Factor For Ischemic Stroke Research Articles

Ischaemic stroke patients present sex differences in gut microbiota.

Gut microbiota plays a role in the pathophysiology of ischaemic stroke (IS) through the bidirectional gut-brain axis. Nevertheless, little is known about sex-specific microbiota signatures in IS occurrence. A total of 89 IS patients and 12 healthy controls were enrolled. We studied the taxonomic differences of the gut microbiota between men and women with IS by shotgun metagenomic sequencing. To evaluate the causal effect of several bacteria on IS risk, we performed a two-sample Mendelian randomisation (MR) with inverse-variance weighting (IVW) using genome-wide association analysis (GWAS) summary statistics from two cohorts of 5959 subjects with genetic and microbiota data and 1,296,908 subjects with genetic and IS data, respectively. α-Diversity analysis measured using Observed Species (p = 0.017), Chao1 (p = 0.009) and Abundance-based Coverage Estimator (p = 0.012) indexes revealed that IS men have a higher species richness compared with IS women. Moreover, we found sex-differences in IS patients in relation to the phylum Fusobacteria, class Fusobacteriia, order Fusobacteriales and family Fusobacteriaceae (all Bonferroni-corrected p < 0.001). MR confirmed that increased Fusobacteriaceae levels in the gut are causally associated with an increased risk of IS (IVW p = 0.02, β = 0.32). Our study is the first to indicate that there are gut microbiome differences between men and women with IS, identifying high levels of Fusobacteriaceae in women as a specific risk factor for IS. Incorporating sex stratification analysis is important in the design, analysis and interpretation of studies on stroke and the gut microbiota.

The Association Between Thymidylate Synthase Gene Polymorphisms and the Risk of Ischemic Stroke in Chinese Han Population

Family history of hypertension, smoking, diabetes and alcohol consumption and atherosclerotic plaque were identified as common risk factors in IS. We aimed at investigating the relationship between Thymidylate Synthase (TS) gene polymorphisms and ischemic stroke (IS).This case–control research selected and genotyped three single nucleotide polymorphisms (SNPs)of TS( rs699517, rs2790, and rs151264360) with Sanger sequencing in Chinese Han population. We also adopted logistic regression analysis in genetic models for calculating odds ratios and 95% confidence intervals. Genotype-Tissue Expression(GTEx) database analyzed the tissue-specific expression and TS polymorphisms. The ischemic stroke patients showed higher low-density lipoprotein cholesterol and total homocysteine (tHcy). It was found that patients with the TT genotype of rs699517 and GG genotype of rs2790 had larger degrees of tHcy than those with CC + CT genotypes and AA + AG genotypes, respectively. The genotype distribution of the three SNPs did not deviate from Hardy–Weinberg equilibrium (HWE). Haplotype analysis showed that T-G-del was the major haplotype in IS, and C-A-ins was the major haplotype in controls. GTEx database indicated that the rs699517 and rs2790 increased the expression of TS in healthy human and associated with TS expression level in a single tissue. In conclusion: This study has shown that TS rs699517 and rs2790 were significantly related to ischemic stroke patients.

Unravelling the genetic causality of immunoglobulin G N-glycans in ischemic stroke.

Evidence suggests that immunoglobulin G (IgG) N-glycosylation is associated with ischemic stroke (IS). However, the causality of IgG N-glycosylation for IS remains unknown. Two-sample Mendelian randomization (MR) analyses were performed to investigate the potential causal effects of genetically determined IgG N-glycans on IS using publicly available summarized genetic data from East Asian and European populations. Genetic instruments were used as proxies for IgG N-glycan traits. IgG N-glycans were analysed using ultra-performance liquid chromatography. Four complementary MR methods were performed, including the inverse variance weighted method (IVW), MR‒Egger, weighted median and penalized weighted median. Furthermore, to further test the robustness of the results, MR based on Bayesian model averaging (MR-BMA) was then applied to select and prioritize IgG N-glycan traits as risk factors for IS. After correcting for multiple testing, in two-sample MR analyses, genetically predicted IgG N-glycans were unrelated to IS in both East Asian and European populations, and the results remained consistent and robust in the sensitivity analysis. Moreover, MR-BMA also showed consistent results in both East Asian and European populations. Contrary to observational studies, the study did not provide enough genetic evidence to support the causal associations of genetically predicted IgG N-glycan traits and IS, suggesting that N-glycosylation of IgG might not directly involve in the pathogenesis of IS.

Observational Study of Patients Hospitalized With Neurologic Events After SARS-CoV-2 Vaccination, December 2020-June 2021.

