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Background: Clinical trial enrollment and completion is challenging, with nearly half of all trials not being completed or not completed on time. In 2014, the National Institutes of Health StrokeNet in collaboration with stroke epidemiologists from GCNKSS (Greater Cincinnati/Northern Kentucky Stroke Study) began providing proposed clinical trials with formal trial feasibility assessments. Herein, we describe the process of prospective feasibility analyses using epidemiological data that can be used to improve enrollment and increase the likelihood a trial is completed. Methods: In 2014, DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) trialists, National Institutes of Health StrokeNet, and stroke epidemiologists from GCNKSS collaborated to evaluate the initial inclusion/exclusion criteria for the DEFUSE 3 study. Trial criteria were discussed and an assessment was completed to evaluate the percent of the stroke population that might be eligible for the study. The DEFUSE 3 trial was stopped early with the publication of DAWN (Thrombectomy 6 to 24 Hours After Stroke With a Mismatch Between Deficit and Infarct), and the Wilcoxon rank-sum statistic was used to analyze whether the trial would have been stopped had the proposed changes not been made, following the DEFUSE 3 statistical analysis plan. Results: After initial epidemiological analysis, 2.4% of patients with acute stroke in the GCNKSS population would have been predicted to be eligible for the study. After discussion with primary investigators and modifying 4 key exclusion criteria (upper limit of age increased to 90 years, baseline modified Rankin Scale broadened to 0–2, time since last well expanded to 16 hours, and decreased lower limit of National Institutes of Health Stroke Scale score to Conclusions: Objectively assessing trial inclusion/exclusion criteria using a population-based resource in a collaborative and iterative process including epidemiologists can lead to improved recruitment and can increase the likelihood of successful trial completion.

Background: Though stroke risk factors such as substance use may vary with age, less is known about trends in substance use over time or about performance of toxicology screens in young adults with stroke. Methods: Using the Greater Cincinnati Northern Kentucky Stroke Study, a population-based study in a 5-county region comprising 1.3 million people, we reported the frequency of documented substance use (cocaine/marijuana/opiates/other) obtained from electronic medical record review, overall and by race/gender subgroups among physician-adjudicated stroke events (ischemic and hemorrhagic) in adults 20 to 54 years of age. Secondary analyses included heavy alcohol use and cigarette smoking. Data were reported for 5 one-year periods spanning 22 years (1993/1994–2015), and trends over time were tested. For 2015, to evaluate factors associated with performance of toxicology screens, multiple logistic regression was performed. Results: Overall, 2152 strokes were included: 74.5% were ischemic, mean age was 45.7±7.6, 50.0% were women, and 35.9% were Black. Substance use was documented in 4.4%, 10.4%, 19.2%, 24.0%, and 28.8% of cases in 1993/1994, 1999, 2005, 2010, and 2015, respectively ( P trend Conclusions: In a population-based study of young adults with stroke, documented substance use increased over time, and documentation of substance use was higher among Black compared with White individuals. Further work is needed to confirm race-based disparities and trends in substance use given the potential for bias in screening and documentation. Findings suggest a need for more standardized toxicology screening.

Background: TIAs serve as an opportunity to identify and modify risk factors and to prevent future events. Given known epidemiologic differences in strokes by race and sex, our objective was to investigate the rates of prior TIAs among those with incident ischemic stroke (IS) in the GCNKSS. Methods: We included all physician adjudicated, incident IS among adults age ≥20 years in the GCNKSS, a population-based stroke surveillance study in a 5-county region of southern Ohio/ northern Kentucky, in 2005, 2010, and 2015. We calculated the frequency of cases in which a TIA (sudden onset of focal neurologic symptoms lasting ≤ 24 hours) was documented in the 365 days prior to IS. Frequencies and proportions of prior TIA were compared by sex, race, and age, and location at which patients sought care for their TIA was described. Finally, multivariable logistic regression was performed to investigate demographic and clinical predictors of cases in which TIA preceded stroke; covariates were chosen a priori. Results: We included 5310 IS events; mean age was 69.7 (SD 14.8) years, 54.7% were female, and 20.4% were Black. A total of 351 patients (6.6%) had a documented TIA the year preceding their IS. Overall, 42.2% did not seek care for their TIA, 21.6% called 911 and/or came to the ED, 6.0% saw a PCP, and 6.6% sought other care. In 22.5% of cases, location of care was unknown. In adjusted results, older age, female sex, history of hypertension, and CAD were associated with having had a prior TIA, while Black race was not. NIHSS was inversely associated with prior TIA (Table). Prior TIAs were similar between study years. Conclusions: We conservatively estimate that ≥ 6% of patients with first-ever IS had a TIA in the preceding year, though underreporting is likely. Many patients did not report seeking care for the TIA, suggesting missed opportunities for risk factor modification. Further research is needed to understand the implications of sex and race differences in frequencies of prior TIA.

Background: Monitoring changes in ischemic stroke severity at the population level is important as changes in risk factors and clinical treatments could influence stroke severity. We describe trends in the distribution of NIHSS across 3 time periods in a population-based epidemiologic stroke study. Methods: In 2005, 2010, and 2015 all adult acute ischemic strokes occurring within the Greater Cincinnati area presenting to 15 hospitals were ascertained using discharge codes (ICD-9 433-436; IDC-10 I63-I68, G45-46). Following physician verification, confirmed ischemic stroke cases underwent chart abstraction including estimation of a retrospective (rNIHSS) score at presentation. Descriptive statistics (rNIHSS median, IQR) were generated by survey year, demographics, and medical history. Using a binary definition of stroke severity (median rNIHSS score &gt 4 versus &lt 4), multivariable logistic regression was used to estimate changes in stroke severity over time, adjusting for potential confounders. Random effects were used to account for multiple admissions occurring in the same subject. Results: The number of ischemic stroke admissions in the 2005, 2010, and 2015 surveys was 1778, 1903, and 1933, respectively (Table). The median (IQR) rNIHSS scores were 3 (2-7), 3 (1-6), and 2 (1-6) across the 3 surveys, respectively; the proportion of admissions with rNIHSS &gt 4 was 48%, 39% and 37%, respectively. After adjusting for demographics, medical history and pre-stroke function, compared to 2005, the odds ratio for more severe stroke was 0.69 (95% CI= 0.60-0.79, p=0.001) in 2010 and 0.63 (95% CI= 0.55-0.73, p=0.001) in 2015. Conclusions: In this population- based study there was a statistically significant change in the severity of ischemic stroke hospitalizations with increases in the proportion of milder strokes over time. Potential reasons for this change need to be explored but could include changes in risk factors, clinical treatments or diagnostic approach.

