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Importance: Approximately 10% to 15% of ischemic strokes are associated with cancer; cancer-associated stroke, particularly when cryptogenic, is associated with high rates of recurrent stroke and major bleeding. Limited data exist on the safety and efficacy of different antithrombotic strategies in patients with cancer and cryptogenic stroke., Objective: To compare apixaban vs aspirin for the prevention of adverse clinical outcomes in patients with history of cancer and cryptogenic stroke., Design, Setting, and Participants: Post hoc analysis of data from 1015 patients with a recent cryptogenic stroke and biomarker evidence of atrial cardiopathy in the Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) trial, a multicenter, randomized, double-blind clinical trial conducted from 2018 to 2023 at 185 stroke centers in North America. Data analysis was performed from October 15, 2023, to May 23, 2024., Exposures: Oral apixaban, 5 mg (or 2.5 mg if criteria met), twice daily vs oral aspirin, 81 mg, once daily. Subgroups of patients with and without cancer at baseline were examined., Main Outcomes and Measures: The primary outcome for this post hoc analysis was a composite of major ischemic or major hemorrhagic events. Major ischemic events were recurrent ischemic stroke, myocardial infarction, systemic embolism, and symptomatic deep vein thrombosis or pulmonary embolism. Major hemorrhagic events included symptomatic intracranial hemorrhage and any major extracranial hemorrhage., Results: Among 1015 participants (median [IQR] age, 68 [60-76] years; 551 [54.3%] female), 137 (13.5%) had a history of cancer. The median (IQR) follow-up was 1.5 (0.6-2.5) years for patients with history of cancer and 1.5 (0.6-3.0) years for those without history of cancer. Participants with history of cancer, compared with those without history of cancer, had a higher risk of major ischemic or major hemorrhagic events (hazard ratio [HR], 1.73; 95% CI, 1.10-2.71). Among those with history of cancer, 8 of 61 participants (13.1%) randomized to apixaban and 16 of 76 participants (21.1%) randomized to aspirin had a major ischemic or major hemorrhagic event; however, the risk was not significantly different between groups (HR, 0.61; 95% CI, 0.26-1.43). Comparing participants randomized to apixaban vs aspirin among those with cancer, events included recurrent stroke (5 [8.2%] vs 9 [11.8%]), major ischemic events (7 [11.5%] vs 14 [18.4%]), and major hemorrhagic events (1 [1.6%] vs 2 [2.6%])., Conclusions and Relevance: Among participants in the ARCADIA trial with history of cancer, the risk of major ischemic and hemorrhagic events did not differ significantly with apixaban compared with aspirin., Trial Registration: ClinicalTrials.gov Identifier: NCT03192215.

Background: ARCADIA compared apixaban to aspirin for secondary stroke prevention in patients with cryptogenic stroke and atrial cardiopathy. One possible explanation for the neutral result is that biomarkers used did not optimally identify atrial cardiopathy. We examined the relationship between biomarker levels and subsequent detection of AF, the hallmark of atrial cardiopathy., Methods: Patients were randomized if they met criteria for atrial cardiopathy, defined as P-wave terminal force >5000 μV*ms in ECG lead V 1 (PTFV 1 ), NT-proBNP >250 pg/mL, or left atrial diameter index (LADI) ⩾3 cm/m 2 . For this analysis, the outcome was AF detected per routine care., Results: Of 3745 patients who consented to screening for atrial cardiopathy, 254 were subsequently diagnosed with AF; 96 before they could be randomized and 158 after randomization. In unadjusted analyses, ln(NT-proBNP) (RR per SD, 1.99; 95% CI, 1.85-2.13), PTFV 1 (RR per SD, 1.15; 95% CI, 1.03-1.28) and LADI (RR per SD, 1.34; 95% CI, 1.20-1.50) were associated with AF. In a model containing all 3 biomarkers, demographics, and AF risk factors, age (RR per 10 years, 1.24; 95% CI, 1.09-1.41), ln(NT-proBNP) (RR per SD, 1.88; 95% CI, 1.67-2.11) and LADI (RR per SD, 1.25; 95% CI, 1.14-1.37) were associated with AF. These three variables together had a c-statistic of 0.82 (95% CI, 0.79-0.85) but only modest calibration. Discrimination was attenuated in sensitivity analyses of patients eligible for randomization who may have been more closely followed for AF., Conclusions: Biomarkers used to identify atrial cardiopathy in ARCADIA were moderately predictive of subsequent AF., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Kamel reports serving as Deputy Editor for JAMA Neurology; serving on clinical trial steering/executive committees for the STROKE-AF (Medtronic), LIBREXIA-AF (Janssen), and LAAOS-4 (Boston Scientific) trials; serving as a consultant or endpoint adjudication committee member for AbbVie, AstraZeneca, Boehringer Ingelheim, and Novo Nordisk; and household ownership interests in TETMedical, Spectrum Plastics Group, and Ascential Technologies. Dr. Healey reports research grants and speaking fees from BMS/Pfizer, Servier, Boston Scientific, and Medtronic. Dr. Kasner reports grant funding from Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Genentech, Medtronic, and Diamedica, consulting fees from AstraZeneca, Abbie, and Novo Nordisk, and royalties from UpToDate. Dr. Elkind reports employment by the American Heart Association, royalties from UpToDate for chapters on stroke, and honoraria for lectures from the Atria Academy for Science and Medicine. The other authors report no conflicts of interest.

