Transcarotid Arterial Revascularization of Symptomatic Internal Carotid Artery Disease: A Systematic Review and Study-Level Meta-Analysis.

BACKGROUND: Transcarotid artery revascularization (TCAR) is an interventional therapy for symptomatic internal carotid artery disease. Currently, the utilization of TCAR is contentious due to limited evidence. In this study, we evaluate the safety and efficacy of TCAR in patients with symptomatic internal carotid artery disease compared with carotid endarterectomy (CEA) and carotid artery stenting (CAS). METHODS: A systematic review was conducted, spanning from January 2000 to February 2023, encompassing studies that used TCAR for the treatment of symptomatic internal carotid artery disease. The primary outcomes included a 30-day stroke or transient ischemic attack, myocardial infarction, and mortality. Secondary outcomes comprised cranial nerve injury and major bleeding. Pooled odds ratios (ORs) for each outcome were calculated to compare TCAR with CEA and CAS. Furthermore, subgroup analyses were performed based on age and degree of stenosis. In addition, a sensitivity analysis was conducted by excluding the vascular quality initiative registry population. RESULTS: A total of 7 studies involving 24 246 patients were analyzed. Within this patient cohort, 4771 individuals underwent TCAR, 12 350 underwent CEA, and 7125 patients underwent CAS. Compared with CAS, TCAR was associated with a similar rate of stroke or transient ischemic attack (OR, 0.77 [95% CI, 0.33-1.82]) and myocardial infarction (OR, 1.29 [95% CI, 0.83-2.01]) but lower mortality (OR, 0.42 [95% CI, 0.22-0.81]). Compared with CEA, TCAR was associated with a higher rate of stroke or transient ischemic attack (OR, 1.26 [95% CI, 1.03-1.54]) but similar rates of myocardial infarction (OR, 0.9 [95% CI, 0.64-1.38]) and mortality (OR, 1.35 [95% CI, 0.87-2.10]). CONCLUSIONS: Although CEA has traditionally been considered superior to stenting for symptomatic carotid stenosis, TCAR may have some advantages over CAS. Prospective randomized trials comparing the 3 modalities are needed.

Advances in Recurrent Stroke Prevention: Focus on Antithrombotic Therapies.

The past decade has seen significant advances in stroke prevention. These advances include new antithrombotic agents, new options for dyslipidemia treatment, and novel techniques for surgical stroke prevention. In addition, there is greater recognition of the benefits of multifaceted interventions, including the role of physical activity and dietary modification. Despite these advances, the aging of the population and the high prevalence of key vascular risk factors pose challenges to reducing the burden of stroke. Using a cause-based framework, current approaches to prevention of cardioembolic, cryptogenic, atherosclerotic, and small vessel disease stroke are outlined in this paper. Special emphasis is given to recent trials of antithrombotic agents, including studies that have tested combination treatments and responses according to genetic factors.

Interleukin-6 Predicts Carotid Plaque Severity, Vulnerability, and Progression.

BACKGROUND: IL-6 (interleukin-6) has important roles in atherosclerosis pathophysiology. To determine if anti-IL-6 therapy warrants evaluation as an adjuvant stroke prevention strategy in patients with carotid atherosclerosis, we tested whether circulating IL-6 levels predict carotid plaque severity, vulnerability, and progression in the prospective population-based CHS (Cardiovascular Health Study). METHODS: Duplex carotid ultrasound was performed at baseline and 5 years. Baseline plaque severity was scored 0 to 5 based on North American Symptomatic Carotid Endarterectomy Trial grade of stenosis. Plaque vulnerability at baseline was the presence of markedly irregular, ulcerated, or echolucent plaques. Plaque progression at 5 years was a ≥1 point increase in stenosis severity. The relationship of baseline plasma IL-6 levels with plaque characteristics was modeled using multivariable linear (severity) or logistic (vulnerability and progression) regression. Risk factors of atherosclerosis were included as independent variables. Stepwise backward elimination was used with P>0.05 for variable removal. To assess model stability, we computed the E-value or minimum strength of association (odds ratio scale) that unmeasured confounders must have with log IL-6 and the outcome to suppress the association. We performed internal validation with 100 bootstrap samples. RESULTS: There were 4334 participants with complete data (58.9% women, mean age: 72.7±5.1 years), including 1267 (29.2%) with vulnerable plaque and 1474 (34.0%) with plaque progression. Log IL-6 predicted plaque severity (ß=0.09, P=1.3×10-3), vulnerability (OR, 1.21 [95% CI, 1.05-1.40]; P=7.4×10-3, E-value=1.71), and progression (OR, 1.44 [95% CI, 1.23-1.69], P=9.1×10-6, E-value 2.24). In participants with >50% predicted probability of progression, mean log IL-6 was 0.54 corresponding to 2.0 pg/mL. Dichotomizing IL-6 levels did not affect the performance of prediction models. CONCLUSIONS: Circulating IL-6 predicts carotid plaque severity, vulnerability, and progression. The 2.0 pg/mL cutoff could facilitate the selection of individuals that would benefit from anti-IL-6 drugs for stroke prevention.

