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To investigate the time-dependent effects of traditional risk factors on functional disability in all-cause mortality post-stroke, we evaluated data from a long-term stroke cohort. Baseline cerebrovascular risk factors (CVRF) and functionality at 1 and 6 months were evaluated in survivors from a prospective stroke cohort using the modified Rankin scale (m-RS), which classifies participants as improvement of disability, unchanged disability (at least moderate), and worsening disability. Cox regression models considering baseline risk factors, medication use, and functionality 6 months after stroke were fitted to identify their time-dependent effects up to 12 years of follow-up. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) are presented. Among 632 survivors (median age 68, 54% male, 71% first-ever episode), age and functional disability (unchanged and worsening) 6 months after ischemic stroke had time-dependent effects on all-cause mortality risk up to 12 years of follow-up. The most impacting risk factors were unchanged (at least moderate) (HR, 2.99; 95%CI: 1.98-4.52) and worsening disability (HR, 2.85; 95%CI: 1.26-6.44), particularly in the first two years after a stroke event (Time 1: ≥6 mo to

The purpose of this study was to examine the potential effect of solar energy on vascular stroke mortality in a Greek region by using neural networks analysis. The time period studied was from 1985 to 1989. We employed the Active Cavity Radiometer Irradiance Monitoring (ACRIM) data as the main representatives of total solar irradiance (TSI) and correlated them with stroke deaths obtained from the Piraeus City Registry. The ACRIM data (parameters included TSI, TSI uncertainty, and EPOCH: time given by ACRIM) were correlated with stroke deaths using Principal Components Analysis (PCA), regressions, and, finally, neural networks. TSI was the most important parameter for the years 1985, 1986, 1987, and 1989, while EPOCH: time given by ACRIM was important for the year 1988. When considering the entire period 1985–1989, the key parameter emerged was EPOCH: time given by ACRIM. Neural networks are useful tools in exposomic investigation regarding solar energy and vascular strokes. [ABSTRACT FROM AUTHOR]

Purpose of Review: Recent data identifies increases in young ischemic and hemorrhagic strokes. We provide a contemporary overview of current literature on stroke among young patients or premature stroke along with directions for future investigation. Recent Findings: Strokes in the young are highly heterogenous and often cryptogenic. Sex distribution and risk factors shift from women among the youngest age groups (< 35) to men over the age of 45, with a coinciding rise in traditional vascular risk factors. Incidence is higher in minority and socioeconomically disadvantaged populations, and the impact of stroke among these communities may be exaggerated by disparities in symptom recognition and access to care. Special diagnostic work-up may be needed, and a lower threshold for diagnosis is warranted as potential misdiagnosis is a concern and may preclude necessary triage and management. Summary: Although "premature strokes" form a relatively small proportion of total incidence, they vary greatly across subgroups and present an outsized impact on quality of life and productivity. [ABSTRACT FROM AUTHOR]

Aim: To investigate the association between medication use and long‐term all‐cause mortality in a Brazilian stroke cohort. Methods: Both ischemic and hemorrhagic stroke were evaluated. Medication use was assessed as: never, only pre‐stroke, only post‐stroke, and continuous use. We evaluated anti‐hypertensives, anti‐diabetics, lipid‐lowering drugs, anti‐platelets, and anti‐coagulants. Cox regression models were adjusted for sociodemographic and cardiovascular risk factors. Results: Among 1173 incident stroke cases (median age: 68; 86.8% were ischemic, 70% first‐ever stroke), medication use was low (overall: 17.5% pre‐stroke, 26.4% post‐stroke, and 40% were under continuous use). Anti‐hypertensives and anti‐platelets (aspirin) were the continuous cardiovascular medications used most often, at 83.5% and 72%, respectively, while statins (39.7%) and anti‐diabetics (31.3%) were the least used. Medication use (pre‐stroke, post‐stroke and continuous use) was associated with a reduction in all‐cause mortality risk, particularly among those under continuous use (multivariable hazard ratio, 0.52; 95% confidence interval (CI), 0.46–0.66) compared with never‐users. Among ischemic stroke patients, this effect was similar (multivariable hazard ratio, 0.52; 95% CI, 0.40–0.68). No significant associations were evident among hemorrhagic stroke patients. Conclusions: The risk of all‐cause mortality was reduced by 48% among those with ischemic stroke under continuous use of medications. Secondary prevention should be emphasized more strongly in clinical practice. Geriatr Gerontol Int 2022; 22: 715–722. [ABSTRACT FROM AUTHOR]

Background and Objectives: The 21-point Brain Care Score (BCS) is an index that ranks behaviors and clinical measurements with the aim of encouraging lifestyle adjustments to lower the incidence of age-related brain disease, including stroke, late-life depression (LLD), and dementia. A higher BCS at baseline is associated with a lower risk of these outcomes. We aimed to investigate whether the associations between BCS and stroke, LLD, and dementia risks are independent of genetic predisposition for these conditions and quantify the effect of healthy lifestyle across genetic risk distributions for these outcomes., Methods: Using the UK Biobank (UKB) prospective cohort study, we computed baseline BCSs and polygenic scores to estimate genetic predisposition for stroke and LLD and APOE ε allele status to stratify dementia risk. As for outcomes again in UKB, we measured incidence of stroke, LLD, and dementia. We used multivariate Cox proportional hazard models to assess associations between BCS, genetic predisposition, and these outcomes. We also conducted stratified and interaction analyses to estimate the incidence of these outcomes across quartiles of genetic risk and BCS., Results: We included 368,340 UKB participants (median age 58 years (interquartile range 51-63 years), 46.3% male). Independent of genetic risk, a 5-point increase in BCS corresponded to lowered hazards of stroke (hazard ratio [HR] 0.70, 95% CI 0.68-0.73), LLD (HR 0.65, 95% CI 0.63-0.67), and dementia (HR 0.82, 95% CI 0.78-0.85). Incidences of all 3 outcomes were higher among participants with high genetic risk of these outcomes. However, these increased risks were offset for individuals with a higher BCS (incidence rates per 1,000 person-years were 2.76 vs 1.19 for stroke, 7.34 vs 4.46 for LLD, and 3.64 vs 2.05 for dementia, when comparing low and high BCS)., Discussion: Across different genetic predispositions for stroke, LLD, and dementia, healthier lifestyle behaviors are protective for brain health, demonstrating the nondeterminism of genetic risk. Furthermore, differences in BCS behave as aggregate risk estimators of all 3 outcomes. Further work is needed to prospectively investigate the utility and performance of the BCS as a targeted intervention in populations at elevated genetic risk of age-related brain disease.

Background and Objectives: The incidence of stroke among young adults was rising globally, but the death burden of stroke in young adults in China is lacking. We aimed to examine the temporal trends in mortality and years of life lost (YLLs) caused by stroke among young adults from 2005 to 2020 across China., Methods: Based on the data from the National Mortality Surveillance System in China, we estimated the number and age-standardized rate of mortality and YLLs due to stroke and its subtypes among young adults aged 15-49 years during 2005-2020, for both China and its 31 mainland provinces., Results: During 2005-2020, the age-standardized mortality rate of stroke among young adults aged 15-49 years in China decreased by 21.0%, from 5.9/100,000 to 4.7/100,000, and the YLL rate decreased from 286.9/100,000 to 229.5/100,000. The age-standardized mortality rate among young adults due to intracerebral hemorrhage (ICH) showed a significant downward trend with a decrease of 26.3% while that of ischemic stroke (IS) and subarachnoid hemorrhage (SAH) decreased by 4.5% and 0.6%, respectively. In 2020, the mortality rate of ICH was 3.5 times higher than that of IS (3.3/100,000 vs 0.9/100,000) among young adults in China. The male/female ratio of age-standardized mortality rate of stroke in young adults increased from 2.0 in 2005 to 3.1 in 2020. The age-standardized mortality rate of IS and SAH in young men increased by 11.0% and 2.5%, respectively. In 2020, Tibet (18.4/100,000), Jilin (10.4/100,000), and Qinghai (8.3/100,000) were the top 3 provinces holding the highest age-standardized mortality rate due to stroke among young adults. Tibet was found to have the highest mortality rate due to ICH and SAH while that of IS was higher in northeast China., Discussion: In China, the death burden caused by ICH among young adults was substantially higher than that of IS. The increasing death burden of IS and SAH among young men requires special attention. Evidence-based intervention strategies are needed to improve the outcomes of stroke and alleviate the death burden due to stroke among young adults in Chinese population.

Background and Objectives: Mounting evidence points to a strong connection between cardiovascular risk during middle age and brain health later in life. The American Heart Association's Life's Essential 8 (LE8) constitutes a research and public health construct capturing key determinants of cardiovascular health. However, the overall effect of the LE8 on global, clinically relevant metrics of brain health is still unknown. We tested the hypothesis that worse LE8 profiles are associated with higher composite risk of the most important clinical endpoints related to poor brain health., Methods: We conducted a two-stage (discovery and replication) prospective study using data from the UK Biobank (UKB) and All of Us (AoU), 2 large population studies in the United Kingdom and the United States, respectively. The primary exposure was the LE8 score, a validated tool that captures 8 modifiable cardiovascular risk factors (blood pressure, glucose, cholesterol, body mass index, smoking, physical activity, diet, and sleep duration), organized in 3 categories (optimal, intermediate, and poor). The primary outcome was a composite of stroke, dementia, or late-life depression. We evaluated associations using multivariable Cox proportional hazard models., Results: The discovery stage included 316,127 UKB participants (mean age 56, 52% female). Over a mean (SD) follow-up time of 4.9 (0.4) years, the unadjusted risk of the composite outcome was 0.7% (95% CI 0.61-0.74), 1.2% (95% CI 1.11-1.22), and 1.8% (95% CI 1.70-1.91) in participants with optimal, intermediate, and poor cardiovascular health, respectively ( p < 0.001). This association remained significant in multivariable Cox models (intermediate vs optimal cardiovascular health hazard ratio [HR], 1.37; 95% CI 1.24-1.52, and poor vs optimal cardiovascular health HR, 2.11; 95% CI 1.88-2.36, p trend <0.001). The replication stage included 68,407 AoU participants (mean age 56, 60% female). Over a mean (SD) follow-up time of 2.9 (1.41) years, the unadjusted risk of the composite outcome was 2.8% (95% CI 2.49-3.05), 6% (95% CI 5.76-6.22), and 9.7% (95% CI 9.24-10.24) in participants with optimal, intermediate, and poor cardiovascular health, respectively ( p < 0.001). This association remained significant in multivariable Cox models (intermediate vs optimal cardiovascular health, HR 1.35; 95% CI 1.21-1.51, and poor vs optimal cardiovascular health, HR 1.94; 95% CI 1.72-2.18; p trend <0.001)., Discussion: Among middle-aged adults enrolled in 2 large population studies, poor cardiovascular health profiles were associated with two-fold higher risk of developing a composite outcome that captures the most important diseases related to poor brain health. Because the evaluated risk factors are all modifiable, our findings highlight the potential brain health benefits of using the Life's Essential 8 to guide cardiovascular health optimization.

