Occurrence Of Ischemic Stroke Research Articles

Microbiota Metabolites and Immune Regulation Affect Ischemic Stroke Occurrence, Development, and Prognosis.

The gut microbiota are not only related to the development and occurrence of digestive system disease, but also have a bidirectional relationship with nervous system diseases via the microbiota-gut-brain axis. At present, correlations between the gut microbiota and neurological diseases, including stroke, are one of the focuses of investigation and attention in the medical community. Ischemic stroke (IS) is a cerebrovascular disease accompanied by focal neurological deficit or central nervous system injury or death. In this review, we summarize the contemporary latest research on correlations between the gut microbiota and IS. Additionally, we discuss the mechanisms of gut microbiota implicated in IS and related to metabolite production and immune regulation. Moreover, the factors of gut microbiota that affecting IS occurrence, and research implicating the gut microbiota as potential therapeutic targets for IS, are highlighted. Our review highlights the evidential relationships and connections between the gut microbiota and IS pathogenesis and prognosis.

Independent external validation of the QRISK3 cardiovascular disease risk prediction model using UK Biobank

ObjectiveTo externally evaluate the performance of QRISK3 for predicting 10 year risk of cardiovascular disease (CVD) in the UK Biobank cohort.MethodsWe used data from the UK Biobank, a large-scale prospective...

Effect of abnormal values of three temperature indicators on ischemic stroke hospital admissions in Guangzhou, China

Abnormal temperature has important effects on the occurrence of ischemic stroke (IS). However, relatively less efforts have been taken to systematically unravel the association between various abnormal temperature and IS hospital admission. Focusing on three temperature indicators (i.e., mean temperature, maximum temperature, and minimum temperature), this study attempts to analyse how their abnormal values affect IS hospital admission. The dataset covers the period between September 17, 2012 and August 28, 2018, and includes a total of 1464 cases who were admitted to the hospital for the first onset of IS and lived in the main urban area of Guangzhou. The study adopts the time-stratified case-crossover analysis. Abnormal values of temperature were measured using the 2.5th and 97.5th quantile values of each temperature indicator, with the former refers to a low value whereas the latter a high one. The effects of abnormal temperature on IS hospital admission were assessed through calculating the relative risks induced by the low and high values (the median values of each temperature indicators were taken as the references). The results show that the risk window periods for IS hospital admission associated with the low values of the temperature indicators are the lags of 3–7 days and 18–19 days. The risks of high temperature values on IS admission, however, are insignificant with either one-day lag or cumulative lag. As to different population groups, females show higher risks of IS hospital admission at low temperature values than males; and elderly people, compared with young people, are more vulnerable to low temperature values. To cities with similar climate of Guangzhou, particular attention should be paid to the impact of low temperature values, especially the low value of minimum temperature, on IS admission, and to females and elderly people who are more sensitive to abnormal temperatures.

A potential relationship between MMP-9 rs2250889 and ischemic stroke susceptibility.

Ischemic stroke (IS), a serious cerebrovascular disease, greatly affects people's health and life. Genetic factors are indispensable for the occurrence of IS. As a biomarker for IS, the MMP-9 gene is widely involved in the pathophysiological process of IS. This study attempts to find out the relationship between MMP-9 polymorphisms and IS susceptibility. A total of 700 IS patients and 700 healthy controls were recruited. The single nucleotide polymorphism (SNP) markers of the MMP-9 gene were genotyped by the MassARRAY analyzer. Multifactor dimensionality reduction (MDR) was applied to generate SNP-SNP interaction. Furthermore, the relationship between genetic variations (allele and genotype) of the MMP-9 gene and IS susceptibility was analyzed by calculating odds ratios (ORs) and 95% confidence intervals (CIs). Our results demonstrated that rs2250889 could significantly increase the susceptibility to IS in the codominant, dominant, overdominant, and log-additive models (p < 0.05). Further stratification analysis showed that compared with the control group, rs2250889 was associated with IS risk in different case groups (age, female, smoking, and non-drinking) (p < 0.05). Based on MDR analysis, rs2250889 was the best model for predicting IS risk (cross-validation consistency: 10/10, OR = 1.56 (1.26-1.94), p < 0.001). Our study preliminarily confirmed that SNP rs2250889 was significantly associated with susceptibility to IS.

