Alcohol consumption may be a risk factor for cerebrovascular stenosis in acute ischemic stroke and transient ischemic attack.

BACKGROUND: Atherosclerosis are well established risk factors for ischemic stroke, however the association between alcohol consumption and atherosclerosis is controversial. This study aims to explore the potential correlation between alcohol consumption and cerebral stenosis in patients with acute ischemic stroke and transient ischemic attack (TIA). METHODS: Nine hundreds and eighty-eight patients with first acute ischemic stroke attack or TIA were recruited retrospectively. Alcohol consumption was classified into five consumption categories (non-drinkers, occasional drinkers, < 140 g per week [mild drinkers], 140-279 g per week [moderate drinkers], ≥ 280 g per week [heavy drinkers]). Computed tomography angiography (CTA) and digital subtraction angiography (DSA) were utilized to assess the carotid and cerebral artery in all patients. Five-step scale for degree of stenosis was applied: normal (0, 0 points), mild (< 50%, 1 point), moderate (50-69%, 2 points), severe (70-99%, 3 points), and occlusion (100%, 4 points). RESULTS: The carotid and cerebral artery stenosis scores were positively correlated with moderate alcohol consumption (B = 1.695, P < 0.001). Compared with nondrinkers, moderate alcohol consumption had significant increasing risk of moderate carotid and cerebral artery stenosis (OR = 4.28, 95% CI: 1.47-12.49, P = 0.008) and severe stenosis (OR = 4.24, 95% CI: 1.55-11.64, P = 0.005) and occlusion (OR = 3.87, 95% CI: 1.65-9.06, P = 0.002). Compared with nondrinkers, heavy alcohol consumption patients had significant higher risk of carotid and cerebral artery occlusion (OR = 2.71, 95% CI: 1.36-5.41, P = 0.005). CONCLUSIONS: Higher alcohol consumption may associate with higher risk and more severity of carotid and cerebrovascular stenosis.

Inflammatory factors mediated the effect of air pollution on ischemic stroke: a two-step, mediation Mendelian randomization study.

OBJECTIVE: Numerous investigations have indicated a correlation between air pollution (AP) and an elevated ischemic stroke (IS) likelihood. The existing literature does not provide a consensus about the possible link between AP and IS. A two-sample Mendelian randomization (MR) analysis was utilized to systematically measure the causal link between AP and ischemic stroke. Furthermore, the mediating impact of inflammatory factors was also performed by a two-step MR. MATERIALS AND METHODS: A two-sample MR analysis was utilized to examine the AP impact on the incidence of IS. Additionally, a two-step MR approach was carried out to account for possible mediating variables. The indirect impact was determined by employing the product approach, which included multiplying the AP impact on inflammatory factors by the inflammatory factors' impacts on IS. The MR effect was identified through inverse variance-weighted (IVW) meta-analysis of each Wald Ratio. Additionally, complementary studies were conducted using the weighted median and MR-egger approaches. RESULTS: The IVW method with random effects showed that the per unit increase in genetically predicted PM2.5 was linked to the 0.362-fold elevated ischemic stroke risk (OR: 1.362, 95% CI: 1.032-1.796, p=0.029). Furthermore, the IVM technique, incorporating random effects, demonstrated that the per unit increase in genetically predicted PM2.5 was related to an elevated Interleukin (IL)-1ß risk (OR: 1.529, 95% CI: 1.191-1.963, p=0.001), IL-6 (OR: 1.498, 95% CI: 1.094-2.052, p=0.012) and IL-17 (OR: 1.478, 95% CI: 1.021-2.139, p=0.038). IL-1ß, IL-6, and IL-17 modulated the PM2.5 impact on ischemic stroke, while the proportion mediated by them was 59.5%. CONCLUSIONS: A positive correlation between genetically predicted PM2.5 levels and elevated ischemic stroke risk is mediated by IL-1ß, IL-6, and IL-17.

Stroke Risk After COVID-19 Bivalent Vaccination Among US Older Adults.

