Risk Of Ischemic Stroke Research Articles

Association of the Triglyceride-Glucose Index and Related Metabolites with sICAS of the Posterior Circulation

ObjectiveThe triglyceride-glucose index (TyG), a reliable marker of insulin resistance (IR), has an unclear association with symptomatic intracranial atherosclerotic stenosis in the posterior circulation (POC-sICAS). This study aimed to investigate the association between the TyG index, associated metabolites, and POC-sICAS. MethodsA total of 106 patients with POC-sICAS and 81 with asymptomatic intracranial atherosclerotic stenosis of the posterior circulation (POC-aICAS) were retrospectively enrolled. The TyG index was calculated using the formula: ln [fasting triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2]. Logistic regression analysis evaluated the correlation between the TyG index and POC-sICAS. Differential metabolic markers were identified using liquid chromatography-tandem mass spectrometry. The predictive value of the TyG index and differential metabolites for POC-sICAS was assessed through receiver operating characteristic (ROC) curve analysis. ResultsPatients with POC-sICAS had a significantly higher TyG index than those with POC-aICAS (9.25 [interquartile range {IQR} 8.79-9.92] vs 8.87 [IQR 8.83-9.26]; P<0.001). The TyG index was an independent risk factor for POC-sICAS (adjusted odds ratio [OR]: 2.20, 95% confidence interval [CI]: 1.09-4.42, P=0.027), particularly in patients with diabetes mellitus (adjusted OR: 14.39, 95% CI: 2.37-87.36, P=0.004). The association was stronger in patients younger than 65 years with a high TyG index (≥8.99) (adjusted OR: 4.35, 95% CI: 1.12-16.94, P=0.034). The TyG index positively correlated with 90-day poor prognosis in those with POC-sICAS (R=0.4042, P=0003), especially in those with diabetes mellitus (R=6405, P<00001) and those younger than 65 years (R=0.4628, P=0002). Moreover, 11 differential metabolites were significantly related to the TyG index. The TyG index combined with pregnanediol showed significant discrimination between patients with POC-sICAS and POC-aICAS (area under the curve [AUC]=1, 95% CI 1.000-1.000; P<0.001). ConclusionsThe TyG index and pregnanediol could help identify patients with a high risk of ischemic stroke in POC-ICAS. Moreover, the TyG index was associated with a poor 90-day prognosis in patients with POC-sICAS.

Zygomatic Anterolateral Temporal Approach for P1/P2 segment complex posterior cerebral aneurysm: a single-center retrospective study.

Treating complex posterior cerebral artery (PCA) aneurysms, such as fusiform, giant, and dissecting aneurysms, poses significant challenges. Parent artery occlusion carries a risk of ischemic stroke and fails to alleviate mass effects. This study aims to analyze the technical nuances and patient outcomes of treating complex PCA aneurysms, ranging from the P1 to P2P segments, using a Zygomatic Anterolateral Temporal Approach(ZATA) combined with flow reconstruction. This study was a retrospective study. Surgical treatment was performed on twelve patients with complex PCA aneurysms located in the P1 to P2P segments. Ten patients underwent flow reconstruction including Superficial Temporal Artery(STA)-Middle Cerebral Artery(MCA),Internal Maxillary Artery(IMA)-Radial Artery(RA)-MCA,STA-PCA(P2), and IMA-RA-PCA(P2). The aneurysm occlusion rate, surgical complications, and patient prognosis, including stroke occurrence/ modified Rankin Scale(mRS), were recorded and analyzed. Using the ZATA, all twelve complex PCA aneurysms were successfully clipped/resected/trapped. This included two high-position aneurysms (> 3mm above the posterior clinoid process) at the P1/P2 junction and three P2P aneurysms. The mass effects of six large or giant aneurysms were resolved or alleviated. Postoperative and follow-up CTA/DSA confirmed the patency of the bypass vessels. Four patients experienced strokes in the perioperative period, with three ischemic and one hemorrhagic. The median follow-up period was 28.5months. At the last follow-up, the good prognosis rate (mRS ≤ 2) was 83.3%, and one patient had died. Clipping/resection/trapping of aneurysms via the ZATA, combined with flow reconstruction, is a feasible option for treating complex PCA aneurysms from the P1 to P2P segments. This approach helps maintain or improve cerebral perfusion in the affected vascular territory.