Introduction: Primary prevention reduces the burden of acute ischemic stroke (AIS), yet cerebrovascular risk factors (RF) remain underdiagnosed in certain populations. We aimed to identify predictors of undiagnosed RF among patients with cerebrovascular ischemic events in a large bi-racial population. Methods: Individuals 20 years and older with an incident TIA or AIS from the population-based Greater Cincinnati/Northern Kentucky 2015 stroke study period were screened for inclusion. We included all hospital ascertained, physician-verified cases of AIS and TIAs. Outpatient and ED-only cases were excluded. Abstracted medical record data included determination of newly diagnosed hypertension (HTN), diabetes mellitus (DM), hyperlipidemia (HLD) or atrial fibrillation (AF). Multivariable models were used to identify predictors for each undiagnosed RF. Model variables included: age, sex, race, insurance status and number of cerebrovascular RF (additionally including coronary artery disease and smoking). Results: A total of 1604 ischemic events were included (1485 stroke, 119 TIA) with 52.9% female; 22.4% Black; median age 70 (IQR 59, 82)). Only 6% (n=102) had no history of RF. The prevalence of each undiagnosed RF was: HTN 4.1%; HLD 7.9%; DM 3.1%; AF 3.2%. In unadjusted bivariate analysis, uninsured/unknown status was predictive of undiagnosed HTN (OR = 3.97, 95% CI 1.48, 10.68; p =.006) and HLD (OR=5.53, 95% CI 2.68, 11.4; p Table 1 ). No relationship was found with race. Conclusions: The most consistent predictor for an undiagnosed RF was absence of other RF and lack of insurance, both suggestive of suboptimal cardiovascular screening in this population. Further studies assessing known but undertreated RF and socioeconomic factors could be of benefit.

Background: Retinal artery occlusion (RAO) is a stroke equivalent that causes significant morbidity. There has been growing emphasis on urgent in-hospital evaluation of these patients, both to facilitate potential thrombolytic therapy and expedite workup; however, little is known regarding its effect on systems of care. We thus examined presenting characteristics and management of hospitalized RAO patients using the Greater Cincinnati Northern Kentucky Stroke Study (GCNKSS). Methods: The GCNKSS is a population-based study of stroke in a 5-county region with a population of 1.3 million representative of the USA in terms of Black race, income, and education. All cases of RAO among Black individuals from July 2019-December 2020 and among White individuals from 2020 were chart abstracted using ICD codes. All cases underwent physician adjudication. Demographic and clinical data were recorded. Results: We identified 57 hospitalizations with acute RAO among 55 patients. Characteristics of their hospitalization and demographics are shown (Table). Notably, 19% (11/57) of patients presented in a thrombolytic window of ≤3.5 and average time from symptom onset to evaluation was 17 hours. Most patients initially interacted with a subspecialist (53%) and presented to the ED in delayed fashion. One patient received thrombolytic therapy, four (7%) patients underwent carotid revascularization, and no patients had newly identified atrial fibrillation, cardiac thrombus, or endocarditis. Discussion: Our population-based study found only a minority of patients presented within a thrombolytic window, suggesting that systems of care need to promote more rapid evaluation of these patients. Very few patients received select intervention, but the high impact of carotid revascularization may warrant urgent evaluation of even low risk patients. Further study of long-term outcomes in this patient population is called for.

Intro: Enrolling women and under-represented minorities into clinical trials is a top priority for the stroke community. Common trial exclusions for medical conditions or demographics may negatively impact enrollment for these groups. We sought to describe the potential impact that various exclusion criteria have on trial eligibility of ischemic stroke (IS) patients by race and sex within the large, biracial Greater Cincinnati/Northern Kentucky Stroke Study (GCNKSS) population. Methods: The GCNKSS is a population-based study of 1.3 million people living in a 5-county area of southern Ohio/ Northern Kentucky. During 7/1/14-12/31/15 for blacks, and 2015 for whites, we captured all hospitalized ischemic strokes by screening ICD-9 codes 430-436 and ICD10 codes I60-I68, and G45-46. Commonly used exclusion criteria from stroke clinical trials were applied to the GCNKSS IS population, and were compared by sex and race. All comparisons were evaluated with chi-square test and corrected for multiple comparisons, as necessary. Results: In 2014-2015, there were 2806 ischemic stroke patients, which were 53% female, and 30% black. Table 1 presents common clinical trial exclusion criteria and the % excluded among IS patients, stratified by sex and race. Every trial exclusion evaluated had significant differences by sex, race, or both. Discussion: Within our population, we found that commonly-used age and disability clinical trial exclusion criteria exclude more women than men, and exclusion of milder strokes affects more men than women. Blood pressure, renal function, and early arrival time criteria exclude more blacks than whites, while older age exclude more whites than blacks. Optimal clinical trial design should be informed by epidemiology data to ensure representation of underrepresented populations in clinical trials. We will continue to provide epidemiology feedback on acute trial exclusion criteria to NIH StrokeNet proposals in the future.

