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In 1924, the founders of the American Heart Association (AHA) envisioned an international society focused on the heart and aimed at facilitating research, disseminating information, increasing public awareness, and developing public health policy related to heart disease. This presidential advisory provides a comprehensive review of the past century of cardiovascular and stroke science, with a focus on the AHA's contributions, as well as informed speculation about the future of cardiovascular science into the next century of the organization's history. The AHA is a leader in fundamental, translational, clinical, and population science, and it promotes the concept of the "learning health system," in which a continuous cycle of evidence-based practice leads to practice-based evidence, permitting an iterative refinement in clinical evidence and care. This advisory presents the AHA's journey over the past century from instituting professional membership to establishing extraordinary research funding programs; translating evidence to practice through clinical practice guidelines; affecting systems of care through quality programs, certification, and implementation; leading important advocacy efforts at the federal, state and local levels; and building global coalitions around cardiovascular and stroke science and public health. Recognizing an exciting potential future for science and medicine, the advisory offers a vision for even greater impact for the AHA's second century in its continued mission to be a relentless force for longer, healthier lives.

Background: Guideline-based hypertension management is integral to the prevention of stroke. We examine trends in antihypertensive medications prescribed after stroke and assess how well a prescriber's blood pressure (BP) medication choice adheres to clinical practice guidelines (BP-guideline adherence)., Methods and Results: The FSR (Florida Stroke Registry) uses statewide data prospectively collected for all acute stroke admissions. Based on established guidelines, we defined optimal BP-guideline adherence using the following hierarchy of rules: (1) use of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker as first-line antihypertensive among diabetics; (2) use of thiazide-type diuretics or calcium channel blockers among Black patients; (3) use of beta blockers among patients with compelling cardiac indication; (4) use of thiazide, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, or calcium channel blocker class as first line in all others; (5) beta blockers should be avoided as first line unless there is a compelling cardiac indication. A total of 372 254 cases from January 2010 to March 2020 are in the FSR with a diagnosis of acute ischemic stroke, hemorrhagic stroke, transient ischemic attack, or subarachnoid hemorrhage; 265 409 with complete data were included in the final analysis. Mean age was 70±14 years; 50% were women; and index stroke subtypes were 74% acute ischemic stroke, 11% intracerebral hemorrhage, 11% transient ischemic attack, and 4% subarachnoid hemorrhage. BP-guideline adherence to each specific rule ranged from 48% to 74%, which is below quality standards of 80%, and was lower among Black patients (odds ratio, 0.7 [95% CI, 0.7-0.83]; P <0.001) and those with atrial fibrillation (odds ratio, 0.53 [95% CI, 0.50-0.56]; P <0.001) and diabetes (odds ratio, 0.65 [95% CI, 0.61-0.68]; P <0.001)., Conclusions: This large data set demonstrates consistently low rates of BP-guideline adherence over 10 years. There is an opportunity for monitoring hypertensive management after stroke.

Background: Short-term dual antiplatelet therapy (DAPT) reduces early stroke recurrence after mild noncardioembolic ischemic stroke (NCIS). We aim to evaluate temporal trends and determinants of DAPT prescription after mild NCIS in the Florida Stroke Registry, a statewide registry across Get With The Guidelines-Stroke participating hospitals., Methods: In this cross-sectional analysis of a cohort study, we included patients with mild NCIS (National Institutes of Health Stroke Scale score ≤3) who were potentially eligible for DAPT across 168 Florida Stroke Registry participating hospitals between January 2010 and September 2022. Using antiplatelet prescription as the dependent variable (DAPT versus single antiplatelet therapy), we fit logistic regression models adjusted for patient-related factors, hospital-related factors, clinical presentation, vascular risk factors, and ischemic stroke subtype, to obtain adjusted odds ratios (aORs) with 95% CIs., Results: From 283 264 Florida Stroke Registry ischemic stroke patients during the study period, 109 655 NCIS were considered eligible. Among these, 37 058 patients with National Institutes of Health Stroke Scale score >3 were excluded, resulting in a sample of 72 597 mild NCIS (mean age 68±14 years; female 47.3%). Overall, 24 693 (34.0%) patients with mild NCIS were discharged on DAPT and 47 904 (66.0%) on single antiplatelet therapy. DAPT prescription increased from 25.7% in 2010 to 52.8% in 2022 ( β /year 2.5% [95% CI, 1.5%-3.4%]). Factors associated with DAPT prescription were premorbid antiplatelet therapy (aOR, 4.66 [95% CI, 2.20-9.88]), large-artery atherosclerosis (aOR, 1.68 [95% CI, 1.43-1.97]), diabetes (aOR, 1.29 [95% CI, 1.13-1.47]), and hyperlipidemia (aOR, 1.24 [95% CI, 1.10-1.39]), whereas female sex (aOR, 0.83 [95% CI, 0.75-0.93]), being non-Hispanic Black patients (compared with non-Hispanic White patients; aOR, 0.78 [95% CI, 0.68-0.90]), admission to a Thrombectomy-capable Stroke Center (compared with Comprehensive Stroke Center; aOR, 0.78 [95% CI, 0.66-0.92]), time-to-presentation 1 to 7 days from last seen well (compared with <24 h; aOR, 0.86 [95% CI, 0.76-0.96]), and small-vessel disease stroke (aOR, 0.81 [95% CI, 0.72-0.94]) were associated with not receiving DAPT at discharge., Conclusions: Despite a temporal trend increase in DAPT prescription after mild NCIS, we found substantial underutilization of evidence-based DAPT associated with significant disparities in stroke care., Competing Interests: Disclosures Drs Del Brutto and Yin receive research salary support from the Florida Stroke Registry (FSR) COHAN-R3. Drs Gardener, Hao, Gutierrez, and Rundek receive research salary support from the FSR COHAN-R2. Dr Rose received honoraria for consulting or speaker bureau from Atricure, Boston Scientific, Cheisi-USA, CSL-Behring, and Medtronic. Dr Alkhachroum is supported by KL2 Career Development Award from the Miami CTSI NCATS UL1TR002736 and by the National Institutes of Health/National Institute of Neurological Disorders and Stroke under Award Number K23NS126577 and R21NS128326. Dr Sur is supported by KL2 Career Development Award from the Miami CTSI NCATS KL2TR002737 and research salary support from the FSR COHAN-R3. Dr Asdaghi receives research salary support from the FSR COHAN-R2 and compensations from the American Heart Association for employment in Stroke editorial board. Dr Romano reports compensation from Genentech USA Inc. for data and safety monitoring services, stock holdings in Vycor Medical, and receives research salary support from the FSR COHAN-R2. The other authors report no conflicts.

Background: Sleep duration is associated with stroke risk and is 1 of 8 essential components of cardiovascular health according to the American Heart Association. As stroke disproportionately burdens Black and Hispanic populations in the United States, we hypothesized that long and short sleep duration would be associated with greater subclinical carotid atherosclerosis, a precursor of stroke, in the racially and ethnically diverse NOMAS (Northern Manhattan Study)., Methods: NOMAS is a study of community-dwelling adults. Self-reported nightly sleep duration and daytime sleepiness were collected between 2006 and 2011. Carotid plaque presence, total plaque area, and intima-media thickness were measured by ultrasound between 1999 and 2008. Linear and logistic regression models examined the cross-sectional associations of sleep duration groups (primary exposure) or daytime sleepiness (secondary exposure) with measures of carotid atherosclerosis. Models adjusted for age, time between ultrasound and sleep data collection, sex, race and ethnicity, education, health insurance, smoking, alcohol use, physical activity, body mass index, hypertension, diabetes, hypercholesterolemia, and cardiac disease., Results: The sample (n=1553) had a mean age of 64.7±8.5 years and was 61.9% female, 64.8% Hispanic, and 18.2% non-Hispanic Black. Of the sample, 55.6% had carotid plaque, 22.3% reported nightly short sleep (<7 hours), 66.6% intermediate sleep (≥7 and <9 hours), and 11.1% had long sleep (≥9 hours). Compared with intermediate sleep, long sleep was associated with greater odds of carotid plaque presence relative to plaque absence (odds ratio, 1.6 [95% CI, 1.1-2.4]) and larger total plaque area (odds ratio, 1.4 [95% CI, 1.0-1.9]) after full covariate adjustment. Short sleep and daytime sleepiness were not significantly associated with any carotid measures., Conclusions: The association between long sleep and subclinical carotid atherosclerosis may explain prior associations between long sleep and stroke., Competing Interests: Disclosures Dr Elkind has received royalties from UpToDate for chapters on stroke; study drug in kind from the Bristol Myers Squibb (BMS)–Pfizer Alliance for Eliquis and ancillary research funding from Roche, both for a federally funded trial of stroke prevention; and is currently employed by the American Heart Association as Chief Clinical Science Officer. The other authors report no conflicts.