Связь полиморфизма rs11546155 гена GGT7 с риском развития ишемического инсульта

Background: Since oxidative stress plays a role in the pathogenesis of ischemic stroke (IS), it is important to investigate the molecular mechanisms contributing to redox homeostasis and glutathione metabolism. The aim of the study: To analyze the association of the rs11546155 polymorphism of gamma-glutamyltransferase 7 (GGT7) gene with the risk of ischemic stroke. Materials and methods: DNA samples from 600 patients with IS and 688 controls were used for genotyping SNP rs11546155 by real-time PCR with allele discrimination using TaqMan probes. Results: It was found that genotypes G/A and A/A are associated with an increased risk of IS in females (OR=1.54, 95%CI 1.02–2.32, Pperm=0.04), while no associations between rs11546155 genotypes were observed in males. In patients with hypodynamia, the rs11546155 polymorphism was associated with an increased risk of IS (OR=1.59, 95%CI 1.01–2.00, Pperm=0.04), while in individuals with normal and increased physical activity, the SNP did not influence disease risk. Moreover, the carriers of allele rs11546155G who did not abuse alcohol possess a decreased risk of IS (OR = 1.59, 95%CI 1.012.00, Pperm = 0.04), while the protective effect of the allele against disease risk was not seen in alcohol abusers. Functional SNP annotation showed that the IS-related rs11546155A allele is associated with decreased expression of the GGT7 gene, as well as genes involved in autophagy and proteasomal protein degradation. Conclusion: This study was the first to establish the association of the rs11546155 polymorphism with the risk of IS. Further studies are needed to clarify the nature of the sex-specific SNP association and gene-environment interactions.

Genetic causality of lipidomic and immune cell profiles in ischemic stroke.

Ischemic stroke (IS) is a global health issue linked to lipid metabolism and immune cell responses. This study uses Mendelian randomization (MR) to identify genetic risk factors for IS subtypes using comprehensive genetic data from lipidomic and immune cell profiles. We assessed genetic susceptibility to IS across 179 lipids and 731 immune cell phenotypes using instrumental variables (IVs) from recent genome-wide association studies. A two-sample MR approach evaluated correlations, and a two-step MR mediation analysis explored the role of immune cell phenotypes in the lipid-IS pathway. Sensitivity analyses, including MR-Egger and Cochran Q tests, ensured robust results. Genetic IVs for 162 lipids and 614 immune cell phenotypes were identified. Significant genetic causality was found between 35 lipids and large artery stroke (LAS), with 12 as risk factors (sterol esters, phosphatidylcholines, phosphatidylethanolamines) and 23 as protective factors (phosphatidylcholines, phosphatidylethanolamines, phosphatidylinositols). For small vessel stroke (SVS), 8 as risk factors (sterol esters, phosphatidylcholines), and 2 as protective factors (phosphatidylinositol, sphingomyelin). For cardioembolic stroke (CS), 2 as risk factors, and 4 as protective factors. Mediation analysis revealed that CCR2 on granulocytes, CD11c on CD62L+ myeloid dendritic cells, and FSC-A on granulocytes mediated the lipid-immune cell-LAS pathway, while CD4 on activated CD4 regulatory T cells and CD4 on activated & secreting CD4 regulatory T cells mediated the lipid-immune cell-SVS pathway. This study identifies genetic links between specific lipids and IS subtypes, highlights immune cells' role in IS risk and mediation, suggests new therapeutic targets, and uncovers IS genetic drivers.