Background and Objectives: Although stroke risk associated with HIV may be greater for women than men, little is known about whether the impact of different factors on cerebrovascular risk varies by sex in people with HIV (PWH) and contributes to stroke risk disparities in this population. The primary objective of this study was to examine whether sex modifies the effect of demographics, cardiometabolic factors, health-related behaviors, and HIV-specific variables on stroke risk in PWH from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort., Methods: In this observational cohort study, we analyzed data from clinical encounters for PWH followed at 5 CNICS sites from approximately 2005 to 2020. All potential stroke events were adjudicated by neurologists. Patient-reported outcomes collected at clinic visits, including substance use and depression, were also available. We used Cox proportional hazards models to determine whether sex modified the association of predictors of interest with incident stroke., Results: Among 13,573 PWH (19% female sex at birth, mean age 44 years, mean follow-up 5.6 years), female sex was associated with a higher risk of stroke only among individuals aged 50 years or younger (hazard ratio [HR] 2.01 at age 40 [1.25-3.21] vs HR 0.60 at age 60 [0.34-1.06]; p = 0.001 for the interaction). Younger female participants who developed a stroke were more likely to have treated hypertension, a higher cardiovascular risk score, and detectable HIV than younger male participants whereas these factors were comparable by sex among older participants who developed a stroke. Sex modified the effect of detectable HIV (HR 4.66 for female participants [2.48-8.74] vs HR 1.30 for male participants [0.83-2.03]; p = 0.001 for the interaction), methamphetamine use (HR 4.78 for female participants [1.47-15.56] vs HR 1.19 for male participants [0.62-2.29]; p = 0.04 for the interaction), and treated hypertension (HR 3.44 for female participants [1.74-6.81] vs HR 1.66 for male participants [1.14-2.41]; p = 0.06 for the interaction) on stroke risk., Discussion: Younger female participants with HIV were at elevated cerebrovascular risk compared with younger male participants. Several risk factors had a greater adverse effect on stroke risk in female participants than in male participants, including HIV viremia, methamphetamine use, and treated hypertension. These findings underscore the importance of a personalized approach to predict and prevent cerebrovascular risk among PWH.

Background: Cerebrospinal fluid creatine kinase BB isoenzyme (CSF CK-BB) after cardiac arrest (CA) has been shown to have a high positive predictive value for poor neurological outcome, but it has not been evaluated in the setting of targeted temperature management (TTM) and modern CA care. We aimed to evaluate CSF CK-BB as a prognostic biomarker after CA., Methods: We performed a retrospective cohort study of patients with CA admitted between 2010 and 2020 to a three-hospital health system who remained comatose and had CSF CK-BB assayed between 36 and 84 h after CA. We examined the proportion of patients at hospital discharge who achieved favorable or intermediate neurological outcome, defined as Cerebral Performance Category score of 1-3, compared with those with poor outcome (Cerebral Performance Category score 4-5) for various CSF CK-BB thresholds. We also evaluated additive value of bilateral absence of somatosensory evoked potentials (SSEPs)., Results: Among 214 eligible patients, the mean age was 54.7 ± 4.8 years, 72% of patients were male, 33% were nonwhite, 17% had shockable rhythm, 90% were out-of-hospital CA, and 83% received TTM. A total of 19 (9%) awakened. CSF CK-BB ≥ 230 U/L predicted a poor outcome at hospital discharge, with a specificity of 100% (95% confidence interval [CI] 82-100%) and sensitivity of 69% (95% CI 62-76%). When combined with bilaterally absent N20 response on SSEP, specificity remained 100% while sensitivity increased to 80% (95% CI 73-85%). Discordant CK-BB and SSEP findings were seen in 13 (9%) patients., Conclusions: Cerebrospinal fluid creatine kinase BB isoenzyme levels accurately predicted poor neurological outcome among CA survivors treated with TTM. The CSF CK-BB cutoff of 230 U/L optimizes sensitivity to 69% while maintaining a specificity of 100%. CSF CK-BB could be a useful addition to multimodal neurological prognostication after CA., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background and Objectives: Cardiovascular disease contributes significantly to disease burden among many Indigenous populations. However, data on stroke incidence in Indigenous populations are sparse. We aimed to investigate what is known of stroke incidence in Indigenous populations of countries with a very high Human Development Index (HDI), locating the research in the broader context of Indigenous health., Methods: We identified population-based stroke incidence studies published between 1990 and 2022 among Indigenous adult populations of developed countries using PubMed, Embase, and Global Health databases, without language restriction. We excluded non-peer-reviewed sources, studies with fewer than 10 Indigenous people, or not covering a 35- to 64-year minimum age range. Two reviewers independently screened titles, abstracts, and full-text articles and extracted data. We assessed quality using "gold standard" criteria for population-based stroke incidence studies, the Newcastle-Ottawa Scale for risk of bias, and CONSIDER criteria for reporting of Indigenous health research. An Indigenous Advisory Board provided oversight for the study., Results: From 13,041 publications screened, 24 studies (19 full-text articles, 5 abstracts) from 7 countries met the inclusion criteria. Age-standardized stroke incidence rate ratios were greater in Aboriginal and Torres Strait Islander Australians (1.7-3.2), American Indians (1.2), Sámi of Sweden/Norway (1.08-2.14), and Singaporean Malay (1.7-1.9), compared with respective non-Indigenous populations. Studies had substantial heterogeneity in design and risk of bias. Attack rates, male-female rate ratios, and time trends are reported where available. Few investigators reported Indigenous stakeholder involvement, with few studies meeting any of the CONSIDER criteria for research among Indigenous populations., Discussion: In countries with a very high HDI, there are notable, albeit varying, disparities in stroke incidence between Indigenous and non-Indigenous populations, although there are gaps in data availability and quality. A greater understanding of stroke incidence is imperative for informing effective societal responses to socioeconomic and health disparities in these populations. Future studies into stroke incidence in Indigenous populations should be designed and conducted with Indigenous oversight and governance to facilitate improved outcomes and capacity building., Registration Information: PROSPERO registration: CRD42021242367.