Background: Previous studies spanning the 1990s-2010s have inconsistently identified a decline in 30-day stroke case-fatality rate (CFR), and little is known about trends in longer term stroke CFR over that period. We studied temporal trends in 30-day and 5-year CFRs in the well-defined Greater Cincinnati/Norther Kentucky (GCNK) stroke population. Methods: The NIH-funded GCNK Stroke Study is a population-based study conducted in a 5-county region that is representative of the USA in terms of Black race, income, and education. The study ascertained all strokes in 1993/4, 1999, 2005, 2010, and 2015 using well-validated methods. All stroke subtypes were included: ischemic strokes (IS), intracerebral hemorrhages (ICH), and subarachnoid hemorrhages (SAHs). Deaths were identified via the National Death Index. Cox proportional hazards models were used to assess all-cause fatality, by subtype, to examine temporal trends adjusting for age, sex, and race. Results: A total of 10372 stroke cases were ascertained over the five study periods (8428 IS, 443 SAH, and 1501 ICH). IS patients did not demonstrate a decline in 30-day CFRs over time, but did show a nonsignificant decrease in 5-year CFR. Among IS patients, female sex was associated with a lower 5-year CFR, whereas Black individuals had a lower 30-day CFR but a higher 5-year CFR. For ICH, there was a small increase in both 30-day and 5-year CFR in later study periods, although this did not reach significance in all years. SAH showed a lower 30-day CFR over time but no change in 5-year CFR. Older age was associated with a higher 30-day and 5-year CFR in all subtypes. Discussion: Despite widespread advances in post-stroke care, adjusted 5-year CFR has not clearly improved for any stroke subtype and may have slightly worsened for ICH. 30-day CFR has shown a modest improvement among SAH patients. Future studies should investigate why Black individuals with IS experience lower early CFR but a higher late CFR.

Background: Accurate identification of stroke by EMS is necessary for triage and pre-notification within stroke systems of care. Our objective was to describe disparities in the documentation of stroke as the patient’s chief complaint (CC) by EMS in a large population-based stroke study. Methods: We included physician-adjudicated strokes and TIAs occurring among adults ≥18 years old in 2015 in the GCNKSS study population, based in a 5-county area of Southern Ohio/Northern Kentucky. Strokes in which EMS was not used and events occurring in the hospital, during EMS transport, at an unknown location, or outside the study region were excluded. The documented CC by EMS (stroke/CVA, MI, seizure, fall, weakness/numbness, headache, or other) were compared between race/sex subgroups. Sequential multivariable logistic regression was performed to identify associations between race, sex, and social determinants of health with an EMS-documented stroke CC. Social determinants included living arrangement and census tract social deprivation index (SDI). Results: A total of 1451 stroke/TIA events were included. White women had the highest proportion of EMS-documented stroke CCs (56%), more than Black women (48%), White men (45%), and Black men (42%), (p=0.02). Black race was inversely associated with an EMS-documented stroke CC in initial models but was collinear with SDI and no longer significant when SDI was included. In the full model, age, previous stroke, and living with others were associated with an EMS-documented stroke CC, while SDI and CAD were inversely associated with EMS-documented stroke CCs. (Table) Conclusion: Patients living in census tracts characterized by social deprivation were less likely to have EMS-documented stroke CCs, suggesting differences in either patient or EMS recognition of stroke. Further work is needed to explore potential confounders including EMS protocols and to improve identification of stroke by patients and EMS providers.

Background: Knowledge of stroke risk factors (RF) and warning signs (WS) may improve adherence to primary stroke prevention and encourage more rapid presentation after symptom onset. As a result, improving stroke knowledge has been a major public health focus. We sought to study trends in stroke knowledge between 1996 and 2021 in a well-defined population. Methods: Surveys were conducted in 1996, 2000, 2005, 2011, 2016, and 2021 in the 5-county Greater Cincinnati Northern Kentucky region, a population of 1.3 million that reflects the USA in terms of Black race, income, and educational attainment. Respondents were selected to reflect the age, race and sex distribution of the local ischemic stroke population. Potential subjects were contacted using random-digit dialing (with adjustment for cell phone use after 2005) and asked open-ended questions regarding stroke WS and RF knowledge. Correct answers for all years were determined based upon current AHA guidelines and public health messaging. Trends in knowledge were then evaluated over time adjusting for age, Race, sex, and education. Multiple logistic regression models and a cumulative model were used for analysis. Results: Over the 25-year period, 12,322 surveys were completed. After adjustment for age, sex, Race, and education, RF and WS knowledge significantly increased between 1996 and 2021 (P Discussion: While stroke RF and WS knowledge has overall improved since 1996, knowledge remains suboptimal and some gains may have been lost in recent years. More research on the most effective methods for improving stroke awareness is needed.

Background: Multi-phenotype analysis of genetically correlated phenotypes can increase the statistical power to detect loci associated with multiple traits, leading to the discovery of novel loci. This is the first study to date to comprehensively analyze the shared genetic effects within different hemostatic traits, and between these and their associated disease outcomes. Objectives: To discover novel genetic associations by combining summary data of correlated hemostatic traits and disease events. Methods: Summary statistics from genome wide-association studies (GWAS) from seven hemostatic traits (factor VII [FVII], factor VIII [FVIII], von Willebrand factor [VWF] factor XI [FXI], fibrinogen, tissue plasminogen activator [tPA], plasminogen activator inhibitor 1 [PAI-1]) and three major cardiovascular (CV) events (venous thromboembolism [VTE], coronary artery disease [CAD], ischemic stroke [IS]), were combined in 27 multi-trait combinations using metaUSAT. Genetic correlations between phenotypes were calculated using Linkage Disequilibrium Score Regression (LDSC). Newly associated loci were investigated for colocalization. We considered a significance threshold of 1.85 × 10−9 obtained after applying Bonferroni correction for the number of multi-trait combinations performed (n = 27). Results: Across the 27 multi-trait analyses, we found 4 novel pleiotropic loci (XXYLT1, KNG1, SUGP1/MAU2, TBL2/MLXIPL) that were not significant in the original individual datasets, were not described in previous GWAS for the individual traits, and that presented a common associated variant between the studied phenotypes. Conclusions: The discovery of four novel loci contributes to the understanding of the relationship between hemostasis and CV events and elucidate common genetic factors between these traits.