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.

Reducing Ischemic Stroke in Diabetes: The Role of GLP-1 RAs.

Stroke is a significant cause of mortality worldwide, and diabetes is an independent risk factor for ischemic stroke occurrence and recurrence. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) lower the risk of ischemic stroke through beneficial effects on traditional stroke risk factors such as hyperglycemia, hypertension, and dyslipidemia. Primary care practitioners (PCPs) can play a substantial role in reducing ischemic stroke; studies have indicated that patients who have a PCP at the time of first stroke have a lower risk of stroke recurrence. Clinical practice guidelines recommend treating type 2 diabetes in patients with or at risk for cardiovascular (CV) disease with glucose-lowering agents with proven CV benefit, such as GLP-1 RAs and sodium-glucose cotransporter-2 (SGLT2) inhibitors. Based on meta-analyses of CV outcomes trials, GLP-1 RAs have a substantial and statistically significant benefit on ischemic stroke risk reduction, whereas SGLT2 inhibitors have a nonsignificant effect. The use of GLP-1 RAs, in addition to non-pharmacologic and pharmacologic management of traditional stroke risk factors, is a key component of complex therapy for ischemic stroke risk reduction.

Left atrial appendage occlusion in the absence of intraprocedural product specialist monitoring: is it time to proceed alone? Results from a multicenter real-world experience.

Percutaneous left atrial appendage occlusion (LAAO) presents many technical complex features, and it is often performed under the intraprocedural surveillance of a product specialist (PS). Our aim is to assess whether LAAO is equally safe and effective when performed in high-volume centers without PS support. Intraprocedural results and long-term outcome were retrospectively assessed in 247 patients who underwent LAAO without intraprocedural PS monitoring between January 2013 and January 2022 at three different hospitals. This cohort was then matched to a population who underwent LAAO with PS surveillance. The primary end point was all-cause mortality at 1 year. The secondary end point was a composite of cardiovascular mortality plus nonfatal ischemic stroke occurrence at 1 year. Of the 247 study patients, procedural success was achieved in 243 patients (98.4%), with only 1 (0.4%) intraprocedural death. After matching, we did not identify any significant difference between the two groups in terms of procedural time (70 ± 19 min vs. 81 ± 30 min, p = 0.106), procedural success (98.4% vs. 96.7%, p = 0.242), and procedure-related ischemic stroke (0.8% vs. 1.2%, p = 0.653). Compared to the matched cohort, a significant higher dosage of contrast was used during procedures without specialist supervision (98 ± 19 vs. 43 ± 21, p < 0.001), but this was not associated with a higher postprocedural acute kidney injury occurrence (0.8% vs. 0.4%, p = 0.56). At 1 year, the primary and the secondary endpoints occurred in 21 (9%) and 11 (4%) of our cohort, respectively. Kaplan-Meier curves showed no significant difference in both primary (p = 0.85) and secondary (p = 0.74) endpoint occurrence according to intraprocedural PS monitoring. Our results show that LAAO, despite the absence of intraprocedural PS monitoring, remains a long-term safe and effective procedure, when performed in high-volume centers.

Neuroprotective Effects of Vinpocetine Against Ischemia-Reperfusion Injury Via Inhibiting NLRP3 Inflammasome Signaling Pathway