Background: Atrial fibrillation (AF) often remains undiagnosed, and it independently raises the risk of ischemic stroke, which is largely reversible by oral anticoagulation. Although randomized trials using longer term screening approaches increase identification of AF, no studies have established that AF screening lowers stroke rates., Objectives: To address this knowledge gap, the GUARD-AF (Reducing Stroke by Screening for Undiagnosed Atrial Fibrillation in Elderly Individuals) trial screened participants in primary care practices using a 14-day continuous electrocardiographic monitor to determine whether screening for AF coupled with physician/patient decision-making to use oral anticoagulation reduces stroke and provides a net clinical benefit compared with usual care., Methods: GUARD-AF was a prospective, parallel-group, randomized controlled trial designed to test whether screening for AF in people aged ≥70 years using a 14-day single-lead continuous electrocardiographic patch monitor could identify patients with undiagnosed AF and reduce stroke. Participants were randomized 1:1 to screening or usual care. The primary efficacy and safety outcomes were hospitalization due to all-cause stroke and bleeding, respectively. Analyses used the intention-to-treat population., Results: Enrollment began on December 17, 2019, and involved 149 primary care sites across the United States. The COVID-19 pandemic led to premature termination of enrollment, with 11,905 participants in the intention-to-treat population. Median follow-up was 15.3 months (Q1-Q3: 13.8-17.6 months). Median age was 75 years (Q1-Q3: 72-79 years), and 56.6% were female. The risk of stroke in the screening group was 0.7% vs 0.6% in the usual care group (HR: 1.10; 95% CI: 0.69-1.75). The risk of bleeding was 1.0% in the screening group vs 1.1% in the usual care group (HR: 0.87; 95% CI: 0.60-1.26). Diagnosis of AF was 5% in the screening group and 3.3% in the usual care group, and initiation of oral anticoagulation after randomization was 4.2% and 2.8%, respectively., Conclusions: In this trial, there was no evidence that screening for AF using a 14-day continuous electrocardiographic monitor in people ≥70 years of age seen in primary care practice reduces stroke hospitalizations. Event rates were low, however, and the trial did not enroll the planned sample size.(Reducing Stroke by Screening for Undiagnosed Atrial Fibrillation in Elderly Individuals [GUARD-AF]; NCT04126486)., Competing Interests: Funding Support and Author Disclosures The Bristol Myers Squibb/Pfizer Alliance funded the GUARD-AF trial but was not involved in data collection, analysis, or interpretation; manuscript preparation; or decision to publish. Dr Lopes has received research grants or contracts from Amgen, Bristol Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi; has received funding for educational activities or lectures from Pfizer, Daiichi-Sankyo, and Novo Nordisk; and has received funding for consulting or other services from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, and Novo Nordisk. Dr Atlas has received sponsored research support from Bristol Myers Squibb/Pfizer and the American Heart Association (18SFRN34250007); and has consulted for Boehringer Ingelheim, Bristol Myers Squibb, Fitbit, Pfizer, and Premier. Dr Go has received a research grant from Bristol Myers Squibb/Pfizer Alliance. Dr Lubitz is an employee of Novartis. Dr McManus has received grants or research support from Apple, Fitbit, Boehringer Ingelheim, Pfizer, Bristol Myers Squibb, and Flexcon; and has received consulting fees from Fitbit, NAMSA, Avania, and Heart Rhythm Society. Dr Rothberg is a consultant for Blue Cross Blue Shield Association. Prof Crosson is a former employee of iRhythm Technologies,. Dr Aronson and Mr Patlakh are employees of Bristol Myers Squibb. Ms. Mills is a former employee of Bristol Myers Squibb, Inc. Dr O’Brien has received institutional research funding from Pfizer. Dr Singer has received research support from Bristol Myers Squibb; and has consulted for the Bristol Myers Squibb, Pfizer, Medtronic, and Fitbit (Google). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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.)

Context: Low bone mineral density (BMD) has been linked to elevated risks of mortality and infections in the general population; however, its association with these outcomes in stroke patients remains unclear., Objective: This study aims to investigate the correlation between low BMD and risks of mortality and infections among stroke patients in a Taiwanese cohort., Methods: In this single-center retrospective cohort study, 905 stroke patients from a Taiwanese database (2000-2022) were analyzed. Patients were grouped based on BMD measurements of the femur and spine. The primary outcome was all-cause mortality, and secondary outcomes included urinary tract infection (UTI) and pneumonia. Accelerated failure time regression model analyses evaluated the association between BMD and these outcomes, while the Kaplan-Meier method and log-rank test assessed survival differences between groups., Results: Among the participants (average age 76.1 years, 70.5% female), 33.82% had osteopenia and 55.25% had osteoporosis. Stroke patients with lower spine and right femur BMD had significantly reduced survival rates, especially when the BMD value fell below 0.842 g/cm2 (spine), and 0.624 g/cm2 (right femur), respectively. Regarding secondary outcomes, lower spine BMD was significantly associated with an increased risk of UTI., Conclusion: Low BMD, particularly in the femur and spine, is a significant predictor of mortality and UTI in stroke patients. These findings highlight the importance of assessing and managing BMD in stroke patients to improve outcomes and reduce complications., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Stroke is predominantly a condition of older age. So, it seems sensible that specialists working in stroke services should understand the primary clinical syndrome of ageing-frailty. Recent studies have highlighted the prevalence of frailty in stroke and its associated poor outcomes, yet frailty does not feature prominently in stroke research, practice or policy. Frailty-informed stroke care may differ from the interventional management that dominates contemporary practice. However, this is not therapeutic nihilism. A person-centred approach ensures that every care decision is appropriate and based on a shared understanding of the person's goals and likely prognosis. We present a primer on frailty in stroke, describing definition(s), epidemiology and prognostic implications. We discuss the challenges surrounding assessment and management of frailty in stroke units and offer practical guidance suitable for the stroke clinician., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Cardiovascular disease (CVD) is the leading cause of death in China. This study compared ethnic disparities and lifestyle determinants in the prevalence of CVD (hypertension, coronary heart disease [CHD], and stroke) among older adults of the Han majority and Ha Ni ethnic minority in rural southwest China, to provide evidence for preventing and controlling CVD among older-adult minority communities., Methods: A multi-stage stratified random sampling method was used to select 1,413 Han majority participants and 1,402 Ha Ni ethnic minority participants aged ≥ 60 years in rural Southwest China. Data on general demographic characteristics, behavioral lifestyle, and self-reported diagnostic information for patients with CHD and stroke were collected using a standardized questionnaire. The height, weight, waist circumference, and blood pressure of each participant were recorded. The relationship between lifestyle factors and CVD was analyzed using multivariate logistic regression., Results: Han majority older adults had a higher prevalence of CHD (6.4% vs. 3.6%) and stroke (7.9% vs. 2.9%) than their Ha Ni minority counterparts (P < 0.01). Han majority participants had a markedly higher prevalence of obesity, central obesity, and physical inactivity than their Ha Ni ethnic minority counterparts (9.2%, 48.3%, and 55.1% vs. 3.4%, 19.1%, and 49.2%, respectively, P < 0.01). By contrast, Ha Ni ethnic minority participants had a higher prevalence of current drinking than Han majority participants (31.2% vs. 14.4%, P < 0.01). Among Han majority and Ha Ni ethnic minority older adults, participants with central obesity (OR = 2.09, 95% CI: 1.62-2.69 vs. OR = 2.66, 95% CI: 1.88-3.76) had a higher risk of hypertension, participants with obesity (OR = 1.99, 95% CI: 1.02-3.67 vs. OR = 3.66, 95% CI: 1.39-9.66) were more likely to suffer from CHD, and participants with physical inactivity (OR = 1.88, 95% CI: 1.18-2.98 vs. OR = 2.29, 95% CI: 1.13-4.64) had a higher probability of suffering from stroke. Furthermore, Current drinking status increased the risk of CHD (OR = 2.31, 95% CI: 1.05-5.08), but decreased the risk of stroke (OR = 0.33, 95% CI: 0.13-0.83) in Ha Ni ethnic minority participants., Conclusion: CHD and stroke are more prevalent among the Han majority older adults in rural Southwest China, and lifestyle factors significantly influence CVD., Competing Interests: Declarations Ethics approval and consent to participate The Ethics Review Committee of Kunming Medical University approved the study, and all participants provided voluntary informed consent. The study was conducted in accordance with the Declaration of Helsinki. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