Impact of Systolic and Diastolic Blood Pressure on Cardiovascular Health Outcomes

Background: One well-known risk factor for cardiovascular (CV) disease that significantly raises morbidity and mortality rates globally is hypertension. Optimising treatment options requires an understanding of the distinct effects of diastolic and systolic blood pressure on CV outcomes. The study aims to examine into how the effects of both systolic hypertension (SH) and diastolic hypertension (DH) affected the frequency of major CV events, such as hemorrhagic, ischemic, and myocardial infarction (MI). Methods: A retrospective cohort research comprising 180 patients was carried out, with automated oscillometric cuffs being used to measure blood pressure. The burdens of SH and DH, which were determined as continuous variables from weighted average blood pressure, were the main predictors. A composite of ischemic stroke, MI, or hemorrhagic stroke was the main result. Logistic regression and bivariate and multivariable Cox survival analyses were included in the statistical studies. Results: The study population had average age of 65.4 years, with 52% males and 48% females. During the observation period, 45 composite outcome events occurred (25% incidence rate). Bivariate Cox analysis showed significant associations between SH burden (HR: 1.45, p&lt;0.001) and diastolic hypertension burden (HR: 1.30, p=0.015) with the composite outcome. Multivariable analysis confirmed these associations, with consistent findings in logistic regression models. Conclusion: Both SH and DH burdens are significant predictors of adverse CV outcomes. Effective management of both blood pressure components is essential for reducing the risk of ischemic stroke, MI, and hemorrhagic stroke. Recommendations: To lower the risk of significant CV events, clinicians should monitor and treat both systolic and diastolic blood pressure in individuals with hypertension. Subsequent studies ought to investigate the underlying mechanisms of these correlations and assess the effectiveness of focused interventions. Keywords: Hypertension, Cardiovascular Outcomes, Diastolic Blood Pressure, Systolic Blood Pressure.

Comparison of Oral Anticoagulants vs. Warfarin for Stroke Prevention in Atrial Fibrillation: A Meta-Analysis

Background: Atrial fibrillation (AF) significantly increases the risk of ischemic stroke, necessitating effective anticoagulation therapy. Warfarin has been the standard treatment, but direct oral anticoagulants (DOACs) have emerged as a safer and more effective alternative.Objective: To compare the efficacy and safety of DOACs versus warfarin in stroke prevention among AF patients.Methods: A comprehensive literature search was conducted in PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus following PRISMA guidelines. Randomized controlled trials and observational studies comparing DOACs (dabigatran, rivaroxaban, apixaban, edoxaban) with warfarin in AF patients were included. Primary outcomes were ischemic stroke or systemic embolism, and secondary outcomes included all-cause mortality, major bleeding, intracranial hemorrhage (ICH), and gastrointestinal bleeding. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a random-effects model.Results: A total of 35 studies involving 172,350 patients were analyzed. DOACs significantly reduced ischemic stroke or systemic embolism (HR: 0.78, 95% CI: 0.72–0.84, p &lt; 0.001) and all-cause mortality (HR: 0.85, 95% CI: 0.79–0.92, p = 0.002). Major bleeding risk was lower (HR: 0.88, 95% CI: 0.80–0.96, p = 0.005), but gastrointestinal bleeding was higher (HR: 1.20, 95% CI: 1.10–1.30, p &lt; 0.001).Conclusion: DOACs provide superior efficacy and safety in stroke prevention compared to warfarin, despite a higher risk of gastrointestinal bleeding.

