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Background and Objectives: Transient ischemic attack (TIA) is associated with a higher short-term incidence of stroke. However, long-term data on this association are lacking. Therefore, this study aimed to determine the long-term incidence of ischemic stroke after TIA according to ABCD 2 score and to identify factors associated with stroke after TIA., Methods: All Danish patients ≥18 years with first-time TIA were included from the Danish Stroke Registry (2014-2020). The study population was stratified into a high-risk (≥4 points) and low-risk (<4 points) group according to the modified ABCD 2 score (age ≥60 years, hypertension, clinical features, and diabetes). The 3-year cumulative incidence of stroke and all-cause mortality was assessed using the Aalen-Johansen and Kaplan-Meier estimators, respectively. Factors associated with 3-year stroke rate were identified using multivariable Cox regression models., Results: In total, 21,433 patients with first-time TIA were included: 1,280 (6.0%) in the high-risk group and 20,153 (94.0%) in the low-risk group. Patients with high-risk ABCD 2 scores were older (median 77.5 [P25-P75 70.8-84.1] vs 70.3 [P25-P75 60.1-78.2]), more often female (53.1%), had more comorbidities (e.g., ischemic heart disease, heart failure, and atrial fibrillation), and received more medication (e.g., any antiplatelet therapy or oral anticoagulants and cholesterol-lowering drugs) at baseline. The 3-year cumulative incidence of stroke after TIA was 6.0% (95% CI 4.6-7.5) in the high-risk group and 4.2% (95% CI 3.9-4.5) in the low-risk group ( p = 0.004) with an unadjusted hazard ratio (HR) 1.56 (95% CI 1.21-2.00). Factors associated with 3-year stroke rate included age ≥60 years (HR 2.21, 95% CI 1.76-2.78), current smoking (HR 1.37, 95% CI 1.13-1.65), unilateral weakness (HR 1.25, 95% CI 1.04-1.51), peripheral artery disease (HR 1.53, 95% CI 1.09-2.14), and chronic kidney disease (HR 1.39, 95% CI 1.01-1.90). The 3-year cumulative incidence of all-cause mortality was 28.9% (95% CI 26.1-31.7) in the high-risk group and 10.3% (95% CI 9.9-10.8) in the low-risk group., Discussion: Patients with high-risk ABCD 2 score had an almost 60% higher associated long-term rate of ischemic stroke compared with those with low-risk ABCD 2 score. Future trials focusing on preventive strategies, including evidence-based antithrombotic strategies, especially for the high-risk group are warranted.

Background: Left ventricular diastolic dysfunction (DD) is associated with adverse cardiovascular outcomes including atrial fibrillation. Whether DD is independently associated with incident stroke and transient ischemic attack (TIA) and with bleeding events is not known. We performed this observational cohort analysis to examine the impact of DD on the risk of stroke/TIA and major bleeding., Methods: Patients who underwent at least 1 cardiac echocardiogram and were followed for at least 3 months were included in this study. Patients with a prior history of stroke, TIA, or major bleeding, as determined by International Classifications of Diseases codes, were excluded. Smart key-phrase search was applied to echocardiographic reports to classify patients into 4 groups based on the most severe DD assessment. Patients in whom the presence of DD could not be determined were excluded. The final study cohort was followed to the end point of hospital admission for stroke/TIA and major bleeding, and independent predictors of these events were evaluated using the multivariable Cox proportional hazards method., Results: The final study cohort (age, 56±18 years; 56% women) had 96 702 patients with no DD and 18 164, 5881, and 1340 patients with DD grades I, II, and III, respectively. Over a median follow-up of 3.4 years, 2938 (2.4%) patients were hospitalized for stroke/TIA and 5567 (4.6%) for major bleeding. After adjusting for age, the CHA 2 DS 2 -VASc score, chronic kidney disease, use of antiplatelet agents, use of anticoagulation agents, the year of echocardiographic testing, household income, and history of atrial fibrillation, DD remained a strong predictor of incident stroke/TIA (hazard ratio, 1.22 per grade increase in DD [95% CI, 1.16-1.29]; P <0.001) and major bleeding (hazard ratio, 1.20 per grade increase in DD [95% CI, 1.16-1.25]; P <0.001)., Conclusions: DD is independently associated with a higher risk of cerebrovascular accidents and major bleeding. DD should be considered when counseling patients regarding their risk profile and management options., Competing Interests: The authors report receiving compensation for consultation from Boston Scientific (Drs Kancharla, Estes III, and Saba) and Medtronic, Inc (Drs Estes III and Saba) and research support from Varian (Dr Kancharla), Boston Scientific (Drs Jain and Saba), Medtronic (Dr Jain), and Abbott (Dr Saba). The other authors report no conflicts.

Introduction: Cardiovascular disease remains a leading cause of morbidity and mortality worldwide, with many individuals presenting with acute ischemic stroke or transient ischemic attack (AIS/TIA) due to underlying vascular risk factors (VRF). While these patients typically undergo routine evaluations for acute treatment, the prevention of these conditions is often underestimated. This study reports the prevalence of non-optimized VRF and estimates their degree of avoidability in a cohort of patients treated in a tertiary care center following AIS/TIA., Methods: This retrospective study enrolled patients older than 18 years who experienced AIS/TIA over a two-year period. Preventability was defined as the degree to which an acute cerebrovascular event could have been prevented if the VRF had been appropriately treated. Using the variables determined at the onset of AIS or TIA, we developed a 10-point scale to classify the degree of preventability (not preventable [score of 0], low preventability [score of 1-3], and high preventability [score of 4 or higher]). We further defined sub-scores based on the effectiveness of treatment of high blood pressure [HBP] (0-2 points), dyslipidemia [DLP] (0-2 points), atrial fibrillation [AF] (1 point), active smoking [AS] (1 point), obesity (1 point), previous coronary heart disease [CHD] (1 point), and previous AIS/TIA (2 points). Demographic factors, etiologies, and imaging findings were evaluated, tabulated independently, and subsequently correlated with clinical findings extracted from the available patient records., Results: Of the 395 patients (334 with AIS and 61 with TIA), 376 (95.19 %) exhibited some degree of preventability, whereas 19 (4.81 %) presented with a nonpreventable event. In total, 296 (74.94 %) presented a low preventable event, and 80 (20.25 %) presented a high preventable event. Applying the Chi-square test of independence to stroke etiology highlighted cardio-aortic embolism and large artery atherosclerosis as groups with a significantly higher burden of risk factors necessitating intervention, while patients with stroke of other etiologies had more adequate control of VRF. In terms of stroke severity, as determined by the National Institutes of Health Stroke Scale (NIHSS), patients with NIHSS scores >5 were more likely to experience preventable events. According to the ABCD2 score, higher risk scores were significantly associated with a higher preventive factor burden; however, age, sex, vascular territory, and Canadian TIA scores were not related to the prevention of AIS/TIA., Conclusions: The high percentage of preventable events reflects the need to study other factors that may contribute to unhealthy lifestyles in this population. Potential reasons for poor health include high levels of stress, sleep deprivation, working conditions and an unhealthy diet. Further studies are required to better understand these phenomena., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Transient ischemic attack (TIA) is a frequent neurological emergency which management and definition have changed radically over the last 15 years. However, recent epidemiological studies of TIA are scarce. We report here on the impact of the shift from a time-based to a tissue-based definition of TIA on its incidence and risk of recurrence in a new population-based cohort with a high rate of patients investigated by MRI., Materials and Methods: We prospectively included all TIAs that occurred between May 2017 and May 2021 from the Normandy Stroke Study, a population-based registry using multiple overlapping sources for exhaustive case identification in Caen la Mer area. TIAs were classified as either time-based (symptoms <24 h) or tissue-based (<24 h and no lesion on brain imaging). Attack and incidence rates were calculated, as was the 90-day ischemic stroke rate., Results: Five hundred and sixty-seven TIAs (549 single patients) were included, with 80.6% having a brain MRI. Four hundred and ten (72.3%) met the definition of tissue-based TIA. The age standardized attack (to the 2013 European population) rate was 39.5 (95% CI 35.7-43.5) and the age-standardized incidence rate (first ever cerebrovascular event) was 29.7 (95% CI 27.3-34.2). The overall recurrent stroke rate at 90 days was 2.7%, with no difference between patients with or without ischemic lesions on MRI., Conclusion: We found that the use of the tissue-based definition of TIA resulted in a 27.5% reduction in incidence as compared to the time-based definition, but had no impact on the 90-day stroke rate. The burden of TIA remains high, and is likely to increase as the population ages., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives . The prevalence of patients with prior stroke is increasing globally. Accordingly, there is a need for up-to-date evidence of patient-related prognostic factors for stroke recurrence, post stroke myocardial infarction (MI) and death based on long-term follow-up of stroke survivors. For this purpose, the RIALTO study was established in 2004. Design. A prospective cohort study in which patients diagnosed with ischemic stroke (IS) or transient ischemic attack (TIA) in three Copenhagen hospitals were included. Data were collected from medical records and by structured interview. Data on first stroke recurrence, first MI and all-cause death were extracted from the Danish National Patient Registry and the Danish Civil Registration System. Results . We included 1215 patients discharged after IS or TIA who were followed up by register data from April 2004 to end of 2018 giving a median follow-up of 3.5-6.9 years depending on the outcome. At the end of follow-up 406 (33%) patients had been admitted with a recurrent stroke, 100 (8%) had a MI and 822 (68%) had died. Long-term prognostic predictors included body mass index, diabetes, antihypertensive and lipid lowering treatment, smoking, a sedentary lifestyle as well as poor self-rated health and psychosocial problems. Conclusions . Long-term risk of recurrent stroke and MI remain high in patients discharged with IS or TIA despite substantial improvements in tertiary preventive care in recent decades. Continued attention to the patient risk profile among patients surviving the early phase of stroke, including comorbidities, lifestyle, and psychosocial challenges, is warranted.