Importance: In January 2023, the US Centers for Disease Control and Prevention and the US Food and Drug Administration noted a safety concern for ischemic stroke among adults aged 65 years or older who received the Pfizer-BioNTech BNT162b2; WT/OMI BA.4/BA.5 COVID-19 bivalent vaccine. Objective: To evaluate stroke risk after administration of (1) either brand of the COVID-19 bivalent vaccine, (2) either brand of the COVID-19 bivalent plus a high-dose or adjuvanted influenza vaccine on the same day (concomitant administration), and (3) a high-dose or adjuvanted influenza vaccine. Design, Setting, and Participants: Self-controlled case series including 11 001 Medicare beneficiaries aged 65 years or older who experienced stroke after receiving either brand of the COVID-19 bivalent vaccine (among 5 397 278 vaccinated individuals). The study period was August 31, 2022, through February 4, 2023. Exposures: Receipt of (1) either brand of the COVID-19 bivalent vaccine (primary) or (2) a high-dose or adjuvanted influenza vaccine (secondary). Main Outcomes and Measures: Stroke risk (nonhemorrhagic stroke, transient ischemic attack, combined outcome of nonhemorrhagic stroke or transient ischemic attack, or hemorrhagic stroke) during the 1- to 21-day or 22- to 42-day risk window after vaccination vs the 43- to 90-day control window. Results: There were 5 397 278 Medicare beneficiaries who received either brand of the COVID-19 bivalent vaccine (median age, 74 years [IQR, 70-80 years]; 56% were women). Among the 11 001 beneficiaries who experienced stroke after receiving either brand of the COVID-19 bivalent vaccine, there were no statistically significant associations between either brand of the COVID-19 bivalent vaccine and the outcomes of nonhemorrhagic stroke, transient ischemic attack, nonhemorrhagic stroke or transient ischemic attack, or hemorrhagic stroke during the 1- to 21-day or 22- to 42-day risk window vs the 43- to 90-day control window (incidence rate ratio [IRR] range, 0.72-1.12). Among the 4596 beneficiaries who experienced stroke after concomitant administration of either brand of the COVID-19 bivalent vaccine plus a high-dose or adjuvanted influenza vaccine, there was a statistically significant association between vaccination and nonhemorrhagic stroke during the 22- to 42-day risk window for the Pfizer-BioNTech BNT162b2; WT/OMI BA.4/BA.5 COVID-19 bivalent vaccine (IRR, 1.20 [95% CI, 1.01-1.42]; risk difference/100 000 doses, 3.13 [95% CI, 0.05-6.22]) and a statistically significant association between vaccination and transient ischemic attack during the 1- to 21-day risk window for the Moderna mRNA-1273.222 COVID-19 bivalent vaccine (IRR, 1.35 [95% CI, 1.06-1.74]; risk difference/100 000 doses, 3.33 [95% CI, 0.46-6.20]). Among the 21 345 beneficiaries who experienced stroke after administration of a high-dose or adjuvanted influenza vaccine, there was a statistically significant association between vaccination and nonhemorrhagic stroke during the 22- to 42-day risk window (IRR, 1.09 [95% CI, 1.02-1.17]; risk difference/100 000 doses, 1.65 [95% CI, 0.43-2.87]). Conclusions and Relevance: Among Medicare beneficiaries aged 65 years or older who experienced stroke after receiving either brand of the COVID-19 bivalent vaccine, there was no evidence of a significantly elevated risk for stroke during the days immediately after vaccination.

Thrombolysis increases the risk of persistent headache attributed to ischemic stroke: A prospective observational study.

BACKGROUND AND OBJECTIVE: Persistent headache attributed to ischemic stroke (PHPIS) is increasingly acknowledged and was added to the 2018 ICHD-3. Intravenous thrombolysis (IVT) is a common treatment for acute ischemic stroke. It remains unknown whether this treatment influences the occurrence of a persistent poststroke headache. We aimed to describe the incidence and clinical characteristics of persistent headaches occurring after acute ischemic stroke in patients with or without IVT and explore the risk factors. METHODS: A prospective observational study was performed between the 234 individuals who received IVT and 226 individuals without IVT in 5 stroke units from Wuhan, China. Subjects were followed for 6 months after stroke via a structured questionnaire. RESULTS: Age, gender, vascular risk factors, and infarct location/ circulation distribution did not differ between the groups, although IVT group had higher initial NIHSS scores. At the end of the follow-up, 12.0% (55/460) of subjects reported persistent headaches after ischemic stroke. The prevalence of persistent headache was significantly higher in the IVT group than non-IVT group (15.4% vs. 8.4%, p = .021). Patients with younger age (p = .033; OR 0.97; 95% CI 0.939-0.997), female sex (p = .007; OR 2.40; 95% CI 1.269-4.520), posterior circulation infarct (p = .024; OR 2.19; 95% CI 1.110-4.311), and IVT (p = .005; OR 2.51; 95% CI 1.313-4.782) were more likely to develop persistent headache after ischemic stroke. CONCLUSION: The potential influence of IVT should be considered when assessing persistent poststroke headache. Future studies will investigate the underlying mechanisms.

Cardiomyopathy in Patients With Acute Ischemic Stroke and Methamphetamine Use: Relevance for Cardioembolic Stroke and Outcome.