Antidiabetic Treatment and Prevention of Ischemic Stroke: A Systematic Review

Background: Diabetes mellitus (DM) is a prevalent disease in the general population and also a well-established risk factor for the development of ischemic stroke. Patients who have been diagnosed with diabetes have a 20% higher risk for developing ischemic stroke in comparison to non-diabetic individuals. The aim of the current systematic review is to provide the latest evidence regarding the association between antidiabetic treatment and the prevention of ischemic stroke. Methods: A comprehensive search in scientific literature databases PUBMED, COCHRANE, and SCOPUS was conducted. The studies that were deemed as eligible for this review were those that examined the clinical benefits of therapeutic strategies in terms of preventing ischemic strokes. Results: A total of 32 studies met the established selection criteria. The included studies showed that pioglitazone treatment significantly reduced the risk for recurrent stroke in patients with DM. Furthermore, in the context of primary prevention, the improvement in glycemic control after treatment with the glucagon-like peptide-1 receptor agonists (GLP-1RA) semaglutide and dulaglutide was associated with a reduction in the risk of ischemic stroke in diabetic subjects. Metformin monotherapy may reduce stroke risk, while dipeptidyl peptidase 4 inhibitors, sodium-glucose co-transporter 2 inhibitors, and insulin do not seem to affect the incidence of stroke. Conclusions: The findings of the present systematic review suggest that pioglitazone and GLP-1RA may decrease the risk of stroke. Further studies are needed to provide additional data regarding the preventive effect of novel antidiabetic drugs, such as dual glucose-dependent insulinotropic polypeptide/GLP-1RA agents, on stroke.

Mechanical versus Biological Valve Prostheses for Infective Endocarditis Presenting with Stroke.

Objectives: This study aimed to compare the clinical outcomes of mechanical and biological valve prostheses in patients with infective endocarditis presenting with stroke. Methods: Ninety-five adults with infective endocarditis complicated by stroke at baseline who underwent aortic and/or mitral valve replacement were analyzed retrospectively. The primary outcome was a composite outcome of all-cause mortality, ischemic stroke, hemorrhagic stroke, and re-endocarditis. Secondary outcomes included the individual components of the composite outcome and modified Rankin scale deterioration during follow-up. Results: Among the study cohort, 34 patients (35.8%) received mechanical valve prostheses and 61 (64.2%) received biological valve prostheses. Implantation of a mechanical valve prosthesis seems to be associated with a decreased risk of attaining the composite outcome (adjusted HR 0.46, 95% CI 0.22-0.96, and p = 0.037). Analyses of the individual components of the composite outcome showed that implantation of a mechanical valve prosthesis might not be associated with an increased risk of ischemic stroke, hemorrhagic stroke, and all-cause mortality during the follow-up period. Further, the risk of re-endocarditis was significantly lower in recipients of a mechanical valve prosthesis (adjusted HR 0.15, 95% CI 0.06-0.77, p = 0.026). Notably, a trend toward decreased risk of modified Rankin scale deterioration throughout the follow-up period was observed in this group (adjusted odds ratio 0.22, 95% CI 0.05-1.02, p = 0.053). Conclusions: Implantation of mechanical valve prostheses in patients presenting with infective endocarditis complicated by stroke seems to be beneficial in terms of a reduced risk of experiencing a composite outcome. Analyses of larger cohorts are required to validate our findings.

Causal relationship between novel antidiabetic drugs and ischemic stroke: a drug-targeted Mendelian randomization study.

The escalating global economic burden of ischemic stroke poses a significant public health challenge amid global aging trends. The broad therapeutic efficacy of new antidiabetic drugs may offer new options in the prevention and treatment of ischemic stroke. Consistent conclusions regarding the relationship between novel antidiabetic agents and the risk of ischemic stroke remain elusive, and the causal relationship deserves further investigation. Three novel antidiabetic drug targets were selected, and cis-expression quantitative trait loci (cis-eQTL) were screened as instrumental variables. Genetic association data for ischemic stroke were obtained from the Genome-wide Association Study (GWAS) database. Mendelian randomization (MR) analysis, facilitated by R software, calculated MR estimates for each single nucleotide polymorphism (SNP), and meta-analysis was performed using five methods. To ensure robustness, sensitivity analyses, heterogeneity analyses, horizontal pleiotropy analyses, and co-localization analyses were conducted for significant MR associations. Three eQTLs for antidiabetic drug genes served as instrumental variables, utilizing a GWAS dataset comprising 34,217 cases and 406,111 controls for ischemic stroke. Genetic variants in glucagon-like peptide-1 receptor agonists (GLP-1 RA) targets exhibited a positive correlation with ischemic stroke risk (OR 1.06, 95% CI 1.04-1.08, P = 0.000), while genetic variation in dipeptidyl peptidase 4 inhibitors (DPP-4i) targets showed a negative association with ischemic stroke risk (OR 0.93, 95% CI 0.89-0.97, P = 0.003). Sensitivity analyses supported robust conclusions, revealing no heterogeneity or horizontal pleiotropy. This study found that GLP-1 RA and DPP-4i were associated with an increased risk of ischemic stroke by MR analysis. Although sensitivity analyses provide support for this result, it contradicts previous knowledge. Therefore, the results of this study still need to treated with caution. Updated and more in-depth GWAS data and high-quality real-world data are expected to validate the results.