Importance: Atrial cardiopathy is associated with stroke in the absence of clinically apparent atrial fibrillation. It is unknown whether anticoagulation, which has proven benefit in atrial fibrillation, prevents stroke in patients with atrial cardiopathy and no atrial fibrillation., Objective: To compare anticoagulation vs antiplatelet therapy for secondary stroke prevention in patients with cryptogenic stroke and evidence of atrial cardiopathy., Design, Setting, and Participants: Multicenter, double-blind, phase 3 randomized clinical trial of 1015 participants with cryptogenic stroke and evidence of atrial cardiopathy, defined as P-wave terminal force greater than 5000 μV × ms in electrocardiogram lead V1, serum N-terminal pro-B-type natriuretic peptide level greater than 250 pg/mL, or left atrial diameter index of 3 cm/m2 or greater on echocardiogram. Participants had no evidence of atrial fibrillation at the time of randomization. Enrollment and follow-up occurred from February 1, 2018, through February 28, 2023, at 185 sites in the National Institutes of Health StrokeNet and the Canadian Stroke Consortium., Interventions: Apixaban, 5 mg or 2.5 mg, twice daily (n = 507) vs aspirin, 81 mg, once daily (n = 508)., Main Outcomes and Measures: The primary efficacy outcome in a time-to-event analysis was recurrent stroke. All participants, including those diagnosed with atrial fibrillation after randomization, were analyzed according to the groups to which they were randomized. The primary safety outcomes were symptomatic intracranial hemorrhage and other major hemorrhage., Results: With 1015 of the target 1100 participants enrolled and mean follow-up of 1.8 years, the trial was stopped for futility after a planned interim analysis. The mean (SD) age of participants was 68.0 (11.0) years, 54.3% were female, and 87.5% completed the full duration of follow-up. Recurrent stroke occurred in 40 patients in the apixaban group (annualized rate, 4.4%) and 40 patients in the aspirin group (annualized rate, 4.4%) (hazard ratio, 1.00 [95% CI, 0.64-1.55]). Symptomatic intracranial hemorrhage occurred in 0 patients taking apixaban and 7 patients taking aspirin (annualized rate, 1.1%). Other major hemorrhages occurred in 5 patients taking apixaban (annualized rate, 0.7%) and 5 patients taking aspirin (annualized rate, 0.8%) (hazard ratio, 1.02 [95% CI, 0.29-3.52])., Conclusions and Relevance: In patients with cryptogenic stroke and evidence of atrial cardiopathy without atrial fibrillation, apixaban did not significantly reduce recurrent stroke risk compared with aspirin., Trial Registration: ClinicalTrials.gov Identifier: NCT03192215.

Background: The modified Rankin Scale (mRS), which measures degree of disability in daily activities, is the most common outcome measure in stroke research. Quality of life (QoL), however, is impacted by factors other than disability. The goal of this study was to assess the correlation between functional dependence and a more patient-centered QoL measure, the European QoL visual analog scale (EQ VAS). Methods: We reviewed prehospital and hospital records from 11 acute care hospitals in Seattle, Washington (USA) from June 2000 to January 2003 for this cohort study. Patients with a final diagnosis of stroke were contacted three to four months after stroke, and mRS and EQ VAS were assessed. Good QoL was defined as EQ VAS ≥65. Results: Of 760 patients with stroke, 346 were available at three to four months. Most (296, 85.5%) had ischemic stroke. Overall, mRS and QoL were negatively correlated (Spearman's ρ -0.53, p  < 0.001). Percentage of good QoL decreased as mRS increased from 0 to 5 (88%, 70%, 52%, 50%, 31%, 20%, respectively, p  < 0.001). However, 36% ( n  = 62) of patients with dependent mRS (3-5, n  = 174) reported good QoL, and 30% ( n  = 52) of patients with independent mRS (0-2, n  = 172) reported poor QoL. In multivariable analysis, older age, male gender, and absence of dementia, were associated with good QoL despite dependent mRS; atrial fibrillation was associated with poor QoL despite independent mRS. Conclusions: QoL decreases with increasing mRS, but exceptions exist with good QoL despite high mRS. To provide patient-centered care, clinicians and researchers should avoid equating disability with QoL after stroke.

Background and Objectives: In 2017, the Centers for Disease Control and Prevention (CDC) issued an alert that, after decades of consistent decline, the stroke death rate levelled off in 2013, particularly in younger individuals and without clear origin. The objective of this analysis was to understand whether social determinants of health have influenced trends in stroke mortality., Methods: We performed a longitudinal analysis of county-level ischemic and hemorrhagic stroke death rate per 100,000 adults from 1999 to 2018 using a Bayesian spatiotemporally smoothed CDC dataset stratified by age (35-64 years [younger] and 65 years or older [older]) and then by county-level social determinants of health. We reported stroke death rate by county and the percentage change in stroke death rate during 2014-2018 compared with that during 2009-2013., Results: We included data from 3,082 counties for younger individuals and 3,019 counties for older individuals. The stroke death rate began to increase for younger individuals in 2013 ( p < 0.001), and the slope of the decrease in stroke death rate tapered for older individuals ( p < 0.001). During the 20-year period of our study, counties with a high social deprivation index and ≥10% Black residents consistently had the highest rates of stroke death in both age groups. Comparing stroke death rate during 2014-2018 with that during 2009-2013, larger increases in younger individuals' stroke death rate were seen in counties with ≥90% (vs <90%) non-Hispanic White individuals (3.2% mean death rate change vs 1.7%, p < 0.001), rural (vs urban) populations (2.6% vs 2.0%, p = 0.019), low (vs high) proportion of medical insurance coverage (2.9% vs 1.9%, p = 0.002), and high (vs low) substance abuse and suicide mortality (2.8 vs 1.9%, p = 0.008; 3.3% vs 1.5%, p < 0.001). In contrast to the younger individuals, in older individuals, the associations with increased death rates were with more traditional social determinants of health such as the social deprivation index, urban location, unemployment rate, and proportion of Black race and Hispanic ethnicity residents., Discussion: Improvements in the stroke death rate in the United States are slowing and even reversing in younger individuals and many US counties. County-level increases in stroke death rate were associated with distinct social determinants of health for younger vs older individuals. These findings may inform targeted public health strategies., (© 2023 American Academy of Neurology.)