Ischemic stroke is one of the main causes of serious disability and death worldwide. NLRP3 inflammasome is an intracellular pattern recognition receptor composed of polyprotein complex, which participates in mediating a series of inflammatory responses and is considered as a potential target for the treatment of ischemic stroke. Vinpocetine, a derivative of vincamine, has been widely used in the prevention and treatment of ischemic stroke. However, the therapeutic mechanism of vinpocetine is not clear, and its effect on NLRP3 inflammasome remains to be determined. In this study, we used the mouse model of transient middle cerebral artery occlusion (tMCAO) to simulate the occurrence of ischemic stroke. Different doses of vinpocetine (5, 10, 15 mg/kg/d) were injected intraperitoneally for 3 days after ischemia–reperfusion in mice. The effects of different doses of vinpocetine on the degree of ischemia–reperfusion injury in mice were observed by TTC staining and modified neurological severity score scale, and the optimal dose was determined. Then, based on this optimal dose, we observed the effects of vinpocetine on apoptosis, microglial proliferation and NLRP3 inflammasome. In addition, we compared the effects of vinpocetine and MCC950 (a specific inhibitor of NLRP3 inflammasome) on NLRP3 inflammasome. Our results show that vinpocetine can effectively reduce the infarct volume and promote the recovery of behavioral function in stroke mice, and the maximal beneficial effects were observed at the dose of 10 mg/kg/d. Vinpocetine can effectively inhibit the apoptosis of peri-infarct neurons, promote the expression of Bcl-2, inhibit the expression of Bax and Cleaved Caspase-3, and reduce the proliferation of peri-infarct microglia. In addition, vinpocetine, like MCC950, can reduce the expression of NLRP3 inflammasome. Therefore, vinpocetine can effectively alleviate the ischemia–reperfusion injury in mice, and the inhibition of NLRP3 inflammasome may be an important therapeutic mechanism of vinpocetine.

Changes in the clinico-functional characteristics of stroke patients in the acute phase during the COVID-19 pandemic.

To compare the sociodemographic and clinico-functional characteristics of patients admitted to a stroke unit immediately before and during two different COVID-19 pandemic phases. This exploratory study was conducted in the stroke unit of a public hospital in Brazil. Patients consecutively admitted to a stroke unit for 18 months with primary stroke aged ≥20 years were included and divided into three groups: G1: Pre-pandemic; G2: Early pandemic; and G3: Late pandemic. The sociodemographic and clinico-functional characteristics of the groups were compared (α=0.05). The study included 383 individuals (G1=124; G2=151; G3=108). The number of risk factors (higher in G2; p≤0.001), smoking (more common in G2; p≤0.01), type of stroke (ischemic more common in G3; p=0.002), stroke severity (more severe in G2; p=0.02), and level of disability (more severe in G2: p≤0.01) were significantly different among the groups. A greater number of serious events and risk factors including smoking and higher level of disability was observed in patients in the beginning of the pandemic than in the late phases. Only the occurrence of ischemic stroke increased in the late phase. Therefore, these individuals may have an increased need for rehabilitation services monitoring and care during their lifespan. Additionally, these results indicate that health promotion and prevention services should be strengthened for future health emergencies.

ASSOCIATION BETWEEN NOCTURNAL VARIATION IN BLOOD PRESSURE AND RISK OF ACUTE ISCHEMIC STROKE: A SYSTEMATIC REVIEW

Objective: Blood pressure (BP) is a dynamic parameter characterized by fluctuations during the 24-hour period. Variability of BP has been associated with cardiovascular risk and the occurrence of acute ischemic stroke (AIS). Circadian variation in BP during the night shows some basic patterns. The purpose of this study is to to correlate deviations from baseline patterns of circadian BP variation with the risk of AIS to select the optimal therapeutic intervention. Design and method: To complete our study, we systematically reviewed the literature from 1990-2022 through electronic medical databases (MEDLINE, Scopus and Cochrane). Results: During the nighttime hours, BP drops 10 - 20% in normotensive and untreated hypertensive patients - a dipping phenomenon, followed by a rapid and gradual increase during waking hours. In the studies being reviewed, patients were classified according to the rate of fall in systolic BP during 24-hour recording into four categories: the extreme-dippers drop &gt;20%, dippers drop &gt;10% and &lt;20%, non-dippers drop &lt;10% and &gt;0%, and reverse-dippers or risers drop &lt;0%. Deviating from standard dipping patterns is associated with an increased risk of AIS and highlights the value of chronotherapy, whereas no significant difference is observed in stroke prognosis. The extreme-dipping phenomenon is associated with the occurrence of ischemic stroke (IS), either due to under-treatment or due to subsequent morning hypertensive spike, whereas aggressive antihypertensive treatment seems to be significantly responsible. Interestingly, the occurrence of microbleeds in IS territory has been strongly associated with the reverse-dipping pattern. Conclusions: Overnight BP variation is an independent and robust predictor of cardiovascular risk, including AIS. Nocturnal BP may constitute a therapeutic target for the prevention of AIS. However, the available data on the effect of antihypertensive drugs and the implementation of chronotherapy with pre-sleep medication are conflicting in terms of improving cardiovascular risk. Therefore, at present, current guidelines for the treatment of BP do not recommend the aforementioned therapeutic approach as the best treatment in day-to-day clinical practice. More extensive and targeted studies are needed in the future to confirm the potential benefits of the application of chronotherapy in the prevention of AIS.