Background: The impact of chronic oral anticoagulant (OACs) use on long-term post-discharge outcomes after coronavirus disease 2019 (COVID-19) hospitalisation remains unclear. Herein, we compared clinical outcomes up to 2-years after COVID-19 hospitalisation between patients on vitamin K antagonists (VKAs), direct-acting OACs (DOACs) and no OAC therapy., Methods: Data from TriNetX, a global federated health research network, were used. Adult patients on VKAs, DOACs or no OAC therapy at diagnosis of COVID-19 between 20 January 2020 and 31 December 2021, who were hospitalised for COVID-19, were included. The primary outcomes were all-cause mortality, ischaemic stroke/transient ischaemic attack (TIA)/systemic embolism (SE) and the composite of intracranial haemorrhage (ICH)/gastrointestinal bleeding, at 2 years after COVID-19 hospitalisation., Results: We included 110,834 patients with COVID-19. Following propensity score matching (PSM), we identified a decreased mortality risk in DOAC-treated patients compared to the no OAC cohort (RR .808, 95% CI .751-.870). A higher risk of ischaemic stroke/TIA/SE was observed in VKA users compared to DOAC users (RR 1.100, 95% CI 1.020-1.220) and in VKA users compared to patients not taking OAC (RR 1.400, 95% CI 1.140-1.720). VKA use was associated with a greater risk of ICH/gastrointestinal bleeding than DOAC users (RR 1.198, 95% CI 1.066-1.347), while DOAC users had a lower risk compared to no OAC-treated patients (RR .840, 95% CI .754-.936)., Conclusion: COVID-19 patients taking prior DOACs were associated with lower long-term mortality risk and ICH/gastrointestinal bleeding than patients not taking OAC. Compared to patients on DOACs, VKA users were associated with higher risks of mortality, ischaemic stroke/TIA/SE and ICH/gastrointestinal bleeding., (© 2024 The Author(s). European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Objective: To evaluate the management in Victorian general practice of people who have been hospitalised with stroke or transient ischaemic attacks (TIA)., Study Design: Retrospective observational study; analysis of linked Australian Stroke Clinical Registry (AuSCR) and general practice data., Setting: 383 general practices in the Eastern Melbourne, South Eastern Melbourne, and Gippsland primary health networks (Victoria), 1 January 2014 - 31 December 2018., Participants: Adults who had been hospitalised with acute stroke or TIA and had at least two encounters with the same general practice during the observation period (7-18 months after the acute event)., Main Outcome Measures: Assessment of cardiometabolic risk factors (blood pressure, serum lipids, blood glucose, urinary protein); prescribing of guideline-recommended prevention medications (blood pressure-, lipid-, or glucose-lowering, antithrombotic agents); attainment of guideline targets for cardiometabolic risk factors at final assessment during observation period., Results: During 2014-2018, 3376 eligible AuSCR registrants (1465 women, 43.4%) had at least two encounters with one of the 383 general practices during the observation period; median age at stroke onset was 73.9 (interquartile range, 64.4-81.9) years, 737 events were TIAs (21.8%). Blood pressure was assessed in 2718 patients (80.5%), serum lipids in 1830 (54.2%), blood glucose in 1708 (50.6%). Prevention medications were prescribed for 2949 patients (87.4%), including lipid-lowering (2427, 71.9%) and blood pressure-lowering agents (2363, 70.0%). Blood glucose targets had been achieved by 1346 of 1708 patients assessed for this risk factor (78.8%), blood pressure targets by 1935 of 2717 (71.2%), and serum lipid targets by 765 of 1830 (41.8%). The incidence of having risk factors assessed was lower among patients aged 60 years or younger (incidence rate ratio [IRR], 0.97; 95% confidence interval [CI], 0.92-1.03) and those over 80 years of age (IRR, 0.92; 95% CI 0.88-0.97) than for those aged 61-80 years, and for women (IRR, 0.91; 95% CI, 0.87-0.95) and people with dementia (IRR, 0.89; 95% CI, 0.81-0.98). The likelihood of having classes of prevention medication prescribed was lower for patients aged 60 years or younger (IRR, 0.92; 95% CI, 0.88-0.97) and those over 80 years of age (IRR, 0.96; 95% CI, 0.92-0.997) than for patients aged 61-80 years, and for women (IRR, 0.95; 95% CI, 0.91-0.98) and people with dementia (IRR, 0.88; 95% CI, 0.78-0.98)., Conclusions: The general practice management of people who have been hospitalised with stroke or TIA could be improved. Effective monitoring of cardiometabolic risk factors will enable general practitioners to optimise care for people who need careful attention to prevent adverse secondary events., (© 2024 AMPCo Pty Ltd.)

Background: We aimed to quantify the incidence of atrial fibrillation (AF) in patients with cryptogenic stroke globally, as well as separately in patients in and outside of Japan, using an implantable loop recorder from a prospective, observational, Reveal LINQ Registry., Methods and Results: Patients developing cryptogenic stroke and monitored by implantable loop recorder for searching AF were studied. The primary end point was incidence of AF within 36 months after insertion. Secondary end points were recurrent ischemic stroke/transient ischemic attack and AF-related treatment strategies. A total of 271 patients (61.6±14.3 years, 170 men, 60 from Japan) were enrolled from 12 countries. AF was detected in 28.2% at 36 months. The median time from enrollment to AF detection was 7.9 months. During the first 12 months, the AF detection rate slope was relatively steeper in the Japanese subgroup versus non-Japanese patients. However, by 3 years, the cumulative incidence of AF detection did not differ between groups. Age was the only variable associated with AF detection (hazard ratio, 1.05 [95% CI, 1.02-1.07] per year), trending higher in older age groups. Of the 271 patients, 11 (4.1%) developed recurrent ischemic stroke/transient ischemic attack; AF was detected by implantable loop recorder in only 1 of these patients. Patients with detected AF were more commonly taking oral anticoagulation than those without AF at the last follow-up (64.7% versus 25.3%, P <0.001)., Conclusions: The rate of AF detection was similar to other studies in stroke populations monitored by implantable loop recorders, including CRYSTAL-AF (Cryptogenic Stroke and Underlying Atrial Fibrillation), STROKE-AF (Stroke of Unknown Cause and Underlying Atrial Fibrillation) and PER-DIEM (Post-Embolic Rhythm Detection With Implantable Versus External Monitoring). Patients with detected AF more commonly initiated anticoagulation than those without AF.

Background: Pioglitazone significantly reduces the risk of stroke in people with diabetes, and in those with prediabetes, it markedly reduces the risk of stroke/myocardial infarction and new-onset diabetes. Low-dose pioglitazone provides most of the clinical benefits of high-dose pioglitazone, with fewer adverse effects. We report an economic evaluation of the cost-effectiveness of low-dose pioglitazone versus placebo from a Canadian public payer perspective in 2023 Canadian dollars., Methods and Results: A Markov model was developed at a lifetime horizon with an annual cycle length and 5 health states (event-free, myocardial infarction, stroke, new-onset diabetes, and death). Transition probabilities were extracted from the IRIS (Insulin Resistance Intervention in Stroke) trial. Health state costs and utilities were based on public sources. Annual discount rates of 1.5% were applied in the reference-case analysis. Probabilistic analyses were conducted to deal with parameter uncertainty through 5000 simulations. The costs were estimated as $24 887 (interquartile range [IQR], $14 632-$41507) for low-dose pioglitazone and $57 301 (IQR, $48 730-$67368) for placebo, resulting in a cost saving of -$30 287 (IQR, -$43 374 to -$14 587) in favor of low-dose pioglitazone. Quality-adjusted life years were estimated as 25.99 (IQR, 24.56-26.81) for the low-dose pioglitazone and 19.44 (IQR, 18.68-20.13) for placebo, resulting in a difference of 6.37 (IQR, 5.07-7.36) in favor of low-dose pioglitazone. Consistent findings were observed from scenario analyses and 1-way probability sensitivity analyses., Conclusions: Holding across a wide range of values in modeling parameters, low-dose pioglitazone is found as the dominant strategy versus a placebo.

Background: Atherosclerotic cardiovascular diseases remain the primary cause of mortality in Italy. Individuals with a history of acute coronary syndrome, peripheral arterial disease, and ischemic stroke/transient ischemic attack face an elevated risk of recurrent major adverse cardiovascular events, including mortality. The population aging, coupled with increasing risk factors such as diabetes mellitus and obesity, exacerbates the disease's economic impact., Objectives: This study aims to comprehensively assess the economic burden of atherosclerotic cardiovascular diseases in Italy, specifically focusing on direct healthcare costs., Methods: We analyzed real-world data from administrative databases in the Marche region and Local Health Unit Umbria 2. The economic burden of patients discharged with acute coronary syndrome, peripheral arterial disease, and ischemic stroke/transient ischemic attack was evaluated, with a focus on direct costs associated with hospitalizations, drugs, and outpatient visits. Results were stratified by age, sex, comorbidities at baseline, and adherence to lipid-lowering therapy and antihypertensive agents., Results: Annually, nearly 350,000 patients were hospitalized for peripheral arterial disease, acute coronary syndrome, or ischemic stroke/transient ischemic attack. Direct health costs averaged €7190 per patient over a 2-year follow-up, with hospitalizations accounting for nearly 70% of the total. Male patients incurred significantly higher costs (€7467) than female patients (€6625). Costs correlated positively with age and with the number of baseline comorbidities, with a range from €5259 (0-1 comorbidities) to €17,095 (4+ comorbidities). Costs were significantly lower in adherent subjects (€6813) compared with non-adherent subjects (€7757)., Conclusions: This study provides valuable insights into the economic implications of atherosclerotic cardiovascular diseases in Italy, emphasizing the necessity of a comprehensive approach to preventive measures, optimal medication adherence, and lifestyle modifications to mitigate its impact., (© 2024. The Author(s).)

Importance: Previous randomized clinical trials did not demonstrate the superiority of endovascular stenting over aggressive medical management for patients with symptomatic intracranial atherosclerotic stenosis (sICAS). However, balloon angioplasty has not been investigated in a randomized clinical trial., Objective: To determine whether balloon angioplasty plus aggressive medical management is superior to aggressive medical management alone for patients with sICAS., Design, Setting, and Participants: A randomized, open-label, blinded end point clinical trial at 31 centers across China. Eligible patients aged 35 to 80 years with sICAS defined as recent transient ischemic attack (<90 days) or ischemic stroke (14-90 days) before enrollment attributed to a 70% to 99% atherosclerotic stenosis of a major intracranial artery receiving treatment with at least 1 antithrombotic drug and/or standard risk factor management were recruited between November 8, 2018, and April 2, 2022 (final follow-up: April 3, 2023)., Interventions: Submaximal balloon angioplasty plus aggressive medical management (n = 249) or aggressive medical management alone (n = 252). Aggressive medical management included dual antiplatelet therapy for the first 90 days and risk factor control., Main Outcomes and Measures: The primary outcome was a composite of any stroke or death within 30 days after enrollment or after balloon angioplasty of the qualifying lesion or any ischemic stroke in the qualifying artery territory or revascularization of the qualifying artery after 30 days through 12 months after enrollment., Results: Among 512 randomized patients, 501 were confirmed eligible (mean age, 58.0 years; 158 [31.5%] women) and completed the trial. The incidence of the primary outcome was lower in the balloon angioplasty group than the medical management group (4.4% vs 13.5%; hazard ratio, 0.32 [95% CI, 0.16-0.63]; P < .001). The respective rates of any stroke or all-cause death within 30 days were 3.2% and 1.6%. Beyond 30 days through 1 year after enrollment, the rates of any ischemic stroke in the qualifying artery territory were 0.4% and 7.5%, respectively, and revascularization of the qualifying artery occurred in 1.2% and 8.3%, respectively. The rate of symptomatic intracranial hemorrhage in the balloon angioplasty and medical management groups was 1.2% and 0.4%, respectively. In the balloon angioplasty group, procedural complications occurred in 17.4% of patients and arterial dissection occurred in 14.5% of patients., Conclusions and Relevance: In patients with sICAS, balloon angioplasty plus aggressive medical management, compared with aggressive medical management alone, statistically significantly lowered the risk of a composite outcome of any stroke or death within 30 days or an ischemic stroke or revascularization of the qualifying artery after 30 days through 12 months. The findings suggest that balloon angioplasty plus aggressive medical management may be an effective treatment for sICAS, although the risk of stroke or death within 30 days of balloon angioplasty should be considered in clinical practice., Trial Registration: ClinicalTrials.gov Identifier: NCT03703635.