Sex discrepancies in the population incidence of stroke and hemorrhage related to atrial fibrillation or flutter.

INTRODUCTION: Atrial fibrillation or flutter (AF) is a well-known risk factor for ischemic stroke. While female sex has been associated with higher stroke risk among AF patients, overall sex-specific real-world burdens of AF-related strokes and hemorrhages are unknown. METHODS: The 2016-2020 National Inpatient Sample was queried for hospitalizations, morbidity, and mortality due to AF-related ischemic strokes and bleeds. Patient demographic information, vascular risk factors, comorbidities, and stroke characteristics were extracted using ICD-10 codes. Overall incidences were calculated using total population estimates provided by the United States Census Bureau, and relative risk was calculated by comparing annual incidences between men and women. RESULTS: 2,420,870 ischemic stroke hospitalizations were identified; 542,635 (22.4%) were associated with AF. Overall, women had similar risk of hospitalization due to AF-related ischemic strokes compared to men; however, women had a higher risk of morbidity and mortality (RR 1.13 and 1.17, respectively; both p<0.001). In contrast, women had lower incidences of hospitalization, morbidity, and mortality due to AF-related bleeds (RR 0.82, 0.94, and 0.74, respectively; all p<0.001). Among patients with AF-related ischemic strokes, women had lower rates of anticoagulation use, higher rates of large vessel occlusion, and higher stroke severity (all p<0.001). These trends persisted among patients 80 years or older (all p<0.001). CONCLUSION: Women in the United States have higher incidences of morbidity and mortality from AF-related ischemic strokes than men. Future studies should investigate strategies to reduce morbidity and mortality due to AF-related strokes in women.

Apixaban to Prevent Recurrence After Cryptogenic Stroke in Patients With Atrial Cardiopathy: The ARCADIA Randomized Clinical Trial.

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.

The impact of sex on stroke care: From epidemiology to outcome.

BACKGROUND: Carotid stenosis and atrial fibrillation are key risk factors for development of hemispheric strokes. In this review we aim to identify sex-specific differences in the pathophysiology and treatment of these risk factors and areas for future study. KEY FINDINGS: Women are underrepresented in research studies of stroke in patients with carotid disease and atrial fibrillation. However, key differences have been found between men and women that suggest that the development of carotid disease and atrial fibrillation occur at later stages of life and are associated with higher severity of stroke. Some treatments, including surgical treatment, seem to have different rates of efficacy and women and women are at higher risk of surgical complications. This suggests that treatment recommendations may need to be sex specific. CONCLUSION: Efforts should be made to address research and treatment gaps in women with stroke risk factors. This may lead to the development of sex-specific recommendations for stroke prevention and treatment.

The BAND score: A simple model for upfront prediction of poor outcomes despite successful stroke thrombectomy.