AORTIC STIFFNESS IS INDEPENDENTLY ASSOCIATED WITH INTRACRANIAL CAROTID ARTERY CALCIFICATION IN PATIENTS WITH ISCHEMIC STROKE

Objective: Intracranial carotid artery calcification (ICAC), as a strong contributor to the occurrence of ischemic stroke, might be present in the medial or intimal arterial layer. Traditional vascular risk factors are associated with ICAC; however, its association with new markers of vascular function are less understood. The paper aims to evaluate the relationship between carotid-femoral pulse wave velocity (CF-PWV) and ICAC subtypes. Design and method: We enrolled 65 patients with acute ischemic stroke. CF-PWV, systolic, diastolic and mean blood pressure, and pulse pressure (SBP, DBP, MBP, PP) were measured within 6±2 days of stroke onset. CT was performed within 24 hours of stroke onset and ICAC on the stroke site was classified by two methods: volume- and score-based. Tertiles of ICAC volume were determined, and low-grade ICAC (T1) was regarded as a reference. According to the score-based method, medial and intimal ICAC subtypes were determined. Data were analyzed with multivariate logistic regression. Results: Medial and intimal ICAC subtypes were found in 34 (52%) and 24 (37%) patients, respectively. In 11% of patients no ICAC calcifications were found. CF-PWV was higher in patients with high-grade ICAC (OR = 1.56, 95%CI = 1.03-2.35, p = 0.035). CF-PWV was higher in patients with the medial ICAC subtype than in patients with the intimal ICAC subtype (OR = 1.60, 95%CI = 1.00-2.55, p = 0.049) after adjustment for age, MBP, diabetes mellitus, arterial hypertension, hyperlipidemia, and smoking status. Conclusions: Our study demonstrates that among patients with ischemic stroke, aortic stiffness is independently associated with ICAC, and that medial ICAC, compared with intimal ICAC, is accompanied by more advanced aortic stiffness.

Effect of the number of unhealthy lifestyles in middle-aged and elderly people on hypertension and the first occurrence of ischemic stroke after the disease.

To determine the relationship between the number of controllable unhealthy lifestyles on the risk of the first occurrence of ischemic stroke after the disease in middle-aged and elderly people in the community, and to provide data support and basis for community physicians to guide hypertensive patients to control modifiable risk factors to prevent the first occurrence of ischemic stroke. The relationship between the number of unhealthy lifestyles and the risk of hypertension was analyzed by binary logistic regression in 584 subjects using a medical record control study. A retrospective cohort study of 629 hypertensive patients was used to analyze the relationship between the number of unhealthy lifestyles and the risk of the first occurrence of ischemic stroke within 5 years of developing hypertensive disease using Cox proportional risk regression models. Logistic regression model analysis showed that taking an unhealthy lifestyle as a reference, the OR (95% CI) values of, 2, 3, 4 and 5 unhealthy lifestyle were 4.050 (2.595-6.324), 4 (2.251-7.108), 9.297 (3.81-22.686), and 16.806 (4.388-64.365), respectively. Cox Proportional risk regression model analysis showed that the risk of ischemic stroke within 5 years after developing hypertension was referenced to 5 unhealthy lifestyles, and the HR (95% CI) for 3, 2, and 1 unhealthy lifestyle were 0.134 (0.023-0.793), 0.118 (0.025-0.564), and 0.046 (0.008-0.256), respectively. The number of controllable unhealthy lifestyles in middle-aged and elderly people was positively associated with the risk of hypertension and first ischemic stroke after hypertension, and there was a dose-effect relationship between them. The risk of hypertension and first ischemic stroke within 5 years after hypertension onset increased with the number of unhealthy lifestyles.