Introduction: Screening for patent foramen ovale (PFO) in patients with ischemic neurological events is becoming more common., Objectives: This study aimed to evaluate clinical characteristics and atrial septum anatomy in relation to age and presence of PFO, as well as factors associated with a history of stroke in patients assessed for cardiac causes of ischemic neurological events., Patients and Methods: A total of 817 patients with a history of neurological episodes (stroke, transient ischemic attack [TIA], or migraine) were prescreened using transcranial Doppler ultrasound. Transesophageal contrast echocardiography (TEE) was employed to confirm PFO and assess the anatomy of the atrial septum and right atrium., Results: Among the patients, 28% had ischemic stroke, 31% had TIA, and 49% had migraines. PFO was confirmed in 79% of the patients. Regardless of the analyzed age group, PFO was associated with higher prevalence of TIA, migraine and syncope history, atrial septal aneurysm (ASA), and Chiari network. There were fewer women in the PFO group, but only in the population aged 45 years or under. Patient age, male sex, typical cardiovascular risk factors, and the presence of ASA were associated with a history of stroke., Conclusions: In patients with ischemic neurological events who were prescreened for PFO, confirmation of PFO on TEE was associated with a higher prevalence of TIA, migraine, syncope, Chiari network, and ASA. Advanced age, typical cardiovascular risk factors, and ASA were associated with stroke history in the study population.

Introduction: In patients suspected of stroke or transient ischemic attack (TIA), rapid triaging is imperative to improve clinical outcomes. For this purpose, balance-eye-face-arm-speech-time (BEFAST) items are used in out-of-hours primary care (OHS-PC). We explored the risk of stroke and TIA among BEFAST positive patients calling to the OHS-PC, and assessed whether additional predictors could improve risk stratification., Methods: This is a cross-sectional study of retrospectively gathered routine care data from telephone triage tape-recordings of patients calling the OHS-PC with neurological deficit symptoms, classified as BEFAST positive. Four models-with the predictors age, sex, a history of cardiovascular or cerebrovascular disease, and cardiovascular risk factors-were fitted using logistic regression to predict the outcome stroke or TIA. Likelihood ratio testing was used to select the best model, which was subsequently internally validated., Results: The risk of stroke or TIA diagnosis was 52% among 1,289 BEFAST positive patients, median age 72 years, 56% female sex. Of patients with the outcome stroke/TIA, 24% received a low urgency allocation, while 92% had signs or symptoms when calling. Only the addition of age and sex improved predicting stroke or TIA (internally validated c-statistic 0.72, 95%CI 0.69-0.75). The predicted risk of stroke or TIA remained below 20% in those aged below 40. Females aged 70 or over and males aged 55 or over, had a predicted risk above 50%., Discussion: Urgency allocation appears to be suboptimal in BEFAST positive patients calling the OHS-PC. Risk stratification could be improved in this setting by adding age and sex., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 van Royen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Patients with atrial fibrillation are frequently nonadherent to oral anticoagulants (OACs) prescribed for stroke and systemic embolism (SSE) prevention. We quantified the relationship between OAC adherence and atrial fibrillation clinical outcomes using methods not previously applied to this problem., Methods and Results: Retrospective observational cohort study of incident cases of atrial fibrillation from population-based administrative data over 23 years. The exposure of interest was proportion of days covered during 90 days before an event or end of follow-up. Cox proportional hazard models were used to evaluate time to first SSE and the composite of SSE, transient ischemic attack, or death and several secondary outcomes. A total of 44 172 patients were included with median follow-up of 6.7 years. For direct OACs (DOACs), each 10% decrease in adherence was associated with a 14% increased hazard of SSE and 5% increased hazard of SSE, transient ischemic attack, or death. For vitamin K antagonist (VKA) the corresponding increase in SSE hazard was 3%. Receiving DOAC or VKA was associated with primary outcome hazard reduction across most the proportion of days covered spectrum. Differences between VKA and DOAC were statistically significant for all efficacy outcomes and at most adherence levels., Conclusions: Even small reductions in OAC adherence in patients with atrial fibrillation were associated with significant increases in risk of stroke, with greater magnitudes for DOAC than VKA. DOAC recipients may be more vulnerable than VKA recipients to increased risk of stroke and death even with small reductions in adherence. The worsening efficacy outcomes associated with decreasing adherence occurred without the benefit of major bleeding reduction.

Background: Cerebrovascular events remain one of the most devastating complications of transcatheter aortic valve implantation (TAVI). Data from real-world contemporary cohorts on longitudinal trends and outcomes remain limited. The aim of this study was to assess incidence, temporal trends, predictors, and outcomes of cerebrovascular events following transfemoral TAVI., Methods and Results: The CENTER2 (Cerebrovascular Events in Patients Undergoing Transcatheter Aortic Valve Implantation With Balloon-Expandable Valves Versus Self-Expandable Valves 2) study includes patients undergoing TAVI between 2007 and 2022. The database contains pooled patient-level data from 10 clinical studies. A total of 24 305 patients underwent transfemoral TAVI (mean age 81.5±6.7 years, 56% women, median Society of Thoracic Surgeon Predicted Risk of Mortality 4.9% [3.1%-8.5%]). Of these patients, 2.2% (n=534) experienced stroke in the first 30 days after TAVI, and 40 (0.4%) had a transient ischemic attack. Stroke rates remained stable during the treatment period (2007-2010: 2.1%, 2011-2014: 2.5%, 2015-2018: 2.1%, 2019-2022: 2.1%; P trend =0.28). Moreover, 30-day cerebrovascular event rates were similar across Society of Thoracic Surgeon Predicted Risk of Mortality risk categories: 2.1% in low-risk, 2.6% in intermediate-risk, and 2.5% in high-risk patients ( P =0.21). Mortality was higher in patients with 30-day stroke than without at 30 days (20.3% versus 4.7%; odds ratio, 5.1 [95% CI, 4.1-6.5]; P <0.001) and at 1 year (44.1% versus 15.0%; hazard ratio, 3.5 [95% CI, 3.0-4.2]; P <0.001). One-year mortality rates for stroke did not decline over time (2007-2010: 46.9%, 2011-2014: 46.0%, 2015-2018: 43.0%, 2019-2022: 39.1%; P trend =0.32). At 1 year, 7.0% of patients undergoing TAVI had a stroke., Conclusions: In 24 305 patients who underwent transfemoral TAVI, 30-day cerebrovascular event incidence remained ≈ 2.2% between 2007 and 2022. Thirty-day stroke rates were similar throughout Society of Thoracic Surgeon Predicted Risk of Mortality risk categories. Mortality rates after stroke remain high., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03588247.