The global spread of the COVID-19 pandemic accelerated the vaccine development time line, regulatory approval, and widespread implementation in the population underscoring the importance of postauthorization/postlicensure vaccine safety surveillance. To monitor for vaccine-related adverse events, we prospectively identified patients hospitalized for prespecified neurologic conditions who received mRNA or adenovirus COVID-19 vaccines and assessed cases for potential risk factors and alternative etiologies of the adverse event. We identified prespecified neurologic conditions in hospitalized individuals within 6 weeks of receipt of a dose of any COVID-19 vaccination between December 11, 2020, and June 22, 2021 (Columbia University Irving Medical Center/New York Presbyterian Hospital, New York City, New York). Clinical data from electronic medical records in these vaccinated patients were reviewed for assessment of contributing risk factors and etiologies for these neurologic conditions by use of a published algorithm. Among 3,830 individuals screened for COVID-19 vaccination status and neurologic conditions, 138 (3.6%) cases were included in this study (126 after mRNA and 6 after Janssen vaccines). The 4 most prevalent neurologic syndromes included ischemic stroke (52, 37.7%), encephalopathy (45, 32.6%), seizure (22, 15.9%), and intracranial hemorrhage (ICH) (13, 9.4%). All 138 cases (100%) had 1 or more risk factors and/or evidence for established causes. Metabolic derangement was the most common etiology for seizures (24, 53.3%) and encephalopathy (5, 22.7%) while hypertension was the most significant risk factor in ischemic stroke (45, 86.5%) and ICH cases (4, 30.8%). All cases in this study were determined to have at least 1 risk factor and/or known etiology accounting for their neurologic syndromes. Our comprehensive clinical review of these cases supports the safety of mRNA COVID-19 vaccines.

Global Burden, Risk Factor Analysis, and Prediction Study of Ischemic Stroke, 1990-2030.

Ischemic stroke (IS), 1 of the 2 main subtypes of stroke, occurs because of brain ischemia caused by thrombosis of a cerebral blood vessel. IS is one of the most important neurovascular causes of death and disability. It is affected by many risk factors, such as smoking and a high body mass index (BMI), which are also critical in the preventive control of other cardiovascular and cerebrovascular diseases. However, there are still few systematic analyses of the current and predicted disease burden and the attributable risk factors of IS. Based on the Global Burden of Disease 2019 database, we used age-standardized mortality rate and disability-adjusted life year to systematically present the geographical distribution and trends of IS disease burden worldwide from 1990 to 2019 by calculating the estimated annual percentage change and to analyze and predict the death number of IS accounted by 7 major risk factors for 2020-2030. Between 1990 and 2019, the global number of IS deaths increased from 2.04 million to 3.29 million and is expected to increase further to 4.90 million by 2030. The downward trend was more pronounced in women, young people, and high sociodemographic index (SDI) regions. At the same time, a study of attributable risk factors of IS found that 2 behavioral factors, smoking and diet in high sodium, and 5 metabolic factors, including high systolic blood pressure, high low-density lipoprotein cholesterol, kidney dysfunction, high fasting plasma glucose, and a high BMI, are major contributors to the increased disease burden of IS now and in the future. Our study provides the first comprehensive summary for the past 30 years and the prediction of the global burden of IS and its attributable risk factors until 2030, providing detailed statistics for decision-making on the prevention and control of IS globally. An inadequate control of the 7 risk factors would lead to an increased disease burden of IS in young people, especially in low SDI regions. Our study identifies high-risk populations and helps public health professionals develop targeted preventive strategies to reduce the global disease burden of IS.

Analysis of the association of CYP450 gene polymorphisms with ischemic stroke

To assess the association of cytochrome P450 (CYP450) gene polymorphisms with the occurrence of ischemic stroke (IS). From January 2020 to August 2022, 390 IS patients treated at the Zhengzhou Seventh People's Hospital were enrolled as the study group, and 410 healthy individuals undergoing physical examination during the same period were enrolled as the control group. Clinical data of all subjects were collected, which included age, sex, body mass index (BMI), smoking history and results of laboratory tests. Chi-square test and independent sample t test were used for comparing the clinical data. Multivariate logistic regression analysis was used to analyze the non-hereditary independent risk factors for IS. Fasting blood samples of the subjects were collected, and the genotypes of rs4244285, rs4986893, rs12248560 of the CYP2C19 gene and rs776746 of the CYP3A5 gene were determined by Sanger sequencing. The frequency of each genotype was calculated by using SNPStats online software. The association between the genotype and IS under the dominant, recessive and additive models was analyzed. The levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL-C), apolipoprotein B (Apo-B) and homocysteine (Hcy) of the case group were significantly higher than those of the control group, whilst the levels of high density lipoprotein (HDL-C) and Apo-A1 (APO-A1) were significantly lower (P < 0.05). Multivariate Logistic regression analysis showed that TC (95%CI = 1.13-1.92, P = 0.02), LD-C (95%CI = 1.03-2.25, P = 0.03), Apo-A1 (95%CI = 1.05-2.08, P = 0.04), Apo-B (95%CI = 1.7-4.22, P < 0.01) and Hcy (95%CI = 1.12-1.83, P = 0.04) were non-genetic independent risk factors for the occurrence of IS. Analysis of the association between the genetic polymorphisms and the risk of IS showed that the AA genotype at rs4244285 of the CYP2C19 gene, the AG genotype and A allele at rs4986893 of the CYP2C19 gene, and the GG genotype and G allele at rs776746 of the CYP3A5 gene were significantly associated with IS. Under the recessive/additive model, dominant model and dominant/additive model, polymorphisms of the rs4244285, rs4986893 and rs776746 loci were also significantly associated with the IS. TC, LDL-C, Apo-A1, Apo-B and Hcy can all affect the occurrence of IS, and CYP2C19 and CYP3A5 gene polymorphisms are closely associated with the IS. Above finding has confirmed that the CYP450 gene polymorphisms can increase the risk of IS, which may provide a reference for the clinical diagnosis.