ImportanceFor walking rehabilitation after stroke, training intensity and duration are critical dosing parameters that lack optimization.ObjectiveTo assess the optimal training intensity (vigorous vs moderate) and minimum training duration (4, 8, or 12 weeks) needed to maximize immediate improvement in walking capacity in patients with chronic stroke.Design, Setting, and ParticipantsThis multicenter randomized clinical trial using an intent-to-treat analysis was conducted from January 2019 to April 2022 at rehabilitation and exercise research laboratories. Survivors of a single stroke who were aged 40 to 80 years and had persistent walking limitations 6 months or more after the stroke were enrolled.InterventionsParticipants were randomized 1:1 to high-intensity interval training (HIIT) or moderate-intensity aerobic training (MAT), each involving 45 minutes of walking practice 3 times per week for 12 weeks. The HIIT protocol used repeated 30-second bursts of walking at maximum safe speed, alternated with 30- to 60-second rest periods, targeting a mean aerobic intensity above 60% of the heart rate reserve (HRR). The MAT protocol used continuous walking with speed adjusted to maintain an initial target of 40% of the HRR, progressing up to 60% of the HRR as tolerated.Main Outcomes and MeasuresThe main outcome was 6-minute walk test distance. Outcomes were assessed by blinded raters after 4, 8, and 12 weeks of training.ResultsOf 55 participants (mean [SD] age, 63 [10] years; 36 male [65.5%]), 27 were randomized to HIIT and 28 to MAT. The mean (SD) time since stroke was 2.5 (1.3) years, and mean (SD) 6-minute walk test distance at baseline was 239 (132) m. Participants attended 1675 of 1980 planned treatment visits (84.6%) and 197 of 220 planned testing visits (89.5%). No serious adverse events related to study procedures occurred. Groups had similar 6-minute walk test distance changes after 4 weeks (HIIT, 27 m [95% CI, 6-48 m]; MAT, 12 m [95% CI, −9 to 33 m]; mean difference, 15 m [95% CI, −13 to 42 m]; P = .28), but HIIT elicited greater gains after 8 weeks (58 m [95% CI, 39-76 m] vs 29 m [95% CI, 9-48 m]; mean difference, 29 m [95% CI, 5-54 m]; P = .02) and 12 weeks (71 m [95% CI, 49-94 m] vs 27 m [95% CI, 3-50 m]; mean difference, 44 m [95% CI, 14-74 m]; P = .005) of training; HIIT also showed greater improvements than MAT on some secondary measures of gait speed and fatigue.Conclusions and RelevanceThese findings show proof of concept that vigorous training intensity is a critical dosing parameter for walking rehabilitation. In patients with chronic stroke, vigorous walking exercise produced significant and meaningful gains in walking capacity with only 4 weeks of training, but at least 12 weeks were needed to maximize immediate gains.Trial RegistrationClinicalTrials.gov Identifier: NCT03760016

INTRODUCTION: We sought to determine the feasibility and validity of estimating post-stroke outcomes using information available in the electronic medical record (EMR) through comparison with outcomes obtained from telephone interviews. METHODS: The Greater Cincinnati Northern Kentucky Stroke Study is a retrospective population-based epidemiology study that ascertains hospitalized strokes in the study region. As a sub-study, we identified all ischemic stroke patients who presented to a system of 4 hospitals during the study period 1/1/2015–12/31/2015 and were discharged alive. Enrolled subjects (or proxies for cognitively-disabled patients) were contacted by telephone at 3 and 6 months post-stroke to determine current place of residence and two functional outcomes—the modified Rankin Score (mRS) and the EuroQol (EQ-5D). Concurrently, the lead study coordinator, blinded to the telephone assessment outcomes, reviewed all available EMRs to estimate outcome status. Agreement between outcomes estimated from the EMR with “gold-standard” data obtained from telephone interviews was analyzed using the kappa statistic or interclass correlation (ICC), as appropriate. For each outcome, EMR-determined results were evaluated for added value beyond the information readily available from the stroke hospital stay. RESULTS: Of 381 ischemic strokes identified, 294 (median [IQR] age 70 [60–79] years, 4% black, 52% female) were interviewed post-stroke. Agreement between EMR and telephone for 3-month residence was very good (kappa=0.84, 95% CI 0.74–0.94), good for mRS (weighted kappa=0.75, 95% CI 0.70–0.80), and good for EQ-5D (ICC=0.74, 95% CI 0.68–0.79). Similar results were observed at 6 months post stroke. At both 3 and 6 months post stroke, EMR-determined outcomes added value in predicting the gold standard telephone results beyond the information available from the stroke hospitalization; the added fraction of new information ranged from 0.25 to 0.59. CONCLUSIONS: Determining place of residence, mRS, and EQ-5D outcomes derived from information recorded in the EMR post-stroke, without patient contact, is feasible and has good agreement with data obtained from direct contact. However, we note that the level of agreement for mRS and EQ-5D was higher for proxy interviews and that the EMR often reflects health care providers’ judgments that tend to overestimate disability and underestimate quality of life.

SUMMARY: Small vessel disease, a disorder of cerebral microvessels, is an expanding epidemic and a common cause of stroke and dementia. Despite being almost ubiquitous in brain imaging, the clinicoradiologic association of small vessel disease is weak, and the underlying pathogenesis is poorly understood. The STandards for ReportIng Vascular changes on nEuroimaging (STRIVE) criteria have standardized the nomenclature. These include white matter hyperintensities of presumed vascular origin, recent small subcortical infarcts, lacunes of presumed vascular origin, prominent perivascular spaces, cerebral microbleeds, superficial siderosis, cortical microinfarcts, and brain atrophy. Recently, the rigid categories among cognitive impairment, vascular dementia, stroke, and small vessel disease have become outdated, with a greater emphasis on brain health. Conventional and advanced small vessel disease imaging markers allow a comprehensive assessment of global brain heath. In this review, we discuss the pathophysiology of small vessel disease neuroimaging nomenclature by means of the STRIVE criteria, clinical implications, the role of advanced imaging, and future directions.