This study aimed to develop and validate a clinical risk model based on clinical factors to predict prognosis in patients with wake-up stroke (WUS) after multimodal magnetic resonance imaging combined with recombinant tissue plasminogen activator intravenous thrombolysis. The study enrolled 263 patients with WUS, who were divided into the training (n = 162) and validation cohorts (n = 101). In the training cohort, patients were stratified based on modified Rankin Scale (mRS) score at 90 days after thrombolysis, with mRS ≤ 2 indicating a good prognosis (n = 117), and mRS > 2 indicating a poor prognosis (n = 45). Multivariate regression analyses were employed to identify independent risk factors and develop clinical risk models. The performance and stability of the clinical risk model were evaluated using receiver operating characteristic analysis and Hosmer-Lemeshow test. The clinical risk nomogram was constructed based on this model, and evaluated using decision curve analyses. Patients with poor prognosis showed a higher proportion of hyperlipidemia and diabetes and showed a higher levels of National Institute of Health Stroke Scale (NIHSS) at admission, NIHSS at 24 hours, triglyceride, and total cholesterol. Diabetes (odds ratio [OR] = 3.823), hyperlipidemia (OR = 7.361), NIHSS at admission (OR = 5.399), NIHSS at 24 hours (OR = 2.869), triglyceride (OR = 13.790), and total cholesterol (OR = 9.719) were independent predictors of poor prognosis in patients with WUS. Hosmer-Lemeshow test showed that the clinical risk model had a good fit in the training (χ2 = 19.573, P = .726) and validation cohorts (χ2 = 19.573, P = .726). The clinical risk model had an area under the curve value of 0.929 (95% confidence interval, 0.886-0.978) in the training cohort and 0.948 (0.906-0.989) in the validation cohort. The decision curve analysis indicated clinical risk nomogram has application value. The clinical risk model can effectively predict WUS prognosis outcomes., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: This observational study compared effectiveness and safety of direct oral anticoagulants (DOACs; apixaban, rivaroxaban, dabigatran) or vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation (NVAF) at high risk for gastrointestinal bleeding (GIB)., Methods: Anticoagulant-naïve adults with NVAF with ≥1 GIB risk factor, initiating anticoagulant treatment January 2016-December 2019, and covered by the French national health data system were eligible. Outcomes included major bleeding (MB) and stroke/systemic embolism (SE). Patient characteristics were balanced using propensity score matching., Results: A total of 314,184 patients were identified with 162,150 (51.5%) in the apixaban cohort, 88,427 (28.1%) in the rivaroxaban cohort, 16,465 (5.2%) in the dabigatran cohort, and 47,142 (15.0%) in the VKA cohort (mean age 79.0 years, standard deviation 10.5; 51.0% female). A total of 45,124 apixaban-VKAs, 38,737 rivaroxaban-VKAs, 16,415 dabigatran-VKAs, 88,414 apixaban-rivaroxaban, 16,464 apixaban-dabigatran, and 16,459 rivaroxaban-dabigatran pairs were retained after propensity score matching. Apixaban had lower risk of MB versus dabigatran (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.63-0.83) and rivaroxaban (HR, 0.63; 95% CI, 0.59-0.66). Apixaban had lower risk of GIB versus dabigatran (HR, 0.46; 95% CI, 0.37-0.56) and rivaroxaban (HR, 0.54; 95% CI, 0.49-0.59). Risk of GIB was similar with dabigatran versus rivaroxaban (HR, 1.05; 95% CI, 0.89-1.24). Apixaban had lower risk of stroke/SE versus rivaroxaban (HR, 0.90; 95% CI, 0.84-0.96), while risk was similar versus dabigatran (HR, 1.1; 95% CI, 0.9-1.3). All DOACs had lower risk of MB and stroke/SE versus VKAs (p<0.001 for all)., Conclusions: DOACs had improved safety and effectiveness from bleeding and stroke/SE, respectively, versus VKAs among patients with NVAF at high risk for GIB. Apixaban was associated with lower MB and GIB risk versus other DOACs. For stroke/SE, apixaban was associated with reduced risk versus rivaroxaban and similar risk versus dabigatran., Competing Interests: GYHL reported serving as a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Anthos outside the submitted work. No fees are received personally. GYHL is a National Institute for Health and Care Research (NIHR) Senior Investigator and co-principal investigator of the AFFIRMO project on multimorbidity in AF, which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 899871. RB reported serving as a consultant for Alfasigma, Medtronic, Falk, Mayoli and Pfizer. ACM reported serving as a consultant and speaker for Abbott, Bayer, BMS/Pfizer, Boehringer Ingelheim, and received research grant from BMS/Pfizer. GP, GG, AK and NQ are employees of Certara, who were paid consultants to Pfizer and Bristol Myers Squibb in connection with the conduct of this study. FD, FS, JC, RS and RM are employees and shareholders of Pfizer. We confirm that this does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Lip 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.)

Numerous studies have suggested that the hemoglobin-to-red blood cell distribution width ratio (HRR) is associated with the onset, progression, and prognosis of various diseases. However, to the best of our knowledge, no research has conducted statistical analyses to determine the association between HRR and stroke. This cross-sectional study was conducted among adults with complete data on hemoglobin-red cell distribution width ratio (HRR) and stroke from the 2005-2018 National Health and Nutrition Examination Survey (NHANES). HRR was calculated by dividing hemoglobin (HGB) in grams per deciliter (g/dL) by the red blood cell distribution width (RDW). Weighted multivariable logistic regression and generalized additive models were employed to investigate the independent and nonlinear relationships between HRR and stroke. Threshold effects were assessed using two-piece linear regression models. Additionally, subgroup analyses and interaction tests were performed. A total of 36,215 participants were included, with 2.92% classified as stroke patients. The prevalence of stroke decreased across increasing tertiles of HRR (Q1: 5.07%; Q2: 2.63%; Q3: 1.69%; P < 0.0001). A negative association between HRR and stroke was observed in both unadjusted and adjusted models. In Model III, each one-unit increase in HRR was associated with a 58% reduction in the likelihood of stroke (Model III: OR = 0.42, 95% CI: 0.29-0.63). Subgroup analyses and interaction tests revealed that the association between HRR and stroke was BMI-dependent (P < 0.05), with the negative association only observed in participants with BMI < = 25 and BMI 25-30, but not in those with BMI > 30. Using a two-piece linear regression model, a threshold effect was identified at a BMI of 30 (K = 1.16). To the left of this breakpoint, there was a negative association between HRR and stroke (OR = 0.55, 95% CI: 0.27-0.97), whereas no such association was detected to the right of the breakpoint (OR = 6.49, 95% CI: 0.75-56.11). HRR is negatively associated with the likelihood of stroke, with a lower risk of stroke in individuals with higher HRR levels., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethics approval The studies involving humans were approved by the National Center for Health Statistics Research Ethics Review Board. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study., (© 2024. The Author(s).)

Background: Stroke is a devastating complication of Sickle Cell Disease (SCD) with significant mortality and substantial morbidity. The burden of prevalent stroke in SCD is highest in sub-Saharan Africa and estimated at 4.2 % to 6.4 % in the era where evidence-based prevention strategies such as use of hydroxyurea therapy and transcranial doppler ultrasound were not routine care., Purpose: To assess the contemporary frequency and factors associated with prevalent stroke across the lifespan in an SCD registry at the tertiary medical center in Ghana., Methods: This is a cross-sectional study conducted at the Komfo Anokye Teaching Hospital, a tertiary medical center in the middle belt of Ghana. The center has comprehensive Sickle Cell Clinics for children, adolescents, and adults with a patient registry established as part of the Sickle Pan-African Research Consortium (SPARCo)-Ghana study from 2017 to date. Data captured in the registry and analyzed for the present study include demographics, stroke status using the WHO criteria supplemented by the Questionnaire for Verifying Stroke Free Status (QVSFS), use of hydroxyurea, and complete blood count. Logistic regression modeling was utilized to assess factors associated with stroke., Results: Among a registry cohort of 4115 individuals with confirmed SCD, 35 (0.85 %, 95 % CI: 0.59-1.18 %) had overt or clinically confirmed stroke. The frequency of stroke differed significantly across the lifespan being 0.38 % (95 % CI: 0.12-0.64 %) among children <10 years, 1.23 % (95 % CI: 0.73-1.94 %) among adolescents aged 10 to 17 years, and 1.44 % (95 % CI: 0.66-2.71 %) among adults 18 years or more, p = 0.007. In adjusted analysis, each 10-year increase in age was associated with odds ratio, OR (95 % CI) of 1.90 (1.42-2.54) and hydroxyurea use, OR of 6.09 (2.65-13.99). The association between hydroxyurea and stroke observed in this cross-sectional study is not causal., Conclusion: Approximately 1 in 120 SCD patients in this large Ghanaian cohort had clinically overt stroke. The gradual uptake of hydroxyurea therapy into routine care for SCD in this resource-limited setting, may partly explain the lower frequency of stroke., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Data regarding unequal diagnostic and therapeutic access in patients with acute stroke based on ethnicity and race are inconclusive in Europeans. The objectives of our study were to evaluate the effect of race/ethnicity on access to acute stroke care and treatments and outcomes., Methods: In this retrospective cohort study, we enrolled adult patients admitted to the emergency department of a comprehensive stroke center for suspected stroke. Based on race/ethnicity, patients were divided into two main groups: Western European Whites (WEW) and non-Western European Whites (nWEW). We also divided the nWEW group into four subgroups based on the Office of Management and Budget classification of human races and ethnicities (White-Others, Hispanic, Asian, Black). Univariate comparisons and logistic regression analyses were also performed., Results: 9167 patients were enrolled in the study: 582 in the nWEW and 8585 in the WEW group. Patients with ischemic stroke in the nWEW group were significantly younger than those in the other group (p < 0.001). Once adjusted for possible confounders, belonging to the nWEW group was found to be an independent predictor of a lower likelihood of receiving revascularization treatments (p = 0.006), regardless similar onset-to-door times. There were no differences in stroke outcomes and prevalence of stroke mimic diagnosis between the groups., Conclusions: Racial/ethnic disparities in healthcare represent a challenging issue, even in universal healthcare systems, that should be addressed promptly through education campaigns of healthcare personnel and implementation measures, such as integrating readily available interpreter staff for medical emergencies., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Available evidence suggests that air pollutants can cause stroke, but little research has investigated the confounding effects of urban-rural differences. Here, we investigated the urban-rural difference in the correlation between particulate matter (PM 2.5 and PM 10 ) exposure and stroke. This cohort study was based on a prospective multi-city community-based cohort (Guizhou Population Health Cohort Study (GPHCS)) in Guizhou Province, China. A total of 7988 eligible individuals (≥18 years) were enrolled with baseline assessments from November 2010 to December 2012, and follow-up was completed by June 2020. Two major particulate matters (PMs, including PM 2.5 and PM 10 ) were assessed monthly from 2000 by using satellite-based spatiotemporal models. The risk of stroke was estimated using a Cox proportional hazard regression model. The association between particulate matters' exposure and stroke in different areas (total, urban, and rural) and the potential modification effect of comorbidities (hypertension, diabetes, and dyslipidemia) and age (≤65/>65 years) were examined using stratified analyses. The risk of stroke increased for every 10 μg/m 3 increase in mean PMs' concentrations during the previous 1 year at the residential address (HR: 1.26, 95%CI: 1.24, 1.29 (PM 2.5 ); HR: 1.13, 95%CI: 1.11, 1.15 (PM 10 )). The presence of diabetes and dyslipidemia increased the risk of PM 10 -induced stroke in whole, urban, and rural areas. Specifically, people living in rural areas were more likely to experience the effects of PMs in causing a stroke. The risk of stroke due to PMs was statistically increased in the young and older populations living in rural areas. In conclusion, long-term exposure to PMs increased the risk of stroke and such association was more pronounced in people living in rural areas with lower income levels. Diabetes and dyslipidemia seemed to strengthen the association between PMs and stroke., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Current treatment recommendations for patients with heart failure and secondary mitral regurgitation include transcatheter edge-to-edge repair and mitral-valve surgery. Data from randomized trials comparing these therapies are lacking in this patient population., Methods: In this noninferiority trial conducted in Germany, patients with heart failure and secondary mitral regurgitation who continued to have symptoms despite guideline-directed medical therapy were randomly assigned, in a 1:1 ratio, to undergo either transcatheter edge-to-edge repair (intervention group) or surgical mitral-valve repair or replacement (surgery group). The primary efficacy end point was a composite of death, hospitalization for heart failure, mitral-valve reintervention, implantation of an assist device, or stroke within 1 year after the procedure. The primary safety end point was a composite of major adverse events within 30 days after the procedure., Results: A total of 210 patients underwent randomization. The mean (±SD) age of the patients was 70.5±7.9 years, 39.9% were women, and the mean left ventricular ejection fraction was 43.0±11.7%. Within 1 year, at least one of the components of the primary efficacy end point occurred in 16 of the 96 patients with available data (16.7%) in the intervention group and in 20 of the 89 with available data (22.5%) in the surgery group (estimated mean difference, -6 percentage points; 95% confidence interval [CI], -17 to 6; P<0.001 for noninferiority). A primary safety end-point event occurred in 15 of the 101 patients with available data (14.9%) in the intervention group and in 51 of the 93 patients with available data (54.8%) in the surgery group (estimated mean difference, -40 percentage points; 95% CI, -51 to -27; P<0.001)., Conclusions: Among patients with heart failure and secondary mitral regurgitation, transcatheter edge-to-edge repair was noninferior to mitral-valve surgery with respect to a composite of death, rehospitalization for heart failure, stroke, reintervention, or implantation of an assist device in the left ventricle at 1 year. (Funded by Abbott Vascular; MATTERHORN ClinicalTrials.gov number, NCT02371512.)., (Copyright © 2024 Massachusetts Medical Society.)