Polymorphism in genes encoding two fatty acid binding proteins increases risk of ischemic stroke in a Chinese Han population.

Background: Dyslipidemia is an independent predictor of ischemic stroke (IS). Genetic variations in lipid-metabolism related genes may increase the risk of IS. Fatty acid-binding protein 1 (FABP1) and fatty acid-binding protein 2 (FABP2) are lipid chaperones responsible for lipid transport and metabolism. The present study aimed to determine the association between FABP1 or FABP2 and ischemic stroke. Methods: A total of 251 participants were recruited composed of 138 patients with ischemic stroke and 113 healthy subjects. DNA was extracted from peripheral blood samples. The rs2241883 polymorphism in FABP1 and rs1799883 polymorphism in FABP2 were genotyped using polymerase chain reaction-restriction fragment length polymorphism. Generalized multifactor dimensionality reduction (GMDR) was used to find out the interaction combinations between two SNPs and environmental factors. Results: The GA genotype of FABP2 rs1799883 increased susceptibility to ischemic stroke under overdominant inheritance model (p = 0.042). After adjusting for the risk factors of IS, it was associated with a significantly higher risk of IS in the codominant inheritance model (adjust OR = 3.431, 95%CI = 1.060-11.103, p = 0.04). The interactions of FABP1 rs2241883 and FABP2 rs1799883 were not associated with IS risk (p = 0.172). Moreover, interaction analysis of two genes (rs1799883 and rs2241883) and two environmental factors (smoking and alcohol consumption) was associated with an increased risk of IS (p = 0.011). Conclusion: The GA genotype of FABP2 rs1799883, interactions between rs1799883, rs2241883 and smoking and alcohol consumption were associated with IS risk in Chinese Han populations.

Polymorphisms of the Matrix Metalloproteinase Genes are Associated with Acute Ischemic Stroke in Chinese Han Population.

Studies have shown that matrix metalloproteinase (MMP-2,3,9) plays an important role in the pathologic process of ischemic stroke (IS). The aim of this study was to investigate the relationship between C1306T, 1612-5A/6A, C-1562T polymorphisms of MMP-2,3,9 genes and IS in Chinese Han population. The polymorphisms of MMP-2(C1306T), -3(1612-5A/6A), -9(C-1562T) gene were detected by PCR-RFLP and SNaPshot sequencing. Then, stratified analysis was used to study the relationship between IS subtypes and MMP-2,3,9 polymorphisms. For the MMP-2 gene C1306T polymorphism, TT genotype and T allele were significantly associated with a reduced risk of IS (P = 0.015, P = 0.003, respectively). T allele was significantly associated with a reduced risk of small artery occlusion (SAO) subtype compared with the control group (P = 0.012, OR = 0.550, 95% CI = 0.065-1.291). For the MMP-3 gene-1612 (5A/6A) polymorphism, 5A/5A genotype was significantly increased in the IS group (P = 0.011, OR = 0.370, 95% CI = 0.168-0.814), especially in the large-artery atherosclerosis (LAA) subtype (P = 0.001, OR = 2.345) as compared to the control group. Our study suggested that the T allele of MMP-2 may be a protective factor of IS, especially in SAO subtype, while the 5A/5A gene of MMP-3 may increase the risk of IS, especially in LAA subtype in Chinese Han population.