ObjectiveTo test the hypothesis that thrombogenic atrial cardiopathy may be relevant to stroke-related racial disparities, we compared atrial cardiopathy phenotypes between Black vs White patients with ischemic stroke.MethodsWe assessed markers of atrial cardiopathy in the Greater Cincinnati/Northern Kentucky Stroke Study, a study of stroke incidence in a population of 1.3 million. We obtained ECGs and reports of echocardiograms performed during evaluation of stroke during the 2010/2015 study periods. Patients with atrial fibrillation (AF) or flutter (AFL) were excluded. Investigators blinded to patients' characteristics measured P-wave terminal force in ECG lead V1 (PTFV1), a marker of left atrial fibrosis and impaired interatrial conduction, and abstracted left atrial diameter from echocardiogram reports. Linear regression was used to examine the association between race and atrial cardiopathy markers after adjustment for demographics, body mass index, and vascular comorbidities.ResultsAmong 3,426 ischemic stroke cases in Black or White patients without AF/AFL, 2,391 had a left atrial diameter measurement (mean, 3.65 ± 0.70 cm). Black race was associated with smaller left atrial diameter in unadjusted (β coefficient, −0.11; 95% confidence interval [CI], −0.17 to −0.05) and adjusted (β, −0.15; 95% CI, −0.21 to −0.09) models. PTFV1 measurements were available in 3,209 patients (mean, 3,434 ± 2,525 μV*ms). Black race was associated with greater PTFV1 in unadjusted (β, 1.59; 95% CI, 1.21–1.97) and adjusted (β, 1.45; 95% CI, 1.00–1.80) models.ConclusionsWe found systematic Black–White racial differences in left atrial structure and pathophysiology in a population-based sample of patients with ischemic stroke.Classification of EvidenceThis study provides Class II evidence that atrial cardiopathy phenotypes differ in Black people with acute stroke compared to White people.

Background: Hypertension awareness, treatment, and control programs were initiated in the United States during the 1960s and 1970s. Whereas blood pressure (BP) control in the population and subsequent reduced hypertension-related disease risks have improved since the implementation of these interventions, it is unclear whether these BP changes can be generalized to diverse and high-risk populations. This report describes the 4-decade change in BP levels for the population in a high disease risk southeastern region of the United States. The objective is to determine the magnitude of the shift in systolic BP (SBP) among Blacks and Whites from the Southeast between 1960 and 2005 with the assessment of the unique population cohorts. Methods: A multicohort study design compared BPs from the CHS (Charleston Heart Study) and ECHS (Evans County Heart Study) in 1960 and the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) 4 decades later. The analyses included participants ≥45 years of age from CHS (n=1323), ECHS (n=1842), and REGARDS (n=6294) with the main outcome of SBP distribution. Results: Among Whites 45 to 54 years of age, the median SBP was 18 mm Hg (95% CI, 16–21 mm Hg) lower in 2005 than 1960. The median shift was a 45 mm Hg (95% CI, 37–51 mm Hg) decline for those ≥75 years of age. The shift was larger for Blacks, with median declines of 38 mm Hg (95% CI, 32–40 mm Hg) at 45 to 54 years of age and 50 mm Hg (95% CI, 33–60 mm Hg) for ages ≥75 years. The 95th percentile of SBP decreased 60 mm Hg for Whites and 70 mm Hg for Blacks. Conclusions: The results of the current analyses of the unique cohorts in the Southeast confirm the improvements in population SBP levels since 1960. This assessment provides new evidence of improvement in SBP, suggesting that strategies and programs implemented to improve hypertension treatment and control have been extraordinarily successful for both Blacks and Whites residing in a high-risk region of the United States. Severe BP elevations commonly observed in the 1960s have been nearly eliminated, with the current 75th percentile of BP generally less than the 25th percentile of BP in 1960.

Introduction:Acute care research (ACR) is uniquely challenged by the constraints of recruiting participants and conducting research procedures within minutes to hours of an unscheduled critical illness or injury. Existing competencies for clinical research professionals (CRPs) are gaining traction but may have gaps for the acute environment. We sought to expand existing CRP competencies to include the specialized skills needed for ACR settings.Methods:Qualitative data collected from job shadowing, clinical observations, and interviews were analyzed to assess the educational needs of the acute care clinical research workforce. We identified competencies necessary to succeed as an ACR-CRP, and then applied Bloom’s Taxonomy to develop characteristics into learning outcomes that frame both knowledge to be acquired and job performance metrics.Results:There were 28 special interest competencies for ACR-CRPs identified within the eight domains set by the Joint Task Force (JTF) of Clinical Trial Competency. While the eight domains were not prioritized by the JTF, in ACR an emphasis on Communication and Teamwork, Clinical Trials Operations, and Data Management and Informatics was observed. Within each domain, distinct proficiencies and unique personal characteristics essential for success were identified. The competencies suggest that a combination of competency-based training, behavioral-based hiring practices, and continuing professional development will be essential to ACR success.Conclusion:The competencies developed for ACR can serve as a training guide for CRPs to be prepared for the challenges of conducting research within this vulnerable population. Hiring, training, and supporting the development of this workforce are foundational to clinical research in this challenging setting.