This report presents the latest statistics on the stroke population in South Korea, sourced from the Clinical Research Collaborations for Stroke in Korea-National Institute for Health (CRCS-K-NIH), a comprehensive, nationwide, multicenter stroke registry. The Korean cohort, unlike western populations, shows a male-to-female ratio of 1.5, attributed to lower risk factors in Korean women. The average ages for men and women are 67 and 73 years, respectively. Hypertension is the most common risk factor (67%), consistent with global trends, but there is a higher prevalence of diabetes (35%) and smoking (21%). The prevalence of atrial fibrillation (19%) is lower than in western populations, suggesting effective prevention strategies in the general population. A high incidence of large artery atherosclerosis (38%) is observed, likely due to prevalent intracranial arterial disease in East Asians and advanced imaging techniques. There has been a decrease in intravenous thrombolysis rates, from 12% in 2017-2019 to 10% in 2021, with no improvements in door-to-needle and door-to-puncture times, worsened by the coronavirus disease 2019 pandemic. While the use of aspirin plus clopidogrel for non-cardioembolic stroke and direct oral anticoagulants for atrial fibrillation is well-established, the application of direct oral anticoagulants for non-atrial fibrillation cardioembolic strokes in the acute phase requires further research. The incidence of early neurological deterioration (13%) and the cumulative incidence of recurrent stroke at 3 months (3%) align with global figures. Favorable outcomes at 3 months (63%) are comparable internationally, yet the lack of improvement in dependency at 3 months highlights the need for advancements in acute stroke care., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Background and Aim: Glycated albumin (GA) is a biomarker monitoring glycemia 2-4 weeks before stroke onset. This study was designed to explore the association between GA levels with poststroke outcomes in patients with acute ischemic stroke or transient ischemic attack (TIA)., Method: Participants with ischemic stroke or TIA who had a baseline GA measurement were included in the Third China National Stroke Registry study. The effect of GA on stroke recurrence, poor functional outcomes, and combined vascular events was examined during the 1-year follow-up period. Multivariate Cox and logistic regression models were performed to evaluate the association. Discrimination tests were used to examine the incremental predictive value of GA when incorporating it into the conventional model., Results: A total of 3861 participants were enrolled. At the 3-month follow-up, the elevated GA level was associated with an increased risk of poor functional outcomes (adjusted odds ratio [OR], 1.45; 95% confidence interval [CI], 1.01-2.09). A similar increase was observed for stroke recurrence (adjusted hazard ratio [HR], 1.56; 95% CI, 1.09-2.24), poor functional outcomes (adjusted OR, 1.62; 95% CI, 1.07-2.45), and combined vascular events (adjusted HR, 1.55; 95% CI, 1.09-2.20) at the 1-year follow-up. In nondiabetic patients, the association between GA and poor functional outcomes was more pronounced (adjusted OR, 1.62; 95% CI, 1.05-2.50). Adding GA into the conventional model resulted in slight improvements in predicting poor functional outcomes (net reclassification improvement [NRI]: 12.30% at 1 year)., Conclusion: This study demonstrated that elevated GA levels in serum were associated with stroke adverse outcomes, including stroke recurrence, poor functional outcomes, and combined vascular events, in patients with ischemic stroke or TIA., (© 2024 The Author(s). Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Purpose: Cerebrovascular accidents (CVAs) and transient ischemic attacks (TIAs) are uncommon neurologic events in women of childbearing age. We aimed to compare pregnancy, delivery, and neonatal outcomes between women who suffered from a CVA and those who experienced a TIA., Methods: A retrospective population-based cohort study was performed using the Healthcare Cost and Utilization Project, Nationwide Inpatient Sample. Included were all pregnant women who delivered or had a maternal death in the US between 2004 and 2014. We compared women with an ICD-9 diagnosis of a CVA before or during pregnancy to those diagnosed with a TIA before, during the pregnancy, or during the delivery admission. Pregnancy and perinatal outcomes were compared between the two groups, using multivariate logistic regression to control for confounders., Results: Among 9,096,788 women in the database, 898 met the inclusion criteria. Of them, 706 women (7.7/100,000) had a CVA diagnosis, and 192 (2.1/100,000) had a TIA diagnosis. Women with a CVA, compared to those with a TIA, had a higher rate of pregnancy-induced hypertension (aOR 3.82,95%CI 2.14-6.81, p < 0.001); preeclampsia (aOR 2.6,95%CI 1.3-5.2, p = 0.007), eclampsia (aOR 13.78,95% CI 1.84-103.41, p < 0.001); postpartum hemorrhage (aOR 4.52,95%CI 1.31-15.56, p = 0.017), blood transfusion (aOR 5.57,95%CI 1.65-18.72, p = 0.006), and maternal death (54 vs. 0 cases, 7.6% vs. 0%), with comparable neonatal outcomes., Conclusion: Women diagnosed with a CVA before or during pregnancy had a higher incidence of myriad maternal complications, including hypertensive disorders of pregnancy, postpartum hemorrhage, and death, compared to women with a TIA diagnosis, with comparable neonatal outcomes, stressing the different prognoses of these two conditions, and the importance of these patients' diligent follow-up and care., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Evaluation and hospitalization rates after a transient ischemic attack (TIA)-like presentation vary widely in clinical practice. This study aimed to examine variations in care settings at initial TIA diagnosis in the United States., Methods: We retrospectively analyzed an adult cohort with a first TIA principal diagnosis between January 1, 2015, and December 31, 2019, from TriNetX Diamond Network. Care settings at TIA diagnosis were defined as hospital care (including inpatient services and observation unit care without admission) and outpatient care (including any outpatient or emergency department visits). We estimated the distribution of care settings at TIA diagnosis and examined the associations of the hospital care setting with baseline age, sex, race, ethnicity, region, and stroke history., Results: Among the 554,315 included patients, 38.8% received hospital care at their initial TIA diagnosis. A higher percentage of hospital care was observed in the age group of 50-64 years (40.3%), Black (46.0%), Hispanic (41.2%), South (40.9%), and Midwest (43.0%) Regions, and with a history of stroke (39.6%). Multivariable logistic regression consistently showed patients who were aged 50-64 years (Odds Ratio=1.09, 95% CI: [1.07, 1.11]), Black (1.28, [1.24, 1.32]), Hispanic (1.13, [1.09, 1.18]), from South (1.20, [1.18, 1.22]) and Midwest Region (1.33, [1.30, 1.35]), and had a history of stroke (1.02, [1.00, 1.04]) to more likely receive hospital care., Conclusions: Although there are TIA care disparities based on demographics, most patients with initial TIA received acute care in outpatient settings. It is imperative to ensure primary providers can risk-stratify TIA patients and provide rapid and proper management., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Background: Clopidogrel resistance (CR) is associated with adverse clinical outcomes in acute ischemic stroke or transient ischemic attack (TIA) patients. However, whether CR affects the long-term clinical prognosis remains to be clarified. The ABCD-GENE score is a novel risk model that identifies CR in cardiovascular disease patients; its diagnostic ability and application in ischemic stroke or TIA remain to be studied. This study aimed to investigate the diagnostic ability of the ABCD-GENE score for CR and analyze the relationship between CR and long-term clinical prognosis in patients with ischemic stroke or TIA., Methods: From January 2018 to January 2021, 251 ischemic stroke or TIA patients who were treated with clopidogrel for more than three months after onset and maintained the medication until the follow-up time were enrolled, and platelet reactivity was detected by thromboelastography. CYP2C19 gene analysis was performed. Adverse clinical outcomes were recorded from 3months after onset. The median follow-up time was 878days., Results: The prevalence of CR was 33.9%. The proportion of CYP2C19 loss-of-function carriers was 62.2%. The ABCD-GENE score≥10 was independently associated with CR (OR=1.82, 95% CI: 1.02-3.24, P=0.041), and the C-statistic value of the score (as a binary and integer variable) on CR was 0.58 and 0.63, respectively. The risk of long-term adverse clinical outcomes was not significantly different between CR and clopidogrel sensitive groups (12.94% vs. 11.44%, HR=1.22, 95% CI: 0.57-2.62, P=0.603). A similar result was observed between ABCD-GENE score≥10 and ABCD-GENE score<10 groups (10.38% vs. 12.64%, HR=1.19, 95% CI: 0.55-2.60, P=0.666)., Conclusions: In ischemic stroke or TIA patients, the ABCD-GENE score could identify the risk of CR. CR was not associated with long-term adverse clinical outcomes., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Objective: Deep vein thrombosis (DVT) is discussed as a source of embolism for cerebral ischemia in the presence of patent foramen ovale (PFO). However, previous studies reported varying rates of DVT in stroke patients, and recommendations for screening are lacking. This study aimed to characterize patients with stroke or transient ischemic attack (TIA) and concomitant PFO and explore the rate of DVT and associated parameters., Methods: Medical records were screened for patients with stroke or TIA and echocardiographic evidence of PFO. Concomitant DVT was identified according to compression ultrasonography of the lower limbs. A variety of demographic, clinical, and laboratory parameters, the RoPE and Wells scores were compared between patients with and without DVT., Results: Three-hundred-thirty-nine patients (mean age 61.2 ± 15.4 years, 61.1% male) with stroke or TIA and PFO, treated between 01/2015 and 12/2020, were identified. Stroke and TIA patients did not differ for demographic and vascular risk factors. DVT was found in 17 cases out of 217 (7.8%) with compression ultrasonography. DVT was associated with a history of DVT, cancer, previous immobilization, calf compression pain, calf circumference difference, and a few laboratory abnormalities, e.g., increased D-dimer. A multivariate regression model with stepwise backward selection identified the Wells score (odds ratio 35.46, 95%-confidence interval 4.71-519.92) as a significant predictor for DVT., Conclusion: DVT is present in a relevant proportion of patients with cerebral ischemia and PFO, which needs to be considered for the individual diagnostic workup. The Wells score seems suitable for guiding additional examinations, i.e., compression ultrasonography., (© 2024. The Author(s).)

Background and Objectives: Incidental diffuse-weighted imaging (DWI)-positive subcortical and cortical lesions, or acute incidental cerebral microinfarcts (CMIs), are a common type of brain ischemia, which can be detected on magnetic resonance DWI for approximately 2 weeks after occurrence. Acute incidental CMI was found to be more common in patients with cancer. Whether acute incidental CMI predicts future ischemic stroke is still unknown. We aimed to examine the association between acute incidental CMI in patients with cancer and subsequent ischemic stroke or transient ischemic attack (TIA)., Methods: This is a retrospective cohort study. We used Clalit Health Services records, representing over half of the Israeli population, to identify adults with lung, breast, pancreatic, or colon cancer who underwent brain MRI between January 2014 and April 2020. We included patients who underwent scan between 1 year before cancer diagnosis and 1 year after diagnosis. Primary outcome was ischemic stroke or TIA using International Classification of Diseases, Ninth Revision codes. Secondary outcomes were intracranial hemorrhage (ICH) and mortality. Records were followed from first MRI until primary outcome, death, or end of follow-up (January 2023). Cox proportional hazards models were used to calculate hazard ratio (HR) for patients with and without acute incidental CMI, as a time-dependent covariate., Results: The study cohort included 1,618 patients with cancer, among whom, 59 (3.6%) had acute incidental CMI on at least 1 brain MRI. The median (interquartile range) time from acute incidental CMI to stroke or TIA was 26 days (14-84). On multivariable analysis, patients with acute incidental CMI had a higher stroke or TIA risk (HR 2.97, 95% CI 1.08-8.18, p = 0.035) compared with their non-CMI counterparts. Acute incidental CMIs were also associated with mortality after multivariable analysis (HR 2.76, 95% CI 2.06-3.71, p < 0.001); no association with ICH was found., Discussion: Acute incidental CMI on brain MRI in patients with active cancer is associated with an increased risk of near-future ischemic stroke or TIA and mortality. This finding might suggest that randomly detected acute incidental CMI in patients with cancer may guide primary cerebrovascular risk prevention and etiologic workup.

Background: The Valve Academic Research Consortium (VARC)-3 definition for neurologic events after transcatheter aortic valve replacement (TAVR) lacks clinical validation., Objectives: This study sought to determine the incidence, predictors, and clinical impact of neurologic events following TAVR as defined by VARC-3 criteria., Methods: This was a multicenter study including 2,924 patients with severe aortic stenosis undergoing TAVR. Based on Neurologic Academic Research Consortium (NeuroARC) classification, neurologic events were classified as NeuroARC type 1 (stroke), NeuroARC type 2 (covert central nervous system injury), and NeuroARC type 3 (transient ischemic attack and delirium). Baseline, procedural, and follow-up data were prospectively collected in a dedicated database., Results: After a median follow-up of 13 (7-37) months, neurologic events occurred in 471 patients (16.1%), NeuroARC type 1, 2, and 3 in 37.4%, 4.7%, and 58.0% of cases, respectively, and the majority (58.6%) were periprocedural. Advanced age, chronic kidney disease, atrial fibrillation, major vascular complications, and in-hospital bleeding determined an increased risk of periprocedural events (P < 0.03 for all). Neurologic events occurring during the periprocedural time frame were independently associated with a substantial increase in mortality at 1 year after the intervention (HR: 1.91; 95% CI: 1.23-2.97; P = 0.004). However, although NeuroARC type 1 was associated with an increased mortality risk (IRR: 3.38; 95% CI: 2.30-5.56; P < 0.001 and IRR: 21.7; 95% CI: 9.63-49.1; P < 0.001 for ischemic and hemorrhagic stroke, respectively), the occurrence of NeuroARC type 3 events had no impact on mortality., Conclusions: Neurologic events after TAVR were associated with poorer short- and long-term survival. This correlation was related to the type of NeuroARC event defined by the VARC-3 criteria. Given the negative impact on clinical outcomes, every attempt should be made to reduce the risk of neurologic complications after TAVR., Competing Interests: Funding Support and Author Disclosures Dr Cepas-Guillén has received a grant from the Fundación Alfonso Martín Escudero. Dr Rodés-Cabau has received institutional research grants and speaker/consultant fees from Edwards Lifesciences and Medtronic, and holds the Research Chair “Fondation Famille Jacques Larivière” for the Development of Structural Heart Interventions (Laval University). All other authors have reported that they have no relationships relevant to the contents of this paper., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Individuals with diabetes exhibit a higher risk of cardiovascular disease and mortality compared to healthy individuals. Following a transient ischemic attack (TIA) the risk of stroke and death increase further. Physical activity engagement after a TIA is an effective way of secondary prevention. However, there's a lack of research on how individuals with diabetes modify physical activity levels and how these adjustments impact survival post-TIA. This study aimed to determine the extent to which individuals with diabetes alter their physical activity levels following a TIA and to assess the impact of these changes on mortality., Methods: This was a nationwide longitudinal study, employing data from national registers in Sweden spanning from 01/01/2003 to 31/12/2019. Data were collected 2 years retro- and prospectively of TIA occurrence, in individuals with diabetes. Individuals were grouped based on decreasing, remaining, or increasing physical activity levels after the TIA. Cox proportional hazards models were fitted to evaluate the adjusted relationship between change in physical activity and all-cause, cardiovascular, and non-cardiovascular mortality., Results: The final study sample consisted of 4.219 individuals (mean age 72.9 years, 59.4% males). Among them, 35.8% decreased, 37.5% kept steady, and 26.8% increased their physical activity after the TIA. A subsequent stroke occurred in 6.7%, 6.4%, and 6.1% of individuals, while death occurred in 6.3%, 7.3%, and 3.7% of individuals, respectively. In adjusted analyses, participants who increased their physical activity had a 45% lower risk for all-cause mortality and a 68% lower risk for cardiovascular mortality, compared to those who decreased their physical activity., Conclusions: Positive change in physical activity following a ΤΙΑ was associated with a reduced risk of mortality. Increased engagement in physical activity should be promoted after TIA, thereby actively supporting individuals with diabetes in achieving improved health outcomes., (© 2024. The Author(s).)