BACKGROUND: While endovascular thrombectomy (EVT) is beneficial for patients with acute large vessel occlusion ischemic strokes, a significant portion of patients still do poorly despite successful recanalization. Identifying patients at high risk for poor outcomes can be helpful for future clinical trial design and optimizing acute stroke triage. METHODS: Consecutive EVT patients were identified from 2016 to 2021 at a Comprehensive Stroke Center, and clinical information was recorded. Poor outcome was defined as a 90-day modified Rankin Scale (mRS) of 4 or greater despite achieving a modified thrombolysis in cerebral infarction (mTICI) score of 2b or greater. Multivariable regression analyses were used to identify risk factors for poor outcomes, and a scoring system was constructed. RESULTS: 483 patients with successful recanalization were identified. From a randomly selected training cohort (n = 357), the 10-point BAND score was constructed from independent risk factors for poor outcomes: baseline disability (1 point: baseline mRS ≥ 2), age (1 point: 60-69 years, 2 points: 70-79 years, 3 points: 80-84 years, 4 points: 85 years or older), NIHSS (2 points: 13-17, 3 points: 18-22, and 4 points: ≥ 23), and delay from last known normal (1 point: ≥ 6 h). The BAND score was significantly associated with rates of poor outcomes (p < 0.001), and it achieved an area under the receiver-operating characteristic curve (AUC) of 0.80 (95 %CI 0.76-0.85) in our training cohort and 0.78 (95 %CI 0.70-0.86) in our validation cohort (n = 126). Overall, the BAND score had a significantly higher AUC value than the widely validated THRIVE score and the THRIVE-EVT calculation (p = 0.001 and 0.029, respectively). Among patients with high BAND scores (7 or higher), 88.2 % had poor outcomes. CONCLUSION: The BAND score is a simple tool to predict poor outcomes despite successful recanalization. Future studies are needed to confirm the BAND score's external validity.

Intensive Blood Pressure Control After Mechanical Thrombectomy for Acute Ischemic Stroke.

Optimal blood pressure targets following successful mechanical thrombectomy remain uncertain. While some observational studies suggest that the relationship between blood pressure and outcomes follows a U-shaped curve, others suggest a linear relationship where lower is better. The recent BP-TARGET study (Blood Pressure Target in Acute Stroke to Reduce Hemorrhage After Endovascular Therapy) did not find a benefit to intensive blood pressure lowering regarding the risk of symptomatic intracranial hemorrhage, but it was not sufficiently powered to detect differences in functional outcomes. On its heels arrived the ENCHANTED2 (Enhanced Control of Hypertension and Thrombectomy Stroke Study)/mechanical thrombectomy trial, the first trial of intensive blood pressure lowering in patients with hypertension following successful mechanical thrombectomy powered to detect a difference in functional outcomes. The trial randomized patients to either a systolic blood pressure less than 120 or 140 to 180 mm Hg. The trial was terminated early due to safety concerns in the more intensive blood pressure-lowering group. In this emerging therapy critique, we explore concerns regarding the generalizability of ENCHANTED2/mechanical thrombectomy, including the high prevalence of intracranial atherosclerosis in the studied population. We survey mechanisms for poor outcomes in patients who receive overly aggressive blood pressure reduction following successful thrombectomy, such as poststroke autoregulatory compromise and persistent microcirculatory hypoperfusion. Finally, we advocate for a more moderate approach, pending further research.

Associations of Osteoarthritis With Thrombectomy Utilization and Outcomes for Large Vessel Acute Ischemic Stroke.

BACKGROUND: Osteoarthritis and other musculoskeletal disorders are the leading causes of disability in the United States. While osteoarthritis is not a direct risk factor for stroke, osteoarthritis may impact patient selection for endovascular thrombectomy (EVT) due to prestroke disability. This study investigates associations of osteoarthritis with EVT utilization and outcomes. METHODS: This was a large-scale cross-sectional study of the 2016 to 2019 National Inpatient Sample database. Adult patients with anterior large vessel ischemic strokes were identified. Patient demographics, stroke risk factors, stroke etiology, presence of osteoarthritis, medical comorbidities, EVT, intravenous thrombolysis treatments, and discharge destinations were recorded. Primary outcome was the rate of EVT treatment. Secondary outcomes include rates of discharge to home and in-hospital mortality. Propensity score matching and multivariable logistic regression models were used to account for possible confounders. RESULTS: Two hundred fifty-two thousand five hundred five patients were identified, of whom 8.5% (21 500 patients) had osteoarthritis. After propensity score matching for 32 clinical variables, osteoarthritis patients were found to be 17.3% less likely to receive EVT than non-osteoarthritis patients (14.4% versus 17.3%, respectively; P<0.001). In multivariable logistic regression analysis, osteoarthritis was associated with 22.6% lower odds of receiving EVT (OR, 0.77 [95% CI, 0.70-0.86]; P<0.001), an effect size larger than any medical comorbidity captured in this study other than dementia and nonstroke neurological disease. Among those treated with EVT, multivariable logistic regression models showed that osteoarthritis was not associated with different odds of being discharged home (OR, 0.99 [95% CI, 0.81-1.21]; P=0.93); however, osteoarthritis was marginally associated with lower odds of in-hospital mortality (OR, 0.74 [95% CI, 0.54-1.01]; P=0.054). CONCLUSIONS: Large vessel ischemic stroke patients with osteoarthritis were significantly less likely to receive EVT therapy despite similar post-EVT outcomes. These results warrant further investigation and prompt a critical review of current patient selection practices for stroke EVT therapy, specifically for patients with baseline disability due to musculoskeletal conditions such as osteoarthritis.