Objective: We conducted a study titled for Investigation on the characteristics of 24-hour blood pressure (BP) dipping patterns in hypertensive stroke patients., Methods: Descriptive research, analysis, and comparison, the research was conducted from July 2019 to September 2020 at the Vietnam Heart Institute - Bach Mai Hospital. There are 100 patients diagnosed with idiopathic hypertension who were divided into two groups (without stroke complications and another group with chronic stroke complications > 6 weeks), both groups were similar in age (45-64 years old)., Results: The daytime systolic BP (SBP) indices, 24-hour BP including SBP, diastolic BP (DBP), and mean arterial pressure (MAP), and particularly night-time BP indices were elevated in the stroke group compared with those without stroke complications (p < 0.05); there were no significant differences observed in daytime DBP and MAP between the two groups. SBP indices were higher in those with hemorrhage stroke compared with those with ischemic stroke, albeit without statistical significance. The prevalence of non-dipper was significantly higher in the stroke group compared with the non-stroke group (p < 0.001)., Conclusion: The daytime SBP indices, 24-hour BP (SBP, DBP, MAP), and particularly night-time BP indices were elevated in the stroke group compared with those without stroke complications. The prevalence of non-dipper was significantly higher in the stroke group compared with the non-stroke group., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Pham et al.)

Abstract: Although patients with homozygous sickle cell anemia (SCA) carry both significant left atrial (LA) remodeling and an increased risk of stroke, the prevalence of atrial arrhythmia (AA) has never been prospectively evaluated. The aim of this study was to identify the prevalence and predictors of atrial arrhythmia in SCA. From 2018 to 2022, consecutive adult patients with SCA were included in the DREPACOEUR prospective registry and referred to the physiology department for cardiac evaluation, including a 24-hour electrocardiogram monitoring (ECG-Holter). The primary endpoint was the occurrence of AA, defined by the presence of excessive supraventricular ectopic activity (ESVEA) on ECG-Holter (ie >720 premature atrial contractions [PACs] or any run ≥ 20 PACs) or any recent history of atrial fibrillation. Overall, 130 patients with SCA (mean age: 45±12 years, 48% of male) were included. AA was found in 34 (26%) patients. Age (52±9 vs. 42±12 years, P=0,002), LA dilation (LAVi, 71±24 vs. 52±14 mL/m², P<0.001) and history of stroke without underlying cerebral vasculopathy (26% vs. 5%, P=0.009, OR=6.6 (95%CI 1.4-30.3]) were independently associated with AA. Age and LAVi correlated with PAC load per 24 hours on ECG-Holter. An age over 47 years or a LAVi >55mL/m² could predict AA with a PPV of 33% and a NPV of 92%. AAs are frequent in middle-aged patients with SCA and increase with age and LA remodeling, leading to a major additional risk factor for ischemic stroke. This study provides arguments and means to early screen for AA and potentially prevent cerebral complications., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: This study aims to analyze and evaluate the correlation between migraines and the onset of stroke, and further explore whether migraines increase the risk of stroke., Methods: Two researchers independently conducted a comprehensive search of Chinese biomedical literature databases (CBM disc), PubMed, Embase, Cochrane Library, and Web of Science databases, using a combination of subject terms and free words. Literature that met the inclusion and exclusion criteria was selected, and quality assessment was performed using The Newcastle-Ottawa Scale (NOS). Data necessary for the study were extracted as effect size as needed, and meta-analysis was conducted using Review Manager 5.4 software and Stata 16 software to calculate the combined odds ratio and its 95% confidence interval. The relevant data were analyzed, and publication bias was evaluated., Results: After conducting a meta-analysis of the 9 final included articles, the heterogeneity test showed chi2 = 10.7, df = 8 (P = .22), I2 = 25%. Therefore, a fixed-effect model was used for analysis. The combined odds ratio (OR) for the risk of stroke in migraine patients compared to non-migraine patients was 2.04, with a 95% confidence interval [1.73, 2.4], which was statistically significant. In the analysis of migraine with aura, the respective ORs were 2.32 with a 95% CI of [1.70-3.18] and 1.77 with a 95% CI of [1.34-2.33]. Subgroup analysis of female migraine patients and young migraine patients showed statistically significant results, with ORs of 2.26 (95% CI [1.67-3.05]) and 2.39 (95% CI [1.9-3.01]), respectively. The relevant literature and results were evaluated for publication bias and assessed using the NOS, indicating the reliability of the results., Conclusion: The results of the meta-analysis indicate that there is a certain relationship between migraine and the onset of stroke, and the results are relatively reliable. The analysis of migraine with aura shows that both the presence and absence of aura are associated with an increased risk of stroke. Subgroup analysis based on gender and age shows that the increased risk of stroke is associated with females and young individuals. However, due to the limited data in subgroup analysis, the above conclusions still require further research for validation., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Assessing the risk of postoperative cardiovascular events before performing non-cardiac surgery is clinically important. The current risk score systems for preoperative evaluation may not adequately represent a small subset of high-risk populations. Accordingly, this study aimed at applying iterative random forest to analyze combinations of factors that could potentially be clinically valuable in identifying these high-risk populations. To this end, we used the Japan Medical Data Center database, which includes claims data from Japan between January 2005 and April 2021, and employed iterative random forests to extract factor combinations that influence outcomes. The analysis demonstrated that a combination of a prior history of stroke and extremely low LDL-C levels was associated with a high non-cardiac postoperative risk. The incidence of major adverse cardiovascular events in the population characterized by the incidence of previous stroke and extremely low LDL-C levels was 15.43 events per 100 person-30 days [95% confidence interval, 6.66-30.41] in the test data. At this stage, the results only show correlation rather than causation; however, these findings may offer valuable insights for preoperative risk assessment in non-cardiac surgery., (© 2024. The Author(s).)

Background: The potential clinical implication of sleep talking in relation to stroke has not been explored to date. This study aimed to prospectively examine the association between sleep talking and the risk of developing stroke in a community-based cohort., Methods and Results: Included were 8001 participants (mean age, 54 years) of the Kailuan Study, China. Sleep talking was measured by a questionnaire in 2012. Cases of incident stroke were confirmed by review of medical records. Cox proportional hazards models were used to explore the association between sleep talking and stroke, adjusting for several sleep parameters (ie, insomnia, daytime sleepiness, sleep duration, snoring, and use of hypnotics) and other potential confounders. During 8 years of follow-up, 333 incident stroke cases were identified. Relative to participants without sleep talking at baseline, those with sleep talking had a higher risk of developing stroke (hazard ratio [HR], 1.30 [95% CI, 1.03-1.65]), adjusting for potential confounders. Compared with participants without probable rapid eye movement sleep behavior disorder and sleep talking, those with sleep talking and probable rapid eye movement sleep behavior disorder had a higher risk of stroke (adjusted HR, 1.93 [95% CI, 1.40-2.66])., Conclusions: The presence of sleep talking was associated with a higher risk of developing stroke. Future studies with cases of clinically confirmed sleep talking and a longer follow-up would be appropriate to further investigate this association.

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.

Aims: Aspirin is considered mandatory after myocardial infarction (MI). However, its long-term efficacy has been questioned. This study investigated the effectiveness of long-term aspirin after MI., Methods and Results: Patients ≥40 years with MI from 2004 to 2017 who were adherent to aspirin 1 year after MI were included from Danish nationwide registries. At 2, 4, 6, and 8 years after MI, continued adherence to aspirin was evaluated. Absolute and relative risks of MI, stroke, or death at 2 years from each time point were calculated using multivariable logistic regression analysis with average treatment effect modelling standardized for age, sex, and comorbidities. Subgroup analyses were stratified by sex and age > and ≤65 years. Among 40 116 individuals included, the risk of the composite endpoint was significantly higher for non-adherent patients at all time points. The absolute risk was highest at 2-4 years after MI for both adherent [8.34%, 95% confidence interval (CI): 8.05-8.64%] and non-adherent patients (10.72%, 95% CI: 9.78-11.66%). The relative risk associated with non-adherence decreased from 4 years after index-MI and onwards: 1.41 (95% CI: 1.27-1.55) at 4-6 years and 1.21 (95% CI: 1.06-1.36) at 8-10 years (Ptrend = 0.056). Aspirin non-adherence in women and individuals >65 years was not associated with increased risk. Pinteraction at each of the time points: Age - <0.001, <0.001, 0.002, 0.51; Sex - 0.25, 0.02, 0.02, 0.82., Conclusion: Non-adherence to long-term aspirin was associated with increased risk of MI, stroke, or death, but not in women or individuals >65 years. The risk decreased from 4 years after MI with near statistical significance., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: Stroke risk factors often exert long-term effects, and Mendelian randomization (MR) offers significant advantages over traditional observational studies in evaluating the causal impact of these factors on stroke. This study aims to consolidate and evaluate the relationships between potential causal factors and stroke risk, drawing upon existing MR research., Methods: A comprehensive search for MR studies related to stroke was conducted up to August 2023 using databases such as PubMed, Web of Science, Embase, and Scopus. This meta-analysis examines the relationships between potential causative factors and stroke risk. Both random-effects and fixed-effects models were utilized to compile the dominance ratios of various causative elements linked to stroke. The reliability of the included studies was assessed according to the Strengthening the Reporting of Observational Studies in Epidemiology incorporating Mendelian Randomization (STROBE-MR) guidelines., Results: The analysis identified several risk factors for stroke, including obesity, hypertension, low-density lipoprotein cholesterol (LDL-C), chronic kidney disease (CKD), and smoking. Protective factors included high-density lipoprotein cholesterol (HDL-C), estimated glomerular filtration rate (eGFR), and educational attainment. Subgroup analysis revealed that type 2 diabetes mellitus (T2DM), diastolic blood pressure (DBP) are risk factors for ischemic stroke (IS)., Conclusion: This study confirms that variables such as obesity, hypertension, elevated LDL-C levels, CKD, and smoking are significantly linked to the development of stroke. Our findings provide new insights into genetic susceptibility and potential biological pathways involved in stroke development., Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024503049., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tian, Tang, Liu and Liu.)