Left Atrial Appendage Occlusion vs Standard of Care After Ischemic Stroke Despite Anticoagulation

Patients with atrial fibrillation (AF) who have ischemic stroke despite taking oral anticoagulation therapy (OAT) have a very high risk of recurrence. Left atrial appendage occlusion (LAAO) is a mechanical stroke prevention strategy that may provide additional protection in patients with thromboembolic events under OAT. To compare percutaneous LAAO with continuing OAT alone regarding stroke prevention in patients with AF who had a thromboembolic event despite taking OAT. This cohort study was a propensity score-matched comparison of the STR-OAC LAAO cohort, an international collaboration of 21 sites combining patients from multiple prospective registries of patients who underwent LAAO between 2010 and 2022. STR-OAC LAAO cohort patients who had follow-up longer than 3 months were propensity score-matched to a previously published control cohort comprising patients from an established international collaboration of investigator-initiated prospective studies. This control cohort included patients with nonvalvular AF, recent ischemic stroke or transient ischemic attack, and follow-up longer than 3 months who were taking OAT before the index event. Analyses were adjusted for imbalances in gender, age, hypertension, diabetes, and CHA2 DS2-VASc score. Left atrial appendage occlusion vs continuation of oral anticoagulation therapy alone (control group). The primary outcome was time to first ischemic stroke. Four hundred thirty-three patients from the STR-OAC LAAO cohort (mean [SD] age, 72 [9] years; 171 [39%] females and 262 [61%] males; mean [SD] CHA2 DS2-VASc score, 5.0 [1.6]) were matched to 433 of 1140 patients (38%) from the control group. During 2-year follow-up, 50 patients experienced ischemic stroke: an annualized event rate of 2.8% per patient-year in the STR-OAC LAAO group vs 8.9% per patient-year in the control group. Left atrial appendage occlusion was associated with a lower risk of ischemic stroke (hazard ratio, 0.33; 95% CI, 0.19-0.58; P < .001) compared with the control group. After LAAO, OAT was discontinued in 290 patients (67%), and the remaining 143 patients (33%) continued OAT after LAAO as an adjunctive therapy. In patients with nonvalvular AF and a prior thromboembolic event despite taking OAT, LAAO was associated with a lower risk of ischemic stroke compared with continued OAT alone. Randomized clinical trial data are needed to confirm that LAAO may be a promising treatment option for this population with a very high risk of stroke.

Adherence to Dietary Approaches to Stop Hypertension (DASH) Diet as a Protective Factor for Ischemic Stroke and Its Influence on Disability Level: A Case-Control Study in Lebanon.