BACKGROUND: Methamphetamine use has emerged as a major risk factor for cardiovascular and cerebrovascular disease in young adults. The aim of this study was to investigate a possible association of methamphetamine use with cardioembolic stroke. METHODS AND RESULTS: We performed a retrospective study of patients with acute ischemic stroke admitted at our medical center between 2019 and 2022. All patients were screened for methamphetamine use and cardiomyopathy, defined as left ventricular ejection fraction ≤45%. Among 938 consecutive patients, 46 (4.9%) were identified as using methamphetamine. Compared with the nonmethamphetamine group (n=892), the methamphetamine group was significantly younger (52.8±9.6 versus 69.7±15.2 years; P<0.001), included more men (78.3% versus 52.8%; P<0.001), and had a significantly higher rate of cardiomyopathy (30.4% versus 14.0%; P<0.01). They were also less likely to have a history of atrial fibrillation (8.7% versus 33.4%; P<0.01) or hyperlipidemia (28.3% versus 51.7%; P<0.01). Compared with patients with cardiomyopathy without methamphetamine use, the patients with cardiomyopathy with methamphetamine use had significantly lower left ventricular ejection fraction (26.0±9.59% versus 32.47±9.52%; P<0.01) but better functional outcome at 3 months, likely attributable to significantly younger age and fewer comorbidities. In the logistic regression model of clinical variables, methamphetamine-associated cardiomyopathy was found to be significantly associated with cardioembolic stroke (odds ratio, 1.79 [95% CI, 1.04-3.06]; P<0.05). CONCLUSIONS: We demonstrate that methamphetamine use is significantly associated with cardiomyopathy and cardioembolic stroke in young adults.

Prevalence and impact of SARS-CoV-2 infection among patients with acute ischaemic stroke: a nationwide register-based cohort study in Denmark.

OBJECTIVES: An increased risk of stroke has been reported among patients with COVID-19 caused by SARS-CoV-2. We aimed to investigate the nationwide prevalence of SARS-CoV-2 among patients with acute ischaemic stroke and to study the impact on stroke severity, quality of care and mortality on an individual patient level. DESIGN: This was a nationwide register-based cohort study. SETTING: We used data from several Danish registers which were linked at an individual patient level using the unique civil registration number assigned to all Danish citizens. Patients were identified from the Danish Stroke Registry and information on SARS-CoV-2 infection status was collected from the Danish National COVID-19 Registry. Concurrent SARS-CoV-2 infection was defined as a positive PCR test within 31 days prior to, and 1 day after, stroke admission. Information on comorbidity was collected from the Danish National Patient Registry and information on vital status was collected from the Danish Civil Registration System. PARTICIPANTS: A total of 11 502 patients admitted with acute ischaemic stroke from 10 March 2020 to 31 May 2021 were included in the study. RESULTS: Among the included patients, the majority (84.6%) were tested for SARS-CoV-2, but only 68 had a positive test. These patients were more prone to have atrial fibrillation and were more often treated with reperfusion therapy. They had a significantly increased risk of severe stroke (adjusted relative risk (aRR) 1.93, 95% CI: 1.22 to 3.04) and a significantly increased 30-day mortality risk (aRR 2.29, 95% CI: 1.19 to 4.39). There was no difference in the proportion of patients fulfilling relevant performance measures on quality of care. CONCLUSION: In this nationwide study, only 0.6% of patients with acute ischaemic stroke were tested positive for a concurrent SARS-CoV-2 infection. The patients with SARS-CoV-2 presented with more severe strokes.

Development and Validation of Machine Learning Algorithms to Predict 1-Year Ischemic Stroke and Bleeding Events in Patients with Atrial Fibrillation and Cancer.

In this study, we leveraged machine learning (ML) approach to develop and validate new assessment tools for predicting stroke and bleeding among patients with atrial fibrillation (AFib) and cancer. We conducted a retrospective cohort study including patients who were newly diagnosed with AFib with a record of cancer from the 2012-2018 Surveillance, Epidemiology, and End Results (SEER)-Medicare database. The ML algorithms were developed and validated separately for each outcome by fitting elastic net, random forest (RF), extreme gradient boosting (XGBoost), support vector machine (SVM), and neural network models with tenfold cross-validation (train:test = 7:3). We obtained area under the curve (AUC), sensitivity, specificity, and F2 score as performance metrics. Model calibration was assessed using Brier score. In sensitivity analysis, we resampled data using Synthetic Minority Oversampling Technique (SMOTE). Among 18,388 patients with AFib and cancer, 523 (2.84%) had ischemic stroke and 221 (1.20%) had major bleeding within one year after AFib diagnosis. In prediction of ischemic stroke, RF significantly outperformed other ML models [AUC (0.916, 95% CI 0.887-0.945), sensitivity 0.868, specificity 0.801, F2 score 0.375, Brier score = 0.035]. However, the performance of ML algorithms in prediction of major bleeding was low with highest AUC achieved by RF (0.623, 95% CI 0.554-0.692). RF models performed better than CHA2DS2-VASc and HAS-BLED scores. SMOTE did not improve the performance of the ML algorithms. Our study demonstrated a promising application of ML in stroke prediction among patients with AFib and cancer. This tool may be leveraged in assisting clinicians to identify patients at high risk of stroke and optimize treatment decisions.

Enhancing the evaluation of acute ischemic stroke risk in individuals with non-valvular atrial fibrillation by including laboratory indicators.