Objective: Stroke is a global public health burden, and therefore it is critical to identify modifiable risk factors to reduce stroke incidence and improve outcomes. Depression is such a risk factor; however, the association between preexisting depression and stroke outcomes, such as independent ambulation, is not well studied, especially among racial-ethnic minority groups. To address this gap in the literature, effects of preexisting depression on ambulatory status at hospital discharge after stroke were evaluated among individuals participating in the racially and ethnically diverse Florida-Puerto Rico Collaboration to Reduce Stroke Disparities project., Methods: Data were analyzed from a total of 42,031 ischemic stroke patients, who were independently ambulatory prior to their stroke, after discharge from 84 hospitals between 2014 and 2017. Preexisting depression was confirmed by medical history or antidepressant medication use. Multilevel multivariate logistic regression analyses were used to assess the association of preexisting depression with independent ambulation at hospital discharge. Effects of sex and race-ethnicity on this association were examined., Results: Of 42,031 participants (mean±SD age=70.4±14.2 years; 48% were female; race-ethnicity: 16% Black, 12% Hispanic living in Florida, and 7% Hispanic living in Puerto Rico), 6,379 (15%) had preexisting depression. Compared with participants without depression, those with preexisting depression were older, were more likely to be female and non-Hispanic White, and had a greater burden of vascular risk factors or comorbid conditions. Independent ambulation at hospital discharge was less frequent among women, Black participants, and individuals with vascular risk factors or comorbid conditions. In multivariate models, preexisting depression decreased the likelihood of independent ambulation at discharge (odds ratio=0.88, 95% CI=0.81, 0.97). No interactions were found between preexisting depression and race-ethnicity or sex., Conclusions: Preexisting depression was independently associated with dependent ambulation at hospital discharge after stroke, regardless of sex and race-ethnicity. Treating depression may contribute to primary stroke prevention and could improve ambulatory status at discharge., Competing Interests: Dr. Starosciak has served as a consultant to Viz.ai. Dr. Gutierrez has received research salary support from the Florida Department of Health. Dr. Rose has received honoraria for serving as a consultant for or on the speaker’s bureau of Boston Scientific, Chiesi USA, CSL Behring, and Medtronic. The other authors report no financial relationships with commercial interests.

Stroke is a disease of disparities, with tremendous racial and ethnic inequities in incidence, prevalence, treatment, and outcomes. The accumulating literature on the relationship between stroke and social determinants of health (ie, the structural conditions of the places where people live, learn, work, and play) contributes to our understanding of stroke inequities. Several interventions have been tested concurrently to reduce racial and ethnic inequities in stroke preparedness, care, recovery, and risk factor control. It is regrettable that no common theoretical framework has been used to facilitate comparison of interventions. In this scientific statement, we summarize, across the stroke continuum of care, trials of interventions addressing racial and ethnic inequities in stroke care and outcomes. We reviewed the literature on interventions to address racial and ethnic inequities to identify gaps and areas for future research. Although numerous trials tested interventions aimed at reducing inequities in prehospital, acute care, transitions in care, and poststroke risk factor control, few addressed inequities in rehabilitation, recovery, and social reintegration. Most studies addressed proximate determinants (eg, medication adherence, health literacy, and health behaviors), but upstream determinants (eg, structural racism, housing, income, food security, access to care) were not addressed. A common theoretical model of social determinants can help researchers understand the heterogeneity of social determinants, inform future directions in stroke inequities research, support research in understudied areas within the continuum of care, catalyze implementation of successful interventions in additional settings, allow for comparison across studies, and provide insight into whether addressing upstream or downstream social determinants has the strongest effect on reducing inequities in stroke care and outcomes.

Perivascular space (PVS) burden is an emerging, poorly understood, magnetic resonance imaging marker of cerebral small vessel disease, a leading cause of stroke and dementia. Genome-wide association studies in up to 40,095 participants (18 population-based cohorts, 66.3 ± 8.6 yr, 96.9% European ancestry) revealed 24 genome-wide significant PVS risk loci, mainly in the white matter. These were associated with white matter PVS already in young adults (N = 1,748; 22.1 ± 2.3 yr) and were enriched in early-onset leukodystrophy genes and genes expressed in fetal brain endothelial cells, suggesting early-life mechanisms. In total, 53% of white matter PVS risk loci showed nominally significant associations (27% after multiple-testing correction) in a Japanese population-based cohort (N = 2,862; 68.3 ± 5.3 yr). Mendelian randomization supported causal associations of high blood pressure with basal ganglia and hippocampal PVS, and of basal ganglia PVS and hippocampal PVS with stroke, accounting for blood pressure. Our findings provide insight into the biology of PVS and cerebral small vessel disease, pointing to pathways involving extracellular matrix, membrane transport and developmental processes, and the potential for genetically informed prioritization of drug targets., (© 2023. The Author(s).)

Importance: The risk of ischemic stroke is higher among patients with left atrial (LA) enlargement. Left atrial strain (LAε) and LA strain rate (LASR) may indicate LA dysfunction when LA volumes are still normal. The association of LAε with incident ischemic stroke in the general population is not well established., Objective: To investigate whether LAε and LASR are associated with new-onset ischemic stroke among older adults., Design: The Cardiovascular Abnormalities and Brain Lesions study was conducted from September 29, 2005, to July 6, 2010, to investigate cardiovascular factors associated with subclinical cerebrovascular disease. A total of 806 participants in the Northern Manhattan Study who were aged 55 years or older without history of prior stroke or atrial fibrillation (AF) were included, and annual follow-up telephone interviews were completed May 22, 2022. Statistical analysis was performed from June through November 2022., Exposures: Left atrial strain and LASR were assessed by speckle-tracking echocardiography. Global peak positive longitudinal LAε and positive longitudinal LASR during ventricular systole, global peak negative longitudinal LASR during early ventricular diastole, and global peak negative longitudinal LASR during LA contraction were measured. Brain magnetic resonance imaging was used to detect silent brain infarcts and white matter hyperintensities at baseline., Main Outcomes and Measures: Risk analysis with cause-specific Cox proportional hazards regression modeling was used to assess the association of positive longitudinal LAε and positive longitudinal LASR with incident ischemic stroke, adjusting for other stroke risk factors, including incident AF., Results: The study included 806 participants (501 women [62.2%]) with a mean (SD) age of 71.0 (9.2) years; 119 participants (14.8%) were Black, 567 (70.3%) were Hispanic, and 105 (13.0%) were White. During a mean (SD) follow-up of 10.9 (3.7) years, new-onset ischemic stroke occurred in 53 participants (6.6%); incident AF was observed in 103 participants (12.8%). Compared with individuals who did not develop ischemic stroke, participants with ischemic stroke had lower positive longitudinal LAε and negative longitudinal LASR at baseline. In multivariable analysis, the lowest (ie, closest to zero) vs all other quintiles of positive longitudinal LAε (adjusted hazard ratio [HR], 3.12; 95% CI, 1.56-6.24) and negative longitudinal LASR during LA contraction (HR, 2.89; 95% CI, 1.44-5.80) were associated with incident ischemic stroke, independent of left ventricular global longitudinal strain and incident AF. Among participants with a normal LA size, the lowest vs all other quintiles of positive longitudinal LAε (HR, 4.64; 95% CI, 1.55-13.89) and negative longitudinal LASR during LA contraction (HR, 11.02; 95% CI 3.51-34.62) remained independently associated with incident ischemic stroke., Conclusions and Relevance: This cohort study suggests that reduced positive longitudinal LAε and negative longitudinal LASR are independently associated with ischemic stroke in older adults. Assessment of LAε and LASR by speckle-tracking echocardiography may improve stroke risk stratification in elderly individuals.