Hypertension is a major risk factor for ischemic stroke. An important strategy in controlling hypertension is dietary modification. The present study evaluates the effect of Dietary Approaches to Stop Hypertension (DASH) diet on the risk of ischemic stroke. A case-control study was carried out, including 214 ischemic stroke cases recruited within the first 48 h of diagnosis and 214 controls, divided equally into hospitalized and non-hospitalized participants. Controls were matched to cases based on age and gender. Socio-demographic characteristics were assessed, in addition to adherence to the DASH diet, which was measured using a preconstructed DASH diet index (ranging from 0 (lowest) to 11 (highest)). For stroke patients, Modified Rankin Score (mRS) was measured to assess disability. Smoking, hypertension, hyperlipidemia, atrial fibrillation, and myocardial infarction were significantly associated with ischemic stroke (p < 0.001). Higher adherence to the DASH diet was correlated to lower rates of stroke, where cases scored 5.042 ± 1.486 compared to 6.654 ± 1.471 for controls (p < 0.001). Eating more grains, vegetables, fruits, dairy products, nuts, seeds, and beans, and lower levels of fat, fewer sweets, and less sodium were associated with lower rates of ischemic stroke (p = 0.038 for sweets and p < 0.001 for all the remaining), while meat, poultry, and fish did not have any significant effect (p = 0.46). A multivariate analysis showed that lower adherence to the DASH diet (p < 0.001, OR: 0.526, CI95% 0.428-0.645) was associated with a higher incidence of ischemic stroke and an increased likelihood of having high disability levels (mRS 5-6) (p = 0.041, OR: 2.49 × 10-8, CI95% 0-2.49 × 10-8). The relation between the DASH diet and risk of stroke highlights the necessity for strict adherence to dietary restrictions, suggesting a protective role for the DASH diet in stroke pathogenesis and prognosis.

Six-year change in high-sensitivity cardiac troponin T with subsequent stroke risk in the general population

BackgroundThe association between change in high-sensitivity cardiac troponin T (hs-cTnT) and stroke risk in the general population remains unknown. We aimed to assess the association of a 6-year change in...

Achievement of guideline-recommended target blood pressure is associated with reducing the risk of hemorrhagic and ischemic stroke in Japanese coronary artery disease patients -the CLIDAS study-

Achievement of guideline-recommended target blood pressure is associated with reducing the risk of hemorrhagic and ischemic stroke in Japanese coronary artery disease patients -the CLIDAS study-

Viral Infection and Ischemic Stroke: Emerging Trends and Mechanistic Insights.

Population studies have suggested that viral infections may be contributing to risk of ischemic stroke, although the mechanisms for this are unclear. In this review, we examine the epidemiological evidence supporting the involvement of viral diseases, including influenza, COVID-19, chronic herpesvirus infections, and hepatitis C in current trends of stroke incidence. To support these associations, we highlight the virus-host interactions that are critical in the context of stroke, including direct effects of acute and persistent viral infections on vascular function, inflammation, and thrombosis. Additionally, we evaluate the systemic changes that occur during viral infection that can predispose individuals to ischemic stroke, including alterations in blood pressure regulation, coagulation, and lipid metabolism. Our review emphasizes the need to further elucidate precise mechanisms involved in viral infections and stroke risk. Future research will inform the development of targeted interventions for stroke prevention in the context of viral diseases.

Identification of Disulfidptosis-Related Genes in Ischemic Stroke by Combining Single-Cell Sequencing, Machine Learning Algorithms, and In Vitro Experiments

BackgroundIschemic stroke (IS) is a severe neurological disorder with a pathogenesis that remains incompletely understood. Recently, a novel form of cell death known as disulfidptosis has garnered significant attention in the field of ischemic stroke research. This study aims to investigate the mechanistic roles of disulfidptosis-related genes (DRGs) in the context of IS and to examine their correlation with immunopathological features.MethodsTo enhance our understanding of the mechanistic underpinnings of disulfidptosis in IS, we initially retrieved the expression profile of peripheral blood from human IS patients from the GEO database. We then utilized a suite of machine learning algorithms, including LASSO, random forest, and SVM-RFE, to identify and validate pivotal genes. Furthermore, we developed a predictive nomogram model, integrating multifactorial logistic regression analysis and calibration curves, to evaluate the risk of IS. For the analysis of single-cell sequencing data, we employed a range of analytical tools, such as "Monocle" and "CellChat," to assess the status of immune cell infiltration and to characterize intercellular communication networks. Additionally, we utilized an oxygen–glucose deprivation (OGD) model to investigate the effects of SLC7A11 overexpression on microglial polarization.ResultsThis study successfully identified key genes associated with disulfidptosis and developed a reliable nomogram model using machine learning algorithms to predict the risk of ischemic stroke. Examination of single-cell sequencing data showed a robust correlation between disulfidptosis levels and the infiltration of immune cells. Furthermore, "CellChat" analysis elucidated the intricate characteristics of intercellular communication networks. Notably, the TNF signaling pathway was found to be intimately linked with the disulfidptosis signature in ischemic stroke. In an intriguing finding, the OGD model demonstrated that SLC7A11 expression suppresses M1 polarization while promoting M2 polarization in microglia.ConclusionThe significance of our findings lies in their potential to shed light on the pathogenesis of ischemic stroke, particularly by underscoring the pivotal role of disulfidptosis-related genes (DRGs). These insights could pave the way for novel therapeutic strategies targeting DRGs to mitigate the impact of ischemic stroke.