To investigate the clinical significance of the CHA2DS2-VASc-60 score, lipoprotein (a) [Lp(a)], red blood cell distribution width (RDW), and their combined effect in patients with non-valvular atrial fibrillation (NVAF) who experience acute ischemic stroke (AIS). This retrospective analysis was conducted on the clinical data of hospitalized patients with NVAF at the Third Affiliated Hospital of Anhui Medical University between April 1, 2020, and April 1, 2023. Based on the diagnosis of acute ischemic stroke (AIS), the patients were divided into two groups: the AIS group (150 cases of NVAF patients with comorbid AIS) and the non-AIS group (163 cases of NVAF patients without AIS). We performed CHA2DS2-VASc-60 scoring for all patients and collected their laboratory indicators and echocardiographic indicators during hospitalization. The study comprised 313 individuals with NVAF in total. There is a statistically significant difference (P < 0.05) in the comparison of CHA2DS2-VASc-60 score (5.68 ± 1.12 vs. 3.67 ± 1.47), Lp(a) [23.98 (13.28, 42.22) vs. 14.32 (7.96, 21.91)] and RDW (13.67 ± 1.25 vs. 12.94 ± 0.76) between NVAF patients with and without concomitant AIS. The results of the Spearman correlation analysis demonstrate a positive association between Lp(a) and RDW levels and both the CHA2DS2-VASc score and the CHA2DS2-VASc-60 score in patients with NVAF. Multivariate logistic regression analysis revealed that CHA2DS2-VASc-60 score [OR = 6.549, 95% CI: 4.110-10.433, P < 0.05], Lp(a) [OR = 1.023, 95% CI: 1.005-1.041, P < 0.05], and RDW [OR = 1.644, 95% CI: 1.071-2.525, P < 0.05] were independent risk factors for AIS in patients with non-valvular atrial fibrillation (NVAF). The receiver operator characteristic (ROC) curves showed that the area under the curve of CHA2DS2-VASc-60 score, Lp(a), RDW, and CHA2DS2-VASc-60 score combined with Lp(a) and RDW predicted that NVAF patients with AIS were 0.881 [95% CI: 0.804-0.906], 0.685 [95% CI: 0.626-0.744], 0.695 [95% CI: 0.637-0.754], and 0.906 [95% CI: 0.845-0.921], respectively. The CHA2DS2-VASc-60 score, Lp(a), and RDW were significantly increased in NVAF patients with AIS, which were independent risk factors for NVAF patients with AIS. The combination of the three has a high predictive capacity for NVAF patients with AIS.

Differences in Receipt of Neurologist Evaluation During Hospitalization for Ischemic Stroke by Race, Sex, Age, and Region: The REGARDS Study.

BACKGROUND AND OBJECTIVES: Improving access to health care providers with clinical expertise in stroke care may influence the use of recommended strategies for reducing disparities in quality of care. Few studies have examined differences in the receipt of evaluation by neurologists during the hospital stay. We examined the proportion of individuals hospitalized for acute ischemic stroke who received evaluation by a neurologist during the hospital stay and characterized differences in receipt of neurologist evaluation by race (Black vs White), sex, age, and study region (Stroke Belt residence vs other) among those experiencing a stroke who were participating in a national cohort study. METHODS: This cross-sectional study was conducted using medical record data abstracted from 1,042 participants enrolled in the national Reasons for Geographic and Racial Differences in Stroke cohort study (2003-2007) who experienced an adjudicated ischemic stroke between 2003 and 2016. Participants with a history of stroke before baseline, in-hospital death, hospice discharge following their stroke, or incomplete records were excluded resulting in 839 cases. Differences were assessed using modified Poisson regression adjusting for participant-level and hospital-level factors. RESULTS: Of the 839 incident strokes, 722 (86%) received evaluation by a neurologist during the hospital stay. There were no significant differences by age, race, or sex, yet Stroke Belt residents and those receiving care in rural hospitals were significantly less likely to receive neurologist evaluation compared with non-Stroke Belt residents (relative risk [RR] 0.95; 95% CI 0.90-1.01) and participants receiving care in urban hospitals (RR 0.74; 95% CI 0.63-0.86). Participants with a greater level of poststroke functional impairment (modified Rankin scale) and those with a greater number of risk factors were more likely to receive neurologist evaluation compared with those with lower levels of poststroke functional impairment (RR 1.04; 95% CI 1.01-1.06) and fewer risk factors (RR 1.02; 95% CI 1.00-1.04). DISCUSSION: While differences in access to neurologists during the hospital stay were partially explained by patient need in our study, there were also significant differences in access by region and urban-rural hospital status. Ensuring access to neurologists during the hospital stay in such settings may require policy-level and/or system-level changes.

Evaluating the risk of ischemic stroke at a young age in patients with autoimmune inflammatory rheumatic diseases: a population-based cohort study in Taiwan.