CYP1B1 Genetic Variants (rs10916 and rs2855658) Are Associated with Increased Risk of Ischemic Stroke in Chinese Han Population

Introduction: Ischemic stroke (IS) is an extremely complex disease caused by the combined action of multiple environmental and genetic factors. CYP1B1 is a member of the cytochrome P450 protein family, and it is an important human drug-metabolizing enzymes. We aimed to explore the association between CYP1B1 genetic variants and IS risk in Chinese Han population. Methods: We recruited 1,150 participants to conduct a “case-control” study. The assessment of association between candidate CYP1B1 genetic variants (rs2855658, rs10916, rs162560, rs2567206) and IS risk was performed by SNPStats online software. In addition, false-positive report probability analysis was used to detect whether the positive findings were just chance or noteworthy observations. Finally, the interaction of candidate SNPs in IS risk was evaluated by multifactor dimensionality reduction. Results: The results showed that CYP1B1-rs2855658 was a risk factor for IS among ≥60-year-old (dominant: p = 0.034; overdominant: p = 0.026), smoking (heterozygote: p = 0.009; dominant: p = 0.004; overdominant: p = 0.012; log-additive: p = 0.003), and drinking participants (homozygous: p = 0.036; dominant: p = 0.019; recessive: p = 0.012; log-additive: p = 0.006). CYP1B1-rs10916 also was a risk factor for IS patients among ≥60-year-old (heterozygote: p = 0.047; overdominant: p = 0.048), smoking (dominant: p = 0.050; overdominant: p = 0.049), and drinking participants (dominant: p = 0.019; overdominant: p = 0.038; log-additive: p = 0.013). Conclusion: CYP1B1-rs10916 and CYP1B1-rs2855658 can increase the IS risk in Chinese Han population who are ≥60 years old, smoking, or drinking alcohol.

Association of methylenetetrahydrofolate reductase (MTHFR) rs1801133 (677C>T) gene polymorphism with ischemic stroke risk in different populations: An updated meta-analysis.

Background: Recently, increasing evidence has implicated methylenetetrahydrofolate reductase (MTHFR) gene mutation as a risk factor for ischemic stroke (IS) in the general population. However, studies have been inconclusive and lack evidence on specific populations. We aim to determine whether the rs1801133 (NC_000001.11 (MTHFR):g. 677C>T (p.Ala222Val) variant, we termed as MTHFR rs1801133 (677C>T), is linked to an increased risk of IS in different age groups and ancestry groups. Methods: The literature relevant to our study was found by searching the PubMed, Cochrane Library, Web of Science, EMBASE, and CNKI databases. A random effect model analysis was used to calculate the pooled odds ratio (OR) and 95% confidence interval (CI) to evaluate any possible association. We conducted a subgroup analysis based on the age and ancestry groups of the included populations. Results: As of March 2022, 1,925 citations had been identified in electronic databases, of which 96 studies involving 34,814 subjects met our eligibility criteria. A strong link was found between IS and the MTHFR gene rs1801133 (677C>T) polymorphism in all genetic models [dominant genetic model (OR = 1.47; 95%CI = 1.33-1.61; p < 0.001), recessive genetic model (OR = 1.52; 95%CI = 1.36-1.71; p < 0.001), heterozygous model (OR = 1.36; 95%CI = 1.24-1.48; p < 0.001), homozygous model (OR = 1.82; 95%CI = 1.58-2.11; p < 0.001), and T allelic genetic model (OR = 1.37; 95%CI = 1.27-1.48; p < 0.001)]. Further subgroup analyses indicated that the MTHFR rs1801133 (677C>T) variant may increase the risk of IS in Asian, Hispanic, or Latin population, middle-aged, and elderly populations (p < 0.001). Conclusion: Our results implied that mutation of the T allele of MTHFR rs1801133 (677C>T) could be a risk factor for IS. A significant association was found among Asian, Hispanic, or Latin population, middle-aged, and elderly people.

Patient Age and Outcome in Ischemic Stroke

Background: Age is the most important prognostic factor in ischemic stroke. Thisstudy was carried out in patients with ischemic stroke to describe the association of age of the patients with stroke severity at presentation and at three months.&#x0D; Materials and Methods: The data, which were collected retrospectively from hospital records, we reanalyzed by using the Statistical Package for the Social Sciences (SPSS) version 26. Age was divided into younger (≤ 50 years) and older (&gt; 50 years) based on standard definition. Age was also divided into younger (&lt; 60 years) and older (≥ 60 years) based on the Senior Citizens Act of Nepal. The associations were analyzed by using Chi-square test.&#x0D; Results: One hundred and fifty-three patients were included in the study. The mean age of the patients was 60.9 years. There was no statistically significant association between baseline stroke severity and the age groups defined both ways. More younger patients had good outcomes (44.4% good outcome vs 25.6% poor outcome in patients ≤ 50 years, p= 0.03; 52.8% good outcome vs 31.6% poor outcome in patients &lt; 60 years, p=0.02). More older patients had poor outcomes (74.4% poor outcome vs 55.6% good outcome in patients &gt; 50 years, p = 0.03; 68.4% poor outcome vs 47.2% good outcome in patients ≥ 60 years, p= 0.02).&#x0D; Conclusion: There was no significant association between young and old patients and the baseline stroke severity; however, more younger patients had good outcomes compared to older patients at three months, the differences being significant.