Importance: The association between nonarteritic anterior ischemic optic neuropathy (NAION) and an increased risk of stroke has been a subject of debate. However, multinational studies on this topic are scarce., Objective: To evaluate the short-term and long-term stroke risk after NAION compared with a matched control group., Design, Setting, and Participants: This global, retrospective, population-based cohort study used aggregated electronic health records from January 1, 2004, through March 19, 2024, sourced from the Global Collaborative Network of TriNetX, which includes data from over 152 million patients across 17 countries. Patients in the study were followed up for a maximum duration of 10 years. Patients with NAION and age-related cataract were included in the analysis. Those with stroke before the diagnosis of NAION and age-related cataract were excluded. Propensity score matching was applied to balance age, sex, race, ethnicity, comorbidities, and medication use., Exposure: International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis code for NAION or age-related cataract., Main Outcomes and Measures: The primary outcome was the relative risk (RR) of stroke (ICD-10 code I60-63) in the NAION cohort vs the matched controls. Multivariable logistic regression analyses were applied to identify potential clinical factors associated with stroke within the NAION cohort., Results: A total of 89 811 patients were identified in both the NAION (mean [SD] age, 57.2 [18.5] years; 38 678 men [43.1%]) and control (mean [SD] age, 57.0 [17.9] years; 40 014 men [44.6%]) cohorts after matching. The NAION cohort demonstrated a significantly higher all-stroke risk at all time points: 1 month (RR, 5.04; 95% CI, 4.41-5.78), 3 months (RR, 3.79; 95% CI, 3.40-4.21), 1 year (RR, 2.50; 95% CI, 2.32-2.70), 5 years (RR, 1.54; 95% CI, 1.45-1.63), and 10 years (RR, 1.33; 95% CI, 1.23-1.43). Sensitivity analysis in patients without comorbidities similarly revealed a significantly increased all-stroke risk across all intervals: 1 month (RR, 7.55; 95% CI, 4.74-12.03), 3 months (RR, 6.70; 95% CI, 4.48-10.04), 1 year (RR, 3.96; 95% CI, 2.94-5.34), 5 years (RR, 2.85; 95% CI, 2.18-3.72), and 10 years (RR, 1.68; 95% CI, 1.25-2.26). Among all the clinical factors of interest, only hypertension was consistently associated with all subtypes of stroke following NAION., Conclusions and Relevance: This cohort study of patients with NAION found a significantly elevated risk of stroke compared with matched controls, independently of comorbidities. These findings underscore the importance of regular stroke workups following the onset of NAION.

This study aimed to determine the longitudinal predictors of lifestyle behaviours among stroke survivors in New South Wales, Australia. This longitudinal study utilised data from the baseline survey (2005-2009) and a sub-study survey (2017) of the 45 and Up Study. Physical activity, alcohol consumption, smoking status, and supplement use were included as dependent variables. Generalised estimating equation models were employed to assess the longitudinal association between the dependent variable and demographic and health status measures. The average age of the participants (n = 576) was 67 (SD = 9) years at baseline and 76 (SD = 9) years at the sub-study survey time, with 54.9% being male. The longitudinal analysis revealed that the likelihood of moderate/high physical activity significantly declined over time and was lower among participants with diabetes, but was higher among those with university education. The likelihood of smoking was significantly higher in females, moderate/high-risk alcohol consumers, and those with depression, but was lower among supplement users. The likelihood of moderate/high-risk alcohol consumption significantly declined with time, and was lower among females, but higher among smokers. The likelihood of supplement use significantly declined over time, but was higher among females and/or those with asthma. Our findings help illustrate that many stroke survivors may benefit from further support in adopting and maintaining a healthy lifestyle as part of their stroke management and long-term rehabilitation, which is crucial to optimising their quality of life and successful secondary stroke prevention., (© 2024. The Author(s).)

Background: Several studies investigated the risks of neurological conditions in patients with inflammatory bowel disease (IBD), with some variability in findings. We aimed to perform a systematic review and meta-analysis of available evidence to elucidate the association between IBD and the risks of common neurological disorders., Methods: We conducted a literature search through Embase, PubMed, Scopus, and ProQuest databases from inception to June 30, 2023, to identify cohort studies assessing the risk of developing stroke, all-cause dementia, Parkinson's disease (PD), multiple sclerosis (MS), seizure/epilepsy, and peripheral neuropathy in adult IBD patients compared with non-IBD population. We combined hazard ratios (HRs) with 95% confidence intervals (CIs) to compute pooled estimates using a random-effects model., Results: In total, 22 cohort studies were included, of which 9 studies reported 7074 stroke events in 202 460 IBD patients, 5 studies reported 3783 all-cause dementia diagnoses in 109 602 IBD patients, 7 studies reported 932 PD diagnoses in 354 792 IBD patients, and 1 study reported 6 MS events in 35 581 IBD patients. We observed increased risks of incident stroke (pooled HR = 1.19; 95% CI, 1.06-1.31), all-cause dementia (pooled HR = 1.22; 95% CI, 1.05-1.38), PD (pooled HR = 1.39; 95% CI, 1.20-1.58), and MS (HR = 2.89; 95% CI, 1.02-8.42). No eligible studies were found on peripheral neuropathy and seizure/epilepsy., Conclusions: Inflammatory bowel disease may be modestly associated with increased risks of stroke, all-cause dementia, and PD. Further longitudinal studies are warranted to investigate potential links with MS, seizure/epilepsy, and peripheral neuropathy, as well as their clinical significance., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Although some randomized trials have reported beneficial effects of protein intake on cardiometabolic risk factors, evidence from prospective studies have not supported a strong link between protein intake and cardiovascular disease (CVD) risk. It is also unclear whether diversity in protein intake plays a role in CVD risk., Objective: We investigated prospective associations of (1) protein intake, overall and by food source and (2) diversity of protein sources with risk of CVD, coronary heart disease (CHD), and stroke., Methods: In a multi-ethnic cohort of 5879 U.S. adults (45-84 years), who were free of CVD at baseline, protein intake was assessed at baseline (2000-2002) using a validated 120-item food frequency questionnaire. Two different aspects of protein diversity were assessed including count (number of protein food consumed at least once/week) and dissimilarity (diversity of the attributes of the protein sources consumed). Relationships with incident CVD outcomes through 2019 were assessed using Cox proportional hazards models adjusting for sociodemographic, lifestyle, and comorbidity factors., Results: During 83,430 person-years, 1045 CVD cases were identified, including 668 CHD and 332 stroke cases. In multivariable models, we found no significant associations between protein intake, overall and by food source, with incident CVD, CHD, or stroke. Protein count, but not protein dissimilarity, was weakly associated with CVD risk. We found no significant associations between diversity of consumption of animal or plant food source and CVD outcomes., Conclusions: Our findings suggest protein consumption may not significantly impact CVD risk in middle-aged adults.

Objectives: This study leveraged the China Health and Retirement Longitudinal Study (CHARLS) to explore the association between diabetes and stroke in middle-aged and older adults in East Asia and assess the causality of this relationship using Mendelian randomization., Methods: Data from the 2011-2020 CHARLS cohort identified individuals with diabetes at baseline. Stroke incidence was self-reported through standardized questionnaires. Logistic regression and restricted cubic spline analysis examined the relationship between diabetes and stroke risk alongside nonlinear correlations between glucose levels and stroke. Mendelian randomization clarified the causal link and analyzed the mediating effect between diabetes and stroke using genetic methods., Results: In the study population aged 45 and above, stroke incidence was 5.99% in normoglycemic, 6.82% in prediabetic, and 9.93% in diabetic individuals. Over 7 years, 473 strokes occurred. Diabetes was associated with a 1.35-fold increased stroke risk compared to normoglycemia (OR = 1.35; 95% CI: 1.03-1.79). Subgroup analyses highlighted higher stroke risks in middle-aged women, nonsmokers, and nondrinkers. Mendelian randomization supports a genetic causal relationship between diabetes and stroke. Diabetes may indirectly lead to stroke through the mediating effects of hypertension and high cholesterol., Conclusion: The findings confirm a significant association and causal link between diabetes and stroke risk in an East Asian population. In addition, the results indicate that controlling blood glucose in prediabetic individuals reduces stroke risk, with no similar benefits in diabetes., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Aims: The CHA2DS2VASc score is recommended for stroke risk stratification in patients with atrial fibrillation (AF). This score assigns one extra point to female sex based on evidence from the early 2000s, suggesting higher thromboembolic risk in women. This incremental risk of thromboembolism in women has decreased over time between 2007 and 2018, becoming non-significant in recent years. The objective of this study was to assess the impact of removing the sex category (Sc) from the CHA2DS2VASc score, thus validating a non-sex CHA2DS2VASc (i.e. CHA2DS2VA) score., Methods and Results: We analysed UK primary and secondary care data comprising 195 719 patients with AF followed between 1998 and 2016 (mean age: 75.9 ± 12.3 years; 49.2% women). Among 126 428 non-anticoagulated patients, we compared the CHA2DS2VASc vs. CHA2DS2VA scores every calendar year. Throughout 413 007 patient-years, a total of 8742 events of ischaemic stroke or systemic embolism were recorded. Sex differences in thromboembolic risk were not observed in the lower-risk population, but higher stroke rates were consistently seen in female patients in the higher-risk category (i.e. CHA2DS2VA ≥2). C-statistics for both CHA2DS2VA and CHA2DS2VASc scores were similar over the years (ranging from 0.62 to 0.71). With CHA2DS2VA, no relevant differences were observed in integrated discrimination improvement, and net reclassification improvement (NRI) resulted in improved reclassification (11%) in lower thromboembolic risk groups. The NRI suggested misclassification in higher thromboembolic risk patients (-7%), but this did not affect their indication for anticoagulation (i.e. patients retained their high-risk status)., Conclusion: Removing Sc from the CHA2DS2VASc score does not affect its ability to discriminate thromboembolic events in the population with AF. The use of CHA2DS2VA may simplify initial decision-making for thromboprophylaxis., Competing Interests: Conflict of interest: G.Y.H.L. is a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, and Anthos. No fees were received personally. The remaining authors have no other conflicts of interest to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background/Objectives: Prospective cohort studies are useful for studying how biomolecular status affects risk of adverse health outcomes. Less well known is that the longer the follow-up time, the lower the association (or "apparent effect") due to "regression dilution". Here, we evaluate how follow-up interval from baseline to "event" affects the relationship between baseline serum 25-hydroxyvitamin D [25(OH)D] concentration and the later incidence of stroke and major cardiovascular events (MACEs). Methods: Findings for the relative risk (RR) of stroke and MACEs with respect to serum 25(OH)D concentrations at baseline from prospective cohort studies were plotted against mean follow-up time. Fifteen studies from mainly European countries and the United States were used for stroke and nine studies for MACEs. Linear regression analyses were used to study data for follow-up periods of up to 10 years and for more than 10 years. Results: For stroke, the linear regression fit for 1-10 years is RR = 0.34 + (0.065 × follow-up [years]), r = 0.84, adjusted r 2 = 0.67, p < 0.001. No significant variations in association were found for studies with follow-up periods of 10-20 years. For MACEs, the linear fit for 1-8.1 years is RR = 0.61 + (0.055 × follow-up [years]), r = 0.81, adjusted r 2 = 0.59, p = 0.03. Discussion: The shorter the follow-up period, the greater the apparent effect of better vitamin D status in reducing risk of stroke and MACEs. In addition, the apparent effect of higher 25(OH)D concentration found for the shortest follow-up time is more than twice as great as the estimate based on average follow-up intervals for all studies. Mechanisms have been found to explain how higher serum 25(OH)D concentrations could reduce risk of stroke and MACEs. Randomized controlled trials have not shown that vitamin D supplementation significantly reduces risk of either stroke or MACEs, probably because risk of both outcomes increases rapidly below 15 ng/mL (38 nmol/L) and it is difficult in Western developed countries to enroll enough participants with concentrations that low. Nonetheless, vitamin D's role in reducing risk of stroke and MACEs could be considered causal on the basis of an evaluation of the evidence using Hill's criteria for causality in a biological system. Conclusions: Serum 25(OH)D concentrations above 20 ng/mL are associated with significantly reduced risk of stroke and MACEs prospectively and in an apparent causal manner. Raising serum 25(OH)D concentrations to >20 ng/mL should, therefore, be recommended for everyone likely to be at risk for stroke or MACEs and indeed in the general population.