Background: Recent studies have demonstrated an increased incidence of ischemic stroke among patients with certain autoimmune inflammatory rheumatic diseases (AIIRDs). However, the associations between young stroke and AIIRDs have not been fully investigated. This study aimed to evaluate the risk of ischemic stroke among young patients with AIIRDs. Methods: The National Health Insurance Research Database in Taiwan was utilized to establish cohorts of patients with AIIRDs diagnosed between 2004 and 2015, who were compared with 1,000,000 control participants. Cox proportional hazards regression models were used to calculate the hazard ratio of ischemic stroke and young ischemic stroke for individual AIIRDs after adjustment for relative risk factors. Results: During the study period, a total of 64,120 patients with AIIRDss and 1,000,000 control patients were identified. The overall mean follow-up time was 5.33 years. There were 223 (0.8%) and 1,923 (0.3%) young ischemic stroke-related hospitalizations among patients with AIIRDs and controls, respectively. The incidence rate of young ischemic stroke was 0.08 in patients with rheumatoid arthritis, 0.08 in patients with Sjögren's syndrome, 0.26 in patients with systemic lupus erythematosus, 0.17 in patients with idiopathic inflammatory myositis, 0.24 in patients with systemic sclerosis, 0.05 in patients with Behçet's disease, and 0.44 in patients with systemic vasculitis, versus 0.05 per 100 person-years in the general population. The adjusted hazard ratios for young ischemic stroke were 1.07 (95% CI 0.70-1.43) for rheumatoid arthritis, 1.39 (95% CI 0.94-2.06) for Sjögren's syndrome, 5.79 (95% CI 4.68-7.17) for systemic lupus erythematosus, 2.07 for idiopathic inflammatory myositis (95% CI 0.98-4.38), 2.79 for systemic sclerosis (95% CI 1.38-5.63), 0.82 for Behçet's disease (95% CI 0.26-2.55), and 4.15 (95% CI 1.96-8.82) for systemic vasculitis. Conclusions: Patients younger than 50 years with systemic lupus erythematosus, systemic sclerosis, or systemic vasculitis have a significantly elevated risk of developing ischemic stroke. Further research is needed to elucidate the pathogenesis of accelerated atherosclerosis in these AIIRDs.

Hourly Heat Exposure and Acute Ischemic Stroke.

Importance: Previous studies have demonstrated the associations of daily high temperature with hospitalizations and mortality from ischemic stroke, but the hourly association of ambient heat and acute ischemic stroke (AIS) onset has been rarely examined. Objectives: To evaluate the association between hourly high ambient temperature and the onset of AIS. Design, Setting, and Participants: This time-stratified case-crossover study was conducted using a nationwide registry that collects data from more than 200 stroke centers in China. Participants were adult patients with AIS who were hospitalized in the warm seasons between January 1, 2019, and December 31, 2021. Exposures: Hourly temperature and single-hour temperature exposure lag up to 24 hours before the AIS onset (lag 0 hours to lag 24 hours). Main Outcomes and Measures: The main outcome was onset of AIS. Associations between hourly mean temperatures and AIS onset were analyzed using conditional logistic regression integrated with the distributed lag nonlinear model. Stratification analyses were applied to examine potential association modifiers. Several sensitivity analyses were conducted to examine the robustness of the results. Results: A total of 82 455 patients with AIS (mean [SD] age, 65.8 [11.9] years; 52 267 males [63.4%]) were included in the final analysis. A monotonically increasing risk of AIS onset was associated with higher temperatures. The excess AIS risk occurred immediately at lag 0 hours and persisted for 10 hours. Compared with the reference temperature (12.1 °C), the cumulative odds ratio (OR) over lag 0 to 10 hours of AIS onset associated with extremely high temperature (33.3 °C) was 1.88 (95% CI, 1.65-2.13) nationwide. The exposure-response curve was steeper in the north than in the south (OR, 1.80 [95% CI, 1.53-2.11] vs 1.57 [95% CI, 1.31-1.87]). The ORs were greater for males and patients with a history of dyslipidemia or atrial fibrillation, but the differences were not significant. Conclusions and Relevance: Results of this study suggest that hourly heat exposure is associated with increased risk of AIS onset. This finding may benefit the formulation of public health strategies to reduce cerebrovascular risk associated with high ambient temperature under global warming.

Causal relationship between lactate dehydrogenase and risk of developing ischemic stroke: A Mendelian randomized study.

BACKGROUND AND OBJECTIVE: Ischemic stroke (IS) is one of the major global health problems. It is not clear whether there is a causal relationship between lactate dehydrogenase (LDH) and the risk of IS attacks. The purpose of this study was to investigate whether LDH has a causal relationship with the development of IS. METHODS: The genome-wide association data of LDH and IS were obtained through a Mendelian randomization-based platform. Single nucleotide polymorphisms (SNP) that were significantly associated with LDH were identified and used as instrumental variables, and a two-sample Mendelian randomization study was used to examine the causal relationship between LDH and IS. The statistical methods included Inverse-variance weighted approach, MR-Egger regression, and weighted median estimator. RESULTS: We selected 15 SNPs of genome-wide significance from Genome-wide association study database with LDH as instrumental variables. A consistent causal association between LDH and IS was observed by different assessment methods. The results of the inverse-variance weighted method suggested an inverse association between LDH and higher genetic predictability of IS risk (OR, 0.997; 95%CI 0.995-0.999). The weighted median estimate showed consistent results with the MR-Egger method (weighted median estimate: OR, 0.995; 95%CI 0.992-0.999; MR-Egger method: OR, 0.996; 95%CI 0.992-0.999). The inverse-variance weighted method indicates a causal association between LDH and IS (ß = -0.002563, SE = 0.00128, p = .0453). MR-Egger analysis (ß = -0.004498, SE = 0.001877, p = .03) and the weighted median method suggested that LDH and IS also existed causal relationship (ß = -0.004861, SE = 0.001801, p = .00695). CONCLUSIONS: Our Mendelian randomization results suggest that LDH is inversely associated with the risk of developing IS, and are contrary to the results of previous observational studies.