Background and Objectives: Plasma proteomics may elucidate novel insights into the pathophysiology of ischemic stroke (IS), identify biomarkers of IS risk, and guide development of nascent prevention strategies. We evaluated the relationship between the plasma proteome and IS risk in the population-based Cardiovascular Health Study (CHS)., Methods: Eligible CHS participants were free of prevalent stroke and underwent quantification of 1,298 plasma proteins using the aptamer-based SOMAScan assay platform from the 1992-1993 study visit. Multivariable Cox proportional hazards regression was used to evaluate associations between a 1-SD increase in the log 2 -transformed estimated plasma protein concentrations and incident IS, adjusting for demographics, IS risk factors, and estimated glomerular filtration rate. For proteins independently associated with incident IS, a secondary stratified analysis evaluated associations in subgroups defined by sex and race. Exploratory analyses evaluated plasma proteomic associations with cardioembolic and noncardioembolic IS and proteins associated with IS risk in participants with left atrial dysfunction but without atrial fibrillation., Results: Of 2,983 eligible participants, the mean age was 74.3 (±4.8) years, 61.2% were women, and 15.4% were Black. Over a median follow-up of 12.6 years, 450 participants experienced an incident IS. N-terminal probrain natriuretic peptide (NTproBNP, adjusted HR 1.37, 95% CI 1.23-1.53, p = 2.08 × 10 -08 ) and macrophage metalloelastase (MMP12, adjusted HR 1.30, 95% CI 1.16-1.45, p = 4.55 × 10 -06 ) were independently associated with IS risk. These 2 associations were similar in men and women and in Black and non-Black participants. In exploratory analyses, NTproBNP was independently associated with incident cardioembolic IS, E-selectin with incident noncardioembolic IS, and secreted frizzled-related protein 1 with IS risk in participants with left atrial dysfunction., Discussion: In a cohort of older adults, NTproBNP and MMP12 were independently associated with IS risk. We identified plasma proteomic determinants of incident cardioembolic and noncardioembolic IS and found a novel protein associated with IS risk in those with left atrial dysfunction., (© 2023 American Academy of Neurology.)

Background and Purpose: Stroke is the leading cause of death and long-term disability worldwide. Previous genome-wide association studies identified 51 loci associated with stroke (mostly ischemic) and its subtypes among predominantly European populations. Using whole-genome sequencing in ancestrally diverse populations from the Trans-Omics for Precision Medicine (TOPMed) Program, we aimed to identify novel variants, especially low-frequency or ancestry-specific variants, associated with all stroke, ischemic stroke and its subtypes (large artery, cardioembolic, and small vessel), and hemorrhagic stroke and its subtypes (intracerebral and subarachnoid)., Methods: Whole-genome sequencing data were available for 6833 stroke cases and 27 116 controls, including 22 315 European, 7877 Black, 2616 Hispanic/Latino, 850 Asian, 54 Native American, and 237 other ancestry participants. In TOPMed, we performed single variant association analysis examining 40 million common variants and aggregated association analysis focusing on rare variants. We also combined TOPMed European populations with over 28 000 additional European participants from the UK BioBank genome-wide array data through meta-analysis., Results: In the single variant association analysis in TOPMed, we identified one novel locus 13q33 for large artery at whole-genome-wide significance ( P <5.00×10 -9 ) and 4 novel loci at genome-wide significance ( P <5.00×10 -8 ), all of which need confirmation in independent studies. Lead variants in all 5 loci are low-frequency but are more common in non-European populations. An aggregation of synonymous rare variants within the gene C6orf26 demonstrated suggestive evidence of association for hemorrhagic stroke ( P <3.11×10 -6 ). By meta-analyzing European ancestry samples in TOPMed and UK BioBank, we replicated several previously reported stroke loci including PITX2 , HDAC9 , ZFHX3 , and LRCH1 ., Conclusions: We represent the first association analysis for stroke and its subtypes using whole-genome sequencing data from ancestrally diverse populations. While our findings suggest the potential benefits of combining whole-genome sequencing data with populations of diverse genetic backgrounds to identify possible low-frequency or ancestry-specific variants, they also highlight the need to increase genome coverage and sample sizes.

Background and Purpose: Intracranial atherosclerotic plaque features are potential factors associated with recurrent stroke, but previous studies only focused on a single lesion, and few studies investigated them with perfusion impairment. This study aimed to investigate the association among whole-brain plaque features, perfusion deficit, and stroke recurrence., Materials and Methods: Patients with ischemic stroke due to intracranial atherosclerosis were retrospectively collected and categorized into first-time and recurrent-stroke groups. Patients underwent high-resolution vessel wall imaging and DSC-PWI. Intracranial plaque number, culprit plaque features (such as plaque volume/burden, degree of stenosis, enhancement ratio), and perfusion deficit variables were recorded. Logistic regression analyses were performed to determine the independent factors associated with recurrent stroke., Results: One hundred seventy-five patients (mean age, 59 [SD, 12] years; 115 men) were included. Compared with the first-time stroke group ( n  = 100), the recurrent-stroke group ( n  = 75) had a larger culprit volume ( P = .006) and showed more intracranial plaques ( P  < .001) and more enhanced plaques ( P  = .003). After we adjusted for other factors, culprit plaque volume (OR, 1.16 per 10-mm 3 increase; 95% CI, 1.03-1.30; P  = .015) and total plaque number (OR, 1.31; 95% CI, 1.13-1.52; P  < .001) were independently associated with recurrent stroke. Combining these factors increased the area under the curve to 0.71., Conclusions: Large culprit plaque and more intracranial plaques were independently associated with recurrent stroke. Performing whole-brain vessel wall imaging may help identify patients with a higher risk of recurrent stroke., (© 2022 by American Journal of Neuroradiology.)