Polygenic Risk Score for Cardiovascular Diseases in Artificial Intelligence Paradigm: A Review.

Cardiovascular disease (CVD) related mortality and morbidity heavily strain society. The relationship between external risk factors and our genetics have not been well established. It is widely acknowledged that environmental influence and individual behaviours play a significant role in CVD vulnerability, leading to the development of polygenic risk scores (PRS). We employed the PRISMA search method to locate pertinent research and literature to extensively review artificial intelligence (AI)-based PRS models for CVD risk prediction. Furthermore, we analyzed and compared conventional vs. AI-based solutions for PRS. We summarized the recent advances in our understanding of the use of AI-based PRS for risk prediction of CVD. Our study proposes three hypotheses: i) Multiple genetic variations and risk factors can be incorporated into AI-based PRS to improve the accuracy of CVD risk predicting. ii) AI-based PRS for CVD circumvents the drawbacks of conventional PRS calculators by incorporating a larger variety of genetic and non-genetic components, allowing for more precise and individualised risk estimations. iii) Using AI approaches, it is possible to significantly reduce the dimensionality of huge genomic datasets, resulting in more accurate and effective disease risk prediction models. Our study highlighted that the AI-PRS model outperformed traditional PRS calculators in predicting CVD risk. Furthermore, using AI-based methods to calculate PRS may increase the precision of risk predictions for CVD and have significant ramifications for individualized prevention and treatment plans.

Atrial Fibrillation Detected After Stroke and Transient Ischemic Attack: A Novel Clinical Concept Challenging Current Views.

Atrial fibrillation (AF) can be newly detected in approximately one-fourth of patients with ischemic stroke and transient ischemic attack without previously recognized AF. We present updated evidence supporting that AF detected after stroke or transient ischemic attack (AFDAS) may be a distinct clinical entity from AF known before stroke occurrence (known atrial fibrillation). Data suggest that AFDAS can arise from the interplay of cardiogenic and neurogenic forces. The embolic risk of AFDAS can be understood as a gradient defined by the prevalence of vascular comorbidities, the burden of AF, neurogenic autonomic changes, and the severity of atrial cardiopathy. The balance of existing data indicates that AFDAS has a lower prevalence of cardiovascular comorbidities, a lower degree of cardiac abnormalities than known atrial fibrillation, a high proportion (52%) of very brief (<30 seconds) AF paroxysms, and is more frequently associated with insular brain infarction. These distinctive features of AFDAS may explain its recently observed lower associated risk of stroke than known atrial fibrillation. We present an updated ad-hoc meta-analysis of randomized clinical trials in which the association between prolonged cardiac monitoring and reduced risk of ischemic stroke was nonsignificant (incidence rate ratio, 0.90 [95% CI, 0.71-1.15]). These findings highlight that larger and sufficiently powered randomized controlled trials of prolonged cardiac monitoring assessing the risk of stroke recurrence are needed. Meanwhile, we call for further research on AFDAS and stroke recurrence, and a tailored approach when using prolonged cardiac monitoring after ischemic stroke or transient ischemic attack, focusing on patients at higher risk of AFDAS and, more importantly, at higher risk of cardiac embolism.

Contemporary Incidence and Burden of Cerebral Venous Sinus Thrombosis in Children of the United States.