Short-Term and Long-Term Risk of Recurrent Vascular Event by Cause After Ischemic Stroke in Young Adults.

Importance: Cause of ischemic stroke in young people is highly variable; however, the risk of recurrence is often presented with all subtypes of stroke grouped together in classification systems such as the Trial of ORG (danaparoid sodium [Orgaran]) 10172 in Acute Stroke Treatment (TOAST) criteria, which limits the ability to individually inform young patients with stroke about their risk of recurrence. Objective: To determine the short-term and long-term risk of recurrent vascular events after ischemic stroke at a young age by stroke cause and to identify factors associated with recurrence. Design, Setting, and Participants: This cohort study used data from the Observational Dutch Young Symptomatic Stroke Study, a prospective, multicenter, hospital-based cohort study, conducted at 17 hospitals in the Netherlands between 2013 and 2021. Eligible participants included 30-day survivors of an initial, neuroimaging-proven ischemic stroke (aged 18-49 years). Data analysis was conducted from June to July 2023. Exposure: Diagnosis of a first-ever, ischemic stroke via neuroimaging. Main Outcome and Measures: The primary outcome was short-term (within 6 months) and long-term (within 5 years) recurrence risk of any vascular event, defined as fatal or nonfatal recurrent ischemic stroke, transient ischemic attack, myocardial infarction, and revascularization procedure. Predefined characteristics were chosen to identify factors associated with risk of recurrence (cause of stroke, age, sex, stroke severity, and cardiovascular health factors). Results: A total of 1216 patients (median [IQR] age, 44.2 [38.4-47.7] years; 632 male [52.0%]; 584 female [48.0%]) were included, with a median (IQR) follow-up of 4.3 (2.6-6.0) years. The 6-month risk of any recurrent ischemic event was 6.7% (95% CI, 5.3%-8.1%), and the 5-year risk was 12.2% (95% CI, 10.2%-14.2%)The short-term risk was highest for patients with cervical artery dissections (13.2%; 95% CI, 7.6%-18.7%). Other factors associated with a recurrent short-term event were atherothrombotic stroke, rare causes of stroke, and hypertension. The long-term cumulative risk was highest for patients with atherothrombotic stroke (22.7%; 95% CI, 10.6%-34.7%) and lowest for patients with cryptogenic stroke (5.8%; 95% CI, 3.0%-8.5%). Cardioembolic stroke was associated with a recurrent long-term event, as were diabetes and alcohol abuse. Conclusions and Relevance: The findings of this cohort study of 1216 patients with an ischemic stroke at a young age suggest that the risk of recurrent vascular events was high and varied by cause of stroke both for short-term and long-term follow-up, including causes that remained concealed when combined into 1 category in the routinely used TOAST criteria. This knowledge will allow for more personalized counseling of young patients with stroke.

Prevalence of Fabry disease and GLA variants in young patients with acute stroke: The challenge to widen the screening. The Fabry-Stroke Italian Registry.

BACKGROUND: Fabry disease (FD) is a treatable X-linked lysosomal storage disorder caused by GLA gene variants leading to alpha-galactosidase A deficiency. FD is a rare cause of stroke, and it is still controversial whether in stroke patients FD should be searched from the beginning or at the end of the diagnostic workup (in cryptogenic strokes). METHODS: Fabry-Stroke Italian Registry is a prospective, multicentric screening involving 33 stroke units. FD was sought by measuring α-galactosidase A activity (males) and by genetic tests (males with reduced enzyme activity and females) in patients aged 18-60 years hospitalized for TIA, ischemic stroke, or intracerebral hemorrhage. We diagnosed FD in patients with 1) already known pathogenic GLA variants; 2) novel GLA variants if additional clinical, laboratory, or family-derived criteria were present. RESULTS: Out of 1906 patients, we found a GLA variant in 15 (0.79%; 95%CI 0.44-1.29) with a certain FD diagnosis in 3 (0.16%; 95%CI 0.03-0.46) patients, none of whom had hemorrhage. We identified 1 novel pathogenic GLA variant. Ischemic stroke etiologies in carriers of GLA variants were: cardioaortic embolism (33%), small artery occlusion (27%), other causes (20%), and undetermined (20%). Mild severity, recurrence, previous TIA, acroparesthesias, hearing loss, and small artery occlusion were predictors of GLA variant. CONCLUSION: In this large multicenter cohort the frequency of FD and GLA variants was consistent with previous reports. Limiting the screening for GLA variants to patients with cryptogenic stroke may miss up to 80% of diagnoses. Some easily recognizable clinical features could help select patients for FD screening.