Aims: Heart disease is associated with an increased risk for ischaemic stroke. However, the predictive value of reduced left ventricular ejection fraction (LVEF) for stroke is controversial and only observed in patients with severe reduction. LV global longitudinal strain (LV GLS) can detect subclinical LV systolic impairment when LVEF is normal. We investigated the prognostic role of LV GLS for incident stroke in a predominantly elderly cohort., Methods and Results: Two-dimensional echocardiography with speckle tracking was performed in the Cardiac Abnormalities and Brain Lesions (CABL) study. Among 708 stroke-free participants (mean age 71.4 ± 9.4 years, 60.9% women), abnormal LV GLS (>-14.7%: 95% percentile of the subgroup without risk factors) was detected in 133 (18.8%). During a mean follow-up of 10.8 ± 3.9 years, 47 participants (6.6%) experienced an ischaemic stroke (26 cardioembolic or cryptogenic, 21 other subtypes). The cumulative incidence of ischaemic stroke was significantly higher in participants with abnormal LV GLS than with normal LV GLS (P < 0.001). In multivariate stepwise logistic regression analysis, abnormal LV GLS was associated with ischaemic stroke independently of cardiovascular risk factors including LVEF, LV mass, left atrial volume, subclinical cerebrovascular disease at baseline, and incident atrial fibrillation [hazard ratio (HR): 2.69, 95% confidence interval (CI): 1.47-4.92; P = 0.001]. Abnormal LV GLS independently predicted cardioembolic or cryptogenic stroke (adjusted HR: 3.57, 95% CI: 1.51-8.43; P = 0.004) but not other subtypes., Conclusion: LV GLS was a strong independent predictor of ischaemic stroke in a predominantly elderly stroke-free cohort. Our findings provide insights into the brain-heart interaction and may help improve stroke primary prevention strategies., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Brain arterial dilation and elongation characterize dolichoectasia, an arteriopathy associated with risk of stroke and death. We aim to determine whether brain arterial elongation increases the risk of stroke and death independent of brain arterial diameters., Methods: We analyzed 1210 stroke-free participants (mean age 71±9 years, 41% men, 65% Hispanic) with available time-of-flight magnetic resonance angiogram from the Northern Manhattan Study, a population-based cohort study across a multiethnic urban community. We obtained baseline middle cerebral artery M1-segment (MCA-M1) and basilar artery (BA) mean lengths and diameters using a semi-automated software. Cox proportional hazards models adjusted for brain arterial diameters and potential confounders yielded adjusted hazards ratios with 95% CIs for the primary outcomes of incident stroke and all-cause mortality, as well as secondary outcomes including noncardioembolic stroke, vascular death, and any vascular event., Results: Neither MCA-M1 nor BA lengths correlated with incident stroke or all-cause mortality. Both MCA-M1 and BA larger diameters correlated with all-cause mortality (MCA-M1 aHR, 1.52 [95% CI, 1.03-2.23], BA aHR, 1.28 [95% CI, 1.02-1.61]), as well as larger MCA-M1 diameters with vascular death (aHR, 1.84 [95% CI, 1.02-3.31]). Larger MCA-M1 and BA diameters did not correlate with incident stroke. However, larger BA diameters were associated with posterior circulation noncardioembolic stroke (aHR, 2.93 [95% CI, 1.07-8.04]). There were no statistical interactions between brain arterial lengths and diameters in relation to study outcomes., Conclusions: In a multiethnic cohort of stroke-free adults, brain arterial elongation did not correlate with risk of stroke or death, nor influenced the significant association between brain arterial dilation and vascular risk.

This study aimed to investigate the influence of stroke lesions in predefined highly interconnected (rich-club) brain regions on functional outcome post-stroke, determine their spatial specificity and explore the effects of biological sex on their relevance. We analyzed MRI data recorded at index stroke and ~3-months modified Rankin Scale (mRS) data from patients with acute ischemic stroke enrolled in the multisite MRI-GENIE study. Spatially normalized structural stroke lesions were parcellated into 108 atlas-defined bilateral (sub)cortical brain regions. Unfavorable outcome (mRS > 2) was modeled in a Bayesian logistic regression framework. Effects of individual brain regions were captured as two compound effects for (i) six bilateral rich club and (ii) all further non-rich club regions. In spatial specificity analyses, we randomized the split into "rich club" and "non-rich club" regions and compared the effect of the actual rich club regions to the distribution of effects from 1000 combinations of six random regions. In sex-specific analyses, we introduced an additional hierarchical level in our model structure to compare male and female-specific rich club effects. A total of 822 patients (age: 64.7[15.0], 39% women) were analyzed. Rich club regions had substantial relevance in explaining unfavorable functional outcome (mean of posterior distribution: 0.08, area under the curve: 0.8). In particular, the rich club-combination had a higher relevance than 98.4% of random constellations. Rich club regions were substantially more important in explaining long-term outcome in women than in men. All in all, lesions in rich club regions were associated with increased odds of unfavorable outcome. These effects were spatially specific and more pronounced in women., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: The Florida Stroke Act, signed into law in 2004, set criteria for Comprehensive Stroke Centers (CSC). For a set time period, Florida hospitals were permitted to either receive national certification (NC) or could self-attest (SA) as fulfilling CSC criteria. The aim of this project was to evaluate the quality of ischemic stroke care in NC versus SA stroke centers in Florida, using well-known, guideline-driven ischemic stroke outcome metrics., Methods: A total of 37 CSCs (74% of Florida CSCs) in the Florida Stroke Registry from January 2013 through December 2018 were analyzed, including 19 SA CSCs and 18 NC (13 CSCs and 5 Thrombectomy-Capable Stroke Center). Hospital- and patient-level characteristics and stroke metrics were evaluated, adjusting for demographics, medical comorbidities, and stroke severity., Results: A total of 78 424 acute ischemic stroke cases, 36 089 from SA CSCs and 42 335 from NC CSC/Thrombectomy-Capable Stroke Centers were analyzed. NC centers had older patients (73 [61-83] versus 71 [60-81]; P <0.001) with more severe strokes (median National Institutes of Health Stroke Scale score of 5 versus 4; P <0.001). NC had higher intravenous tissue-type plasminogen activator utilization (15% versus 13%; P <0.001), endovascular treatment (10% versus 7%; P <0.001) and faster median door-to-computed tomography (23 minutes [11-73] versus 31 [12-78]; P <0.001), door-to-needle (37 minutes [26-50] versus 45 [34-58]; P <0.001) and door-to-puncture times (77 minutes [50-113] versus 93 [62-140]; P <0.001). In adjusted analysis, patients arriving to NC hospitals by 3 hours were more likely to get intravenous tissue-type plasminogen activator in the 3- to 4.5-hour window (adjusted odds ratio, 1.87 [95% CI, 1.30-2.68]; P =0.001) and more likely to be treated with intravenous tissue-type plasminogen activator within 45 minutes (adjusted odds ratio, 1.61 [95% CI, 1.04-2.50]; P =0.04) compared with SA CSCs., Conclusions: Among Florida-Stroke Registry CSCs, acute ischemic stroke performance and treatment measures at NC centers are superior to SA CSCs. These findings have implications for stroke systems of care in Florida and support legislation updates requiring NC and removal of SA claims.

Background and Objectives: While chronological age is one of the most influential determinants of poststroke outcomes, little is known of the impact of neuroimaging-derived biological "brain age." We hypothesized that radiomics analyses of T2-FLAIR images texture would provide brain age estimates and that advanced brain age of patients with stroke will be associated with cardiovascular risk factors and worse functional outcomes., Methods: We extracted radiomics from T2-FLAIR images acquired during acute stroke clinical evaluation. Brain age was determined from brain parenchyma radiomics using an ElasticNet linear regression model. Subsequently, relative brain age (RBA), which expresses brain age in comparison with chronological age-matched peers, was estimated. Finally, we built a linear regression model of RBA using clinical cardiovascular characteristics as inputs and a logistic regression model of favorable functional outcomes taking RBA as input., Results: We reviewed 4,163 patients from a large multisite ischemic stroke cohort (mean age = 62.8 years, 42.0% female patients). T2-FLAIR radiomics predicted chronological ages (mean absolute error = 6.9 years, r = 0.81). After adjustment for covariates, RBA was higher and therefore described older-appearing brains in patients with hypertension, diabetes mellitus, a history of smoking, and a history of a prior stroke. In multivariate analyses, age, RBA, NIHSS, and a history of prior stroke were all significantly associated with functional outcome (respective adjusted odds ratios: 0.58, 0.76, 0.48, 0.55; all p -values < 0.001). Moreover, the negative effect of RBA on outcome was especially pronounced in minor strokes., Discussion: T2-FLAIR radiomics can be used to predict brain age and derive RBA. Older-appearing brains, characterized by a higher RBA, reflect cardiovascular risk factor accumulation and are linked to worse outcomes after stroke., (© 2022 American Academy of Neurology.)