Background:  There is limited data available regarding the prevalence of intracranial arterial stenosis (ICAS) among acute ischemic stroke (AIS) patients in Brazil and Latin America., Objective:  The present study sought to investigate the frequency and predictors of ICAS among patients with AIS or transient ischemic attack (TIA) in a Brazilian center, with transcranial color-coded duplex sonography (TCCS) technique., Methods:  Consecutive AIS and TIA patients, admitted to an academic public comprehensive stroke center in Brazil from February to December 2014, evaluated by TCCS were prospectively selected. Vascular narrowings > 50% were considered as ICAS, based on ultrasound criteria previously defined in the literature., Results:  We assessed 170 consecutive patients with AIS or TIA, of whom 27 (15.9%) were excluded due to an inadequate transtemporal acoustic bone window. We confirmed ICAS in 55 patients (38.5%). The most common location was the proximal segment of the middle cerebral artery (28.2%), followed by the vertebral (15.4%), posterior cerebral (13.6%), terminal internal carotid (9.1%) and basilar (8.2%) arteries. On multivariate models adjusting for potential confounders, systolic blood pressure (OR: 1.03, 95%CI: 1.01-1.04; p  = 0.008) was independently associated with ICAS., Conclusion:  We found significant ICAS in approximately ⅓ of patients admitted with symptoms of AIS or TIA in a public tertiary academic stroke center in Brazil. The TCCS is an accessible and noninvasive technique that can be used to investigate the presence of moderate and severe ICAS, especially in patients who cannot be exposed to more invasive exams, such as the use of intravenous contrast agents., Competing Interests: The authors have no conflict of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)

Background: Few studies have evaluated the association between asymptomatic cholesterol emboli on fundoscopy (known as Hollenhorst plaque) and the subsequent risk of stroke or death. 1 ., Aim: To evaluate the association between the presence of asymptomatic cholesterol retinal emboli and the risk of cerebrovascular events, with assessment of the need for carotid intervention., Methods: PubMed, Embase, and Cochrane Library databases were searched using appropriate terms. The systematic review was conducted according to PRISMA guidelines., Results: Initial search revealed 43 in Medline and 46 in Embase databases. Twenty-four potentially eligible studies were included after duplicate and non-related studies were excluded based on title and abstract. Three more studies were identified from reference lists. Seventeen studies were included in the final analysis. Asymptomatic cholesterol emboli were present in 1343 patients. Approximately 17.8% ( n = 181) had history of either cerebro-vascular Accident (CVA) or transient ischaemic attacks (TIAs) at presentation (more than 6 months). Nine studies mentioned the incidence of cerebrovascular events during follow-up. Of 780 patients, 93 evolved to stroke, TIAs, or death from a major carotid event during the follow-up period (6-86 m), an incidence of about 12%. Death due to stroke was documented in 3 studies ( n = 12)., Conclusion: The presence of asymptomatic retinal emboli indicates a risk of a cerebrovascular event when compared to patients with no plaques seen on fundoscopy. The evidence suggests that these patients warrant referral for medical optimization of cardiovascular risk factors. Currently, there is no recommendation to support carotid endarterectomy in patients with Hollenhorst plaques, or retinal emboli, and further studies are needed to assess this., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The World Health Organisation has expanded the definition of stroke to include people with symptoms less than 24 h if they have evidence of stroke on neuroimaging. The impact is that people previously diagnosed as having a transient ischaemic attack (TIA) would now be considered to have had a stroke. This change will impact incidence and outcomes of stroke and increase eligibility for secondary prevention. We aimed to evaluate the new ICD-11 criteria retrospectively to previous TIA studies to understand the change in incidence and outcomes of this type of stroke., Methods: We conducted a systematic review of observational studies of the incidence and outcomes of clinically defined TIA. We searched PubMed, EMBASE, and Google Scholar from inception to 23rd May 2023. Study quality was assessed using a risk of bias tool for prevalence studies., Findings: Our review included 25 studies. The rate of scan positivity for stroke among those with clinically defined TIA was 24 %, (95 % CI, 16-33 %) but with high heterogeneity (I 2 = 100 %, p <0.001). Sensitivity analyses provided evidence that heterogeneity could be explained by methodology and recruitment method. The scan positive rate when examining only studies at low risk of bias was substantially lower, at 13 % (95 % CI, 11-15 %, I 2 = 0, p = 0.77). We estimate from population-based incidence studies that ICD-11 would result in an increase stroke incidence between 4.8 and 10.5 per 100,000 persons/year. Of those with DWI-MRI evidence of stroke, 6 % (95 % CI, 3-11 %) developed a recurrent stroke in the subsequent 90 days, but with substantial heterogeneity (I 2 = 67 %, p = 0.02)., Conclusion: The impact of the ICD-11 change in stroke definition on incidence and outcomes may have been overestimated by individual studies. Community-based stroke services with access to DWI MRI are likely to accurately diagnose greater numbers of people with mild ICD-11 stroke, increasing access to effective prevention., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Background: Statin agents play a major role in secondary prevention after acute cerebral ischemia (ACI) events but are not indicated in all patients with ischemic stroke and transient ischemic attack. National guidelines recommend statins for patients with ACI of large or small vessel atherosclerotic origin and without these stroke mechanisms but coexisting coronary artery disease or primary prevention indications. The potential adverse effect burden of statin overuse in the remaining ACI patients have not been well delineated., Methods: Per Preferred Reporting Items of Systematic Reviews and Meta-Analyses guidelines, we performed systematic meta-analyses of: (1) statin randomized clinical trials to determine absolute risk increases for 6 major adverse events; (2) large clinical series to determine the proportion of ACI events due to large or small vessel atherosclerotic disease; and (3) the proportion of remaining patients with coronary artery disease/primary prevention statin indications., Results: For adverse effects, data were available from 63 randomized clinical trials enrolling 155 107 patients. Statin therapy was associated with an increased risk of the occurrence of 6 conditions: diabetes, myalgia or muscle weakness, myopathy, liver disease, renal insufficiency, and eye disease. Across 55 large series enrolling 53 501 patients, the rate of ACI due to large and small artery atherosclerosis was 45.0% (large artery atherosclerosis 21.6%, small vessel disease 23.4%), the rate of remaining patients with coronary artery disease/primary prevention statin indications was 31.8%, and the rate of patients without statin indications was 23.2%. Data synthesis indicated that, in the United States, were all patients with ACI without statin indications treated with statins, a total of 5601 patients would develop needless adverse events each year, most commonly diabetes, myopathy, and eye disease., Conclusions: More than one-fifth of patients with ACI do not have an indication for statins, and statin overuse in these patients could annually lead to over 5600 adverse events each year in the United States, including diabetes, myopathy, and eye disease. These findings emphasize the importance of adhering to guideline indications for the start of statin therapy in ACI., Competing Interests: Dr Saver reports receiving research support from the National Institutes of Health and the American Heart Association; receives contracted hourly payments from Medtronic, Stryker, Cerenovus, Boehringer Ingelheim, Roche, Genentech, Bayer, CSL Behring, Phillips Medical, and stock options or stock from Rapid Medical, MindRhythm, Argenx, Let’s Get Proof, NeuroMerit, and Neuronics for service on clinical trial steering, Data Safety and Monitoring Board, and other committees advising on rigorous trial design and conduct. The other author reports no conflict.

Background: Transient ischemic attack (TIA) is defined as a transient episode of neurologic dysfunction, without acute infarction or tissue injury lasting less than 24 h. Previous data suggest TIA precedes 15% of ischemic strokes, with a higher risk in the first week. Current practice guidelines advise evaluation through rapid neurological visit or admission to hospital. We provide data on TIA incidence in Trieste, and we compare three different types of assessment: day hospital (DH), stroke unit (SU), and emergency department/outpatients (ED)., Methods: This is a 5-year retrospective study of transient cerebrovascular events admitted in the University Hospital of Trieste (230.623 inhabitants), between 2016 and 2020. We calculated TIA prevalence in Trieste district's general population. Our primary endpoint is ischemic recurrences within 90 days, and we evaluate the possible association between different types of management., Results: TIA incidence rate was 0.54/1000 inhabitants. In the multivariate analysis remained significantly associated with primary endpoint: ABCD2 (OR 1.625, CI 95% 1.114-2.369, p = 0.012) and DH evaluation (OR 0.260, CI 95% 0.082-0.819, p = 0.021)., Conclusions: Incidence of TIA in Trieste district is in line with previous data. We demonstrate the crucial role of DH evaluation over the outpatient/ED in reducing overall mortality and recurrence rate. Prompt recognition of patients at high risk for cerebrovascular events and specialist follow-up may reduce the incidence of major vascular events and death., (© 2024. Fondazione Società Italiana di Neurologia.)