Recurrent vascular events partially explain association between diabetes and poor prognosis in young ischemic stroke patients.

BACKGROUND AND AIMS: Stroke is the second leading cause of death and third leading cause of disability worldwide. There is an increasing incidence of stroke among the young. In this study, we aimed to identify factors associated with poor long-term prognosis in young stroke patients. METHODS: In this longitudinal observational study, we recruited 147 young ischemic stroke patients within one week of ischemic stroke and followed them up for functional outcome (modified Rankin score (mRS)), recurrent vascular events, and recurrent hospitalisation. Poor function was labelled as mRS score of 3 and above. We performed univariate and multivariable logistic regression analyses to determine factors associated with poor long term functional outcome. RESULTS: At a median follow-up of 7-years, 32 (22%) of the 147 patients had poor functional outcome. In multivariable analyses, diabetes mellitus (OR = 9.01, CI 3.15 to 26.92), was the only independent predictor of poor function. In analyses stratified by diabetic status, recurrent vascular events (OR = 4.47, CI 1.40 to 14.28) were associated with poor functional outcome within young diabetic patients but not in non-diabetic patients. CONCLUSIONS: Our findings suggest that diabetes mellitus affects long-term functional outcome in young ischemic stroke and that its effect is mediated partly by recurrent vascular events. DATA ACCESS STATEMENT: Data obtained from Multi-Centre Retinal study (MCRS), Singapore site. Data cannot be made publicly available due to potentially identifiable research participant information.

Blood Pressure Trajectories and Outcomes After Endovascular Thrombectomy for Acute Ischemic Stroke.

BACKGROUND: Data on systolic blood pressure (SBP) trajectories in the first 24 hours after endovascular thrombectomy (EVT) in acute ischemic stroke are limited. We sought to identify these trajectories and their relationship to outcomes. METHODS: We combined individual-level data from 5 studies of patients with acute ischemic stroke who underwent EVT and had individual blood pressure values after the end of the procedure. We used group-based trajectory analysis to identify the number and shape of SBP trajectories post-EVT. We used mixed effects regression models to identify associations between trajectory groups and outcomes adjusting for potential confounders and reported the respective adjusted odds ratios (aORs) and common odds ratios. RESULTS: There were 2640 total patients with acute ischemic stroke included in the analysis. The most parsimonious model identified 4 distinct SBP trajectories, that is, general directional patterns after repeated SBP measurements: high, moderate-high, moderate, and low. Patients in the higher blood pressure trajectory groups were older, had a higher prevalence of vascular risk factors, presented with more severe stroke syndromes, and were less likely to achieve successful recanalization after the EVT. In the adjusted analyses, only patients in the high-SBP trajectory were found to have significantly higher odds of early neurological deterioration (aOR, 1.84 [95% CI, 1.20-2.82]), intracranial hemorrhage (aOR, 1.84 [95% CI, 1.31-2.59]), mortality (aOR, 1.75 [95% CI, 1.21-2.53), death or disability (aOR, 1.63 [95% CI, 1.15-2.31]), and worse functional outcomes (adjusted common odds ratio,1.92 [95% CI, 1.47-2.50]). CONCLUSIONS: Patients follow distinct SBP trajectories in the first 24 hours after an EVT. Persistently elevated SBP after the procedure is associated with unfavorable short-term and long-term outcomes.

First-ever acute ischemic strokes in HIV-infected persons: A case-control study from stroke units.

OBJECTIVE: The stroke risk for persons living with human immunodeficiency virus (PLHIVs) doubled compared to uninfected individuals. Stroke-unit (SU)-access, acute reperfusion therapy-use and outcome data on PLHIVs admitted for acute ischemic stroke (AIS) are scarce. METHODS: AIS patients admitted (01 January 2017 to 31 January 2021) to 10 representative Paris-area SUs were screened retrospectively from the National Hospitalization Database. PLHIVs were compared to age-, initial NIHSS- and sex-matched HIV-uninfected controls (HUCs). Outcome was the 90-day modified Rankin Scale score. RESULTS: Among 126 PLHIVs with confirmed first-ever AIS, ~80% were admitted outside the thrombolysis-administration window. Despite antiretrovirals, uncontrolled plasma HIV loads exceeded 50 copies/mL (26% of all PLHIVs; 38% of those ≤55 years). PLHIVs' stroke causes by decreasing frequency were large artery atherosclerosis (LAA), undetermined, other cause, cerebral small-vessel disease (CSVD) or cardioembolism. No stroke etiology was associated with HIV duration or detectable HIVemia. MRI revealed previously unknown AIS in one in three PLHIVs, twice the HUC rate (p = 0.006). Neither group had optimally controlled modifiable cardiovascular risk factors (CVRFs): 20%-30% without specific hypertension, diabetes, and/or dyslipidemia treatments. Their stroke outcomes were comparable. Multivariable analyses retained good prognosis associated solely with initial NIHSS or reperfusion therapy. Older age and hypertension were associated with CSVD/LAA for all PLHIVs. Standard neurovascular care and reperfusion therapy were well-tolerated. INTERPRETATION: The high uncontrolled HIV-infection rate and suboptimal CVRF treatment support heightened vigilance to counter suboptimal HIV suppression and antiretroviral adherence, and improve CVRF prevention, mainly for younger PLHIVs. Those preventive, routine measures could lower PLHIVs' AIS risk.