BACKGROUND: The incidence of cerebral venous thrombosis (CVT) in children of the United States is unknown, and it is uncertain how the burden of CVT hospitalizations in children changed over the last decade. METHODS: We conducted a retrospective cohort study using the State Inpatient Database and Kid's inpatient database. All new CVT cases in children (0-19 years) in the New York 2006 to 2018 State Inpatient Database (n=705), and all cases of CVT in the entire US contained in the 2006 to 2019 Kid's inpatient database (weighted n=6115) were identified using validated International Classification of Diseases (ICDs) codes. Incident counts were combined with census data to compute incidence. Between-group differences in incidence were tested using 2-proportions Z-test, and Joinpoint regression was used to trend incidence over time. RESULTS: Across the study period, 48.2% of all incident CVT cases and 44.6% of all CVT admissions nationally were in girls. Of all incident cases, 27.2% were infants and 65.8% of these infants were neonates. Average incidence across the study period was (1.1/100 000/year, SE:0.04) but incidence in infants (6.4/100 000/year) was at least 5 times the incidence in other age groups (1-4 years: 0.7/100 000/year, 15-19 years: 1.2/100 000/year). Incidence and national burden of CVT admissions was higher in girls in adolescents 15 to 19 years, but overall burden was higher in boys in other age groups. Age- and sex-standardized CVT incidence increased by 3.8% annually (95% CI, 0.2%-7.6%), while the overall burden of admissions increased by 4.9% annually (95% CI, 3.6%-6.2%). CONCLUSIONS: CVT incidence in New York and national burden of CVT increased significantly over the last decade.

Black-White Differences in Ischemic Stroke Risk Factor Burden in Young Adults.

BACKGROUND AND PURPOSE: Although the US Black population has a higher incidence of stroke compared with the US White population, few studies have addressed Black-White differences in the contribution of vascular risk factors to the population burden of ischemic stroke in young adults. METHODS: A population-based case-control study of early-onset ischemic stroke, ages 15 to 49 years, was conducted in the Baltimore-Washington DC region between 1992 and 2007. Risk factor data was obtained by in-person interview in both cases and controls. The prevalence, odds ratio, and population-attributable risk percent (PAR%) of smoking, diabetes, and hypertension was determined among Black patients and White patients, stratified by sex. RESULTS: The study included 1044 cases and 1099 controls. Of the cases, 47% were Black patients, 54% were men, and the mean (±SD) age was 41.0 (±6.8) years. For smoking, the population-attributable risk percent were White men 19.7%, White women 32.5%, Black men 10.1%, and Black women 23.8%. For diabetes, the population-attributable risk percent were White men 10.5%, White women 7.4%, Black men 17.2%, and Black women 13.4%. For hypertension, the population-attributable risk percent were White men 17.2%, White women 19.3%, Black men 45.8%, and Black women 26.4%. CONCLUSIONS: Modifiable vascular risk factors account for a large proportion of ischemic stroke in young adults. Cigarette smoking was the strongest contributor to stroke among White patients while hypertension was the strongest contributor to stroke among Black patients. These results support early primary prevention efforts focused on smoking cessation and hypertension detection and treatment.

Black-white Differences in Left Ventricular Hypertrophy Rates Among Young Adults with Ischemic Stroke.

OBJECTIVES: Few studies have addressed Black-White differences in left ventricular hypertrophy (LVH) in young stroke patients without a history of hypertension. METHODS: A case-only cross-sectional analysis performed in 2019 of data from the Stroke Prevention in Young Adults Study, a population-based case-control study of ischemic stroke patients ages 15-49. The main outcomes were hypertension indicators at the time of stroke hospitalization: self-reported history of hypertension, LVH by echocardiography (Echo-LVH) and LVH by electrocardiogram (ECG-LVH). The prevalence of Echo-LVH was further determined in those with and without a history of hypertension. Adjusted odds ratios and 95% confidence intervals comparing blacks and whites were calculated by logistic regression. RESULTS: The study population included 1028 early-onset ischemic stroke patients, 48% Black cases, 54% men, median age 43 years (interquartile range, 38-46 years). Overall, the prevalence of hypertension history, Echo-LVH and ECG-LVH were 41.3%, 34.1% and 17.5%, respectively. Each of the hypertension indicators were more frequent in men than in women and in Black cases than in White cases. Black patients without a history of hypertension had higher rates of Echo-LVH than their white counterparts, 40.3% vs 27.7% (age and obesity adjusted OR 1.8; 95% CI 1.02-3.4) among men and 20.9% vs 7.6% (adjusted OR 2.7; 95% CI 1.2-6.2) among women. CONCLUSIONS: LVH was common in young patients with ischemic stroke, regardless of self-reported history of hypertension. These findings emphasize the need for earlier screening and more effective treatment of hypertension in young adults, particularly in the Black population.