This study aims to explore the risk factors for carotid plaque (CP) and carotid common artery intima-media thickening (CCAIMT) and clarify the relationship between the risk factors with the number of CPs and the side of CCAIMT in a high-stroke-risk population in Qujing, Yunnan, China. Carotid ultrasonography was performed in 430 participants with high stroke risk, who were divided into different groups according to their ultrasound results. The risk factors and blood biochemical indices were recorded for assessment. The prevalence rates of CP and CCAIMT were 88.1% and 70.5%, respectively. Multivariate logistic regression analysis identified age and lack of physical exercise as risk factors of CP. Compared to participants without CP, participants who performed little physical exercise were prone to have one CP, while participants with risk factors for smoking, older age, and physical inactivity were more likely to have several CPs. Risk factors for CCAIMT were older age, male, and the levels of low density lipoprotein cholesterol. Risk factors for left CCAIMT included a history of hyperlipidemia and low density lipoprotein cholesterol, while male sex was the sole risk factor for right CCAIMT. Finally, male sex and advanced age were identified as risk factors for dual CCAIMT. The research reveals the risk factors for CP and CCAIMT, also clarifies the relationship between the risk factors, CP numbers, and the side of CCAIMT., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Objective: The triglyceride-glucose (TyG) index, a surrogate marker for insulin resistance, has been proposed as a predictor of cardiovascular events. However, the combined impact of the TyG index and obesity indicators, such as body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR), on stroke risk was not fully understood. This study aimed to investigate the association between the TyG index combined with these obesity indicators and stroke risk in the Chinese population., Materials and Methods: Data on 17,708 participants aged 45 years or older for this study were collected from the China Health and Retirement Longitudinal Study (CHARLS) from baseline (2011) to the Wave 5 follow-up (2020). Cox proportional hazards model, restricted cubic spline (RCS) and receiver operating characteristic (ROC) analysis were employed to examine the association between the TyG index and its combined obesity-related indicators with stroke. Mediation analysis was conducted to explore the mutual potential mediating role of TyG and obesity indicators in the above relationships., Results: A total of 8,207 participants with an average age of 58.2 years were investigated, of which 11.0% were stroke individuals, 44.80% were men and 84.6% were from rural areas. TyG, TyG-BMI, TyG-WHtR, TyG-WC were significantly higher in stroke subjects than in the non-stroke subjects (P < 0.001), and were significantly and positively associated with stroke in all 3 models (P < 0.05). Restricted cubic spline models revealed nonlinear associations between TyG and TyG-BMI with stroke (P-overall < 0.001, P-nonlinear = 0.003 for TyG, and P-overall < 0.001, P-nonlinear = 0.028 for TyG-BMI), while TyG-WC and TyG-WHtR (P-overall < 0.001 and P-nonlinear > 0.05) demonstrated linear associations with stroke after adjusting for covariates. TyG-WHtR, TyG-BMI and TyG-WC had more robust predictive power than TyG for risk of stroke. TyG-WHtR or TyG-WC had the highest predictive power for stroke (AUC:0.696, 95% CI 0.677-0.715), slightly higher than the other indicators. Associations between TyG, TyG-WC, TyG-WHtR, and TyG-BMI with stroke were found to be stronger among individuals who were ≥ 55 years of age, male. The relationship between TyG and stroke was significantly mediated by BMI, WHtR and WC (15.79%, 21.72%, and 24.06% respectively), while the relationship between these obesity measures and stroke was significantly mediated by TyG (18.48%, 14.45%, and 14.70% respectively)., Conclusion: The combination of TyG and obesity-related indicators was significantly associated with stroke risk, and could improve predictive power for stroke compared to the single TyG. Obesity indicators and TyG mediated each other in their respective associations with stroke risk., (© 2024. The Author(s).)

Background: The prospective, single-arm, observational, phase 4 ETNA-AF Europe study collected real-world data about safety, effectiveness and therapeutic adherence in European patients with non-valvular atrial fibrillation newly prescribed with edoxaban and followed up for 4 years., Methods: Overall, 13 164 patients were included in the full-analysis set, which means that they had at least one documentation after baseline at 4 years. The current paper reports about the 3329 Italian patients out of the whole European population., Results: In the Italian cohort, median age was 76.0 (69.0-82.0) years, with 57.4% of the patients being ≥75 years old. The CHA2DS2-VASc score was >4 in 586 (18.1%) patients. At baseline, 670 (20.8%) patients were classified as frail by the investigators. Edoxaban 30 mg/day was prescribed to 1013 (31.8%) patients: these were older, with more comorbidities and a lower estimated creatinine clearance compared with those receiving 60 mg/day. All-cause mortality was 4.1%/year and there were very low yearly rates of bleeding and thromboembolic events: major bleeding, 0.9%; intracranial hemorrhage, 0.2%; ischemic stroke, 0.3%; systemic embolism, <0.1%. These events were more frequent in patients ≥75 years or in patients with renal impairment or treated with edoxaban 30 mg/day. Advancing age was not associated with an increased incidence of intracranial bleeding., Conclusions: These findings confirm the favorable long-term safety and effectiveness profile of edoxaban in non-valvular atrial fibrillation patients treated in routine clinical care in Italy.

While the majority of stroke researchers use frequentist statistics to analyze and present their data, Bayesian statistics are becoming more and more prevalent in stroke research. As opposed to frequentist approaches, which are based on the probability that data equal specific values given underlying unknown parameters, Bayesian approaches are based on the probability that parameters equal specific values given observed data and prior beliefs. The Bayesian paradigm allows researchers to update their beliefs with observed data to provide probabilistic interpretations of key parameters, for example, the probability that a treatment is effective. In this review, we outline the basic concepts of Bayesian statistics as they apply to stroke trials, compare them to the frequentist approach using exemplary data from a randomized trial, and explain how a Bayesian analysis is conducted and interpreted., Competing Interests: Dr Ospel is a consultant for Nicolab. Dr Goyal is a consultant for Mentice, Medtronic, MicroVention, and Stryker. Dr Brown reports compensation from MicroVention, Inc, for consultant services and compensation from the Faculty of Arts, University of Calgary, for consultant services. Dr Rinkel reports grants from the Niels Stensen Fellowship. Dr Ganesh reports compensation from Figure 1 for consultant services; grants from the Heart and Stroke Foundation of Canada; compensation from Atheneum for consultant services; grants from the Canadian Cardiovascular Society; compensation from Creative Research Designs for consultant services; grants from Campus Alberta Neuroscience; grants from the Government of Canada; stock options in TheRounds.com; compensation from DeepBench for consultant services; grants from the Alzheimer Society of Canada; grants from Rhodes Scholarships; grants from the Canadian Institutes of Health Research; compensation from the Canadian Association of Neuroscience Nurses for consultant services; grants from Alberta Innovates; stock holdings in Collavidence, Inc; grants from Wellcome Trust; travel support from the American Academy of Neurology; travel support from the American Heart Association; travel support from the University of Calgary; service as an editorial board member for the journal Stroke for American Heart Association; stock options in SnapDx, Inc; grants from MicroVention, Inc; service as a review editor for Stroke for Frontiers in Neurology; compensation from Alexion Pharmaceuticals for other services; grants from Panmure House; compensation from Biogen for other services; compensation from MD Analytics for consultant services; compensation from MyMedicalPanel for consultant services; compensation from CTC Communications Corporation for consultant services; service as an editorial board member for the journals Neurology and Neurology: Clinical Practice for the American Academy of Neurology; grants from the Fondation Brain Canada; and grants from the Sunnybrook Research Institute. Dr Hill reports grants from Boehringer Ingelheim, Medtronic, MicroVention, Inc, the Canadian Institutes of Health Research, NoNO, Inc, and Medtronic; compensation from Merck for end point review committee services; grants from Stryker Corporation; a patent issued for Systems and Methods for Assisting in Decision-Making and Triaging for Acute Stroke Patients licensed to Circle NVI; compensation from Brainsgate Ltd for consultant services; grants from Biogen, Inc, and Medtronic; and employment by the University of Calgary. The other authors report no conflicts.