Clinical markers of atrial abnormality as predictors of cardioembolic events in patients with embolic stroke of undetermined source

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Unrestrictive grant for fellowship support - Abbot Medical Background Embolic stroke of undetermined source (ESUS) represents 17% of ischemic strokes. The lack of etiology leads to unsuitable treatment, higher stroke recurrence, and death. Several features presume atrial cardiomyopathy (ACM) as a potential etiology of embolism among ESUS population, but its causative role is not steadily grounded. Purpose To assess predictors, focusing on markers of ACM, of diagnosis of a cardioembolic source in ESUS patients during a long-term follow-up. Methods (Figure 1) - This study was an observational, retrospective, monocentric, cohort trial designed to assess predictors of cardioembolic events occurrence in an ESUS population along a 9-year follow-up. 128 ESUS patients who faced an ischemic stroke with a negative extensive etiological assessment from 2009 to 2012 were consecutively included. Upon ESUS diagnosis, clinical, echocardiographic (including transthoracic and transoesophageal echocardiogram), electrocardiographic (ECG), and Holter-ECG features were recorded. The occurrence of atrial fibrillation (AF) and the recurrence of ischemic stroke were registered during follow-up. Diagnosis of a cardioembolic source, a composite outcome, was defined as AF occurrence and/or recurrence of ischemic stroke, for which a cardioembolic cause was diagnosed secondary to the etiologic evaluation. Results (Figure 2) - AF and a cardioembolic source were diagnosed in 13 patients (10.2%) and 17 patients (13.3%) respectively, during the 9-year follow-up. Overall ischemic stroke recurrence was diagnosed in 13 patients (10.2%). Through univariate analyses, age higher than 65 (HR=4.9, p&amp;lt;0.01, 95%CI:1.5-16.1), abnormal P-wave axis (HR=4.3, p=0.01, 95%CI:1.4-13.2), increased PAC burden (HR=6.0, p&amp;lt;0.01, 95%CI:2.0-18.5), left atrial (LA) dilation (HR=6.1, p&amp;lt;0.01, 95%CI:2.0-18.7), and abnormal LA appendage outflow velocity (HR=8.6, p&amp;lt;0.01, 95%CI:1.8-41.7) were associated with AF occurrence. The AF occurrence was independently predicted by LA dilation (HR=6.69, 95%CI:1.17-37.47, p=0.02) and abnormal P-wave axis (HR=5.91, 95%CI:1.37-25.56,p=0.02). High blood pressure(HR=4.7, p=0.04, 95%CI:1.1-20.6), CHA2DS2-VASc score higher than 2 (HR=3.3, p=0.03, 95%CI:1.1-9.3), age higher than 65 (HR=3.5, p=0.02, 95%CI:1.5-16.1), increased of PAC burden (HR=6.2, p&amp;lt;0.01, 95%CI:2.2-17.1), and LA dilation (HR=4.2, p&amp;lt;0.01, 95%CI=1.6-10.9) were found as predictors of the diagnosis of a cardioembolic source during follow-up. The abnormal P-wave axis was an independent predictor of the diagnosis of a cardioembolic source (HR=3.82, 95%CI:1.03-14.09, p=0.04) in ESUS population. No risk marker assessed at baseline was associated to the recurrence of overall ischemic stroke recurrence. Conclusion LA dilation and abnormal P-wave axis are significant and independent predictors of the diagnosis of cardioembolic source and AF occurrence in ESUS population. ACM seems to be involved in the cardioembolic process in a significant portion of ESUS population.