Background: We assessed whether key biomarkers of endothelial activation and hemostasis/thrombosis were elevated in individuals receiving effective antiretroviral therapy (ART) in the year before ischemic stroke., Methods: We conducted a case-control study nested in the CFAR Network of Integrated Clinical Systems cohort, comparing 42 adjudicated cases with ischemic stroke with 83 controls matched for ART regimen. Angiopoietin-1, angiopoietin-2, C-reactive protein, interleukin-6, plasminogen activation inhibitor-1, P-selectin, serum amyloid-A, soluble CD14, ICAM-1, VCAM-1, apolipoprotein A1, ADAMTS13, and von Willebrand factor (VWF) were measured in stored plasma collected before the stroke event. We used conditional logistic regression to identify associations with ischemic stroke, with and without adjustment for Atherosclerotic Cardiovascular Disease (ASCVD) and Veterans Aging Cohort Study (VACS) scores., Results: After adjustment for age and sex, higher plasma viral load and higher angiopoeitin-2, soluble CD14, and VWF were associated with increased odds of ischemic stroke; higher nadir CD4 count was associated with decreased odds of ischemic stroke. VWF remained associated with subsequent ischemic stroke after adjustment for ASCVD score (adjusted odds, 1.74; 95% CI, 1.01-2.98 per log 2 increment). In a separate model adjusting for VACS score, only VWF (adjusted odds, 1.80; 95% CI, 1.04-3.12 per log 2 increment) was associated with subsequent ischemic stroke. In a sensitivity analysis excluding participants with viral load ≥400 copies/mL, associations between VWF and ischemic stroke were attenuated, with risk estimates ranging from 1.59 to 1.64 per log 2 increment., Conclusions: Endothelial activation and related release and attachment of VWF may play an important role in ischemic stroke among persons with treated HIV infection., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: Management of left ventricular assist device (LVAD)-associated intracranial hemorrhage (ICH) is complicated by the competing concerns of hematoma expansion and the risk of thrombosis. Strategies include reversal or withholding of anticoagulation (AC) and neurosurgical (NSG) interventions. The consequences of these decisions can significantly impact both short- and long-term survival. Currently no guidelines exist. We reviewed medical and NSG practices following LVAD-associated ICH and analyzed outcomes., Materials and Methods: Retrospective analysis of data collected between 2012-2018 was performed. Survival probability following ICH was calculated using the Kaplan-Meier method., Results: Out of 283 patients, 32 (11%) had 34 ICHs: 16 intraparenchymal (IPH, 47%), 4 subdural (SDH, 12%), and 14 subarachnoid (SAH, 41%). IPH tended to occur sooner (median 138 [IQR 48 - 258] days post-LVAD placement) and be more neurologically devastating (mean GCS 11.4 [4.4]). Antithrombotics were reversed in 27 (79%); 1 thrombotic event occurred while off AC. Following resumption, re-hemorrhage occurred in 7 (25%), a median of 13 days (IQR 8-30) post-ICH. Five underwent NSG intervention and 6 (18%) went on to receive heart transplant. Overall, 30-day mortality was 26% (38% in IPH, 0% in SDH, and 29% in SAH), but rose to 44% at 6 months., Conclusion: ICH is a common post-LVAD complication with high short- and long-term mortality, though ICH subtypes may not be equally devastating. Despite this, some may benefit from neurosurgical intervention and do well following cardiac transplant. Anticoagulation is frequently reversed after ICH. Resumption however should be approached cautiously in patients with LVADs given their possible baseline coagulopathy., 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 © 2021 Elsevier Inc. All rights reserved.)

The American Heart Association/American Stroke Association released the adult stroke rehabilitation and recovery guidelines in 2016. A working group of stroke rehabilitation experts reviewed these guidelines and identified a subset of recommendations that were deemed suitable for creating performance measures. These 13 performance measures are reported here and contain inclusion and exclusion criteria to allow calculation of rates of compliance in a variety of settings ranging from acute hospital care to postacute care and care in the home and outpatient setting.

Background: Type 2 diabetes mellitus (T2DM) has shown to be associated with carotid plaque vulnerability. However, the impact of T2DM on intracranial artery atherosclerosis is not well-understood., Purpose: To evaluate the association of diabetes and glycemic control with intracranial atherosclerotic plaque characteristics identified by three-dimensional contrast enhanced MR vessel wall imaging in patients after acute ischemic stroke., Study Type: Prospective., Population: Two hundred and eighty-eight symptomatic patients with acute ischemic stroke due to intracranial atherosclerotic plaque., Field Strength/sequence: T 1 WI volume isotropic turbo spin-echo acquisition sequence at 3.0 T., Assessment: Clinical profiles, blood biomarkers, the number of intracranial plaques, plaque enhanced score, and the features (location, luminal stenotic rate, intraplaque hemorrhage, length, burden, enhancement grade, and ratio) of culprit plaque (defined as the most stenotic lesion ipsilateral to the ischemic event) and nonculprit plaque were analyzed by three radiologists., Statistical Tests: Analysis of variance (ANOVA), Shapiro-Wilk normality test, Levene's test, ANOVA with Bonferroni post-hoc test, Kruskal Wallis H test with subsequent pairwise comparisons, chi-square with Bonferroni post-hoc test, generalized linear regression, Pearson correlation test, Kendall's W and intra-class correlation coefficient., Results: Two hundred and twenty-five participants (age 60 ± 10 years, 58.7% male) with 958 intracranial plaques were included. More intracranial plaques were found in the T2DM group than the non-T2DM group (4.80 ± 2.22 vs. 3.60 ± 1.78, P < 0.05). Patients with poorly-controlled T2DM exhibited higher culprit plaque enhancement ratio than patients with well-controlled T2DM and non-T2DM (2.32 ± 0.61 vs. 1.60 ± 0.62 and 1.39 ± 0.39; respectively, P < 0.05). After adjusting for other clinical variables, T2DM was independently associated with increased intracranial plaque number (β = 0.269, P < 0.05), and HbA1c level was independently associated with culprit plaque enhancement ratio (β = 0.641, P < 0.05) in multivariate analysis., Data Conclusion: T2DM is associated with an increased intracranial plaque number. Higher HbA1c is associated with stronger plaque enhancement. 3D contrast enhanced MR vessel wall imaging may help better understand the association of T2DM and glycemic control with intracranial plaque., Level of Evidence: 1 TECHNICAL EFFICACY STAGE: 3., (© 2021 International Society for Magnetic Resonance in Medicine.)

