VST after intervention). The V-VST assessment were be trained in two senior nurses and all AIS patients were assessed by V-VST during July 1and Dec 30 th , 2017. Among 299 AIS patients with suspected, all clinical data were analyzed. The comparison of their rate of pneumonia in hospital and withdraw rate of tubefeeding before discharge were performed between patients post-intervention (January 1, 2018-June 30, 2019)and those admitted before the intervention (January 1, 2016-June 30, 2017). Results: The baseline characteristics of the pre- and post- intervention AIS groups were similar in age, gender, NIHSS. The implementation of V-VST have a statistically significant reducing the risk of pneumonia with an adjusted HR (0.60, 95% CI 0.43-0.84, P=0.003). Additionally, follow-up V-VST were likely to be associated the withdraw rate of tube-feeding at discharge (29/168 vs 38/131 P=0.016).There is also a trend of length of tube-feeding decreasing (8.32±12.27 vs 6.84±8.61 P=0.241). Conclusion: In our study, the V-VST is a feasible bedside tool. The implemental might be associated with the reduction of post-stroke pneumonia. Therefore, it meets the requirements of a clinical screening test for dysphagia in acute stroke patients at bedside. Large prospective interventional study is needed to confirm our findings. V-VST: Volume-viscosity Swallow Test WST: Water Swallow Test AIS: Acute Ischemic Stroke HR: hazard ratio


Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Yasuhisa Akaiwa ◽  
Hiroki Takano ◽  
Hiroyuki Arakawa ◽  
Itaru Ninomiya ◽  
Masahiro Uemura ◽  
...  

Background: : Intake of omega-3 polyunsaturated fatty acids, such as EPA, has been reported to have protective effects on various diseases including ischemic stroke. However, there have been few studies concerning the effect of omega-3 polyunsaturated fatty acids on hemorrhagic stroke. We studied associations of serum levels of EPA with stroke subtypes including primary ICH Methods: We have examined serum EPA and arachidonic acid (AA) levels in routine practice since 2009. To calibrate the EPA values, we calculated EPA/AA ratio. A total of 212 consecutive acute stroke patients and 27 control subjects were included. The patients 40 years old or younger were excluded. Ischemic stroke subtypes were determined based on TOAST criteria. Primary ICH was classified into lobar or nonlobar types, according to the region of the brain in which it occurred. Results: Of all the 157 ischemic stroke patients (female 47, mean age 72.9 years), 62 were classified with cardioembolic stroke (CES), 25 large-artery atherosclerotic (LAA), 22 small-vessel disease (SVD), and 48 other/undetermined causes (O/U). Of all the 55 ICH patients (female 23, mean age 71.0), 34 patients had nonlobar type, and 21 had lobar one. There were no significant intergroup differences in the mean EPA/AA ratio (p=0.525) among CES (EPA/AA= 0.67±0.42), LAA (0.70±0.30), SVD (0.65±0.45), O/U (0.62±0.38), nonlobar ICH (0.51±0.30), lobar ICH (0.64±0.33), and control (0.60±0.42) groups. However, the EPA/AA ratio of the nonlobar ICH group was considerably low. The EPA/AA ratio of the nonlobar ICH group was significantly (p=0.033) lower than that of the whole other groups (0.65±0.39) and significantly (p=0.003) lower than that of the entire ischemic stroke groups (0.67±0.40). Although the significant differences between the nonlobar ICH and the whole ischemic groups were also observed in systolic and diastolic blood pressure (195±37/107±25 mmHg vs 159±35/82±19 mmHg, p<0.001), multiple linear regression analyses showed the association between the EPA/AA and nonlobar ICH was independent from the blood pressure. Conclusions: Although the strongest risk factor for nonlobar ICH is hypertension, low EPA/AA ratio might play a role in the development of nonlobar ICH.


2019 ◽  
Vol 16 (1) ◽  
pp. 29-34
Author(s):  
Reema Rajbhandari ◽  
Parmatma Prajuli ◽  
K K Oli

The aim of this study is to show the subtype, risk factors and predictors of poor outcomes in young ischemic stroke patients. Materials and Methods: It is a prospective study where only young onset ischemic stroke patients are analyzed. 8% of total ischemic stroke sufferers were young adults; more prevalent in female (57.1%), with risk factors of smoking (47.6%) subtype cardio embolic (42.9%) was common. High NIHSS score was related to new event and correlation to mortality. Three month follow up showed MRS 2.86 ± 1.02. 57.1% of cases had significant disability (defined as MRS ≥ 3). There was a positive correlation of the cardio embolic subtype and the unclassified subtype to all three forms of poor outcomes, along with a positive correlation of the large artery atherothrombotic subtype to new events Recurrence of events (new stroke, sudden increase in symptoms and new TIAs) was observed in 14.3 %. Death was reported in 9.5% of cases.   Etiological diagnosis can be reached in majority of cases if an aggressive approach is maintained. This small scale study has provided an overview of the distribution of subtypes, risk factors and poor outcomes and their predictors. Cardiac diseases (esp. valvular disease) need to be taken more seriously to prevent cardio embolic strokes, while addressing other traditional risk factors to prevent the atherothrombotic subtypes.


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