Trends in age and sex-specific prevalence of cancer and cancer subtypes in acute ischemic stroke from 2007-2019.

OBJECTIVE: To describe age and sex-specific prevalence of cancer in acute ischemic stroke (AIS) hospitalizations in the United States over the last decade. METHODS: We conducted a retrospective serial cross-sectional study using all primary AIS discharges (weighted n=5,748,358) with and without cancer in the 2007-2019 National Inpatient Sample. Admissions with primary central nervous system cancers were excluded. Joinpoint regression was used to compute the average annualized percentage change (AAPC) in cancer prevalence over time. RESULTS: Across the study period, 12.7% of AIS admissions had previous/active cancer, while 4.4% had active cancer. Of these, 18.8% were hematologic cancers, 47.2% were solid cancers without metastasis and 34.0% were metastatic cancers of any type. Age-adjusted active cancer prevalence differed by sex (males:4.8%; females:4.0%) and increased with age up to age 70-79 years (30-39 years 1.4%; 70-79 years:5.7%). Amongst cancer admissions, lung (18.7%) and prostate (17.8%) were the most common solid cancers in men, while lung (19.6%) and breast (13.7%) were the most prevalent in women. Active cancer prevalence increased over time (AAPC 1.7%, p<0.05) but the pace of increase was significantly faster in women (AAPC 2.8%) compared to men (AAPC 1.1%) (p-comparison =0.003). Fastest pace of increased prevalence was seen for genitourinary cancers in women and for gastrointestinal cancers in both sexes. Genitourinary cancers in men declined over time (AAPC -2.5%, p<0.05). Lung cancer prevalence increased in women (AAPC 1.8%, p<0.05) but remained constant in men. Prevalence of head/neck, skin/bone, gastrointestinal, hematological and metastatic cancers increased over time at similar pace in both sexes. CONCLUSION: Prevalence of cancer in AIS admissions increased in the US over the last decade but the pace of this increase was faster in women compared to men. Gastrointestinal cancers in both sexes and genitourinary cancers in women are increasing at the fastest pace. Additional studies are needed to determine whether this increase is from co-occurrence or causation of AIS by cancer.

Optimal Management of Asymptomatic Carotid Stenosis in 2021: The Jury is Still Out. An International, Multispecialty, Expert Review and Position Statement.

OBJECTIVES: The recommendations of international guidelines for the management of asymptomatic carotid stenosis (ACS) often vary considerably and extend from a conservative approach with risk factor modification and best medical treatment (BMT) alone, to a more aggressive approach with a carotid intervention plus BMT. The aim of the current multispecialty position statement is to reconcile the conflicting views on the topic. MATERIALS AND METHODS: A literature review was performed with a focus on data from recent studies. RESULTS: Several clinical and imaging high-risk features have been identified that are associated with an increased long-term ipsilateral ischemic stroke risk in patients with ACS. Such high-risk clinical/imaging features include intraplaque hemorrhage, impaired cerebrovascular reserve, carotid plaque echolucency/ulceration/ neovascularization, a lipid-rich necrotic core, a thin or ruptured fibrous cap, silent brain infarction, a contralateral transient ischemic attack/stroke episode, male patients < 75 years and microembolic signals on transcranial Doppler. There is growing evidence that 80-99% ACS indicate a higher stroke risk than 50-79% stenoses. CONCLUSIONS: Although aggressive risk factor control and BMT should be implemented in all ACS patients, several high-risk features that may increase the risk of a future cerebrovascular event are now documented. Consequently, some guidelines recommend a prophylactic carotid intervention in high-risk patients to prevent future cerebrovascular events. Until the results of the much-anticipated randomized controlled trials emerge, the jury is still out regarding the optimal management of ACS patients.

New Avenues for Optimal Treatment of Atrial Fibrillation and Stroke Prevention.

One in 3 individuals free of atrial fibrillation (AF) at index age 55 years is estimated to develop AF later in life. AF increases not only the risk of ischemic stroke but also of dementia, even in stroke-free patients. In this review, we address recent advances in the heart-brain interaction with focus on AF. Issues discussed are (1) the timing of direct oral anticoagulants start following an ischemic stroke; (2) the comparison of direct oral anticoagulants versus vitamin K antagonists in early secondary stroke prevention; (3) harms of bridging with heparin before direct oral anticoagulants; (4) importance of appropriate direct oral anticoagulants dosing; (5) screening for AF in high-risk populations, including the role of wearables; (6) left atrial appendage occlusion as an alternative to oral anticoagulation; (7) the role of early rhythm-control therapy; (8) effect of lifestyle interventions on AF; (9) AF as a risk factor for dementia. An interdisciplinary approach seems appropriate to address the complex challenges posed by AF.