Background: Migraine prevalence has been estimated to be as high as 25% during reproductive years. Despite this, and the known significantly lower odds of acute stroke being correctly diagnosed among women versus men, little is known about the migraine-stroke connection in this vulnerable population. Our study seeks to provide a consolidated examination of cerebrovascular and obstetric complications of migraines in pregnant women and to evaluate the role of concurrent comorbidities. Methods: We utilized the 2016-2020 Healthcare Cost and Utilization Project's National Inpatient Sample with the International Classification of Diseases, 10th Revision diagnostic codes to compare pregnant patients with migraines with those without migraines. Multivariable logistic regression was used to examine the incidence of subtypes of stroke while controlling for confounding variables. Results: Overall, 19,825,525 pregnant patients were evaluated; 219,175 (1.1%) had a concomitant diagnosis of migraine. Pregnant patients with migraines were more likely to suffer ischemic (0.1% versus 0.0%) or hemorrhagic stroke (0.3% versus 0.1%). On multivariate analysis, acute ischemic stroke was most strongly associated with migraine with aura (odds ratio [OR], 23.26; 95% confidence interval [CI], 18.46-29.31), followed by migraine without aura (OR, 8.15; 95% CI, 4.79-13.88). Conclusions: Pregnant women with migraine are at a significantly increased risk for both ischemic and hemorrhagic stroke. Pregnant women with migraines should be cautioned that they may be at an increased risk of stroke, particularly if they are experiencing an aura, and encouraged to contact their medical providers to rule out neurological complications.

Introduction: Migraine is an established risk factor for cerebral ischemic stroke, with an especially robust association in patients with migraine with aura. However, it is not known if migraine is a risk factor for retinal stroke (central or branch retinal artery occlusion; CRAO or BRAO)., Methods: We performed a retrospective, observational, cohort study using population-based data from the State Inpatient Databases and State Emergency Department Databases from New York (2006-2015), California (2003-2011), and Florida (2006-2015) to determine the association between hospital-documented migraine and retinal stroke. The primary exposure was hospital-documented migraine (ascertained from admission or emergency department diagnosis codes). The primary endpoint was time to hospital-documented CRAO (ICD-9-CM code 362.31 in the primary diagnosis position) and secondary endpoints included time to BRAO and any retinal artery occlusion (RAO). Cause-specific hazard models were used to model the association between migraine and subsequent CRAO., Results: Of 39,835,024 patients included in the study, 1109,140 had migraine documented during our two year ascertainment window. Patients with migraine were younger (40.2±15.2 vs. 46.9±19.8, standardized difference (SD) 0.38), more likely to be female (81.4 % vs. 54.7 %, SD 0.6), and had a lower burden of atrial fibrillation (4.5 % vs. 6.9 %, SD 0.1), chronic kidney disease (1.9 % vs. 3.6 %, SD 0.2), and congestive cardiac failure (2.7 % vs. 5.1 %, SD 0.12). Migraine was not associated with CRAO in the primary diagnostic position (adjusted hazard rate (aHR) 1.15 (95 % CI: 0.79-1.67). However, it was associated with CRAO in any diagnostic position (aHR 1.39 (95 % CI: 1.08-1.78). As positive controls, we replicated previously established associations of migraine with cerebral ischemic stroke (aHR 1.35 (95 % CI: 1.32-1.38) and embolic ischemic stroke (aHR 1.15 (95 % CI: 1.08-1.22)., Conclusions: In a large, nationally-representative, claims-based study of patients from 3 regions in the United States (US), we did not find an adjusted association between migraine and a primary discharge diagnosis of CRAO. Our hypothesis-generating finding that migraine was associated with CRAO when using a broader definition sets the stage for future work leveraging both outpatient and pharmacy based claims to further explore this finding., Competing Interests: Declaration of Competing Interest JL reported none. AS reported none. SU reported none. HRA reported none. ADH is supported by NIH-NINDS (K23NS105924), has received investigator initiated clinical research funding from the AAN, has received consultant fees from Integra and Novo Nordisk, has equity in TitinKM and Certus, and receives author fees from UpToDate. VB is supported by the National Institutes of Health’s National Eye Institute core grant P30-EY06360 (Department of Ophthalmology, Emory University School of Medicine) and by a departmental grant from Research to Prevent Blindness (New York, NY), and is a consultant for GenSight Biologics and Neurophoenix. MS is supported by the National Institutes of Health (R56AG074279, K76AG060001, R01AG078803, RF1NS129735, RF1NS130334 and R21AG070859). He has received fees from Labaton Sucharow and Raymond James and Associates for consulting unrelated to this work and receives a stipend for chairing the DSMB for the ongoing REVISION trial. ES reported none. SP received research support from BMS/Pfizer, Boehringer-Ingelheim, Daiichi Sankyo, European Union, German Federal Joint Committee Innovation Fund, and German Federal Ministry of Education and Research, Helena Laboratories and Werfen as well as speakers’ honoraria/consulting fees from Alexion, AstraZeneca, Bayer, Boehringer-Ingelheim, BMS/Pfizer, Daiichi Sankyo, Portola, and Werfen (all outside the submitted work). NOP reported none. YX is funded by the NIA (R01AG062770, R01AG066672), has research funding from the American Heart Association, Genentech, Daiichi Sankyo and Janssen and has received honoraria from Boehringer Ingelheim, and Portola. EO reported none. BMG is supported by the National Institutes of Health (K23HL161426) and the American Heart Association (23MRFSCD1077188)., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Air pollution is one of the main causes of global disease burden, especially in low-income and middle-income countries. Estimation of the current situation and prediction of the future health effects of death and incidence of stroke and coronary heart disease (CHD) attributed to PM 2.5 were done using BenMAP-CE software. Estimating and forecasting the economic burden of these diseases were done in 4 scenarios: Stability of the current PM 2.5 concentration, annual 10 % reduction of PM 2.5 concentration, reduction to 5 µg/m3, and reduction to 12 µg/m3, with three approaches for calculating the economic burden in mortality costs, including the human capital(HC), years of life lost(YLL) and value of statistical life(VSL) was performed. With the stability of the PM 2.5 concentration, the economic burden of stroke attributed to PM 2.5 with the approach of calculating the cost of death with the HC, the YLL, and VSL will reach from 64, 82 and 172 million USD in 2020-849, 1120 and 2703 million USD in 2030 and these costs for CHD in the mentioned approaches of calculating the cost of death will reach respectively from 499, 568 and 898 million USD in 2020-7096, 8088, and 13,621 million USD in 2030. We find that the morbidity economic burden (including direct, indirect, and intangible costs) of stroke compared to the cost of death with the HC, and YLL approaches are 67.58 times, 3.15 times respectively, and in the VSL approach is 47.32 % of stroke death cost. Also, the costs of CHD morbidity economic burden compared to the cost of death in the method of calculating the cost of death with the HC, YLL, and VSL approaches are 42.09, 7.25, and 1.16 times, respectively. This study provides comprehensive baseline information for health policymakers to understand the benefits of air pollution control policies globally, especially in LMICs., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Zohreh Kazemi reports financial support was provided by Iran National Science Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The incidence and outcomes of early cardiac complications in patients with intracerebral hemorrhage (ICH) are poorly understood. These cardiac complications may be part of the so-called stroke-heart syndrome in patients with ICH. We investigated this issue in an individual patient data pooled analysis from an international repository of clinical trial data., Methods: We used the Virtual International Stroke Trials Archive to investigate the incidence of cardiac complications within 30 days post-ICH or acute ischemic stroke (AIS). These complications included acute coronary syndrome encompassing myocardial injury, heart failure/left ventricular dysfunction, atrial fibrillation/atrial flutter, other arrhythmia/ECG abnormalities, and cardiorespiratory arrest. We used propensity score matching to compare the incidence of patients with stroke-heart syndrome in patients with ICH with those following AIS. Factors associated with 90-day mortality were evaluated using multivariate logistic regression analysis in the ICH cohort., Results: We pooled data from 8698 participants recruited in acute stroke trials (mean age, 68±12 years; 56% male), of whom 914 (11%) were patients with ICH. Among the patients with ICH, 123 (13%) had stroke-heart syndrome in patients with ICH. Following propensity score matching, a total of 1828 patients (914 for each of the cohorts) were analyzed. While the overall incidence of cardiac events tended to be lower in the ICH group compared with the AIS group (the cumulative incidence freedom from the event, 86.3% [95% CI, 84.1-88.6] versus 83.6% [95% CI, 81.2-86.0]; P =0.100), the incidences cardiac events other than atrial fibrillation/atrial flutter were comparable between the 2 matched groups. The incidence of atrial fibrillation/atrial flutter was significantly lower in the ICH group than in the AIS group ( P <0.001). The multivariate-adjusted analysis found that stroke-heart syndrome in patients with ICH was associated with 90-day mortality (adjusted odds ratio, 1.12 [95% CI, 1.06-1.19]; P <0.001)., Conclusions: Cardiac events are common and negatively affect prognosis in patients with ICH, just as seen in AIS., Competing Interests: Dr Dawson received speaker fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Medtronic, and Pfizer and a travel fee from MicroTransponder, Inc. Dr Dawson also received investigator-initiated research funding grant from the Stroke Association United Kingdom. Dr Lip is a consultant and a speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi Sankyo, and Anthos. No fees are received personally. He is a National Institute for Health and Care Research Senior Investigator and a co-principal investigator of the AFFIRMO project on multimorbidity in AF (grant agreement 899871), the TARGET project on digital twins for personalized management of atrial fibrillation and stroke (grant agreement 101136244), and the ARISTOTELES project on artificial intelligence for management of chronic long-term conditions (grant agreement 101080189), which are all funded by the Horizon Europe Research and Innovation Programme of the European Union. The other authors report no conflicts.

Background: Evidence is lacking regarding long-term patterns of change in Life's Essential 8 (LE8) and their association with the risk of stroke. We aim to evaluate LE8 trajectories and examine their association with the risk of stroke in China., Methods: This study, conducted in a workplace setting, recruited 26 719 participants (average age, 46.02±11.27 years and a male population of 73.73%) who had no history of stroke and consecutively participated in 6 surveys from 2006 to 2016. Repeated LE8 measurements were determined by taking the unweighted average of the 8 component scores ranging from 0 to 100. People with higher scores had better overall cardiovascular health. By examining the medical records of the participants, stroke cases were identified for the period from 2016 to 2020. A latent mixture model was applied to classify the trajectory clusters of LE8 from 2006 to 2016, and Cox proportional hazard models were used to analyze the data., Results: Five LE8 trajectories were detected between 2006 and 2016. Four hundred ninety-eight incident strokes including 55 (11.04%) hemorrhagic and 458 (91.97%) ischemic strokes were documented. After adjusting for covariates, the hazard ratios and 95% CIs for the association between stable-low, moderate-increasing, moderate-stable, and high-stable trajectories and incident stroke, compared with the moderate-decreasing trajectory, were 1.42 (1.11-1.84), 0.73 (0.56-0.96), 0.49 (0.39-0.62), and 0.19 (0.11-0.32), respectively. Individuals with high LE8 status (LE8≥80) exhibited a significantly reduced risk of stroke compared with those with low one (LE8≤49; P -trend <0.001). A faster annual growth in LE8 was related to a lower risk of stroke., Conclusions: Maintaining high LE8 over an extended period and high baseline LE8 status were related to a decreased risk of stroke. Despite the initial low level of LE8, improvement in LE8 attenuates or even reverses the risk of stroke., Competing Interests: None.