Objective: To test the genetic contribution of rare missense variants in COL4A1 and COL4A2 in which common variants are genetically associated with sporadic intracerebral hemorrhage (ICH), we performed rare variant analysis in multiple sequencing data for the risk for sporadic ICH., Methods: We performed sequencing across 559 Kbp at 13q34 including COL4A1 and COL4A2 among 2,133 individuals (1,055 ICH cases; 1,078 controls) in United States-based and 1,381 individuals (192 ICH cases; 1,189 controls) from Scotland-based cohorts, followed by sequence annotation, functional impact prediction, genetic association testing, and in silico thermodynamic modeling., Results: We identified 107 rare nonsynonymous variants in sporadic ICH, of which 2 missense variants, rs138269346 (COL4A1 I110T ) and rs201716258 (COL4A2 H203L ), were predicted to be highly functional and occurred in multiple ICH cases but not in controls from the United States-based cohort. The minor allele of rs201716258 was also present in Scottish patients with ICH, and rs138269346 was observed in 2 ICH-free controls with a history of hypertension and myocardial infarction. Rs138269346 was nominally associated with nonlobar ICH risk ( p = 0.05), but not with lobar ICH ( p = 0.08), while associations between rs201716258 and ICH subtypes were nonsignificant ( p > 0.12). Both variants were considered pathogenic based on minor allele frequency (<0.00035 in European populations), predicted functional impact (deleterious or probably damaging), and in silico modeling studies (substantially altered physical length and thermal stability of collagen)., Conclusions: We identified rare missense variants in COL4A1 / A2 in association with sporadic ICH. Our annotation and simulation studies suggest that these variants are highly functional and may represent targets for translational follow-up., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: Studies indicate that the functional outcome evolves in the year after ischemic stroke onset. However, the traditional outcome measure in stroke trials is the modified Rankin Scale (mRS) at 90 days from onset. To determine mRS fluctuations in the first year after stroke, we examined data from 3 major stroke trials., Methods: In a secondary analysis, we evaluated intrapatient mRS between 90 days and 1 year from stroke onset, the mRS shift (∆mRS = 1 year-day 90), and the trials' primary outcome at day 90 and 1 year., Results: We included 624 patients from the National Institute of Neurological Disorders and Stroke rt-PA Stroke Study, 587 from Albumin Treatment for Acute Ischaemic Stroke, and 611 from Interventional Management of Stroke III, for which the proportion of patients with a ∆mRS change between day 90 and 1 year was 36.5%, 41.7%, and 36.0%. However, the trials' primary outcomes did not differ at 1 year vs 90 days. Similar findings were seen in a second cohort where we pooled the trials and excluded patients with recurrent stroke or death during the follow-up. In those 1,314 patients, 544 (41.4%) had a ∆mRS change, of which 379 (28.9%) had improvement and 165 (12.5%) had worsening, apart from death., Conclusion: We describe the patient-level spectrum of mRS change from day 90 to 1 year after ischemic stroke in 3 high-quality randomized trials. The patient-level shifts consisted of a sufficiently counterbalanced number of mRS improvements and declines, which masked clinical evolution occurring in over one-third of patients. These results may have important implications, both for clinical trial design and outcome adjudication in stroke research and duration of rehabilitative therapy., (© 2021 American Academy of Neurology.)

Background: Rates of stroke are higher in people living with HIV compared with age-matched uninfected individuals. Causes of elevated stroke risk, including the role of viremia, are poorly defined., Methods: Between 1 January 2006 and 31 December 2014, we identified incident strokes among people living with HIV on antiretroviral therapy at five sites across the United States. We considered three parameterizations of viral load (VL) including (1) baseline (most recent VL before study entry), (2) time-updated, and (3) cumulative VL (copy-days/mL of virus). We used Cox proportional hazards models to estimate hazard ratios (HRs) for stroke risk comparing the 75th percentile ("high VL") to the 25th percentile ("low VL") of baseline and time-updated VL. We used marginal structural Cox models, with most models adjusted for traditional stroke risk factors, to estimate HRs for stroke associated with cumulative VL., Results: Among 15,974 people living with HIV, 139 experienced a stroke (113 ischemic; 18 hemorrhagic; eight were unknown type) over a median follow-up of 4.2 years. Median baseline VL was 38 copies/mL (interquartile interval: 24, 3,420). High baseline VL was associated with increased risk of both ischemic (HR: 1.3; 95% CI = 0.96-1.7) and hemorrhagic stroke (HR: 3.1; 95% CI = 1.6-5.9). In time-updated models, high VL was also associated with an increased risk of any stroke (HR: 1.8; 95% CI = 1.4-2.3). We observed no association between cumulative VL and stroke risk., Conclusions: Our findings are consistent with the hypothesis that elevated HIV VL may increase stroke risk, regardless of previous VL levels., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: Despite known Indigenous health and socioeconomic disadvantage in countries with a Very High Human Development Index, data on the incidence of stroke in these populations are sparse. With oversight from an Indigenous Advisory Board, we will undertake a systematic review of the incidence of stroke in Indigenous populations of developed countries or regions, with comparisons between Indigenous and non-Indigenous populations of the same region, though not between different Indigenous populations. Methods: Using PubMed, OVID-EMBASE, and Global Health databases, we will examine population-based incidence studies of stroke in Indigenous adult populations of developed countries published 1990-current, without language restriction. Non-peer-reviewed sources, studies including <10 Indigenous People, or with insufficient data to determine incidence, will be excluded. Two reviewers will independently validate the search strategies, screen titles and abstracts, and record reasons for rejection. Relevant articles will undergo full-text screening, with standard data extracted for all studies included. Quality assessment will include Sudlow and Warlow's criteria for population-based stroke incidence studies, the Newcastle-Ottawa Scale for risk of bias, and the CONSIDER checklist for Indigenous research. Results: Primary outcomes include crude, age-specific and/or age-standardized incidence of stroke. Secondary outcomes include overall stroke rates, incidence rate ratio and case-fatality. Results will be synthesized in figures and tables, describing data sources, populations, methodology, and findings. Within-population meta-analysis will be performed if, and where, methodologically sound and comparable studies allow this. Conclusion: We will undertake the first systematic review assessing disparities in stroke incidence in Indigenous populations of developed countries. Data outputs will be disseminated to relevant Indigenous stakeholders to inform public health and policy research., 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. The Handling Editor declared a past co-authorship with two of the authors, AD and MP., (Copyright © 2021 Balabanski, Dos Santos, Woods, Thrift, Kleinig, Suchy-Dicey, Siri, Boden-Albala, Krishnamurthi, Feigin, Buchwald, Ranta, Mienna, Zavaleta, Churilov, Burchill, Zion, Longstreth, Tirschwell, Anand, Parsons, Brown, Warne, Harwood and Katzenellenbogen.)