Is Moderate/Large Residual Shunt After PFO Closure Justifiable for a Patient with a Prior History of Cryptogenic Stroke and Transient Ischemic Attack?

A 36-year-old woman suffered from an embolic stroke of an undetermined source documented by magnetic resonance imaging with residual right arm weakness. She underwent percutaneous patent foramen ovale (PFO) closure with an 18/25 mm device in another center. One year later, the patient suffered from a transient ischemic attack with dysarthria. She asked for a second opinion at our institution and a contrast-transthoracic (cTTE) /transesophageal echocardiography showed a large residual right-to-left shunt (RLS) through a still patent tunnel after PFO closure. Written informed consent for a redo procedure was obtained from the patient. A catheter-based closure of the residual shunt was therefore planned under local anesthesia and rotational intracardiac echo monitoring. A second equally sized disc (18/18 mm) device was successfully implanted without complications. The patient was discharged home the following day in good clinical condition. Dual antiplatelet therapy was recommended for the first 2 months and then single antiplatelet therapy up to 6 months. At the 6-month follow-up, the cTTE color Doppler showed the stable position of the two nitinol double-disc devices and the c-transcranial Doppler confirmed the abolition of the residual RLS.

Acute ischemic stroke prediction and predictive factors analysis using hematological indicators in elderly hypertensives post-transient ischemic attack.

Elderly hypertensive patients diagnosed with transient ischemic attack (TIA) are at a heightened risk for developing acute ischemic stroke (AIS). This underscores the critical need for effective risk prediction and identification of predictive factors. In our study, we utilized patient data from peripheral blood tests and clinical profiles within hospital information systems. These patients were followed for a three-year period to document incident AIS. Our cohort of 11,056 individuals was randomly divided into training, validation, and testing sets in a 5:2:3 ratio. We developed an XGBoost model, developed using selected indicators, provides an effective and non-invasive method for predicting the risk of AIS in elderly hypertensive patients diagnosed with TIA. Impressively, this model achieved a balanced accuracy of 0.9022, a recall of 0.8688, and a PR-AUC of 0.9315. Notably, our model effectively encapsulates essential data variations involving mixed nonlinear interactions, providing competitive performance against more complex models that incorporate a wider range of variables. Further, we conducted an in-depth analysis of the importance and sensitivity of each selected indicator and their interactions. This research equips clinicians with the necessary tools for more precise identification of high-risk individuals, thereby paving the way for more effective stroke prevention and management strategies.

Changing or Retaining Direct Oral Anticoagulant After Ischemic Stroke Despite Direct Oral Anticoagulant Treatment.

BACKGROUND: The optimal antithrombotic strategies for patients with atrial fibrillation who experience ischemic stroke (IS) despite direct oral anticoagulant (DOAC) therapy remain inconclusive. This study compared outcomes for patients with DOAC treatment failure who changed or retained their prestroke DOAC. METHODS AND RESULTS: This retrospective cohort study analyzed data from the National Health Insurance Research Database from 2012 to 2020. Patients with atrial fibrillation who experienced IS during DOAC therapy were assigned to either (1) the DOAC-change group: changing prestroke DOAC or (2) the DOAC-retain group: retaining prestroke DOAC. The primary outcome was a composite of recurrent IS and transient ischemic attack. The secondary outcomes included intracranial hemorrhage, major bleeding, systemic thromboembolism, and all-cause death. Propensity score-based inverse probability of treatment weighting was applied to balance the baseline characteristics between the DOAC-change and DOAC-retain groups. The Cox proportional hazards model compared the risk of outcomes between the 2 groups. In total, 1979 patients were enrolled (609 DOAC-change patients and 1370 DOAC-retain patients). The incidence rates of recurrent IS or transient ischemic attack were 7.20 and 6.56 per 100 person-years in the DOAC-change and DOAC-retain groups, respectively (hazard ratio [HR], 1.07 [95% CI, 0.87-1.30]). A nonsignificantly higher incidence rate of intracranial hemorrhage was observed in the DOAC-change group compared with the DOAC-retain group (0.75 versus 0.53 per 100-person-years; HR, 1.49 [95% CI, 0.78-2.83]). The systemic thromboembolism, major bleeding, and death rates were comparable between the DOAC-change and DOAC-retain groups. CONCLUSIONS: Changing prestroke DOAC does not reduce the risk of recurrent cerebral ischemia in patients with atrial fibrillation who develop IS during DOAC therapy. However, future studies should continue to observe the potential trends of increased intracranial hemorrhage risk.