Aims: To investigate the impact of diagnosis age of type 2 diabetes mellitus (T2DM) on subsequent adverse outcomes within the Chinese population., Methods: 549,959 eligible T2DM patients were included from Ningbo and Jinhua city in Zhejiang province, China. Standardized ratio was used to evaluate the risks of coronary heart disease (CHD), stroke, cancer and all-cause death in different T2DM diagnosis age groups., Results: For all adverse outcomes, higher excess risks were observed in the youngest age group (30-39) than in the oldest age group (≥80) with T2DM. The standardized incidence ratios (SIR) were 5.93 (95% CI: 3.46, 10.14) for CHD, 5.45 (95% CI: 3.72, 7.99) for stroke and 1.85 (95% CI: 1.38, 2.49) for cancer in the youngest age group, and were 1.32 (95% CI: 1.08, 1.60) for CHD, 1.25 (95% CI: 1.08, 1.44) for stroke, and 0.78 (95% CI: 0.56, 1.09) for cancer, respectively, in the oldest age group. The standardized mortality ratios (SMR) for all-cause death were 3.15 (1.69, 5.84) vs. 1.12 (0.88, 1.43). These excess risks decreased with increasing diagnosis age (all P value < 0.001). Consistent results were observed when individuals were stratified by sex or further excluded with the time from T2DM diagnosis to endpoints less than 1 or 2 years., Conclusions: Th earlier the diagnosis of T2DM, the higher the risk for subsequent adverse outcomes. It is imperative to enhance the management and monitoring of early-onset patients during follow-up., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Recent guidelines have recognized several factors, including blood pressure (BP), body mass index (BMI), low-density lipoprotein cholesterol (LDL-C), hemoglobin A1c (HbA1c), smoking, and physical activity, as key contributors to stroke risk. However, the impact of simultaneous management of these risk factors on stroke susceptibility in individuals with hypertension remains ambiguous. This study involved 238 388 participants from the UK Biobank, followed up from their recruitment date until April 1, 2023. Cox proportional hazard models with hazard ratios (HRs) and 95% confidence intervals (CIs) were used to illustrate the correlation between the joint modifiable risk factor control and the stroke risk. As the degree of risk factor control increased, a gradual reduction in stroke risk was observed. Hypertensive patients who had the optimal risk factor control (≥5 risk factor controls) had a 14.6% lower stroke risk than those who controlled 2 or fewer (HR: 0.854; 95% CI: 804-0.908; p < 0.001). The excess risk of stroke linked to hypertension slowly diminished as the number of controlled risk factors increased. However, the risk was still 25.1% higher for hypertensive patients with optimal risk factor control as compared to the non-hypertensive population (HR: 1.251; 95% CI: 1.100-1.422; p < 0.001). The protective effect of joint risk factor control against the stroke risk due to hypertension was stronger in medicated hypertensive patients than in those not medicated. This finding leads to the conclusion that joint risk factor control combined with pharmacological treatment could potentially eliminate the excess risk of stroke associated with hypertension., (© 2024 The Author(s). The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Introduction: Despite advancements in coronary artery disease (CAD) management, major adverse cardiovascular events persist. Vitamin K antagonists and direct oral anticoagulants present bleeding risks. Low-dose rivaroxaban (2.5 mg) is approved by the European Society of Cardiology and the US Food and Drug Administration for CAD. The survival advantage and risk-benefit profile of combining low-dose rivaroxaban with aspirin for CAD patients remain uncertain. This meta-analysis aims to compare the efficacy of low-dose rivaroxaban plus aspirin versus aspirin monotherapy in CAD patients., Methods: We systematically searched databases for randomized controlled trials exploring low-dose rivaroxaban with aspirin in CAD patients. Of the 6220 studies screened, five met the inclusion criteria. Primary outcomes included myocardial infarction, stroke, major bleeding events, and all-cause mortality. The analysis employed a fixed-effects model, calculating hazard ratios (HRs) and 95% confidence intervals (CIs)., Results: Five randomized controlled trials involving 41,351 participants were included. Rivaroxaban (2.5 mg) significantly reduced all-cause mortality (HR, 0.88; 95% CI, 0.81-0.95; P = 0.002), myocardial infarction (HR, 0.81; 95% CI, 0.70-0.94; P = 0.006), and stroke (HR, 0.61; 95% CI, 0.49-0.76; P < 0.00001) compared to aspirin alone. However, it increased major bleeding risk (HR, 1.66; 95% CI, 1.40-1.97; P < 0.01). Meta-regression revealed no dose-dependent impact on all-cause mortality., Conclusion: Low-dose rivaroxaban demonstrates survival benefits and reduces myocardial infarction and stroke risks in CAD patients, albeit with an increased risk of major bleeding. Consideration of patient bleeding risk is crucial when adding rivaroxaban to antiplatelet therapy. Further research is warranted to compare its effectiveness and safety with dual antiplatelet therapy or P2Y12 inhibitors., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Risk models to identify patients at high risk of asymptomatic carotid artery stenosis (ACAS) can help in selecting patients for screening, but long-term outcomes in these patients are unknown. We assessed the diagnostic and prognostic value of the previously published Prevalence of ACAS (PACAS) risk model to detect ACAS at baseline and to predict subsequent risk of stroke and cardiovascular disease (CVD) during follow-up., Methods: We validated the discrimination and calibration of the PACAS risk model to detect severe (≥70% narrowing) ACAS with patients from the Reduction of Atherothrombosis for Continued Health registry. We subsequently calculated the incidence rates of stroke and CVD (fatal and nonfatal stroke or myocardial infarction or vascular death) during follow-up in 4 risk groups (low, medium, high, and very high, corresponding to sum scores of ≤9, 10-13, 14-17, and ≥18, respectively)., Results: Among 26 384 patients, aged between 45 and 80 years, without prior carotid procedures, 1662 (6.3%) had severe baseline ACAS. During ≈70 000 patient-years of follow-up, 1124 strokes and 2484 CVD events occurred. Discrimination of the PACAS model was 0.67 (95% CI, 0.65-0.68), and calibration showed adequate concordance between predicted and observed risks of severe baseline ACAS after recalibration. Significantly higher incidence rates of stroke ( P trend <0.011) and CVD ( P trend <0.0001) during follow-up were found with increasing PACAS risk groups. Among patients with high PACAS sum score of ≥14 (corresponding to 27.7% of all patients), severe baseline ACAS prevalence was 11.4%. In addition, 56.6% of incident strokes and 64.9% of incident CVD events occurred in this group., Conclusions: The PACAS risk model can reliably identify patients at high risk of severe baseline ACAS. Incidence rates of stroke and CVD during follow-up were significantly higher in patients with high PACAS sum scores. Selective screening of patients with high PACAS sum scores may help to prevent future stroke or CVD., Competing Interests: Dr Bhatt discloses the following relationships: advisory board: Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, and Stasys; board of directors: American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), and High Enroll (stock); consultant: Broadview Ventures, Hims, SFJ, and Youngene; data monitoring committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial [Portopulmonary Hypertension Treatment With Macitentan: A Randomized Clinical Trial], funded by St. Jude Medical, now Abbott), Boston Scientific (chair: the PEITHO trial [Pulmonary Embolism Thrombolysis]), Cleveland Clinic, Contego Medical (chair: PERFORMANCE 2 [Protection Against Emboli During Carotid Artery Stenting Using the Neuroguard IEP System]), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical; for ALLAY-HF [Safety and Efficacy of the Alleviant System for No-Implant Interatrial Shunt Creation in Patients With Chronic Heart Failure], funded by Alleviant Medical), Novartis, Population Health Research Institute, and Rutgers University (for the National Institutes of Health-funded MINT trial [Myocardial Ischemia and Transfusion]); honoraria: American College of Cardiology (senior associate editor: Clinical Trials and News, ACC.org; chair: ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; the RE-DUAL PCI [Evaluation of Dual Therapy With Dabigatran vs Triple Therapy With Warfarin in Patients With AF That Undergo a PCI With Stenting] Clinical Trial Steering Committee funded by Boehringer Ingelheim; AEGIS-II [Study to Investigate CSL112 in Subjects With Acute Coronary Syndrome] Executive Committee funded by CSL Behring), Belvoir Publications (editor-in-chief: Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial [A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease], funded by Ferring Pharmaceuticals), HMP Global (editor-in-chief: Journal of Invasive Cardiology), Journal of the American College of Cardiology (guest editor, associate editor), K2P (co-chair: interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (Continuing Medical Education [CME] steering committees), MJH Life Sciences, Oakstone CME (course director: Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS [Cardiovascular Outcomes for People Using Anticoagulation Strategies] Operations Committee, Publications Committee, Steering Committee, and USA national coleader, funded by Bayer), WebMD (CME steering committees), and Wiley (steering committee); other: Clinical Cardiology (deputy editor); patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women’s Hospital that assigned to Lexicon; neither he nor Brigham and Women’s Hospital receive any income from this patent); research funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; royalties: Elsevier (editor: Braunwald’s Heart Disease); site coinvestigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; trustee: American College of Cardiology; and unfunded research: FlowCo. Dr Steg discloses the following relationships: employment: Assistance Publique-Hôpitaux de Paris and Université Paris-Cité; research grants: Bayer; consulting: Amarin, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Janssen, Pfizer, PhaseBio, Novartis, NovoNordisk, Regeneron, Sanofi, and Servier; and patent issued as coinventor of use of alirocumab to reduce cardiovascular risk (patent assigned to Sanofi). The other authors report no conflicts.

Introduction: Audits are an integral part of effective modern healthcare. The collection of data for audits can be resource intensive. Large language models (LLM) may be able to assist. This pilot study aimed to assess the feasibility of using a LLM to extract stroke audit data from free-text medical documentation., Method: Discharge summaries from a one-month retrospective cohort of stroke admissions at a tertiary hospital were collected. A locally-deployed LLM, LLaMA3, was then used to extract a variety of routine stroke audit data from free-text discharge summaries. These data were compared to the previously collected human audit data in the statewide registry. Manual case note review was undertaken in cases of discordance., Results: Overall, there was a total of 144 data points that were extracted (9 data points for each of the 16 patients). The LLM was correct in 135/144 (93.8%) of individual datapoints. This performance included binary categorical, multiple-option categorical, datetime, and free-text extraction fields., Conclusions: LLM may be able to assist with the efficient collection of stroke audit data. Such approaches may be pursued in other specialties. Future studies should seek to examine the most effective way to deploy such approaches in conjunction with human auditors and researchers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)