BACKGROUND AND OBJECTIVES: High-intensity interval training (HIIT) is a promising strategy for improving gait and fitness after stroke, but optimal parameters remain unknown. We tested the effects of short vs long interval type and over-ground vs treadmill mode on training intensity. METHODS: Using a repeated measures design, 10 participants with chronic hemiparetic gait performed 12 HIIT sessions over 4 weeks, alternating between short and long-interval HIIT sessions. Both protocols included 10 minutes of over-ground HIIT, then 20 minutes of treadmill HIIT and another 10 minutes over-ground. Short-interval HIIT involved 30 second bursts at maximum safe speed and 30–60 second rest periods. Long-interval HIIT involved 4-minute bursts at ~90% of peak heart rate (HR(peak)) and 3-minute recovery periods at ~70% HR(peak). RESULTS: Compared with long-interval HIIT, short-interval HIIT had significantly faster mean overground speeds (0.75 vs 0.67 m/s) and treadmill speeds (0.90 vs 0.51 m/s), with similar mean treadmill HR (82.9 vs 81.8 %HR(peak)) and session perceived exertion (16.3 vs 16.3), but lower overground HR (78.4 vs 81.1 %HR(peak)) and session step counts (1481 vs 1672). For short-interval HIIT, training speeds and HR were significantly higher on the treadmill vs. overground. For long-interval HIIT, the treadmill elicited HR similar to overground training at significantly slower speeds. CONCLUSIONS: Both short and long-interval HIIT elicit high intensities but emphasize different dosing parameters. Based on these preliminary findings and previous studies, we hypothesize that overground and treadmill short-interval HIIT could be optimal for improving gait speed and overground long-interval HIIT could be optimal for improving gait endurance.

Background: In acute stroke, reducing delays between symptom onset and treatment can improve outcomes. While in-hospital delays have been successfully reduced, pre-hospital delays have persisted. Public health campaigns have attempted to reduce these delays by increasing stroke symptom awareness, but it is unknown whether these efforts have improved the percentage of patients presenting early after symptom onset. Methods: We performed an analysis of the Greater Cincinnati/Northern Kentucky Stroke Study, a population-based study of all stroke patients in a large geographic area. We looked at the 2010 and 2015 study years. All stroke cases (ischemic and hemorrhagic) presenting to the 16 regional EDs were included. We examined the time between symptom onset and ED arrival times, dichotomized into ≤3.5 hours and >3.5 hours. In cases without a clear onset, estimates were derived using wake-up or last known well times. Comparisons were made using multivariable logistic regression. Results: Among 4633 total stroke patients, 1359 patients presented early (29%). Results of the multivariable analysis are shown in the Table . There was no improvement the rate of early presentation in 2015 (aOR 1.01, 95% CI 0.89-1.16). EMS utilization, night arrival, higher NIHSS scores, and better premorbid function were associated with early arrival. Patients who lived alone were less likely to arrive early. Conclusion: We found no evidence for improvement in the rate of early presentation over the years studied. Work is needed to address other barriers to early hospital arrival, including underutilization of EMS.

Introduction: Disparities in acute ischemic stroke (IS) care due to patients’ pre-stroke disabilities remain understudied. Using the Greater Cincinnati Northern Kentucky (GCNK) Stroke Study, we aimed to understand the differences in acute stroke presentation and care according to patients’ pre-stroke functional status. Methods: We ascertained all hospitalized IS patients ≥18 years old presenting to emergency departments in the GCNK region in 2015 using ICD-9 430-436; ICD-10 I60-I67, G45-G46; all cases were physician-reviewed. Trained nurses ascertained pre-stroke functional status from the medical record. Acute IS presentation, time metrics, and treatment were compared between patients with pre-stroke mRS 0-1 vs ≥2 using Wilcoxon rank-sum or chi-square tests. Logistic regression was used to evaluate the association between pre-stroke mRS and intravenous thrombolysis (IVT) and endovascular treatment adjusting for age, presenting NIHSS, time to presentation, and baseline anticoagulation use. Results: Of 2191 patients with IS, 1134 had a pre-stroke mRS ≥2. Patients in the latter group were older, more likely be female, had higher rates of medical comorbidities, had higher presenting NIHSS (3[1-8] vs 2[1-5], p Conclusions: Acute IS patients with pre-stroke disability presented later, with more severe strokes, and were less likely to receive reperfusion treatments. Further research into factors driving acute stroke medical decision-making for patients with a pre-stroke disability is needed to ensure optimal acute neurovascular care for all IS patients across the nation and worldwide.

Background: Antithrombotic medications (AT) are often withheld before procedures to reduce risk of bleeding. In 2005, members of our team reported that 5.2% of ischemic strokes were associated with the withdrawal of AT in the preceding 60 days. Subsequently, new medications, including DOACs, have become widely used. Given changing prescription and practice patterns we sought to compare rates of stroke in the setting of antithrombotic withdrawal in 2010 and 2015. Methods: The GCNKSS is a population-based stroke study from the Greater Cincinnati region. In 2005, 2010, and 2015, we captured all strokes in the Greater Cincinnati/Northern Kentucky 5 county area by screening ICD9 codes 430-436 and ICD10 (2015) codes I60-I68, and G45-46. Study nurses abstracted all cases and physicians adjudicated each event. Data regarding the withdrawal of AT and timing were captured. 2005 data was included as a reference. Fisher’s exact test was used to examine differences by years. Results: In 2010 and 2015, 4768 cases of ischemic stroke were identified. Across the study periods, those that were on AT at time of stroke versus those who stopped AT Conclusions: The withdrawal of AT is associated with 228 (4.8%) of ischemic strokes within 60 days in our study population. These rates remain consistent across our study periods. This highlights that despite new agents, stroke in the setting of AT withdrawal remains consistent and the decision to stop AT must be carefully considered.