Background: Our objective is to describe adoption of the posthospitalization behaviors associated with successful transition of care and related baseline characteristics., Methods: This study includes 550 participants in the Transition of Care Stroke Disparities Study, a prospective observational cohort derived from the Florida Stroke Registry. Participants had an ischemic stroke (2018-2021), discharged home or to rehabilitation, with modified Rankin Scale score=0-3 (44% women, 24% Black, 48% White, 26% Hispanic, 35% foreign-born). We collected baseline sociodemographic and clinical characteristics. A structured telephone interview at 30-day postdischarge evaluated outcomes including medication adherence, medical appointment attendance, outpatient therapy, exercise, diet modification, toxic habit cessation, and a calculated composite adequate transition of care measure. Multivariable analyses assessed the association of baseline characteristics with 30-day behaviors., Results: At 30 days, medication adherence was achieved by 89%, medical appointments by 82%, outpatient therapy by 76%, exercise by 71%, diet modification by 68%, toxic habit cessation by 35%, and adequate transition of care measure by 67%. Successful adequate transition of care participants were more likely to be used full-time (42% versus 31%, P =0.02), live with a spouse (60% versus 47%, P =0.01), feel close to ≥3 individuals (84% versus 71%, P <0.01), have history of dyslipidemia (45 versus 34%, P =0.02), have thrombectomy (15% versus 8%, P =0.02), but less likely to have a history of smoking (17% versus 32%, P <0.001), coronary artery disease (14% versus 21%, P =0.04), and heart failure (3% versus 11%, P <0.01). Multivariable logistic regression analyses revealed that multiple socio-economic factors and prestroke comorbid diseases predicted fulfillment of transition of care measures. There was no difference in outcomes during the Covid-19 pandemic (2020-2021) compared with prepandemic years (2018-2019)., Conclusions: One in 3 patients did not attain adequate 30-day transition of care behaviors. Their achievement varied substantially among different measures and was influenced by multiple socioeconomic and clinical factors. Interventions aimed at facilitating transition of care from hospital after stroke are needed., Registration: URL: https://clinicaltrials.gov/; Unique identifier: NCT03452813.

Background: We examined the association between asymptomatic intracranial artery stenosis (aICAS) and cortical thickness using brain magnetic resonance morphometry in two cohorts., Methods: This cross-sectional study included stroke-free participants from the Northern Manhattan Study (NOMAS) and the National Alzheimer's Coordinating Center (NACC). We represented the predictor aICAS in NOMAS as a continuous global stenosis score reflecting an overall burden of stenosis (possible range 0-44) assessed by magnetic resonance angiography and in NACC as a dichotomous autopsy-determined Circle of Willis (CoW) atherosclerosis (none-mild vs moderate-severe). The primary outcome of interest was total cortical thickness. We analyzed each dataset separately using multivariable linear regression., Results: The analysis included 1209 NOMAS (46% had any stenosis, 5% had ≥70% stenosis of at least one vessel; stenosis score range 0-11) and 392 NACC (36% moderate-severe CoW atherosclerosis) participants. We found an inverse relationship between stenosis score and total cortical thickness (β-estimate [95% confidence interval (CI)]: -2.98 [-5.85, -0.11]) in adjusted models. We replicated these results in NACC (β-estimate [95% CI]: -0.06 [-0.11, -0.003]). Post-hoc, we segregated stenosis scores by location and only posterior circulation stenosis score was associated with total cortical thickness (anterior β-estimate [95% CI]: -0.90 [-5.16, 3.36], posterior β-estimate [95% CI]: -7.25 [-14.30, -0.20])., Conclusion: We found both radiographically and neuropathologically determined aICAS to be associated with global cortical thinning. Interestingly, posterior circulation stenoses appeared to drive this association with global cortical thinning, raising the possibility of pathophysiologic mechanisms for cortical thinning other than impaired hemodynamics., Competing Interests: Declaration of Competing Interest AVM is on the Steering Committee of the Alzheimer's disease Cooperative Study and is a council member for the Alzheimer's Association International Research Grants Program. DY, FK, TR, CW, ME, RS, and JG have no relevant conflicts of interest to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Although protective in secondary stroke prevention of intracranial arterial stenosis (ICAS), it is uncertain if the benefits of leisure time physical activity (LTPA) extend to asymptomatic ICAS or extracranial carotid stenosis (ECAS). Therefore, we sought to determine LTPA's relationship with ECAS and ICAS in a stroke-free, race-ethnically diverse cohort., Methods: This cross-sectional study included participants from the magnetic resonance imaging substudy of the Northern Manhattan Study, of whom 1274 had LTPA assessments at enrollment. LTPA was represented continuously as metabolic equivalent score (MET-score) and ordinally as model-based cluster analysis (LTPA-cluster), both based on the same LTPA assessments. We evaluated ECAS sonographically using carotid intima-media thickening and number of carotid plaques. ICAS was assessed with time-of-flight magnetic resonance angiograph and defined as ≥50% or ≥70% stenosis. We applied regression analyses to evaluate the association between LTPA with ECAS and ICAS, adjusting for confounders., Results: Of 1274 included participants (mean age 71±9 years; 60% women; 65% Hispanic), the mean MET-score was 10±16 and 60% were in a LTPA-cluster with any activity. Among those with carotid ultrasound (n=1234), the mean carotid intima-media thickening was 0.97±0.09 mm, and 56% of participants had at least one carotid plaque identified. Among those with magnetic resonance angiograph (n=1211), 8% had ≥50% ICAS and 5% had ≥70% ICAS. For ICAS, MET-score was associated with ≥70% ICAS (adjusted odds ratio per unit increase in MET-score [95% CI, 0.97 [0.94-0.99]) but not with ECAS measures (carotid intima-media thickening, adjusted β-estimate per unit increase in MET-score [95% CI], 0.002 [-0.003 to 0.006] or number of plaques, adjusted β-estimate [95% CI], 0.0001 [-0.0001 to 0.0003]). Substituting MET-score with LTPA-clusters replicated the association between ≥70% ICAS and LTPA (adjusted odds ratio per each increased LTPA-cluster [95% CI], 0.83 [0.70-0.99])., Conclusions: In this diverse stroke-free population, we found LTPA most strongly associated with asymptomatic ≥70% ICAS. Given the high-risk nature of ≥70% ICAS, these findings may emphasize the role of LTPA in people at risk for ICAS.

Background and Objectives: To examine whether high white matter hyperintensity (WMH) burden is associated with greater stroke severity and worse functional outcomes in lesion pattern-specific ways., Methods: MR neuroimaging and NIH Stroke Scale data at index stroke and the modified Rankin Scale (mRS) score at 3-6 months after stroke were obtained from the MRI-Genetics Interface Exploration study of patients with acute ischemic stroke (AIS). Individual WMH volume was automatically derived from fluid-attenuated inversion recovery images. Stroke lesions were automatically segmented from diffusion-weighted imaging (DWI) images, parcellated into atlas-defined brain regions and further condensed to 10 lesion patterns via machine learning-based dimensionality reduction. Stroke lesion effects on AIS severity and unfavorable outcomes (mRS score >2) were modeled within purpose-built Bayesian linear and logistic regression frameworks. Interaction effects between stroke lesions and a high vs low WMH burden were integrated via hierarchical model structures. Models were adjusted for age, age 2 , sex, total DWI lesion and WMH volumes, and comorbidities. Data were split into derivation and validation cohorts., Results: A total of 928 patients with AIS contributed to acute stroke severity analyses (age: 64.8 [14.5] years, 40% women) and 698 patients to long-term functional outcome analyses (age: 65.9 [14.7] years, 41% women). Stroke severity was mainly explained by lesions focused on bilateral subcortical and left hemispherically pronounced cortical regions across patients with both a high and low WMH burden. Lesions centered on left-hemispheric insular, opercular, and inferior frontal regions and lesions affecting right-hemispheric temporoparietal regions had more pronounced effects on stroke severity in case of high compared with low WMH burden. Unfavorable outcomes were predominantly explained by lesions in bilateral subcortical regions. In difference to the lesion location-specific WMH effects on stroke severity, higher WMH burden increased the odds of unfavorable outcomes independent of lesion location., Discussion: Higher WMH burden may be associated with an increased stroke severity in case of stroke lesions involving left-hemispheric insular, opercular, and inferior frontal regions (potentially linked to language functions) and right-hemispheric temporoparietal regions (potentially linked to attention). Our findings suggest that patients with specific constellations of WMH burden and lesion locations may have greater benefits from acute recanalization treatments. Future clinical studies are warranted to systematically assess this assumption and guide more tailored treatment decisions., (© 2022 American Academy of Neurology.)