Genetic variation within the pri-let-7f-2 in the X chromosome predicting stroke risk in a Chinese Han population from Liaoning, China: From a case-control study to a new predictive nomogram.

Stroke is the most common cause of disability and the second cause of death worldwide. Therefore, there is a need to identify patients at risk of developing stroke. This case-control study aimed to create and verify a gender-specific genetic signature-based nomogram to facilitate the prediction of ischemic stroke (IS) risk using only easily available clinical variables. A total of 1,803 IS patients and 1,456 healthy controls from the Liaoning province in China (Han population) were included which randomly divided into training cohort (70%) and validation cohort (30%) using the sample function in R software. The distribution of the pri-let-7f-2 rs17276588 variant genotype was analyzed. Following genotyping analysis, statistical analysis was used to identify relevant features. The features identified from the multivariate logistic regression, the least absolute shrinkage and selection operator (LASSO) regression, and univariate regression were used to create a multivariate prediction nomogram model. A calibration curve was used to determine the discrimination accuracy of the model in the training and validation cohorts. External validity was also performed. The genotyping analysis identified the A allele as a potential risk factor for IS in both men and women. The nomogram identified the rs17276588 variant genotype and several clinical parameters, including age, diabetes mellitus, body mass index (BMI), hypertension, history of alcohol use, history of smoking, and hyperlipidemia as risk factors for developing IS. The calibration curves for the male and female models showed good consistency and applicability. The pri-let-7f-2 rs17276588 variant genotype is highly linked to the incidence of IS in the northern Chinese Han population. The nomogram we devised, which combines genetic fingerprints and clinical data, has a lot of promise for predicting the risk of IS within the Chinese Han population.

CYP4 subfamily V member 2 (CYP4V2) polymorphisms were associated with ischemic stroke in Chinese Han population

BackgroundCYP4 subfamily V member 2 (CYP4V2) polymorphisms are related to venous thromboembolism. However, the influence of CYP4V2 polymorphisms on the susceptibility to ischemic stroke (IS) remains undetermined.MethodsWe selected and genotyped five polymorphisms of CYP4V2 in 575 cases and 575 controls to test whether CYP4V2 variants were associated with the risk for IS in a Chinese Han population. Genotyping of CYP4V2 polymorphisms was performed using the Agena MassARRAY platform. Logistic regression analysis was used to assess the association between CYP4V2 polymorphisms and IS risk by calculating odds ratios (ORs) and 95% confidence interval (CI). False-positive report probability analysis was applied to assess the noteworthy relationship of the significant findings.ResultsCYP4V2 rs1398007 might be a risk factor for IS (OR = 1.34, 95% CI 1.05–1.71, p = 0.009). Specially, confounding factors (age, gender, smoking and drinking status) might affect the relationship between rs1398007 and IS susceptibility. Moreover, rs1053094 and rs56413992 were associated with IS risk in males. Multifactor dimensionality reduction analysis showed the combination of rs13146272 and rs3736455 had the strongest interaction effect (information gain value of 0.40%). Furthermore, genotypes of rs1398007 (p = 0.006) and rs1053094 (p = 0.044) were associated with the levels of high-density lipoprotein cholesterol (HDL-C) among healthy controls.ConclusionOur results first provided evidence that CYP4V2 rs1398007 might be a risk factor for IS, which provides instructive clues for studying the mechanisms of CYP4V2 to the pathogenesis of IS.