Cerebral Embolic Protection Devices: Are There Any Indications in Transcatheter Aortic Valve Replacement?

Stroke following transcatheter aortic valve replacement (TAVR) is a significant and life-threatening adverse event. The vast majority of these incidents occur during the TAVR procedure or within the first 24 h following TAVR, with a notable prevalence of cerebral embolic events. In response to this concern, cerebral embolic protection devices (CEPDs) have been designed to mitigate the risk of peri-procedural ischemic stroke during TAVR. The primary objective of CEPDs is to diminish the intraprocedural burden associated with new silent ischemic brain injuries. Despite the development of several CEPDs, their clinical efficacy remains uncertain. In this review, we delve into a comprehensive analysis of the utilization of CEPDs in patients undergoing TAVR, exploring insights from the existing literature. Additionally, we aim to present future perspectives and discuss the clinical implications associated with the incorporation of CEPDs in TAVR procedures.

Comprehensive analysis of molecular, physiological, and functional biomarkers of aging with neurological diseases using Mendelian randomization.

An increasing burden of neurological diseases (NDs) has been a public health challenge in an aging society. Age, especially biological age, is the most important risk factor for NDs. Identification of biomarkers of aging to capture NDs might lead to a better understanding of the underlying mechanisms of pathological brain aging and the implementation of effective intervention. We conducted a comprehensive two-sample Mendelian Randomization (MR) study to investigate the association between various biomarkers of aging and three leading causes of NDs: Alzheimer's disease (AD), vascular dementia (VaD), and ischemic stroke. Publicly available GWAS summary statistics on people from European ancestry were obtained for six molecular biomarkers, two physiological biomarkers, and eight functional biomarkers, and three NDs. Genetic variants serving as instrumental variables (IVs) were identified for each biomarker. The MR analysis included inverse variance weighted (IVW), weighted median, MR-Egger, and MR-PRESSO. We found that short telomere length and decrease in appendicular lean mass were associated with an increased risk for AD (OR IVW = 1.12 per 1SD decrease, 95% confidence interval 1.02-1.22, and OR IVW = 1.11, 1.06-1.16, respectively), whereas high frailty index showed a protective effect for AD. Accelerated BioAge appeared to be associated with increased risk for ischemic stroke (OR IVW = 1.3 per year in BioAge acceleration, 95% CI 1.19-1.41). Our findings implied a causal association of short telomere length and a decrease in appendicular lean mass with an increased risk for AD, while BioAge appeared to be a good biomarker for ischemic stroke. Further studies are needed to validate these associations and explore underlying mechanisms.

Obesity and Environmental Risk Factors Significantly Modify the Association between Ischemic Stroke and the Hero Chaperone C19orf53.