The management of patients with stroke is often multidisciplinary, involving various specialties and healthcare professionals. Given the common shared risk factors for stroke and cardiovascular disease, input may also be required from the cardiovascular teams, as well as patient caregivers and next-of-kin. Ultimately, the patient is central to all this, requiring a coordinated and uniform approach to the priorities of post-stroke management, which can be consistently implemented by different multidisciplinary healthcare professionals, as part of the patient 'journey' or 'patient pathway,' supported by appropriate education and tele-medicine approaches. All these aspects would ultimately aid delivery of care and improve patient (and caregiver) engagement and empowerment. Given the need to address the multidisciplinary approach to holistic or integrated care of patients with heart disease and stroke, the European Society of Cardiology Council on Stroke convened a Task Force, with the remit to propose a consensus on Integrated care management for optimizing the management of stroke and associated heart disease. The present position paper summarizes the available evidence and proposes consensus statements that may help to define evidence gaps and simple practical approaches to assist in everyday clinical practice. A post-stroke ABC pathway is proposed, as a more holistic approach to integrated stroke care, would include three pillars of management: A: Appropriate Antithrombotic therapy.B: Better functional and psychological status.C: Cardiovascular risk factors and Comorbidity optimization (including lifestyle changes)., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.)

Background We sought to determine recurrent stroke predictors among patients with embolic strokes of undetermined source (ESUS). Methods and Results We applied Cox proportional hazards models to identify clinical features associated with recurrent stroke among participants enrolled in RE-SPECT ESUS (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) trial, an international clinical trial evaluating dabigatran versus aspirin for patients with ESUS. During a median follow-up of 19 months, 384 of 5390 participants had recurrent stroke (annual rate, 4.5%). Multivariable models revealed that stroke or transient ischemic attack before the index event (hazard ratio [HR], 2.27 [95% CI, 1.83-2.82]), creatinine clearance <50 mL/min (HR, 1.69 [95% CI, 1.23-2.32]), male sex (HR, 1.60 [95% CI, 1.27-2.02]), and CHA 2 DS 2 -VASc ≥4 (HR, 1.55 [95% CI, 1.15-2.08] and HR, 1.66 [95% CI, 1.21-2.26] for scores of 4 and ≥5, respectively) versus CHA 2 DS 2 -VASc of 2 to 3, were independent predictors for recurrent stroke. Conclusions In RE-SPECT ESUS trial, expected risk factors previously linked to other common stroke causes were associated with stroke recurrence. These data help define high-risk groups for subsequent stroke that may be useful for clinicians and for researchers designing trials among patients with ESUS. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02239120.

Introduction: The association between cervical internal carotid artery (cICA) tortuosity and atherosclerosis is a matter of debate. Additionally, some genetic syndromes characterized by connective tissue remodeling are associated with arterial tortuosity, raising the possibility that cICA tortuosity may not only be atherosclerotic. In this study, we hypothesized that cICA tortuosity is not associated with imaging biomarkers of atherosclerosis., Methods: The Northern Manhattan Study (NOMAS) was a prospective, multiethnic cohort of stroke-free individuals who underwent brain MRA, carotid ultrasound and transthoracic echocardiogram from 2003-2008. The cICA tortuosity was scored in each carotid as 0 = no tortuosity, 1 = tortuosity <90°, 2 = tortuosity ≥90°. A summary cICA tortuosity score (possible range 0-4) was created by adding up the tortuosity score from each carotid. Participants were assessed for atherosclerotic markers by using B‑mode carotid sonography and transthoracic echocardiography., Results: Of 558 participants 178 (31.9%) had any cervical ICA tortuosity (tortuosity score >0). The cICA tortuosity score was higher in women and was associated with diastolic and systolic blood pressures and height (all P < 0.05). In models adjusted for demographics and risk factors, only the association with diastolic blood pressure remained significant (β = 0.002, P = 0.02). Similarly, cICA tortuosity was associated with larger aortic root diameter (B = 1.03 ± 0.36, P = 0.004) but not with other markers of carotid or aortic atherosclerosis., Conclusion: Cervical ICA tortuosity is associated with a higher diastolic blood pressure and larger aortic root diameter but not with other measures of atherosclerosis. Determining the risks of vascular events associated with this non-atherosclerotic phenotype may help for a better risk stratification for individuals with cICA tortuosity., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Intracranial large artery stenosis (ILAS) is an important contributor to ischemic stroke in the United States and worldwide. There is evidence to suggest that chronic exposure to certain infectious agents may also be associated with ILAS. We aimed to study this association further in an ethnically diverse, prospective, population-based sample of Northern Manhattan., Methods: We enrolled a random sample of stroke-free participants from an urban, racially, and ethnically diverse community in 1993. Participants have been followed prospectively and a subset underwent brain magnetic resonance angiograms from 2003 to 2008. Intracranial stenoses of the circle of Willis and vertebrobasilar arteries were scored as 0=no stenosis, 1≤50% (or luminal irregularities), 2=50% to 69%, 3≥70% stenosis, and 4=flow gap. We summed the individual score of each artery to produce a global ILAS score (possible range, 0-44). Past infectious exposure to Chlamydia pneumoniae , Helicobacter pylori , cytomegalovirus, and herpes simplex virus 1 and 2 was determined using serum antibody titers., Results: Among 572 NOMAS (Northern Manhattan Study) participants (mean age 71.0±8.0 years, 60% women, 68% Hispanic) with available magnetic resonance angiogram and serological data, herpes simplex virus 2 (beta=0.051, P <0.001) and cytomegalovirus (beta=0.071, P <0.05) were associated with ILAS score after adjusting for demographics and vascular risk factors. Stratifying by anterior and posterior circulations, herpes simplex virus 2 remained associated with the anterior circulation (beta=0.055 P <0.01) but not with posterior circulation ILAS score., Conclusions: Chronic infectious exposures, specifically herpes simplex virus 2 and cytomegalovirus were associated with asymptomatic ILAS as seen on magnetic resonance angiogram imaging. This may represent an additional target of intervention in the ongoing effort to stem the substantial global burden of strokes related to ILAS.

Background and Objectives: Early consciousness disorder (ECD) after acute ischemic stroke (AIS) is understudied. ECD may influence outcomes and the decision to withhold or withdraw life-sustaining treatment., Methods: We studied patients with AIS from 2010 to 2019 across 122 hospitals participating in the Florida Stroke Registry. We studied the effect of ECD on in-hospital mortality, withholding or withdrawal of life-sustaining treatment (WLST), ambulation status on discharge, hospital length of stay, and discharge disposition., Results: Of 238,989 patients with AIS, 32,861 (14%) had ECD at stroke presentation. Overall, average age was 72 years (Q1 61, Q3 82), 49% were women, 63% were White, 18% were Black, and 14% were Hispanic. Compared to patients without ECD, patients with ECD were older (77 vs 72 years), were more often female (54% vs 48%), had more comorbidities, had greater stroke severity as assessed by the National Institutes of Health Stroke Scale (score ≥5 49% vs 27%), had higher WLST rates (21% vs 6%), and had greater in-hospital mortality (9% vs 3%). Using adjusted models accounting for basic characteristics, patients with ECD had greater in-hospital mortality (odds ratio [OR] 2.23, 95% CI 1.98-2.51), had longer hospitalization (OR 1.37, 95% CI 1.33-1.44), were less likely to be discharged home or to rehabilitation (OR 0.54, 95% CI 0.52-0.57), and were less likely to ambulate independently (OR 0.61, 95% CI 0.57-0.64). WLST significantly mediated the effect of ECD on mortality (mediation effect 265; 95% CI 217-314). In temporal trend analysis, we found a significant decrease in early WLST (<2 days) (R 2 0.7, p = 0.002) and an increase in late WLST (≥2 days) (R 2 0.7, p = 0.004)., Discussion: In this large prospective multicenter stroke registry, patients with AIS presenting with ECD had greater mortality and worse discharge outcomes. Mortality was largely influenced by the WLST decision., (© 2022 American Academy of Neurology.)