Prevalence of the JAK2V617F Mutation in Patients with Ischemic Stroke

Introduction: Patients with the Philadelphia negative myeloproliferative neoplasms (MPN) have an increased risk of thromboembolic events, ischemic cerebrovascular events in particular. The somatic mutation JAK2V617F is associated with MPN with a prevalence of 96% in polycythemia vera (PV), 55% in essential thrombocythemia (ET), and 65% in primary myelofibrosis (PMF). The JAK2V617F mutation is found to be an independent risk factor for thrombosis in patients with MPN. However, whether the JAK2V617F mutation is a risk factor for arterial thrombosis in the absence of an MPN diagnosis is still uncertain. The sensitivity of the assay used for detection is crucial when assessing the presence of the JAK2V617F mutation. A higher sensitivity enables detection of lower allele burdens. This is illustrated by the varying prevalences (0.1-3.1%) in background population studies. In the Danish population study GESUS of approximately 20.000 individuals, the JAK2V617F mutation was detected by droplet digital PCR (ddPCR) with an assay sensitivity of 0.009%. The GESUS study found a JAK2V617F prevalence of 3.1%. Similarly, prevalence studies of JAK2V617F mutation in stroke have varying detection limits from 0.01-5% mutant alleles. The vast majority of these studies are retrospective studies in younger subpopulations of stroke patients. We aimed to investigate the prevalence of the JAK2V617F mutation in a prospective design of consecutively enrolled unselected patients with ischemic stroke or transient ischemic attack by the highly sensitive ddPCR. Method: We recruited 90 consecutive patients with ischemic stroke or transient ischemic attack during admission at the Department of Neurology, Zealand University Hospital, Denmark. A blood sample was taken within 7 days of the onset of symptoms and screened for the JAK2V617F mutation by ddPCR. Patients unable to give informed consent were excluded from the study. Results: Out of 90 patients (mean age 71, range 46-92; female 37%) with ischemic stroke or transient ischemic attack, the JAK2V617F mutation was found in 11 patients (12.2%). Allele burdens ranged from 0.0021 to 24. All 11 patients suffered an ischemic stroke. Six out of 11 patients with the JAK2V617F mutation had elevated blood cell levels i.e. erythrocytosis, thrombocytosis, and/or leukocytosis at the time of recruitment. Only three patients had continuously elevated blood cell levels after 1 month. Patient no. 6 with a JAK2V617F mutation allele burden of 34% had blood cell levels meeting the diagnostic criteria for MPN and was diagnosed with ET. Patient no. 2 had a JAK2V617F allele burden of 14% and increased levels of hemoglobin and platelet count, which both normalized spontaneously after 1 month. The patient was referred for a hematological workup and was found to have mild splenomegaly and a bone marrow biopsy showing myeloproliferative features. In light of the normal blood cell parameters, patient no. 2 was diagnosed with MPN-U. The patients with a JAK2V617F mutation are presented in table 1. Additional data will be presented at ASH. Conclusion and implications: The present study reveals a JAK2V617F mutation prevalence (12.2%) in a stroke population that is substantially higher compared to the background population (GESUS) in the same region of Denmark, using the same assay. The GESUS study showed a JAK2V617F mutationprevalence of 3.1% and for individuals above age 60 a prevalence of 4.1%. Given the fact that the JAK2V617F mutation is present in patients with and without cytosis, our results highly suggest that the JAK2V617F mutation per se is a thrombogenic factor in ischemic stroke. This calls for an exploration of the pathophysiological mechanisms and potential treatments to prevent future thrombotic events in individuals with and without cytosis. Table legend: Clinical and paraclinical characteristics of ischemic stroke patients with the JAK2V617F mutation. IS, ischemic stroke; TIA, transient ischemic attack; HTN, hypertension; HLP, hyperlipidemia; AF, atrial fibrillation; IHD, ischemic heart disease; DM2, diabetes mellitus type 2; Hb, hemoglobin; PLT, platelet count; WBC, white blood cells. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Combination effect between gut microbiota and traditional potentially modifiable risk factors for first-ever ischemic stroke in Tujia, Miao and Han populations in China.

China has had explosive growth in ischemic stroke (IS) burden with significant ethnic and geographic disparities. The aim of this study was to explore the possible combination effect between gut microbiota and traditional potentially modifiable risk factors for IS among two ethnic minorities (Tujia and Miao) and the Han population. Herein, we first used the 16 S rRNA sequencing to compare the gut microbial compositions of 82 patients with first-ever IS vs. 82 normal controls (NCs) among Han, Tujia, and Miao people between 1 May 2018 and 30 April 2019, from Xiangxi Tujia and Miao Autonomous Prefecture in China. An additive model was used to study the interaction between traditional risk factors and gut microbiota with R software. Linear discriminant analysis (LDA) and LDA effect size (LEfSe) results showed that the identified key gut microbiota's taxonomic composition varied in different ethnicity between the IS patients and NCs. Furthermore, families Lactobacillaceae, Enterococcaceae, Streptococcaceae, and Enterobacteriaceae were found to be positively correlated with high-risk factors and negatively correlated with preventive factors in the IS patients, but families Ruminococcaceae and Lachnospiraceae were just the opposite in the NCs. There were additive interactions between traditional risk factors (systolic blood pressure, diastolic blood pressure, and high-sensitive C-reactive protein) and family Enterococcaceae for first-ever IS with the attributable proportion due to the interaction was 0.74, 0.71, and 0.85, respectively; and the synergy index was 4.45, 3.78, and 7.01, respectively. This preliminary but promising study showed that the gut microbiota disturbances may potentially interact to IS with different ethnic host's traditional risk factors.