Background: Sexual dysfunction affects at least one half of patients after a stroke. Problems related to sexual function are rarely assessed or addressed by physicians., Objective: To determine the frequency and factors associated with sexual dysfunction among stroke survivors and self-reported barriers of physicians to discuss sexual dysfunction during regular consultation., Methods: We administered a questionnaire to a cross-sectional sample of stroke survivors to assess the frequency and factors associated with sexual dysfunction and the aspects of sexuality most commonly affected by stroke in a reference hospital in Peru. A qualitative approach was used to determine the willingness to address sexual issues and related barriers among neurology physicians participating in the study., Results: Among 150 patients, sexual dysfunction was identified in 89 (59%). Only 10% self-reported their sexual function as optimal. Markedly decreased frequency of sexual encounters (49%) and markedly decreased sexual desire (33%) were the aspects of sexual function most commonly reported by patients after a stroke. Fear of having a new stroke [OR:3.2, 95% CI (1.5-6.3)], depression [OR:2.1, 95% CI (1.0-4.3)], and self-perception of having impaired motor function [OR:2.5, 95% CI (1.2-5.0)] were significantly associated with sexual dysfunction. In the qualitative assessment of physicians (N = 15), when asked how often they addressed sexual aspects during regular consultation with a stroke survivor, none answered "very often", and only 8 (51%) answered "sometimes". At the end of the study, 10 (66%) physicians verbalized the perception that addressing this issue encouraged their patents to be more open to personal concerns and prompted a stronger doctor-patient relationship., Conclusion: Sexual dysfunction affected more than a half of stroke survivors, and was significantly associated with depression, fear of having a new stroke, and with the self-perception of impaired motor function. Addressing sexual issues during the regular consult by physicians was infrequent. Barriers reported by physicians included limited time during regular consultation and the belief that this issue should be addressed under the scope of other specialties., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Most studies of stroke in people living with HIV (PLWH) do not use verified stroke diagnoses, are small, and/or do not differentiate stroke types and subtypes., Setting: CNICS, a U.S. multisite clinical cohort of PLWH in care., Methods: We implemented a centralized adjudication stroke protocol to identify stroke type, subtype, and precipitating conditions identified as direct causes including infection and illicit drug use in a large diverse HIV cohort., Results: Among 26,514 PLWH, there were 401 strokes, 75% of which were ischemic. Precipitating factors such as sepsis or same-day cocaine use were identified in 40% of ischemic strokes. Those with precipitating factors were younger, had more severe HIV disease, and fewer traditional stroke risk factors such as diabetes and hypertension. Ischemic stroke subtypes included cardioembolic (20%), large vessel atherosclerosis (13%), and small vessel (24%) ischemic strokes. Individuals with small vessel strokes were older, were more likely to have a higher current CD4 cell count than those with cardioembolic strokes and had the highest mean blood pressure of the ischemic stroke subtypes., Conclusion: Ischemic stroke, particularly small vessel and cardioembolic subtypes, were the most common strokes among PLWH. Traditional and HIV-related risk factors differed by stroke type/subtype. Precipitating factors including infections and drug use were common. These results suggest that there may be different biological phenomena occurring among PLWH and that understanding HIV-related and traditional risk factors and in particular precipitating factors for each type/subtype may be key to understanding, and therefore preventing, strokes among PLWH., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To evaluate the effect of intensive rehabilitation on the modified Rankin Scale (mRS), a measure of activities limitation commonly used in acute stroke studies, and to define the specific changes in body structure/function (motor impairment) most related to mRS gains., Methods: Patients were enrolled >90 days poststroke. Each was evaluated before and 30 days after a 6-week course of daily rehabilitation targeting the arm. Activity gains, measured using the mRS, were examined and compared to body structure/function gains, measured using the Fugl-Meyer (FM) motor scale. Additional analyses examined whether activity gains were more strongly related to specific body structure/function gains., Results: At baseline (160 ± 48 days poststroke), patients (n = 77) had median mRS score of 3 (interquartile range, 2-3), decreasing to 2 [2-3] 30 days posttherapy ( p < 0.0001). Similarly, the proportion of patients with mRS score ≤2 increased from 46.8% at baseline to 66.2% at 30 days posttherapy ( p = 0.015). These findings were accounted for by the mRS score decreasing in 24 (31.2%) patients. Patients with a treatment-related mRS score improvement, compared to those without, had similar overall motor gains (change in total FM score, p = 0.63). In exploratory analysis, improvement in several specific motor impairments, such as finger flexion and wrist circumduction, was significantly associated with higher likelihood of mRS decrease., Conclusions: Intensive arm motor therapy is associated with improved mRS in a substantial fraction (31.2%) of patients. Exploratory analysis suggests specific motor impairments that might underlie this finding and may be optimal targets for rehabilitation therapies that aim to reduce activities limitations., Clinical Trial: Clinicaltrials.gov identifier: NCT02360488., Classification of Evidence: This study provides Class III evidence that for patients >90 days poststroke with persistent arm motor deficits, intensive arm motor therapy improved mRS in a substantial fraction (31.2%) of patients., (© 2021 American Academy of Neurology.)

Competing Interests: Disclosures: Dr. Mahr serves as consultant for Medtronic and Abbott Laboratories (Thoratec). The other authors have no conflicts of interest to report.