Stroke remains the second-leading cause of death and the third-leading cause of death and disability combined (as expressed by disability-adjusted life-years lost - DALYs) in the world. The estimated global cost of stroke is over US$721 billion (0.66% of the global GDP). From 1990 to 2019, the burden (in terms of the absolute number of cases) increased substantially (70.0% increase in incident strokes, 43.0% deaths from stroke, 102.0% prevalent strokes, and 143.0% DALYs), with the bulk of the global stroke burden (86.0% of deaths and 89.0% of DALYs) residing in lower-income and lower-middle-income countries (LMIC). This World Stroke Organisation (WSO) Global Stroke Fact Sheet 2022 provides the most updated information that can be used to inform communication with all internal and external stakeholders; all statistics have been reviewed and approved for use by the WSO Executive Committee as well as leaders from the Global Burden of Disease research group.

Background and Purpose: Lifelong treatment with antiplatelet drugs is recommended following a transient ischemic attack or ischemic stroke. Bleeding complications may offset the benefit of antiplatelet drugs in patients at increased risk of bleeding and low risk of recurrent ischemic events. We aimed to investigate the net benefit of antiplatelet treatment according to an individuals’ bleeding risk., Methods: We pooled individual patient data from 6 randomized clinical trials (CAPRIE [Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events], ESPS-2 [European Stroke Prevention Study-2], MATCH [Management of Atherothrombosis With Clopidogrel in High-Risk Patients], CHARISMA [Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance], ESPRIT [European/Australasian Stroke Prevention in Reversible Ischemia Trial], and PRoFESS [Prevention Regimen for Effectively Avoiding Second Strokes]) investigating antiplatelet therapy in the subacute or chronic phase after noncardioembolic transient ischemic attack or stroke. Patients were stratified into quintiles according to their predicted risk of major bleeding with the S2TOP-BLEED score. The annual risk of major bleeding and recurrent ischemic events was assessed per quintile for 4 scenarios: (1) aspirin monotherapy, (2) aspirin-clopidogrel versus aspirin or clopidogrel monotherapy, (3) aspirin-dipyridamole versus clopidogrel, and (4) aspirin versus clopidogrel. Net benefit was calculated for the second, third, and fourth scenario., Results: Thirty seven thousand eighty-seven patients were included in the analyses. Both risk of major bleeding and recurrent ischemic events increased over quintiles of predicted bleeding risk, but risk of ischemic events was consistently higher (eg, from 0.7%/y (bottom quintile) to 3.2%/y (top quintile) for major bleeding on aspirin and from 2.5%/y to 10.2%/y for risk of ischemic events on aspirin). Treatment with aspirin-clopidogrel led to more major bleedings (0.9%–1.7% per year), than reduction in ischemic events (ranging from 0.4% to 0.9/1.0% per year) across all quintiles. There was no clear preference for either aspirin-dipyridamole or clopidogrel according to baseline bleeding risk., Conclusions: Among patients with a transient ischemic attack or ischemic stroke included in clinical trials of antiplatelet therapy, the risk of recurrent ischemic events and of major bleeding increase in parallel. Antiplatelet treatment cannot be individualized solely based on bleeding risk assessment.

[Figure: see text].

Background: Prolonged monitoring of cardiac rhythm has been used to screen for subclinical atrial fibrillation (AF); little is known about other arrhythmias in the general population, especially in the elderly, who are at higher risk of arrhythmias., Methods: We evaluated the frequency of arrhythmias in the tri-ethnic (white, Black, Hispanic), community-based Subclinical Atrial Fibrillation and Risk of Ischemic Stroke (SAFARIS) study using a patch-based recorder for up to 14 days in 527 participants free of AF, congestive heart failure (CHF) or history of stroke. Differences according to gender, age, ethnicity and presence of hypertension, diabetes and pertinent ECG and echocardiographic variables were examined., Results: Mean age was 77.2 ± 6.8 years (37.2% men, 62.8% women). AF was present in 10 participants (1.9%), only 2 of them symptomatic. Supraventricular tachycardia (SVT) and ventricular tachycardia (VT) episodes were observed in 84.4% and 25.0% but only 13.5% and 10.6% of participants reported symptoms, respectively. Severe bradycardia (<40 bpm) was present in 12.5%. Sinus pauses and high-degree atrioventricular blocks were infrequent (2.1% and 1.5%, respectively). Most arrhythmias were more frequent in participants > 75 years; ventricular arrhythmias and severe bradycardia were more common in men. Whites had significantly more episodes of AF than Hispanics, SVT than Blacks and VT ≥ 10 beats than Hispanics and Blacks. Hypertensives had more episodes of severe bradycardia. LV hypertrophy or LVEF <55% were associated with more frequent ventricular and supraventricular arrhythmias., Conclusions: Prolonged cardiac rhythm monitoring revealed moderate frequency of AF, but higher than expected frequencies of AF-predisposing arrhythmias. Ventricular arrhythmias were relatively frequent, whereas severe bradyarrhythmias were infrequent., Competing Interests: Declaration of Competing Interest Dr. Biviano has served an advisory Boards for Boston Scientific and Biosense Webster. Dr. Elkind reports receiving study drug in kind from the BMS-Pfizer Alliance for Eliquis and ancillary funding from Roche for the NIH-funded ARCADIA trial of apixaban vs aspirin for stroke prevention; and Dr. Elkind's institution, Columbia University, received payments through a service agreement for his participation in analyses of study data. Dr. Elkind received no personal compensation for any of these activities. Dr. Homma reports being a consultant for St. Jude Medical, Daiichi-Sankyo, Bristol Meyers Squibb, Pfizer. Dr. Sacco has received research grants from NINDS, NCATS, AHA, Evelyn McKnight Brain Foundation and Boehringer Ingelheim. The other authors have no disclosures., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of stroke worldwide and confers a high risk of stroke recurrence, despite aggressive management of risk factors., Objectives: This study identified the role of risk factors and risk of vascular events in subjects with asymptomatic ICAS for improved risk stratification., Methods: Stroke-free participants in the NOMAS (Northern Manhattan Study) trial, prospectively followed since 1993, underwent a brain magnetic resonance angiogram from 2003 to 2008. The study rated stenosis in 11 brain arteries as: 0: no stenosis; 1: <50% or luminal irregularities; 2: 50%-69%; and 3: ≥70% stenosis or flow gap. The study ascertained vascular events during the post-magnetic resonance imaging (MRI) period. Proportional odds regression quantified the association of pre-MRI exposures, and proportional hazard adjusted models were built to identify the risk of events in the post-MRI period., Results: The included sample included 1,211 participants from NOMAS (mean age: 71 ± 9 years; 59% women; 65% Hispanic; 45% had any stenosis). Older age (OR: 1.02 per year; 95% CI: 1.01 to 1.04), hypertension duration (OR: 1.01 per year; 95% CI: 1.00 to 1.02), higher number of glucose-lowering drugs (OR: 1.64 per each medication; 95% CI: 1.24 to 2.15), and high-density lipoprotein (OR: 0.96 per mg/dL; 95% CI: 0.92 to 0.99) were associated with ICAS. The highest event risk was noted among participants with ICAS ≥70% (5.5% annual risk of vascular events; HR: 2.1; 95% CI:1.4 to 3.2; compared with those with no ICAS)., Conclusions: ICAS is an imaging marker of established atherosclerotic disease in stroke-free subjects, and incidental diagnosis of ICAS should trigger a thorough assessment of vascular health., Competing Interests: Funding Support and Author Disclosures This work was supported by the National Institutes of Health (grants R01 AG057709, R01 AG066162, R01 NS36286). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. All rights reserved.)

Background and Purpose: IV tPA (intravenous thrombolysis with alteplase) and mechanical thrombectomy (MT) utilization increased in acute ischemic stroke hospitalizations in the United States over the last decade. It is uncertain whether this increase occurred equally across all age, sex, and racial groups., Methods: Adult acute ischemic stroke hospitalizations (weighted n=4 442 657) contained in the 2008 to 2017 National Inpatient Sample were identified using International Classification of Diseases codes. Proportions of hospitalizations with IV tPA and MT were computed according to age, sex, and race. Joinpoint and multivariable-adjusted logistic regression models were used to evaluate trends over time., Results: Across this period, 32.4% of all hospitalizations were in patients ≥80 years, and 64.7% of these were women. IV tPA and MT use differed by age with highest proportion of utilization of both treatments in patients aged 18 to 39 years (IV tPA, 12.3%) and lowest percentage in patients aged ≥90 years (IV tPA, 7.9%). Utilization of both procedures increased over time in all age groups, but the pace of increase was faster in patients ≥90 years compared with patients aged 18 to 39 years (MT: odds ratio, 1.25 [95% CI, 1.20–1.35] per unit increase in year, P interaction <0.001). Frequency of utilization of IV tPA and MT was lower in Black patients compared with White patients in most age groups. Usage of both procedures increased over time in all races and after 2015, IV tPA utilization was >10% in all demographic subgroups except in Black patients 60 to 79 years and Black patients ≥80 years. Analysis of race-by-time interaction revealed the Black-vs-White treatment gaps for IV tPA (odds ratio, 1.02 [95% CI, 1.01–1.03]) and MT (odds ratio, 1.08 [95% CI,1.05–1.12]) declined over time (both P interaction <0.01). Sex-related differences in IV tPA use were noted, but this gap also declined over time., Conclusions: Age- and sex-related treatment gaps in IV tPA and MT reduced over the last decade. Racial disparity in IV tPA and MT utilization persists with particularly lower frequency of usage of both acute stroke treatments in Black patients compared with White patients, but race-associated treatment gaps also declined over time.