Usefulness of echocardiographic parameters in predicting the incidence of ischemic stroke in Japanese patients with non-valvular atrial fibrillation

Abstract Background Atrial fibrillation (AF) is a risk factor for ischemic stroke (IS). We developed a novel risk score of IS (HELT-E2S2 score) in non-valvular atrial fibrillation (NVAF) patients from the combined database of 5 major AF registries in Japan. However, this score does not include echocardiographic (Echo) parameters that have been reported to be risk factors of IS, such as left atrial diameter (LAD) enlargement or increased relative wall thickness (RWT) of left ventricle (LV). Purpose To investigate the predictive value of Echo parameters in Japanese patients with NVAF. Methods After excluding patients without the Echo data, 6,032 NVAF patients were analyzed in the present study. LAD was measured in the parasternal long axis view at the end-ventricular systole. RWT was calculated as (2x posterior wall thickness)/ LV end-diastolic dimension. We compared clinical characteristics and the incidence of IS between NVAF patients divided by LAD level (High/Low LAD group) and RWT level (High/Low RWT group). To balance the follow-up period among the registries, event data from individuals whose follow-up period exceeded 730 days were excluded from the analysis. Results The optimal cut-off value of LAD and RWT to predict the incidence of IS with the receiver operating characteristic analysis was 43.3 mm and 0.4167, respectively. Between the High/Low LAD groups (High LAD: n=2,640 vs. Low LAD: n=3,392), age (70.3±12.1 vs. 68.3±12.5 years; p&amp;lt;0.001), CHA2DS2-VASc score (3.02±1.84 vs. 2.57±1.78; p&amp;lt;0.001), HELT-E2S2 score (2.20±1.31 vs. 1.55±1.33; p&amp;lt;0.001), the prescription of oral anticoagulants (OACs) (69.5 vs. 51.5%; p&amp;lt;0.001), LV ejection fraction (60.4±13.4 vs. 64.4±10.7%; p&amp;lt;0.001) and RWT (0.401±0.091 vs. 0.396±0.082; p=0.02) were significantly different. Between the High/Low RWT groups (High RWT: n=2,293 vs. Low RWT: n=3,739), percentage of female (35.6 vs. 27.8%; p&amp;lt;0.001), age (71.2±12.1 vs. 68.0±12.4 years; p&amp;lt;0.001), CHA2DS2-VASc score (3.08±1.82 vs. 2.58±1.79; p&amp;lt;0.001), HELT-E2S2 score (2.10±1.39 vs. 1.67±1.31; p&amp;lt;0.001), the prescription of OACs (62.6 vs. 57.4%; p&amp;lt;0.001), LV ejection fraction (65.5±9.9 vs. 60.9±13.0%; p&amp;lt;0.001) and LAD (43.0±8.1 vs. 42.4±8.3; p=0.004) were significantly different. In Kaplan-Meier analysis, the incidence of IS was different between the groups during the median follow-up period of 730 days (High LAD vs. Low LAD; 1.82 vs. 1.00 per 100 person-years; p&amp;lt;0.001, by log-rank test, High RWT vs. Low RWT; 1.86 vs. 1.06; p&amp;lt;0.001) (Figure). Both High LAD (hazard ratio: 1.65, 95% CI: 1.12–2.46; p=0.01) and High RWT (hazard ratio: 1.43, 95% CI: 1.01–2.04; p=0.045) were independent predictors of the incidence of IS after adjustment by the components of the HELT-E2S2 score and other clinically relevant variables including co-existing diseases, gender, and the prescription of OACs (Table). Conclusion Echo parameters, LAD and RWT, were independently associated with the incidence of IS among Japanese patients with NVAF. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Japan Agency for Medical Research and Development

Association of uric acid as a risk factor in ischemic stroke – A hospital-based observational study

Background: The second most prevalent cause of mortality globally, next to coronary artery disease, is stroke. In humans, uric acid is the final catabolite in the metabolism of purine. Aims and Objectives: The aims of this study were to determine the importance of blood uric acid levels in stroke patients in South Indian population. Materials and Methods: In this observational study, we evaluated acute stroke patients who were admitted to Melmaruvathur Adhiparasakthi Institute of Medical Sciences and Research (MAPIMS) Hospital from December 2021 to May 2022. One hundred patients meeting the inclusion standards were enrolled and divided into two groups randomly following acquisition of ethical approval and informed consent. Results: In our study consisting of both study and control groups, low-density lipoprotein cholesterol (P=0.034), non-high-density lipoprotein cholesterol (HDL-C) (P=0.0127), total cholesterol (P=0.0196), HDL-C (P=0.042), and triglyceride (P=0.0266) were found to be statistically significant. Mean serum uric acid (SUA) level between cases (6.94±1.97 mg/dL) and controls (5.49±1.27 mg/dL) were also statistically significant (P=0.0306 and P=0.049). Conclusion: Our study showed that stroke patients had a significant occurrence of hyperuricemia. In keeping cardiovascular risk factors such as diabetes, hypertension, triglyceride level, total cholesterol level, coronary heart disease, and tobacco use under control, SUA was observed to be substantially linked with the initial phase of ischemic stroke.