Background: Bleeding risk brought by intensive lipid-lowering therapy and low low-density lipoprotein cholesterol is concerning, while evidence regarding the relationship between remnant cholesterol and bleeding is frightening. This study aimed to investigate the association between remnant cholesterol at admission and an in-hospital bleeding event after acute ischemic stroke or transient ischemic attack (TIA)., Methods and Results: A total of 3222 eligible patients admitted to Shanghai Huashan Hospital between 2015 and 2021 with complete lipid data were analyzed. Patients were classified into low (<20.0 mg/dL), moderate (20.0-29.9 mg/dL), and high (≥30 mg/dL) groups by remnant cholesterol. The mean age of patients was 63.0± 13.1 years, including 2301 (71.4%) men and 651 (20.2%) with TIA. The median (interquartile range) of remnant cholesterol was 18.6 (13.5-25.9) mg/dL. After adjustment for confounding variables, patients with low remnant cholesterol had a higher risk of bleeding events (odds ratio, 2.56 [95% CI, 1.12-6.67]) than those with moderate remnant cholesterol. The high remnant cholesterol group was not significantly associated with bleeding risk. Combined assessment of low-density lipoprotein cholesterol and remnant cholesterol further identified patients with the highest risk of bleeding events., Conclusions: Low remnant cholesterol levels were associated with bleeding events during the acute stage of ischemic stroke and TIA. The assessment of remnant cholesterol could inform the bleeding risk during hospitalization both for patients and physicians in clinical practice.

Objectives: The objectives are to assess smoking abstinence and its effects on vascular risk and to report tobacco-cessation counselling and pharmacotherapy use in patients who had a recent minor stroke or transient ischaemic attack (TIA)., Design and Setting: The TIA registry.org project is a prospective, observational registry of patients with TIA and minor stroke that occurred in the previous 7 days with a 5-year follow-up, involving 61 sites with stroke specialists in 21 countries (Europe, Asia, Latin America and Middle East). Of those, 42 sites had 5-year follow-up data on more than 50% of their patients and were included in the present study., Participants: From June 2009 through December 2011, 3847 patients were eligible for the study (80% of the initial cohort)., Outcomes: Tobacco counselling and smoking-cessation pharmacotherapy use in smoking patients were reported at discharge. Association between 3-month smoking status and risk of a major cardiovascular event (MACE) was analysed with multivariable Cox regression model., Results: Among 3801 patients included, 835 (22%) were smokers. At discharge, only 35.2% have been advised to quit and 12.5% had smoking-cessation pharmacotherapy prescription. At 3 months, 383/835 (46.9%) baseline smokers were continuers. Living alone and alcohol abuse were associated with persistent smoking; high level of education, aphasia and dyslipidaemia with quitting. The adjusted HRs for MACE at 5 years were 1.13 (95% CI 0.90 to 1.43) in former smokers, 1.31 (95% CI 0.93 to 1.84) in quitters and 1.31 (95% CI 0.94 to 1.83) in continuers. Using time-varying analysis, current smoking at the time of MACE non-significantly increased the risk of MACE (HR 1.31 (95% CI 0.97 to 1.78); p=0.080)., Conclusion: In the TIAregistry.org, smoking-cessation intervention was used in a minority of patients. Surprisingly, in this population in which, at 5 years, other vascular risk factors were well controlled and antithrombotic treatment maintained, smoking cessation non-significantly decreased the risk of MACE., Competing Interests: Competing interests: PL has nothing to disclose. PA reports receipt of research grant support from Pfizer, Sanofi, Bristol-Myers-Squibb, AstraZeneca, Boston Scientific, AltheraPharmaceutical, and from the French government, and consulting fees from Pfizer, BMS, AstraZeneca, Johnson and Johnson, Kowa, Amgen, and lecture fees from Amgen, Pfizer, Sanofi. P-JT reports royalties from IP in IMT Company and is a stockholder in IMT. GWA reports equity interest: iSchemaView, and consultant fees from Medtronic, iSchemaView, Janssen, and Biogen. GAD reports unrestricted research grant from Sanofi, speaker and advisory board fees from Boehringer Ingelheim, Bristol Myer Squibb, Pfizer and Bayer companies. JMF reports having received fees as speakers bureau from Boehringer-Ingelheim, consultant fees from GSK, Ferrer and Servier. PGS discloses the following relationships: research grants: Amarin, AstraZeneca, Bayer, Sanofi, and Servier Clinical Trials (Steering committee, CEC, DSMB): Amarin, AstraZeneca, Bayer, Bristol-Myers Squibb, Idorsia, Janssen, Novartis, PhaseBio, Pfizer, Sanofi, Servier Consulting or speaking: Amarin, Amgen, BMS, Novo-Nordisk, Regeneron Senior Associate Editor at Circulation Bayer, Boehringer-Ingelheim, BristolMyersSquibb, Idorsia, Mylan, NovoNordisk, Novartis, Pfizer, Regeneron, Sanofi, Servier. HC has nothing to disclose. JL has nothing to disclose. MGH has nothing to disclose. SU reports receipt of research grants, consultancy fees, and lecture fees from Sanofi, Bayer, Otsuka, Boehringer-Ingelheim, and Daiichi-Sankyo, and research grants from the Japanese Ministry of Health, Labour, and Welfare and Japan Cardiovascular Research Foundation. EV reports Consulting/speaking honoraria from Abbott, Amgen, BMS, Fresenius, GSK, Medtronic, Pfizer, Sanofi, Stallergenes. LKSW reports honoraria as a member of a steering committee for Johnson & Johnson, Astra Zeneca and Bayer; honoraria for participation in clinical trials, contributions to advisory boards, or oral presentations from Bayer, Sanofi-Aventis, Bristol-Myers Squibb, Boehringer Ingelheim, and Pfizer. CAM serves in the Steering Committee of CLOTBUST-ER trial (Cerevast); SOCRATES (AstraZeneca), IMPACT-24b (Brainsgate), REVASCAT (Fundació Ictus Malaltia Vascular). He has received honoraria for participation in clinical trials, contribution to advisory boards or oral presentations from: Astra Zeneca: Boeringher Ingelheim, Daichii Sankyo, BMS, Covidien, Cerevast, Brainsgate. CAM has no ownership interest and does not own stocks of any pharmaceutical or medical device company. PR has received Advisory Board fees from Pfizer, Sanofi, Bristol-Myers-Squibb, AstraZeneca, Boehringer-Ingelheim, Bayer and Daiichi-Sankyo., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Subclinical atrial fibrillation (AF) is associated with increased risk of progression to clinical AF, stroke, and cardiovascular death. We hypothesized that in pacemaker patients requiring dual-chamber rate-adaptive (DDDR) pacing, closed loop stimulation (CLS) integrated into the circulatory control system through intra-cardiac impedance monitoring would reduce the occurrence of atrial high-rate episodes (AHREs) compared with conventional DDDR pacing., Methods and Results: Patients with sinus node dysfunctions (SNDs) and an implanted pacemaker or defibrillator were randomly allocated to dual-chamber CLS (n = 612) or accelerometer-based DDDR pacing (n = 598) and followed for 3 years. The primary endpoint was time to the composite endpoint of the first AHRE lasting ≥6 min, stroke, or transient ischaemic attack (TIA). All AHREs were independently adjudicated using intra-cardiac electrograms. The incidence of the primary endpoint was lower in the CLS arm (50.6%) than in the DDDR arm (55.7%), primarily due to the reduction in AHREs lasting between 6 h and 7 days. Unadjusted site-stratified hazard ratio (HR) for CLS vs. DDDR was 0.84 [95% confidence interval (CI), 0.72-0.99; P = 0.035]. After adjusting for CHA2DS2-VASc score, the HR remained 0.84 (95% CI, 0.71-0.99; P = 0.033). In subgroup analyses of AHRE incidence, the incremental benefit of CLS was greatest in patients without atrioventricular block (HR, 0.77; P = 0.008) and in patients without AF history (HR, 0.73; P = 0.009). The contribution of stroke/TIA to the primary endpoint (1.3%) was low and not statistically different between study arms., Conclusion: Dual-chamber CLS in patients with SND is associated with a significantly lower AHRE incidence than conventional DDDR pacing., Competing Interests: Conflict of interest: G.L.B. received speaker’s fee from Abbott, Biotronik, Boston Scientific, Medtronic, and MicroPort. M.D.M., D.G., and A.G. are employees of Biotronik Italia S.p.A., an affiliate of Biotronik SE & Co. KG (study sponsor and manufacturer of investigational devices). All remaining authors have declared no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The influence of burden of atherosclerosis in the brain supplying arteries on mortality in patients with acute ischemic stroke or transient ischemic attack is poorly known. We assessed whether total burden of atherosclerosis within cervicocerebral arteries is associated with long-term mortality., Methods and Results: A total of 406 patients (median age, 71.8 years; 57.9% male) with acute ischemic stroke or transient ischemic attack were included and their cervicocerebral arteries imaged with computed tomography angiography. The presence of atherosclerotic findings was scored for 25 artery segments and points were summed as a Cervicocerebral Atherosclerosis Burden (CAB) score, analyzed as quartiles. Data on all-cause mortality came from Statistics Finland. After a median follow-up of 7.3 years, 147 (33.5%) patients had died. Compared with surviving patients, those who died had a higher median CAB score (5, interquartile range 2-10 versus 11, 7-16; P <0.001). Cumulative mortality increased from 8.9% (95% CI, 7.0-10.8) in the lowest to 61.4% (95% CI, 55.4-67.4) in the highest quartile of CAB score. Adjusted for demographics, cardiovascular risk factors, secondary preventive medication, and admission National Institute of Health Stroke Scale score, every CAB score point increased probability of death by 3%. Analyzed in quartiles, the highest CAB quartile was associated with a 2.5-fold likelihood of all-cause mortality., Conclusions: The main findings of our study were the increasing mortality with the total burden of computed tomography angiography-defined atherosclerosis in the brain supplying arteries after ischemic stroke or transient ischemic attack and that the CAB score-integrating this pathology-independently increased all-cause mortality.

Background: The authors aimed to elucidate the relationship between latest ischemic event and the incidence of subsequent ischemic stroke in patients with symptomatic artery occlusion., Methods and Results: We analyzed the association between qualifying event-the latest ischemic event (transient ischemic attack [TIA] or stroke)-and the incidence of ipsilateral ischemic stroke in patients with symptomatic artery occlusion treated with medical therapy alone in CMOSS (Carotid or Middle Cerebral Artery Occlusion Surgery Study). The incidence of CMOSS primary outcomes, including any stroke or death within 30 days after randomization or ipsilateral ischemic stroke between 30 days and 2 years, between the bypass surgical and medical groups, stratified by qualifying events, was also compared. Of the 165 patients treated with medical therapy alone, 75 had a TIA and 90 had a stroke as their qualifying event. The incidence of ipsilateral ischemic stroke did not significantly differ between patients with a TIA and those with a stroke as their qualifying event (13.3% versus 6.7%, P =0.17). In multivariate analysis, the qualifying event was not associated with the incidence of ipsilateral ischemic stroke. There were no significant differences in the CMOSS primary outcomes between the surgical and medical groups, regardless of the qualifying event being TIA (10.1% versus 12.2%, P =0.86) or stroke (6.7% versus 8.9%, P =0.55)., Conclusions: Among patients with symptomatic artery occlusion and hemodynamic insufficiency, the risk of subsequent ipsilateral ischemic stroke does not appear to be lower in patients presenting with a TIA compared with those with a stroke., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01758614.