Objective: To examine etiologic stroke subtypes and vascular risk factor profiles and their association with white matter hyperintensity (WMH) burden in patients hospitalized for acute ischemic stroke (AIS)., Methods: For the MRI Genetics Interface Exploration (MRI-GENIE) study, we systematically assembled brain imaging and phenotypic data for 3,301 patients with AIS. All cases underwent standardized web tool-based stroke subtyping with the Causative Classification of Ischemic Stroke (CCS). WMH volume (WMHv) was measured on T2 brain MRI scans of 2,529 patients with a fully automated deep-learning trained algorithm. Univariable and multivariable linear mixed-effects modeling was carried out to investigate the relationship of vascular risk factors with WMHv and CCS subtypes., Results: Patients with AIS with large artery atherosclerosis, major cardioembolic stroke, small artery occlusion (SAO), other, and undetermined causes of AIS differed significantly in their vascular risk factor profile (all p < 0.001). Median WMHv in all patients with AIS was 5.86 cm 3 (interquartile range 2.18-14.61 cm 3 ) and differed significantly across CCS subtypes ( p < 0.0001). In multivariable analysis, age, hypertension, prior stroke, smoking (all p < 0.001), and diabetes mellitus ( p = 0.041) were independent predictors of WMHv. When adjusted for confounders, patients with SAO had significantly higher WMHv compared to those with all other stroke subtypes ( p < 0.001)., Conclusion: In this international multicenter, hospital-based cohort of patients with AIS, we demonstrate that vascular risk factor profiles and extent of WMH burden differ by CCS subtype, with the highest lesion burden detected in patients with SAO. These findings further support the small vessel hypothesis of WMH lesions detected on brain MRI of patients with ischemic stroke., (© 2020 American Academy of Neurology.)

Background and Purpose- The RE-SPECT ESUS trial (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) tested the hypothesis that dabigatran would be superior to aspirin for the prevention of recurrent stroke in patients with embolic stroke of undetermined source. This exploratory subgroup analysis investigates the impact of age, renal function (both predefined), and dabigatran dose (post hoc) on the rates of recurrent stroke and major bleeding. Methods- RE-SPECT ESUS was a multicenter, randomized, double-blind trial of dabigatran 150 or 110 mg (for patients aged ≥75 years and/or with creatinine clearance 30 to <50 mL/minute) twice daily compared with aspirin 100 mg once daily. The primary outcome was recurrent stroke. Results- The trial, which enrolled 5390 patients from December 2014 to January 2018, did not demonstrate superiority of dabigatran versus aspirin for prevention of recurrent stroke in patients with embolic stroke of undetermined source. However, among the population qualifying for the lower dabigatran dose, the rate of recurrent stroke was reduced with dabigatran versus aspirin (7.4% versus 13.0%; hazard ratio, 0.57 [95% CI, 0.39-0.82]; interaction P =0.01). This was driven mainly by the subgroup aged ≥75 years (7.8% versus 12.4%; hazard ratio, 0.63 [95% CI, 0.43-0.94]; interaction P =0.10). Stroke rates tended to be lower with dabigatran versus aspirin with declining renal function. Risks for major bleeding were similar between treatments, irrespective of renal function, but with a trend for lower bleeding rates with dabigatran versus aspirin in older patients. Conclusions- In subgroup analyses of RE-SPECT ESUS, dabigatran reduced the rate of recurrent stroke compared with aspirin in patients qualifying for the lower dose of dabigatran. These results are hypothesis-generating. Aspirin remains the standard antithrombotic treatment for patients with embolic stroke of undetermined source. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02239120.

Background Physical exercise and cognitive training have been recommended to improve cognitive outcomes poststroke, but a multifaceted strategy including aerobic, resistance, and cognitive training to facilitate poststroke recovery has not been investigated. We aimed to assess the feasibility, adherence, and safety of a combined aerobic, resistance, and cognitive training intervention (CARET+CTI) after stroke. Methods and Results We prospectively randomized patients presenting with recent stroke to a comparison of a supervised 12-week CARET+CTI program and a control group receiving sham CARET+CTI. Participants were scheduled for 3 weekly CARET and CTI sessions. All participants underwent pre- and postintervention assessments of strength, endurance, and cognition. The primary outcomes were feasibility and adherence, defined as the ratio of scheduled and observed visits, and safety. We enrolled 131 participants, of whom 37 withdrew from the study. There were 17 (20%) withdrawals in the CARET+CTI and 20 (44%) in the control group. The observed-over-expected visit ratio was significantly higher in the intervention than in the control group (0.74±0.30 versus 0.54±0.38; P =0.003). A total of 99 adverse events were reported by 59 participants, none of which were serious and related to the intervention. Greater gains in physical, cognitive, and mood outcomes were found in the CARET+CTI group than in the control group, but were not statistically significant after adjustments. Conclusions A CARET+CTI intervention, after stroke, is safe, feasible, and has satisfactory participant adherence over 12 weeks. REGISTRATION URL: https://www.clini​caltr​ials.gov. Unique identifier: NCT02272426.

Objective: To determine whether brain volume is associated with functional outcome after acute ischemic stroke (AIS)., Patients and Methods: This study was conducted between July 1, 2014, and March 16, 2019. We analyzed cross-sectional data of the multisite, international hospital-based MRI-Genetics Interface Exploration study with clinical brain magnetic resonance imaging obtained on admission for index stroke and functional outcome assessment. Poststroke outcome was determined using the modified Rankin Scale score (0-6; 0 = asymptomatic; 6 = death) recorded between 60 and 190 days after stroke. Demographic characteristics and other clinical variables including acute stroke severity (measured as National Institutes of Health Stroke Scale score), vascular risk factors, and etiologic stroke subtypes (Causative Classification of Stroke system) were recorded during index admission., Results: Utilizing the data from 912 patients with AIS (mean ± SD age, 65.3±14.5 years; male, 532 [58.3%]; history of smoking, 519 [56.9%]; hypertension, 595 [65.2%]) in a generalized linear model, brain volume (per 155.1 cm 3 ) was associated with age (β -0.3 [per 14.4 years]), male sex (β 1.0), and prior stroke (β -0.2). In the multivariable outcome model, brain volume was an independent predictor of modified Rankin Scale score (β -0.233), with reduced odds of worse long-term functional outcomes (odds ratio, 0.8; 95% CI, 0.7-0.9) in those with larger brain volumes., Conclusion: Larger brain volume quantified on clinical magnetic resonance imaging of patients with AIS at the time of stroke purports a protective mechanism. The role of brain volume as a prognostic, protective biomarker has the potential to forge new areas of research and advance current knowledge of the mechanisms of poststroke recovery., (Copyright © 2020. Published by Elsevier Inc.)