The unique chaperone-like properties of C19orf53, discovered in 2020 as a "hero" protein, make it an intriguing subject for research in relation to ischemic stroke (IS). Our pilot study aimed to investigate whether C19orf53 SNPs are associated with IS. DNA samples from 2138 Russian subjects (947 IS and 1308 controls) were genotyped for 7 C19orf53 SNPs using probe-based PCR. Dominant (D), recessive (R), and log-additive (A) regression models in relation to the effect alleles (EA) were used to interpret associations. An increased risk of IS was associated with rs10104 (EA G; Pbonf(R) = 0.0009; Pbonf(A) = 0.0004), rs11666524 (EA A; Pbonf(R) = 0.003; Pbonf(A) = 0.02), rs346158 (EA C; Pbonf(R) = 0.006; Pbonf(A) = 0.045), and rs2277947 (EA A; Pbonf(R) = 0.002; Pbonf(A) = 0.01) in patients with obesity; with rs11666524 (EA A; Pbonf(R) = 0.02), rs346157 (EA G; Pbonf(R) = 0.036), rs346158 (EA C; Pbonf(R) = 0.005), and rs2277947 (EA A; Pbonf(R) = 0.02) in patients with low fruit and vegetable intake; and with rs10104 (EA G; Pbonf(R) = 0.03) and rs11666524 (EA A; Pbonf(R) = 0.048) in patients with low physical activity. In conclusion, our pilot study provides comprehensive genetic and bioinformatic evidence of the involvement of C19orf53 in IS risk.

Migraine and Stroke: A Scoping Review.

An increased risk of ischemic stroke in migraine with aura (MA) has been consistently demonstrated. The pathophysiology of risk factors is not yet well understood. Several mechanisms have been proposed to explain the association between MA and ischemic stroke including decreased focal cerebral blood flow and other phenomena linked with cortical spreading depression (CSD) as well as neurovascular pathology, which appear to play a key role in MA. In addition to genetic predisposition, other classic stroke risk factors such as atrial fibrillation, emboli, migraine-associated vasculopathy, endothelial dysfunction, platelet dysfunction, coagulation pathway abnormalities, and inflammatory factors have been examined and investigated. For further clarification, distinctions have been made between features of migrainous infarctions and non-migrainous infarctions among migraineurs. Furthermore, the association is less clear when considering the mixed results studying the risk of ischemic stroke in migraines without aura (MO) and the risk of hemorrhagic stroke in people with all types of migraine. Translational research is investigating the role of biomarkers which can help identify vascular links between stroke and migraine and lead to further treatment developments. We performed a scoping review of the PubMed database to further characterize and update the clinical connections between migraine and stroke.

Are There any Differences in the Outcome of Non-valvular AF Patients with Moderate CKD, Taking Rivaroxaban or Warfarin?

Background: Warfarin has long been a reliable anticoagulant, prized for its affordability and extensive track record. However, with advancements in anticoagulant therapies, many uses of warfarin have been replaced by Novel Oral Anticoagulant (NOAC) agents. Atrial fibrillation (AF) is the most common heart rhythm disorder, affecting approximately 3% of the population. This arrhythmia significantly increases the risk of both morbidity and mortality, with the risk of ischemic stroke being five times higher compared to those without AF. The outcomes for patients with different comorbidities may vary when treated with either Rivaroxaban or Warfarin. Objectives: This study aims to evaluate renal function outcomes in AF patients with moderate chronic kidney disease (CKD) who are treated with either Warfarin or Rivaroxaban. Methods: This prospective cohort study involved 99 patients recently diagnosed with non-valvular AF (&lt; 1 year) and moderate CKD, who were treated with either Warfarin or Rivaroxaban. These patients were followed for one year after their initial presentation to our center. Laboratory data and other relevant documents were collected at each visit until the conclusion of the study year. Data were analyzed using SPSS version 27, with chi-square tests and t-tests applied as appropriate. Results: The study included two groups: 25 patients on Warfarin and 74 patients on Rivaroxaban. Gender and other demographic factors were evenly distributed between the two groups. The mean glomerular filtration rate (GFR) in the Rivaroxaban group improved non-significantly at 6 and 12 months, whereas a slight, non-significant decrease in GFR was observed in the Warfarin group. Acute kidney injury (AKI) occurred in 2 patients in the Rivaroxaban group. Gastrointestinal bleeding was reported in 5 patients, with incidents evenly distributed between the two groups. Conclusions: There was no significant difference in renal outcomes between patients with newly diagnosed non-valvular AF (&lt; 1 year) with moderate CKD treated with Warfarin or Rivaroxaban. However, for women with hypertension or high-risk thrombosis, Rivaroxaban may be associated with better renal outcomes.