Impact of concomitant proton pump inhibitor during oral anticoagulant treatment

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction Proton pump inhibitor is commonly used for gastroprotective effect in patients with a combination of antiplatelets and anticoagulants. However, data quantifying the concomitant proton pump inhibitor for clinical adverse outcomes other than gastrointestinal bleedings of oral anticoagulant is lacking. Purpose We aimed to explore the effect of concomitant proton pump inhibitor on the effectiveness and safety of oral anticoagulant in patients with atrial fibrillation. Methods The medical records were retrospectively reviewed from four tertiary referral hospitals between January 1, 2012, and December 31, 2020. Concomitant use of drug was quantified as the overlapping proportion over the duration of oral anticoagulant therapy. Primary endpoint was the time to occurrence of ischemic stroke, systemic embolism, intracardiac thrombus, major bleeding events, or death. Results Data were analyzed for 20,750 episodes with oral anticoagulant and atrial fibrillation (median [IQR] age, 71 [63-78] years; female, 42.5%; warfarin, 37.3%; median [IQR] CHA2DS2-VASc score, 3 [2-5]). The risk of primary endpoint was greatest in the group of persistent use (80% or more of overlapping proportion) of proton pump inhibitor among the other groups with less overlapping proportion (adjusted hazard ratio, 1.88; 95% confidence interval, 1.63–2.16; P for groups, &amp;lt;0.001). Concomitant proton pump inhibitor was not associated with the risk of major bleeding from the gastrointestinal tract. Conclusion Among patients with atrial fibrillation receiving oral anticoagulant, concomitant use of proton pump inhibitor increased the rate of thromboembolism, major bleeding, or death in proportion of overlapping period.

Association Between CYP2C19 Genotypes With Clinical Phenotypes and Adipokine Levels Among Ischemic Stroke Patients: A Prospective Observational Study.

Background Cytochrome P450 system is implicated in vascular pathologies, including stroke. Besides its role as a drug metabolizer, it also plays an important role in the metabolism of several endogenous substances like fatty acids, arachidonic acid, etc., which have pro-inflammatory effects. On the other hand, leptin and adiponectin are two of the most common adipose tissue-derived cytokines (adipokines), which are pro-inflammatory andanti-inflammatory in nature,respectively. Both of them are implicated in the pathogenesis of stroke. Methods We prospectively recruited ischemic stroke patients (within three months of occurrence of an attack of stroke). The occurrence of composite outcome (recurrence of transient ischemic attack/ischemic stroke or death)was evaluated for association with genetic variants of CYP2C19 (allele *2, *17, *3, and *4, i.e., single nucleotide polymorphism (SNP) 1/2/3/4, identified using TaqMan assays and DNA sequencing). Adiponectin and leptin levels weredetermined usingan enzyme-linked immunosorbent assay. Comparisons were made betweenstroke vs. control patients and between CYP2C19 intermediate metabolizer (IM)/poor metabolizer (PM) vs. extensive metabolizer (EM)/ultra metabolizer (UM) (PM: *2/*2; IM: *1/*2vs. EM: *1/*1; UM: *1/*17). P < 0.05 was taken as the threshold for statistical significance. Results A total of 204 patients and 101 controls were recruited. With regardto the occurrence of stroke, SNP2 showed a significant positive association. Haplotypes (SNP1/SNP2) AC (OR = 1.75 (1.08-2.83), p= 0.024) and GT (OR = 3.33 (1.53-7.22), p = 0.0026) were strongly associated with the occurrence of ischemic stroke even after adjustment for age and sex (global haplotype association p-value: 0.0062). Haplotype phenotype gender interaction was evident. Among stroke patients, with regardto composite outcome, only SNP1 showed a positive association. The AC haplotype was significantly associated with the occurrence of composite outcome (OR = 2.27 (1.17-4.41), p = 0.016). Among stroke patients, a significant positive association was seen between death and SNP1 (OR = 2.35 (1.13-4.90), p = 0.021) and AC haplotype (OR = 2.73 (1.20-6.22), p = 0.018). However, none of the SNPs or haplotypes showed any association with recurrence. Significant higher leptin and lower adiponectin levels were observed among stroke patients compared to controls.Leptin levels were higher in IM/PM group. IM/PM phenotypes showed a higher incidence of occurrence of composite outcome (hazard ratio = 2.07 (0.96-4.47), p = 0.056). Conclusion CYP2C19 polymorphisms may play a significant role in the pathogenesis of stroke. Leptin could serve as a prominent biomarker of atherosclerosis and inflammation in the early post-stroke period; however, further study is warranted with a larger sample size.