Background: Prior studies have demonstrated a rising incidence of infective endocarditis related stroke (IERS) in the US due to the opioid epidemic. The Greater Cincinnati/Northern Kentucky (GCNK) region has one of the highest opioid abuse rates in the nation. A modern epidemiologic description is necessary to understand the impact of the opioid epidemic on the clinical phenotype of IERS. Methods: Using the GCNK Stroke Study, all patients hospitalized with IERS in 2005, 2010, and 2015 were abstracted and physician reviewed. IERS was defined as an acute stroke clinically attributed to infective endocarditis in patients meeting modified Duke Criteria for possible or definite endocarditis. Comparison between years were by chi-square or Fisher’s exact test for categorical variables; ANOVA or Kruskal-Wallis test for numerical variables. Cochran-Armitage test was used to examine trend. Secondary analysis compared characteristics between intravenous drug users (IVDU) and non-IVDU. Results: A total of 54 patients with IERS were identified in 2005, 2010, and 2015. Over the period, there was a significant decline in hypertension (91.7% in 2005, 36.0% in 2015; p=0.0005) and increase in IVDU (8.3% in 2005, 44.0% in 2015; p=0.02). They trended towards increased white race, younger age, and fewer vascular risk factors. Compared to non-IVDU, IVDU were significantly younger (41.1±14.1vs 63.1±14.3 years; p Conclusion: From 2005 to 2015, IERS was increasingly associated with IVDU and an absence of hypertension. These trends likely reflect the demographics of the opioid epidemic, which has affected younger patients with less comorbidities.

Background:The American Heart Association, in conjunction with the National Institutes of Health, annually reports 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 2022 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 and an enhanced focus on social determinants of health, adverse pregnancy outcomes, vascular contributions to brain health, and the global burden of cardiovascular disease and healthy life expectancy.Results:Each of the 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, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Introduction: Existing stroke family caregiver interventions are limited in the use of technology and lack focus on caregiver health. The Telehealth Assessment and Skill-Building Kit (TASK III) was optimized based on caregiver preferences for technology and goal setting to improve caregiver health. The purpose of this study was to test feasibility of the TASK III program compared with an Information, Support, and Referral group (ISR) for improving caregiver depressive symptoms, life changes, and unhealthy days. Methods: Using randomized control trial design and an intent-to-treat analysis, 74 stroke family caregivers were randomized to TASK III (n=36) or ISR (n=38). The TASK III Resource Guide was provided by hard copy, website, eBook, and USB drive. TASK III and ISR groups received an American Stroke Association (ASA) pamphlet, access to the ASA website, and 8 weekly calls from a nurse (telephone/videoconferencing), with a booster call a month later. Data trends from baseline to 8 and 12 weeks were explored for depressive symptoms (PHQ-9), life changes (Bakas Caregiving Outcomes Scale), and unhealthy days. Minutes on calls with the nurse were controlled in analyses. Results: Among caregivers with mild to severe depressive symptoms at baseline (PHQ-9 > 5) (n=31), TASK III showed a greater reduction in depressive symptoms relative to ISR from baseline to 8 and 12 weeks (Mean group difference in change scores -3.7, p=.02 at 8 weeks; -3.7, p=.04 at 12 weeks). Using the full sample (N=74), life changes improved for TASK III relative to ISR from baseline to 8 and 12 weeks (Mean 8.1, p=.03; 14.9, p Conclusions: Data trends supported feasibility of TASK III relative to ISR for improving depressive symptoms and life changes, including changes in emotional well-being and physical health. Unhealthy days were highly skewed and not sensitive to change. Testing efficacy of TASK III relative to ISR is warranted in a future, well-powered trial.

IntroductionLocomotor high-intensity interval training (HIIT) is a promising intervention for stroke rehabilitation that typically involves bursts of fast treadmill walking alternated with recovery periods. However, overground translation of treadmill speed gains has been somewhat limited, some important outcomes have not been tested and baseline response predictors are poorly understood. This pilot study aimed to guide future research by assessing preliminary outcomes of combined overground and treadmill HIIT.MethodsTen participants >6 months post stroke completed a multi-domain assessment battery before and after a 4-week no-intervention control phase, then again after a 4-week treatment phase involving 12 sessions of overground and treadmill HIIT. The primary analyses assessed relative changes in overground and treadmill walking speeds after HIIT, evaluated responsiveness of different outcome measures and estimated effects of baseline gait speed on treatment response.ResultsOverground and treadmill gait function both improved during the treatment phase relative to the control phase, with overground speed changes averaging 61% of treadmill speed changes (95% CI: 33-89%). Moderate or larger effect sizes were observed for measures of gait performance, balance, fitness, cognition, fatigue, perceived change and brain volume. Participants with baseline comfortable gait speed DiscussionFuture locomotor HIIT studies should consider including: 1) both overground and treadmill training; 2) measures of cognition, fatigue and brain volume, to complement typical motor & fitness assessment; and 3) baseline gait speed as a covariate.

Background and Research QuestionWalking impairment remains a major limitation to functional independence after stroke. Yet, comprehensive and effective strategies to improve walking function after stroke are presently limited. Backward Locomotor Treadmill Training (BLTT) is a promising training approach for improving walking function; however, little is known about its mechanism of effect or the relationship between backward walking training and resulting overground forward walking performance. This study aims to determine the effects of serial BLTT on spatial aspects of backward and forward walking in chronic post-stroke individuals with residual walking impairment.MethodsThirty-nine adults (>6 months post-stroke) underwent 6 days of BLTT (3 × /week) over 2 weeks. Outcome measures included PRE-POST changes in backward and forward walking speeds, paretic and non-paretic step lengths, and single-support center of pressure distances. To determine the association between BLTT and overground walking, correlation analyses comparing training-related changes in these variables were performed.ResultsWe report an overall improvement in BLTT and overground walking speeds, bilateral step lengths, and single-support center of pressure distances over six training sessions. Further, there were weak positive associations between PRE-POST changes in BLTT speed, BLTT paretic step length, and overground forward walking speed.Conclusion and SignificanceOur findings suggest that individuals with chronic post-stroke walking impairment experience improvements in spatial walking measures during BLTT and overground. Therefore, BLTT may be a potential adjunctive training approach for post-stroke walking rehabilitation.