Augmented risk of ischemic stroke in hypertrophic cardiomyopathy patients without documented atrial fibrillation

Although atrial fibrillation (AF) is a well-established risk factor for ischemic stroke (IS) in hypertrophic cardiomyopathy (HCM), the risk of IS in HCM patients without documented AF is less recognized. This nationwide population-based cohort study using Korean National Health Insurance database included 8,328 HCM patients without documented AF and 1:2 propensity score-matched 16,656 non-HCM controls between 2010 and 2016. The primary outcome was an incident IS. During a mean follow-up of 6.1 years, IS occurred in 328/8,328 (3.9%) patients with HCM and 443/16,656 (2.7%) controls. The overall incidence of IS was 0.72/100 person-years in the HCM group, which was significantly higher than that in the control group (0.44/100 person-years) (HR 1.64; 95% CI 1.424–1.895; P < 0.001). The overall incidence of IS was 1.36/100 person-years in HCM patients aged ≥ 65 and 2.32/100 person-years years in those with heart failure, respectively. In the HCM group, age ≥ 65 years (adjusted HR 2.74; 95% CI 2.156–3.486; P < 0.001) and chronic heart failure (adjusted HR 1.75; 95% CI 1.101–2.745; P = 0.018) were independent risk factors for IS. HCM patients without documented AF are at a greater risk of IS, especially in those 65 years of age or older or those with chronic heart failure.

The role of lipocalin 2 in brain injury and recovery after ischemic and hemorrhagic stroke.

Ischemic and hemorrhagic stroke (including intracerebral hemorrhage, intraventricular hemorrhage, and subarachnoid hemorrhage) is the dominating cause of disability and death worldwide. Neuroinflammation, blood–brain barrier (BBB) disruption, neuronal death are the main pathological progress, which eventually causes brain injury. Increasing evidence indicated that lipocalin 2 (LCN2), a 25k-Da acute phase protein from the lipocalin superfamily, significantly increased immediately after the stroke and played a vital role in these events. Meanwhile, there exists a close relationship between LCN2 levels and the worse clinical outcome of patients with stroke. Further research revealed that LCN2 elimination is associated with reduced immune infiltrates, infarct volume, brain edema, BBB leakage, neuronal death, and neurological deficits. However, some studies revealed that LCN2 might also act as a beneficial factor in ischemic stroke. Nevertheless, the specific mechanism of LCN2 and its primary receptors (24p3R and megalin) involving in brain injury remains unclear. Therefore, it is necessary to investigate the mechanism of LCN2 induced brain damage after stroke. This review focuses on the role of LCN2 and its receptors in brain injury and aiming to find out possible therapeutic targets to reduce brain damage following stroke.

Migraine and its relation to other risk factors in patients with acute ischemic stroke and acute coronary syndrome

BackgroundMigraine has been recently studied as a risk factor for ischemic stroke (IS) and a possible link to a broader range of ischemic vascular disorders including angina and myocardial infarction is suggested.Objectivesto study migraine and its relation to other risk factors in patients with acute IS and acute coronary syndrome (ACS).Patients and methodsWe studied 200 patients, 114 patients had acute IS and 86 patients with ACS, in addition to 850 control participants. All patients were subjected to detailed clinical and laboratory evaluation; including evaluation of traditional risk factors. All stroke patients were subjected to CT scan. Diagnosis of acute coronary syndrome was established clinically by ECG and cardiac specific enzymes. Migraine was diagnosed according to the international headache society and assessment of migraine severity was measured by the Migraine Disability Assessment (MIDAS) questionnaire.ResultsIn patients with ischemic stroke, Risk Ratios (RR) of migraine was 3.3 for all migrainous patients, higher for migraine with aura (MA). In the cardiovascular group, it was 2.75 and again higher in MA. A positive correlation between migraine severity and both stroke severity and cardiac affection severity was found though non-significant in the cardiovascular group. There was no significant difference in hospital outcome in migrainous patients in both groups.ConclusionsPatients with migraine have higher risk than non-migrainous patients for both cerebrovascular and coronary vascular diseases. Risk is stronger in MA in both conditions. Considering migraine in risk stratification of cerebrovascular and cardiovascular diseases is recommended.