Objective: Transient ischemic attack (TIA) is rare in women of reproductive age. We aimed to compare perinatal outcomes between women who suffered from a TIA to those who did not., Methods: A retrospective population-based cohort study utilizing the Healthcare Cost and Utilization Project, Nationwide Inpatient Sample (HCUP-NIS). All women who delivered or had a maternal death in the US (2004-2014) were included in the study. Pregnancy, delivery, and neonatal outcomes were compared between women with an ICD-9 diagnosis of a TIA to those without., Results: Overall, 9 096 788 women met the inclusion criteria. Of these, 203 women (2.2/100000) had a TIA (either before or during pregnancy). Women with TIA, compared to those without, were more likely to be older than 35 years of age, white, in the highest income quartile, be insured by private insurance and suffer from obesity and chronic hypertension. Patients in the TIA group, compared to those without, had a higher rate of pregnancy-induced hypertension (aOR 2.5, 95% CI: 1.55-4.05, P < 0.001), pre-eclampsia (aOR 3.77, 95% CI: 2.15-6.62, P < 0.001), eclampsia (aOR 28.05, 95% CI: 6.91-113.95, P < 0.001), preterm delivery (aOR 1.78, 95% CI: 1.03-3.07, P = 0.039), and maternal complications such as deep vein thrombosis (aOR 33.3, 95% CI: 8.07-137.42, P < 0.001). Regarding neonatal outcomes, patients with a TIA, compared to those without, had a higher rate of congenital anomalies (aOR 7.04, 95% CI: 2.86-17.32, P < 0.001)., Conclusion: Women with a TIA diagnosis before or during pregnancy had a higher rate of maternal complications, including hypertensive disorders of pregnancy and venous thromboembolism, as well as an increased risk of congenital anomalies., (© 2024 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Background: Sneddon syndrome is an occlusive vasculopathy that presents clinically with generalized livedo racemosa on the skin and transient ischemic attacks, strokes, and cognitive or motor deficits in the central nervous system. Antiplatelet or anticoagulant therapy is recommended. Due to the limited therapeutic efficacy and the resulting serious complications, we propose combination therapy with additional infusion cycles of alprostadil and captopril and report initial long-term results., Patients and Methods: We performed a systematic retrospective analysis of all patients with primary Sneddon syndrome who received combination therapy in our clinic between 1995 and 2020. Therapeutic outcomes were evaluated using descriptive statistics compared to historical controls receiving monotherapy. We also analyzed the event rate of complications when combination therapy was discontinued., Results: During the 99.7 patient-years of follow-up, there were no transient ischemic attacks and the stroke rate dropped to 0.02 per patient-year. In comparison, the rates of transient ischemic attacks and strokes in the historical controls ranged from 0.08 to 0.035 per patient-year. After discontinuation of alprostadil therapy, eight events occurred in three patients., Conclusions: Combination therapy reduces the long-term incidence of ischemic events in patients with primary Sneddon syndrome., (© 2024 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by Wiley‐VCH GmbH on behalf of Deutsche Dermatologische Gesellschaft.)

Objective: Routine left atrial appendage closure during mitral repair in patients without atrial fibrillation (AF) is controversial. We aimed to compare the incidence of stroke after mitral repair in patients without recent AF according to left atrial appendage closure., Methods: An institutional registry identified 764 consecutive patients without recent AF, endocarditis, prior appendage closure, or stroke undergoing isolated robotic mitral repair between 2005 and 2020. Left atrial appendages were closed via left atriotomy using a double-layer continuous suture in 5.3% (15 out of 284) patients before 2014, versus 86.7% (416 out of 480) after 2014. The cumulative incidence of stroke (including transient ischemic attack) was determined using statewide hospital data. Median follow-up was 4.5 years (range, 0-16.6 years)., Results: Patients undergoing left atrial appendage closure were older (63 vs 57.5 years, P < .001), with higher prevalence of remote AF requiring cryomaze (9%, n = 40 vs 1%, n = 3, P < .001). After appendage closure there were fewer reoperations for bleeding (0.7% [n = 3] vs 3% [n = 10]; P = .02), and more AF (31.8% [n = 137] vs 25.2% [n = 84]; P = .047). Two-year freedom from >2+ mitral regurgitation was 97%. Six strokes and 1 transient ischemic attack occurred after appendage closure compared with 14 and 5 in patients without (P = .002), associated with a significant difference in 8-year cumulative incidence of stroke/transient ischemic attack (hazard ratio, 0.3; 95% CI, 0.14-0.85; P = .02). This difference persisted in the sensitivity analysis, excluding patients undergoing concomitant cryomaze procedures., Conclusions: Routine left atrial appendage closure during mitral repair in patients without recent AF appears safe and was associated with a lower risk of subsequent stroke/transient ischemic attack., (Copyright © 2023. Published by Elsevier Inc.)

Background and Aims: In recent decades, nighttime temperatures have increased faster than daytime temperatures. The increasing prevalence of nocturnal heat exposure may pose a significant risk to cardiovascular health. This study investigated the association between nighttime heat exposure and stroke risk in the region of Augsburg, Germany, and examined its temporal variations over 15 years., Methods: Hourly meteorological parameters, including mean temperature, relative humidity, and barometric pressure, were acquired from a local meteorological station. A data set was obtained consisting of 11 037 clinical stroke cases diagnosed during warmer months (May to October) between the years 2006 and 2020. The average age of cases was 71.3 years. Among these cases, 642 were identified as haemorrhagic strokes, 7430 were classified as ischaemic strokes, and 2947 were transient ischaemic attacks. A time-stratified case-crossover analysis with a distributed lag non-linear model was used to estimate the stroke risk associated with extreme nighttime heat, as measured by the hot night excess (HNE) index after controlling for the potential confounding effects of daily maximum temperature and other climatic variables. Subgroup analyses by age group, sex, stroke subtype, and stroke severity were performed to identify variations in susceptibility to nighttime heat., Results: Results suggested a significant increase in stroke risk on days with extreme nighttime heat (97.5% percentile of HNE) (odds ratio 1.07, 95% confidence interval 1.01-1.15) during the full study period. When comparing the results for 2013-20 with the results for 2006-12, there was a significant increase (P < .05) in HNE-related risk for all strokes and specifically for ischaemic strokes during the more recent period. Furthermore, older individuals, females, and patients with mild stroke symptoms exhibited a significantly increased vulnerability to nighttime heat., Conclusions: This study found nocturnal heat exposure to be related to elevated stroke risk after controlling for maximum daytime temperature, with increasing susceptibility between 2006 and 2020. These results underscore the importance of considering nocturnal heat as a critical trigger of stroke events in a warming climate., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Purpose: Multiple factors play important roles in the occurrence and prognosis of stroke. However, the roles of monogenic variants in all-cause ischaemic stroke have not been systematically investigated. We aim to identify underdiagnosed monogenic stroke in an adult ischaemic stroke/transient ischaemic attack (TIA) cohort (the Third China National Stroke Registry, CNSR-III)., Methods: Targeted next-generation sequencing for 181 genes associated with stroke was conducted on DNA samples from 10 428 patients recruited through CNSR-III. The genetic and clinical data from electronic health records (EHRs) were reviewed for completion of the diagnostic process. We assessed the percentages of individuals with pathogenic or likely pathogenic (P/LP) variants, and the diagnostic yield of pathogenic variants in known monogenic disease genes with associated phenotypes., Results: In total, 1953 individuals harboured at least one P/LP variant out of 10 428 patients. Then, 792 (7.6%) individuals (comprising 759 individuals harbouring one P/LP variant in one gene, 29 individuals harbouring two or more P/LP variants in different genes and 4 individuals with two P/LP variants in ABCC6 ) were predicted to be at risk for one or more monogenic diseases based on the inheritance pattern. Finally, 230 of 792 individuals manifested a clinical phenotype in the EHR data to support the diagnosis of stroke with a monogenic cause. The most diagnosed Mendelian cause of stroke in the cohort was cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. There were no relationships between age or family history and the incidence of first symptomatic monogenic stroke in patients., Conclusion: The rate of monogenic cause of stroke was 2.2% after reviewing the clinical phenotype. Possible reasons that Mendelian causes of stroke may be missed in adult patients who had an ischaemic stroke/TIA include a late onset of stroke symptoms, combination with common vascular risks and the absence of a prominent family history., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We aimed to correlate left atrial appendage (LAA) structure and function with the history of stroke/transient ischemic attack (TIA) in patients with atrial fibrillation (AF). We analyzed the data of 649 patients with AF who were scheduled for catheter ablation. Patients underwent cardiac computed tomography and transesophageal echocardiography before ablation. The LAA morphologies depicted by cardiac computed tomography were categorized into 4 groups: cauliflower, chicken wing, swan, and windsock shapes. The mean age was 61.3 ± 10.5 years, 33.9% were women. The prevalence of stroke/TIA was 7.1%. After adjustment for the main risk factors, the LAA flow velocity ≤35.3 cm/s (odds ratio [OR] 2.18, 95% confidence interval [CI] 1.09 to 4.61, p = 0.033) and the swan LAA shape (OR 2.69, 95% CI 0.96 to 6.86, p = 0.047) independently associated with a higher risk of stroke/TIA, whereas the windsock LAA morphology proved to be protective (OR 0.32, 95% CI 0.12 to 0.77, p = 0.017) compared with the cauliflower LAA shape. Comparing the differences between the LAA morphology groups, we measured a significantly smaller LAA orifice area (389.3 ± 137.7 mm 2 in windsock vs 428.3 ± 158.9 ml in cauliflower, p = 0.021) and LAA volume (7.4 ± 3.0 mm 2 in windsock vs 8.5 ± 4.8 mm 2 in cauliflower, p = 0.012) in patients with windsock LAA morphology, whereas the LAA flow velocity did not differ significantly. Reduced LAA function and swan LAA morphology were independently associated with a higher prevalence of stroke/TIA, whereas the windsock LAA shape proved to be protective. Comparing the differences between the various LAA morphology types, significantly lower LAA volume and LAA orifice area were measured in the windsock LAA shape than in the cauliflower LAA shape., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Severe sleep apnea (SA) affects one-third of stroke patients. Sleepiness, one of the cardinal symptoms of SA, negatively impacts functional stroke outcomes. The impact of continuous positive airway pressure (CPAP) on post-stroke sleepiness is poorly described. We aimed to compare through a propensity score matching the trajectories of self-reported sleepiness post-stroke with matched individuals including SA patients adherent or not to CPAP., Patients and Methods: Sixty five (80.2%) ischemic stroke and 16 (19.8%) TIA patients (median [Q1;Q3] age = 67.0 [58.0;74.0] years, 70.4% male, body mass index [BMI] = 26.1 [24.5;29.8] kg·m -2 , admission NIHSS = 3.0 [1.0;5.0]), with polysomnography and an Epworth Sleepiness Scale (ESS) performed within 1 year following stroke and with a follow-up ESS (delay = 236 [147;399] days) were included in the analysis. A 2:1 propensity score matching based on age, gender, BMI, and the apnea-hypopnea index was performed to identify 162 matched individuals referred for SA suspicion, free of stroke or TIA. Multivariable negative binomial regression models were performed to identify the determinants of sleepiness trajectories post-stroke., Results: Baseline ESS was comparable between stroke/TIA and matched individuals (median [Q1; Q3] ESS = 7 [4;10] versus 6 [4;10], p  = 0.86). The range of improvement in ESS was higher in stroke patients compared to controls (∆ESS = -2 [-4;1] vs -1 [-3;2], p  = 0.03). In multivariable analysis, comorbid SA and CPAP treatment did not influence trajectories of sleepiness post-stroke., Discussion and Conclusion: Sleepiness improvement was unexpectedly higher in stroke patients compared to matched individuals, with no significant influence of comorbid SA and CPAP on its trajectory. Sleepiness may not be primarily indicative of SA in stroke or TIA patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: The very old, although a minority in many populations, experience stroke with distinct risk factors and more complications. We sought to understand the profile, stroke subtypes, risk factors and outcomes among the very old compared to younger stroke patients in our population in the Philippine Neurological Association One Database-Stroke (PNA1DB-Stroke)., Methods: The PNA1DB-Stroke registry (clinicaltrial.gov NCT04972058) is a multi-centre, prospective database of all patients hospitalised for transient ischaemic attack or acute stroke in 11 neurology residency training institutions., Results: Of the 6314 patients with stroke, 463 (7%) were 80 years or older, and among them, 320 (69%) were women. Traditional risk factors were more frequent in the very old compared to the younger group (hypertension 76% vs. 66%, diabetes mellitus 26% vs. 19%, previous stroke 14% vs. 10%, atrial fibrillation 13% vs. 3%; p ≤ .005), while current smoking (5%) and excess alcohol consumption (4%) were less common than in younger stroke patients (p < .001). Overall, in-hospital fatality was not remarkably increased in our very old compared to younger stroke patients, with comparable rates between cases of ischaemic stroke (18%) and intracerebral haemorrhage (20%). However, they had longer hospital stay (mean 13.4 ± 17.2 days vs. 10.9 ± 15.4 days, p = .001), had more medical complications (p < .001) and were more functionally dependent at discharge (p < .0001)., Conclusions: Very old stroke patients have relatively more risk factors for stroke. In-hospital fatality rates are comparable between ischaemic and haemorrhagic strokes. Risk factor modification, prevention of medical complications and optimisation of functional recovery are potential strategies in managing stroke in the very old., (© 2024 AJA Inc’.)