Background and Purpose- An excess incidence of strokes among blacks versus whites has been shown, but data on disparities related to Hispanic ethnicity remain limited. This study examines race/ethnic differences in stroke incidence in the multiethnic, largely Caribbean Hispanic, NOMAS (Northern Manhattan Study), and whether disparities vary by age. Methods- The study population included participants in the prospective population-based NOMAS, followed for a mean of 14±7 years. Multivariable-adjusted Cox proportional hazards models were constructed to estimate the association between race/ethnicity and incident stroke of any subtype and ischemic stroke, stratified by age. Results- Among 3298 participants (mean baseline age 69±10 years, 37% men, 24% black, 21% white, 52% Hispanic), 460 incident strokes accrued (400 ischemic, 43 intracerebral hemorrhage, 9 subarachnoid hemorrhage). The most common ischemic subtype was cardioembolic, followed by lacunar infarcts, then cryptogenic. The greatest incidence rate was observed in blacks (13/1000 person-years), followed by Hispanics (10/1000 person-years), and lowest in whites (9/1000 person-years), and this order was observed for crude incidence rates until age 75. By age 85, the greatest incidence rate was in Hispanics. Blacks had an increased risk of stroke versus whites overall in multivariable models that included sociodemographics (hazard ratio, 1.51 [95% CI, 1.13-2.02]), and stratified analyses showed that this disparity was driven by women of age ≥70. The increased rate of stroke among Hispanics (age/sex-adjusted hazard ratio, 1.48 [95% CI, 1.13-1.93]) was largely explained by education and insurance status (a proxy for socieoeconomic status; hazard ratio after further adjusting for these variables, 1.17 [95% CI, 0.85-1.62]) but remained significant for women age ≥70. Conclusions- This study provides novel data regarding the increased stroke risk among Caribbean Hispanics in this elderly population. Results highlight the need to create culturally tailored campaigns to reach black and Hispanic populations to reduce race/ethnic stroke disparities and support the important role of low socioeconomic status in driving an elevated risk among Caribbean Hispanics.

Background and Purpose- To test the hypothesis that covert brain infarcts (CBIs) are more likely to be located in noneloquent brain areas compared with clinical strokes and that CBI etiological subtypes carry a differential risk of vascular events compared with people without CBI. Methods- We used brain magnetic resonance imaging from 1290 stroke-free participants in the NOMAS (Northern Manhattan Study) to evaluate for CBI. We classified CBI as cardioembolic (ie, known atrial fibrillation), large artery atherosclerosis (extracranial and intracranial), penetrating artery disease, and cryptogenic (no apparent cause). CBI localized in the nonmotor areas of the right hemisphere were considered noneloquent. We then evaluated risk of events by CBI subtype with adjusted Cox proportional models. Results- At the time of magnetic resonance imaging, 236 participants (18%) had CBI (144 [61%] distal cryptogenic, 29 [12%] distal cardioembolic, 26 [11%] large artery atherosclerosis, and 37 [16%] penetrating artery disease). Smaller (per mm, odds ratio, 0.8 [0.8-0.9]) and nonbrain stem infarcts (odds ratio, 0.2 [0.1-0.6]) were more likely to be covert. During the follow-up period (10.4±3.1 years), 398 (31%) died (162 [13%] of vascular death) and 117 (9%) had a stroke (99 [85%]) were ischemic. Risks of events varied by CBI subtype, with the highest risk of stroke (hazard ratio, 2.2 [1.3-3.7]) and vascular death (hazard ratio, 2.24 [1.29-3.88]) noted in participants with intracranial large artery atherosclerosis-related CBI. Conclusions- CBI can be classified into subtypes that have differential outcomes. Certain CBI subtypes such as those related to intracranial large artery atherosclerosis have a high risk of adverse vascular outcomes and could warrant consideration of treatment trials.

Objective: To examine racial/ethnic disparities in 30-day all-cause readmission after stroke., Methods: Thirty-day all-cause readmission was compared by race/ethnicity among Medicare fee-for-service beneficiaries discharged for ischemic stroke from hospitals in the Florida Stroke Registry from 2010 to 2013. We fit a Cox proportional hazards model that censored for death and adjusted for age, sex, length of stay, discharge home, and comorbidities to assess racial/ethnic differences in readmission., Results: Among 16,952 stroke patients (54% women, 75% white, 8% black, and 15% Hispanic), 30-day all-cause readmission was 15% (17.2% for blacks, 16.7% for Hispanics, 14.4% for whites, and 14.7% for others; P = .003). There was a median of 11 days between discharge and first readmission. In adjusted analyses, there was no significant difference in readmission for blacks (hazard ratio 1.15, 95% confidence interval 0.99-1.33), Hispanics (1.00, .90-1.13), and those of other race/ethnicity (.91, .71-1.16) compared with whites. Nearly 1 in 4 readmissions were attributable to acute cerebrovascular events: 16.6% ischemic stroke or transient ischemic attack, 1.5% hemorrhagic stroke, and 5.2% cerebral artery interventions. Interventions were more common among whites and those of other race than blacks and Hispanics (P = .029). Readmission due to pneumonia or urinary tract infection was 8.2%., Conclusions: Readmissions attributable to acute cerebrovascular events were common and generally occurred within 2 weeks of hospital discharge. Racial/ethnic disparities were present in readmissions for arterial interventions. Our results underscore the importance of postdischarge transitional care and the need for better secondary prevention strategies after ischemic stroke, particularly among minority populations., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Rationale: Although mild and rapidly improving stroke symptoms are the most common first stroke presentation, this group has been understudied in acute stroke trials. Observational and retrospective studies suggest residual disability in one third of patients., Aims: To elucidate long-term outcomes of patients with mild and rapidly improving stroke, evaluate the predictors of outcome, and examine the association with alteplase treatment., Sample Size: The initial estimate of 2650 participants to detect a 9% difference in non-disabled 90-day outcomes between alteplase-treated and untreated participants was revised to 2000 after a pre-planned re-estimation based on actual treatment rates., Methods and Design: Prospective observational study of patients with mild ischemic stroke (NIHSS ≤ 5) or rapidly improving stroke symptoms evaluated within 4.5 h from onset., Outcomes: The primary outcome is the proportion of patients with modified Rankin Scale (mRS) ≥ 2 at 90 days; the primary safety outcome is symptomatic hemorrhagic transformation within 36 h among those treated with alteplase. Secondary outcomes include the 90-day Barthel Index, Stroke Impact Scale 16, European Quality of Life scale, mRS at 30 days, and 30- and 90-day mortality., Discussion: MaRISS will define outcomes and their predictors and clarify the effects of alteplase in patients with mild and rapidly improving stroke symptoms, providing clinicians with important information to manage this population.

Stroke survivors carry a high risk of recurrence. Antithrombotic medications are paramount for secondary prevention and thus crucial to reduce the overall stroke burden. Appropriate antithrombotic agent selection should be based on the best understanding of the physiopathological mechanism that led to the initial ischemic injury. Antiplatelet therapy is preferred for lesions characterized by atherosclerosis and endothelial injury, whereas anticoagulant agents are favored for cardiogenic embolism and highly thrombophilic conditions. Large randomized controlled trials have provided new data to support recommendations for the evidence-based use of antiplatelet agents and anticoagulant agents after stroke. In this review, the authors cover recent trials that have altered clinical practice, cite systematic reviews and meta-analyses, review evidence-based recommendations based on older landmark trials, and indicate where there are still evidence-gaps and new trials being conducted., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background and Purpose- We aimed to evaluate the current practice patterns, safety and outcomes of patients who receive endovascular therapy (EVT) having mild neurological symptoms. Methods- From Jan 2010 to Jan 2018, 127,794 ischemic stroke patients were enrolled in the Florida-Puerto Rico Stroke Registry. Patients presenting within 24 hours of symptoms who received EVT were classified into mild (National Institutes of Health Stroke Scale [NIHSS] ≤5) or moderate/severe (NIHSS>5) categories. Differences in clinical characteristics and outcomes were evaluated using multivariable logistic regression. Results- Among 4110 EVT patients (median age, 73 [interquartile range=20] years; 50% women), 446 (11%) had NIHSS ≤5. Compared with NIHSS >5, those with NIHSS ≤5 arrived later to the hospital (median, 138 versus 101 minutes), were less likely to receive intravenous alteplase (30% versus 43%), had a longer door-to-puncture time (median, 167 versus 115 minutes) and more likely treated in South Florida (64% versus 53%). In multivariable analysis younger age, private insurance (versus Medicare), history of hypertension, prior independent ambulation and hospital size were independent characteristics associated with NIHSS ≤5. Among EVT patients with NIHSS ≤5, 76% were discharged home/rehabilitation and 64% were able to ambulate independently at discharge as compared with 53% and 32% of patients with NIHSS >5. Symptomatic intracerebral hemorrhage occurred in 4% of mild stroke EVT patients and 6.4% in those with NIHSS >5. Conclusions- Despite lack of evidence-based recommendations, 11% of patients receiving EVT in clinical practice have mild neurological presentations. Individual, hospital and geographic disparities are observed among endovascularly treated patients based on the severity of clinical symptoms. Our data suggest safety and overall favorable outcomes for EVT patients with mild stroke.