Introduction: Patients with stroke-like symptoms may be underutilising emergency medical services and avoiding hospitalisation during the COVID-19 pandemic. We investigated a decline in admissions for stroke and transient ischaemic attack (TIA) and emergency department (ED) stroke alert activations., Methods: We retrospectively compiled total weekly hospital admissions for stroke and TIA between 31 December 2018 and 21 April 2019 versus 30 December 2019 and 19 April 2020 at five US tertiary academic comprehensive stroke centres in cities with early COVID-19 outbreaks in Boston, New York City, Providence and Seattle. We collected available data on ED stroke alerts, stroke severity using the National Institutes of Health Stroke Scale (NIHSS) and time from symptom onset to hospital arrival., Results: Compared with 31 December 2018 to 21 April 2019, a decline in stroke/TIA admissions and ED stroke alerts occurred during 30 December 2019 to 19 April 2020 ( p trend <0.001 for each). The declines coincided with state stay-at-home recommendations in late March. The greatest decline in hospital admissions was observed between 23 March and 19 April 2020, with a 31% decline compared with the corresponding weeks in 2019. Three of the five centres with 2019 and 2020 stroke alert data had a 46% decline in ED stroke alerts in late March and April 2020, compared with 2019. Median baseline NIHSS during these 4 weeks was 10 in 2020 and 7 in 2019. There was no difference in time from symptom onset to hospital arrival., Conclusion: At these five large academic US hospitals, admissions for stroke and TIA declined during the COVID-19 pandemic. There was a trend for fewer ED stroke alerts at three of the five centres with available 2019 and 2020 data. Acute stroke therapies are time-sensitive, so decreased healthcare access or utilisation may lead to more disabling or fatal strokes, or more severe non-neurological complications related to stroke. Our findings underscore the indirect effects of this pandemic. Public health officials, hospital systems and healthcare providers must continue to encourage patients with stroke to seek acute care during this crisis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The coronavirus 2019 (COVID-19) pandemic requires drastic changes in allocation of resources, which can affect the delivery of stroke care, and many providers are seeking guidance. As caregivers, we are guided by 3 distinct principles that will occasionally conflict during the pandemic: (1) we must ensure the best care for those stricken with COVID-19, (2) we must provide excellent care and advocacy for patients with cerebrovascular disease and their families, and (3) we must advocate for the safety of health care personnel managing patients with stroke, with particular attention to those most vulnerable, including trainees. This descriptive review by a diverse group of experts in stroke care aims to provide advice by specifically addressing the potential impact of this pandemic on (1) the quality of the stroke care delivered, (2) ethical considerations in stroke care, (3) safety and logistic issues for providers of patients with stroke, and (4) stroke research. Our recommendations on these issues represent our best opinions given the available information, but are subject to revision as the situation related to the COVID-19 pandemic continues to evolve. We expect that ongoing emergent research will offer additional insights that will provide evidence that could prompt the modification or removal of some of these recommendations., (© 2020 American Academy of Neurology.)

Background: The availability of intravenous tissue plasminogen activator (IV-tPA) remains limited worldwide, especially in low-income countries, where the burden of disability due to ischemic stroke is the highest., Aims: To evaluate outcomes and safety of IV-tPA at the only Peruvian reference institute for neurologic diseases., Methods: We conducted a prospective, observational study of stroke patients who received IV-tPA between 2009 and 2016. We assessed characteristics associated with good outcome (modified Rankine scale 0-2) at 3 months using a multivariate regression model; and factors correlated with clinical improvement (delta National Institute of Health Stroke Scale (NIHSS)) using linear regression., Results: Only 1.98% (39/1,1962) of patients presenting with ischemic stroke received IV-tPA. Nearly half (41%) were younger than 60 years, 56.4 % were men, and most strokes were cardioembolic (46.2%). The majority (64.1%) were treated within 3-4.5 hours. The median NIHSS on admission and discharge was 9 and 4, respectively; 42.1% of patients had an mRS of 0-1 at 3 months. Three patients (7.7%) developed hemorrhagic conversion, and 1 patient died (2.6%). Patients with good outcomes had lower pretreatment systolic blood pressure (138.9 versus 158.1 mm Hg, P < .007), fewer complications during hospitalization (5 versus 9 events, P < .001), shorter hospital stay (14 versus 21 days, P < .03) and, paradoxically, longer last known well -to-door times (148.3 versus 105 minutes, P < .0022). Clinical improvement was associated with shorter door-to-tPA times and obesity., Conclusions: Our findings indicate that IV-tPA has similar safety and outcomes compared to developed countries. All internal metrics (door-to-tPA, door-to-CT, and CT-to-tPA time) improved over time, highlighting areas for future implementation science studies to further expedite the administration of IV-tPA., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Observational studies point to an inverse correlation between low-density lipoprotein (LDL) cholesterol levels and risk of intracerebral hemorrhage (ICH), but it remains unclear whether this association is causal. We tested the hypothesis that genetically elevated LDL is associated with reduced risk of ICH., Methods: We constructed one polygenic risk score (PRS) per lipid trait (total cholesterol, LDL, high-density lipoprotein [HDL], and triglycerides) using independent genomewide significant single nucleotide polymorphisms (SNPs) for each trait. We used data from 316,428 individuals enrolled in the UK Biobank to estimate the effect of each PRS on its corresponding trait, and data from 1,286 ICH cases and 1,261 matched controls to estimate the effect of each PRS on ICH risk. We used these estimates to conduct Mendelian Randomization (MR) analyses., Results: We identified 410, 339, 393, and 317 lipid-related SNPs for total cholesterol, LDL, HDL, and triglycerides, respectively. All four PRSs were strongly associated with their corresponding trait (all p < 1.00 × 10 -100 ). While one SD increase in the PRSs for total cholesterol (odds ratio [OR] = 0.92; 95% confidence interval [CI] = 0.85-0.99; p = 0.03) and LDL cholesterol (OR = 0.88; 95% CI = 0.81-0.95; p = 0.002) were inversely associated with ICH risk, no significant associations were found for HDL and triglycerides (both p > 0.05). MR analyses indicated that 1mmol/L (38.67mg/dL) increase of genetically instrumented total and LDL cholesterol were associated with 23% (OR = 0.77; 95% CI = 0.65-0.98; p = 0.03) and 41% lower risks of ICH (OR = 0.59; 95% CI = 0.42-0.82; p = 0.002), respectively., Interpretation: Genetically elevated LDL levels were associated with lower risk of ICH, providing support for a potential causal role of LDL cholesterol in ICH. ANN NEUROL 2020 ANN NEUROL 2020;88:56-66., (© 2020 American Neurological Association.)

Background: The American Heart Association, in conjunction with the National Institutes of Health, annually reports on the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs)., Methods: The American Heart Association, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update. The 2020 Statistical Update is the product of a full year's worth of effort by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year's edition includes data on the monitoring and benefits of cardiovascular health in the population, metrics to assess and monitor healthy diets, an enhanced focus on social determinants of health, a focus on the global burden of cardiovascular disease, and further evidence-based approaches to changing behaviors, implementation strategies, and implications of the American Heart Association's 2020 Impact Goals., Results: Each of the 26 chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics., Conclusions: The Statistical Update represents a critical resource for the lay public, policy makers, media professionals, clinicians, healthcare administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.