85 An Approach to Test Effects on Secondary Organs via Lung Cells Exposed at the Air Liquid Interphase

Abstract Air pollutions are shown to increase the occurrence of cardiovascular diseases and ischemic stroke. These effects imply an indirect exposure of secondary organs downstream of the respiratory system as the primary target of exposure. Mechanistic studies of air pollution on secondary organs have traditionally been performed on organ specific monocultures at submerged conditions. Direct exposure to organ specific cells secondary exposed to air pollution have the drawback that it does not imply realistic exposure conditions. In this study we have indirectly exposed organ specific cells to particulate matter via exposure of a bronchial lung model at the air liquid interphase (ALI). The lung model was exposed to a model diesel particle (DEP) and an equivalent dose of an acetone extract of the DEP. The DEP induced induction of IL-6 formation of which the DEP was more potent than the DEP extract. The DEP extract inhibited CXCL8 formation, which appeared contradictory since both the DEP and DEP-extract increased expression of CXCL8 mRNA. Our results showed a substantial increased expression of CyP1A1 and CyP1B1 in both epithelial and endothelial cells in the lung model of which no differences were observed between the DEP and DEP-extract. However, the solvent extract induced the CYPs with a higher potency in the secondary exposed HepG2 liver cells, probably due to faster permeation of dissolved substances in the DEP extract through the lung barrier. Thus, organ specific cell models can be combined to achieve a more realistic so-called body-specific model to study secondary effects.

Identification of the lncRNA-miRNA‒mRNA regulatory network for middle cerebral artery occlusion-induced ischemic stroke.

Stroke known as a neurological disease has significant rates of disability and mortality. Middle cerebral artery occlusion (MCAO) models in rodents is crucial in stroke research to mimic human stroke. Building the mRNA and non-conding RNA network is essential for preventing MCAO-induced ischemic stroke occurrence. Herein, genome-wide mRNA, miRNA, and lncRNA expression profiles among the MCAO group at 3h, 6h, and 12h after surgery and controls using high-throughput RNA sequencing. We detected differentially expressed mRNAs (DE-mRNAs), miRNAs (DE-miRNAs), and lncRNAs (DE-lncRNAs) between the MCAO and control groups. In addition, biological functional analyses were conducted, including GO/KEGG enrichment analysis, and protein-protein interaction analysis (PPI). GO analysis indicated that the DE-mRNAs were mainly enriched in several important biological processes as lipopolysaccharide, inflammatory response, and response to biotic stimulus. The PPI network analysis revealed that the 12 DE-mRNA target proteins showed more than 30° with other proteins, and the top three proteins with the highest node degree were Alb, IL-6, and TNF. In the DE-mRNAs, we found the mRNA of Gp6 and Elane interacting with two miRNAs (novel_miR_879 and novel_miR_528) and two lncRNAs (MSTRG.348134.3 and MSTRG.258402.19). As a result of this study, a new perspective can be gained into the molecular pathophysiology leading to the formation of MCAO. The mRNA-miRNA‒lncRNA regulatory networks play an important role in MCAO-induced ischemic stroke pathogenesis and could be applied to the treatment and prevention of ischemic stroke in the future.

Incidence, temporal profile and neuroanatomic correlates of poststroke epilepsy.

The relationship between ischemic stroke site and occurrence of poststroke epilepsy (PSE) is incompletely understood. This study intended to evaluate incidence and temporal profiles of seizures and to correlate ischemic lesion sites with PSE using voxel-based lesion symptom mapping (VLSM). Patients with imaging-confirmed first-ever ischemic stroke without prior history of epilepsy were prospectively included. Demographic data, cardiovascular risk factors, and National Institute of Health Stroke Scale (NIHSS) scores were assessed. Data on seizures and modified Rankin scale scores were determined within a 90-day period after stroke onset. Ischemic lesion sites were correlated voxel wise with occurrence of PSE using nonparametric permutation test. Age- and sex-matched patients with first-ever ischemic strokes without PSE after 90days served as controls for the VLSM analysis. The stroke database contained 809 patients (mean age: 68.4±14.2years) with first-ever imaging-confirmed ischemic strokes without history of epilep. Incidence of PSE after 90-day follow-up was 2.8%. Five additional patients were admitted to the emergency department with a seizure after 90-day follow-up. Fifty percent of the seizures occurred in the acute phase after stroke. PSE patients had higher NIHSS scores and infarct volumes compared to controls without PSE (p<.05). PSE patients had infarcts predominantly involving the cerebral cortex. The hemisphere-specific VLSM analysis shows associations between PSE and damaged voxels in the left-hemispheric temporo-occipital transition zone. The data indicate that PSE occurs in a small proportion of patients with rather large ischemic strokes predominantly involving the cerebral cortex. Especially patients with ischemic lesions in the temporo-occipital cortex are vulnerable to develop PSE.