Purpose: Radiation-induced cerebrovascular toxicity is a well-documented sequelae that can be both life-altering and potentially fatal. We performed a meta-analysis of the relevant literature to create practical models for predicting the risk of cerebral vasculopathy after cranial irradiation., Methods and Materials: A literature search was performed for studies reporting pediatric radiation therapy (RT) associated cerebral vasculopathy. When available, we used individual patient RT doses delivered to the Circle of Willis (CW) or optic chiasm (as a surrogate), as reported or digitized from original publications, to formulate a dose-response. A logistic fit and a Normal Tissue Complication Probability (NTCP) model was developed to predict future risk of cerebrovascular toxicity and stroke, respectively. This NTCP risk was assessed as a function of prescribed dose., Results: The search identified 766 abstracts, 5 of which were used for modeling. We identified 101 of 3989 pediatric patients who experienced at least one cerebrovascular toxicity: transient ischemic attack, stroke, moyamoya, or arteriopathy. For a range of shorter follow-ups, as specified in the original publications (approximate attained ages of 17 years), our logistic fit model predicted the incidence of any cerebrovascular toxicity as a function of dose to the CW, or surrogate structure: 0.2% at 30 Gy, 1.3% at 45 Gy, and 4.4% at 54 Gy. At an attained age of 35 years, our NTCP model predicted a stroke incidence of 0.9% to 1.3%, 1.8% to 2.7%, and 2.8% to 4.1%, respectively at prescribed doses of 30 Gy, 45 Gy, and 54 Gy (compared with a baseline risk of 0.2%-0.3%). At an attained age of 45 years, the predicted incidence of stroke was 2.1% to 4.2%, 4.5% to 8.6%, and 6.7% to 13.0%, respectively at prescribed doses of 30 Gy, 45 Gy, and 54 Gy (compared with a baseline risk of 0.5%-1.0%)., Conclusions: Risk of cerebrovascular toxicity continues to increase with longer follow-up. NTCP stroke predictions are very sensitive to model variables (baseline stroke risk and proportional stroke hazard), both of which found in the literature may be systematically erring on minimization of true risk. We hope this information will assist practitioners in counseling, screening, surveilling, and facilitating risk reduction of RT-related cerebrovascular late effects in this highly sensitive population., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Apixaban is commonly used to prevent stroke in older adults with nonvalvular atrial fibrillation (AF). Although its package insert has specific dose reduction criteria, providers may dose reduce outside of these parameters based on clinical scenarios., Objective: The primary objective was to determine the incidence of apixaban off-label reduced dosing, while secondarily determining the safety and efficacy outcomes associated with such dosing., Methods: A retrospective analysis of patients aged 65 and older with orders for apixaban for AF was institutional review board (IRB)-approved and conducted across 3 academic medical centers. Patients receiving off-label reduced-dose apixaban (ie, "underdosed") were matched to a cohort of patients dosed according to the package insert at the standard dosing (5 mg twice daily) using stratified random sampling. Secondary outcomes included 1-year incidence of major bleeding, clinically relevant non-major bleeding (CRNMB), stroke or transient ischemic attack (TIA), and mortality. The Fisher exact tests were used to compare between-group differences., Results: Of the 1172 patients meeting initial inclusion criteria, 201 (17%) were dosed off-label, with 175 (15%) "underdosed." The 147 "underdosed" patients with documented follow-up were matched with 139 patients receiving standard Food and Drug Administration (FDA)-labeled dosing. There were no significant differences in incidence of stroke (2.7% vs 2.2%), major bleeding (0% vs 0.7%), and CRNMB (2.7% vs 1.4%) in the off-label reduced dosing versus standard dosing groups. All-cause mortality was higher in the off-label reduced-dose group (16 [10.9%] vs 2 [1.4%], P < 0.05)., Conclusion and Relevance: Older adults with nonvalvular AF are commonly prescribed lower-than-recommended doses of apixaban. However, no significant association was found between empiric off-label reduced dosing and stroke or bleeding outcomes., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Seasonality in the incidence of stroke has been examined in numerous studies, yet data on whether it differs with age are limited. To fill this gap, we utilized a largescale dataset from Israel., Patients and Methods: We retrieved data of all hospitalizations for ischemic stroke (IS), transient ischemic attack (TIA) and intra cerebral hemorrhage (ICH) from 2000 to 2020. We maintained separate datasets for IS/TIA and ICH, divided into five age groups: 18-49, 50-59, 60-69, 70-79, and 80+. We modeled the monthly incidence using a generalized additive model. The seasonal effect was defined by the rate ratio (RR) of each month compared to the annual mean., Results: The analysis included 317,586 and 23,789 events of IS/TIA and ICH respectively. We found an interaction between age and seasonality, accounting for a phase shift with age in the seasonal pattern of IS/TIA incidence. For cases under 70 years, the peak was during summertime and the RRs increased with decreasing age, reaching 1.11 (95% CI 1.09-1.13) at the youngest age group. In contrast, among the elderly, a winter peak was observed and the RRs increased with age to 1.07 (95% CI 1.06-1.08) at the oldest age group. For ICH, a winter/autumn peak was identified and the RRs increased with age to 1.20 (95% CI 1.16-1.24)., Conclusions: Our finding of age-dependent seasonal patterns in the occurrence of stroke, suggests closer monitoring of cardiovascular risk factors during wintertime among elderly individuals. The mechanism governing the seasonal phase shift with age in IS/TIA incidence, requires further investigation., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Basilar artery dolichoectasia (BADE) refers to abnormal enlargement or displacement of the basilar artery (BA). The previously reported prevalence of BADE among patients with stroke is 0.3 to 33.1%, however, it might vary among studied populations. We aim is to determine the prevalence of BADE in patients presenting with acute ischemic stroke (AIS) or transient ischemic attack (TIA) in a Stroke Unit in a single center in Spain., Patients and Methods: Patients 50 years old or older presenting with AIS or TIA were eligible for inclusion. Demographic and clinical data were prospectively collected. Two neuroradiologists, blind to each other, assessed BA morphology., Results: Among 126 patients, 34.1% fulfilled the criteria for BADE (ectasia or dolichosis). BADE was associated with advanced age (p = 0.04). Patients with fetal-type circle of Willis presented smaller BA diameters (2.9 ± 0.1 vs. 3.5 ± 0.1; p < 0.001), whereas patients with lacunar strokes presented a greater diameter than other stroke subtypes (3.8 ± 0.3 mm vs. 3.3 ± 0.1 mm; p = 0.04)., Discussion and Conclusions: In this single-center study of patients presenting with AIS or TIA, the prevalence of BADE (ectasia or dolichosis) is high. Further studies focusing on Spaniards should confirm our results.

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., (© 2024. The Author(s).)

Background: Cardiovascular discharge diagnoses may serve as endpoints in epidemiological studies if they have a high validity. Aim was to study if diagnoses-specific characteristics like type, sub-categories, and position of cardiovascular diagnoses affected diagnostic accuracy., Methods: Patients (n = 7,164) with a discharge diagnosis of acute myocardial infarction, heart failure or cerebrovascular disease were included. Data were presented as positive predictive values (PPV) and sensitivity., Results: PPV was high (≥88%) for acute myocardial infarction (n = 2,189) (except for outpatients). For heart failure (n = 4,026) PPV was 67% overall, but higher (>99%) when etiology or echocardiography was included. For hemorrhagic (n = 257) and ischemic (n = 1,034) strokes PPVs were 87% and 80%, respectively, with sensitivity of 79% and 75%. Transient ischemic attacks (n = 926) had PPV 56%, but sensitivity 86%. Primary diagnoses showed higher validity than subsequent diagnoses and inpatient diagnoses were more valid than outpatient diagnoses (except for transient ischemic attack). The diagnoses of acute myocardial infarction and heart failure where most valid when placed at cardiology units, while ischemic stroke when discharged from an internal medicine unit., Conclusions: The diagnoses of acute myocardial infarction and stroke had excellent validity when placed during hospital stays. Similarly, heart failure diagnoses had excellent validity when echocardiography was performed before placing the diagnosis, while overall the diagnoses of heart failure and transient ischemic attack were less valid. In conclusion, the results indicate that cardiovascular diagnoses based on objective findings such as acute myocardial infarction and stroke have excellent validity and may be used as endpoints in clinical epidemiological studies with less rigid validation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Rye et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)