Baseline Cognitive Impairment in Patients With Asymptomatic Carotid Stenosis in the CREST-2 Trial.

BACKGROUND AND PURPOSE: Studies of carotid artery disease have suggested that high-grade stenosis can affect cognition, even without stroke. The presence and degree of cognitive impairment in such patients have not been reported and compared with a demographically matched population-based cohort. METHODS: We studied cognition in 1000 consecutive CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial) patients, a treatment trial for asymptomatic carotid disease. Cognitive assessment was after randomization but before assigned treatment. The cognitive battery was developed in the general population REGARDS Study (Reasons for Geographic and Racial Differences in Stroke), involving Word List Learning Sum, Word List Recall, and Word List fluency for animal names and the letter F. The carotid stenosis patients were >45 years old with ≥70% asymptomatic carotid stenosis and no history of prevalent stroke. The distribution of cognitive performance for the patients was standardized, accounting for age, race, and education using performance from REGARDS, and after further adjustment for hypertension, diabetes, dyslipidemia, and smoking. Using the Wald Test, we tabulated the proportion of Z scores less than the anticipated deviate for the population-based cohort for representative percentiles. RESULTS: There were 786 baseline assessments. Mean age was 70 years, 58% men, and 52% right-sided stenosis. The overall Z score for patients was significantly below expected for higher percentiles (P<0.0001 for 50th, 75th, and 95th percentiles) and marginally below expected for the 25th percentile (P=0.015). Lower performance was attributed largely to Word List Recall (P<0.0001 for all percentiles) and for Word List Learning (50th, 75th, and 95th percentiles below expected, P≤0.01). The scores for left versus right carotid disease were similar. CONCLUSIONS: Baseline cognition of patients with severe carotid stenosis showed below normal cognition compared to the population-based cohort, controlling for demographic and cardiovascular risk factors. This cohort represents the largest group to date to demonstrate that poorer cognition, especially memory, in this disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02089217.

Marijuana Use and the Risk of Early Ischemic Stroke: The Stroke Prevention in Young Adults Study.

BACKGROUND AND PURPOSE: Few studies have examined the dose-response and temporal relationships between marijuana use and ischemic stroke while controlling for important confounders, including the amount of tobacco smoking. The purpose of our study was to address these knowledge gaps. METHODS: A population-based case-control study with 1090 cases and 1152 controls was used to investigate the relationship of marijuana use and early-onset ischemic stroke. Cases were first-ever ischemic stroke between the ages of 15 and 49 identified from 59 hospitals in the Baltimore-Washington region. Controls obtained by random digit dialing from the same geographic region were frequency-matched to cases by age, sex, region of residence and, except for the initial study phase, race. After excluding subjects with cocaine and other vasoactive substance use, the final study sample consisted of 751 cases and 813 controls. All participants underwent standardized interviews to characterize stroke risk factors and marijuana use. Unconditional logistic regression analysis was used to assess the relationships between marijuana use and risk of ischemic stroke, adjusting for age, sex, race, study phase, the amount of current tobacco smoking, current alcohol use, hypertension, and diabetes. RESULTS: After adjusting for other risk factors, including the amount of current tobacco smoking, marijuana use was not associated with ischemic stroke, regardless of the timing of use in relationship to the stroke, including ever use, use within 30 days, and use within 24 hours. There was a nonsignificant trend towards increased stroke risk among those who smoked marijuana at least once a week (odds ratio, 1.9 [95% CI, 0.8-4.9]). CONCLUSIONS: These analyses do not demonstrate an association between marijuana use and an increased risk of early-onset ischemic stroke, although statistical power was limited for assessing the association among very heavy users.

Ten-Year Trend in Age, Sex, and Racial Disparity in tPA (Alteplase) and Thrombectomy Use Following Stroke in the United States.

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, 1.20­1.35] 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, 1.01­1.03]) and MT (odds ratio, 1.08 [95% CI,1.05­1.12]) 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.