PO-05-200 GENDER DISPARITIES IN MANAGEMENT AND OUTCOMES OF ATRIAL FIBRILLATION IN A MODERN LOUISIANA COHORT

Female gender is associated with a lower lifetime risk of developing atrial fibrillation (AF) when compared to males. Other gender differences in atrial fibrillation comorbidities, treatments, and outcomes have been described with often conflicting results. We sought to investigate gender differences in comorbidities, treatments, and outcomes of atrial fibrillation patients from a recent Louisiana population. Data on patients aged ≥18 years diagnosed with atrial fibrillation between January 2010 and December 2019 was pulled from the Research Action for Health Network database (REACHnet). The primary outcome was defined as the first occurrence of ischemic stroke, transient ischemic attack (TIA), intracranial bleeding, gastrointestinal bleeding, hospitalization, or death. Chi-squared test was used to study categorical variables. Poisson regression was used to examine the effect of gender on outpatient visits per year, adjusted for comorbidities. 2592 patients were included in this study, 35.1% of whom were females. Female patients were younger (62.2 vs 63.3 years p <0.001), had less coronary artery disease (OR=0.68, p <0.001), and less chronic kidney disease (OR=0.89, p=0.005), but a more frequent stroke history (OR=1.4, p<0.001) at baseline (figure). Females were less likely to receive antiarrhythmic drug therapy (AAD) (OR=0.75, p=0.018). Among those who received AADs, female patients were less likely to receive amiodarone (OR=0.69, p=0.003), and more likely to receive flecainide (OR=3.45, p=0.048). Patients with at least 1 non-gender CHA2DS2-VASc risk factor had similar odds of receiving oral anticoagulation in general, and similar odds for receiving direct oral anticoagulants in particular. Females had one more outpatient visit per year than males did, even after accounting for comorbidity differences (p <0.001). Female patients had higher odds of achieving our primary outcome of stroke, TIA, intracranial bleeding, gastrointestinal bleeding, hospitalization, or death (OR=1.19, p=0.041). Female atrial fibrillation patients have a different comorbidity profile than their male counterparts. We found persistent gender disparities in the management and prognosis of atrial fibrillation in a modern Louisiana population.

Role of CYP19A1 Loci (rs28757157 and rs3751591) with Ischemic Stroke Risk in the Chinese Han Population.

Ischemic stroke (IS) is a multifactorial and polygenic disease, which is affected by genetic factors. In this study, we explored the role of CYP19A1 single nucleotide polymorphisms (SNPs) in IS in the Chinese population. 1302 subjects (651 controls and 651 cases) were recruited in this case-control study. Four candidate SNPs (rs28757157 C/T, rs3751592 C/T, rs3751591 G/A, rs59429575 C/T) of CYP19A1 were selected by the 1000 genomes project database. The association between CYP19A1 SNPs and IS risk was assessed using logistic regression analysis with odds ratio (OR) and 95% confidence intervals (CIs). False-positive report probability (FPRP) analysis further verified the positive results. The interaction of SNP-SNP was analyzed by multi-factor dimensionality reduction (MDR) to predict is risk. In the research, CYP19A1 loci (rs28757157 and rs3751591) were associated with the occurrence of IS. The two variants conferred an increased susceptibility to IS in the subjects aged over 60 years old, smokers and drinkers. Rs28757157 was related to the risk of IS in females, non-smokers and subjects with BMI less than 24, while rs59429575 was related to the risk of IS in males and subjects with BMI greater than 24. The study revealed that there is a significant association between CYP19A1 loci (rs28757157 and rs3751591) and IS risk in the Chinese Han population, providing a theoretical basis for further exploring its specific role in the pathogenesis of IS.