ObjectiveThe purpose of this study was to examine depressive symptoms as a risk factor for incident stroke and determine whether depressive symptomatology was differentially predictive of stroke among Black and White participants.MethodsThe study comprised 9,529 Black and 14,516 White stroke-free participants, aged 45 and older, enrolled in the REasons for Geographic and Racial Differences in Stroke (2003–2007). Incident stroke was the first occurrence of stroke. Association between baseline depressive symptoms (assessed via the 4-item Center for Epidemiologic Studies Depression Scale [CES-D-4]: 0, 1–3, or ≥4) and incident stroke was analyzed with Cox proportional hazards models adjusted for demographics, stroke risk factors, and social factors.ResultsThere were 1,262 strokes over an average follow-up of 9.21 (SD 4.0) years. Compared to participants with no depressive symptoms, after demographic adjustment, participants with CES-D-4 scores of 1–3 had 39% increased stroke risk (hazard ratio [HR] = 1.39, 95% confidence interval [CI] = 1.23–1.57), with slight attenuation after full adjustment (HR = 1.27, 95% CI = 1.11–1.43). Participants with CES-D-4 scores of ≥4 experienced 54% higher risk of stroke after demographic adjustment (HR = 1.54, 95% CI = 1.27–1.85), with risk attenuated in the full model similar to risk with 1–3 symptoms (HR = 1.25, 95% CI = 1.03–1.51). There was no evidence of a differential effect by race (p = 0.53).ConclusionsThe association of depressive symptoms with increased stroke risk was similar among a national sample of Black and White participants. These findings suggest that assessment of depressive symptoms should be considered in primary stroke prevention for both Black and White participants.

Purpose We previously described the magnitude of rural-urban differences in the prevalence of stroke risk factors and stroke mortality. In this report, we sought to extend the understanding of rural-urban differences in the prevalence of stroke risk factors by using an enhanced definition of rural-urban status and assessing the impact of neighborhood socioeconomic status (nSES) on risk factor differences. Methods This analysis included 28,242 participants without a history of stroke from the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort. Participants were categorized into the 6-level ordinal National Center for Health Statistics Urban-Rural Classification Scheme. The prevalence of stroke risk factors (hypertension, diabetes, smoking, atrial fibrillation, left ventricular hypertrophy, and heart disease) was assessed across the rural-urban scale with adjustment for demographic characteristics and further adjustment for nSES score. Findings Hypertension, diabetes, and heart disease were more prevalent in rural than urban regions. Higher odds were observed for these risk factors in the most rural compared to the most urban areas (odds ratios [95% CI]: 1.25 [1.11-1.42] for hypertension, 1.15 [0.99-1.33] for diabetes, and 1.19 [1.02-1.39] for heart disease). Adjustment for nSES score partially attenuated the odds of hypertension and heart disease with rurality, completely attenuated the odds of diabetes, and unmasked an association of current smoking. Conclusions Some of the higher stroke mortality in rural areas may be due to the higher burden of stroke risk factors in rural areas. Lower nSES contributed most notably to rural-urban differences for diabetes and smoking.

Background Stroke results in neurologic impairments and aerobic deconditioning that contribute to limited walking capacity which is a major barrier post-stroke. Current exercise recommendations and stroke rehabilitation guidelines recommend moderate-intensity aerobic training post-stroke. Locomotor high-intensity interval training is a promising new strategy that has shown significantly greater improvements in aerobic fitness and motor performance than moderate-intensity aerobic training in other populations. However, the relative benefits and risks of high-intensity interval training and moderate-intensity aerobic training remain poorly understood following stroke. In this study, we hypothesize that locomotor high-intensity interval training will result in greater improvements in walking capacity than moderate-intensity aerobic training. Methods Using a single-blind, 3-site randomized controlled trial, 50 chronic (> 6 months) stroke survivors are randomly assigned to complete 36 locomotor training sessions of either high-intensity interval training or moderate-intensity aerobic training. Main eligibility criteria are age 40–80 years, single stroke for which the participant received treatment (experienced 6 months to 5 years prior to consent), walking speed ≤ 1.0 m/s, able to walk at least 3 min on the treadmill at ≥ 0.13 m/s (0.3 mph), stable cardiovascular condition (American Heart Association class B), and the ability to walk 10 m overground without continuous physical assistance. The primary outcome (walking capacity) and secondary outcomes (self-selected and fast gait speed, aerobic fitness, and fatigue) are assessed prior to initiating training and after 4 weeks, 8 weeks, and 12 weeks of training. Discussion This study will provide fundamental new knowledge to inform the selection of intensity and duration dosing parameters for gait recovery and optimization of aerobic training interventions in chronic stroke. Data needed to justify and design a subsequent definitive trial will also be obtained. Thus, the results of this study will inform future stroke rehabilitation guidelines on how to optimally improve walking capacity following stroke. Trial registration ClinicalTrials.govNCT03760016. Registered on November 30, 2018.

ObjectiveWe studied circulating interleukin (IL)–6, IL-8, and IL-10 concentrations and incident ischemic stroke risk in a biracial cohort, and determined if these cytokines mediated the racial disparity in stroke incidence affecting the black population.MethodsThe Reasons for Geographic and Racial Differences in Stroke study enrolled 30,237 black and white men and women age ≥45 in 2003-2007. We measured baseline IL-6, IL-8, and IL-10 in a case–cohort study of 557 participants with incident stroke over 5.4 years and 951 participants in a cohort sample.ResultsIL-6, but not IL-8 or IL-10, was higher in cases compared to the cohort sample (mean 4.5 vs 3.7 ng/mL; p < 0.001). Only IL-6 was associated with stroke risk factors. Adjusting for age, sex, and race, the hazard ratio (HR; 95% confidence interval) for incident stroke for the highest vs lowest quartile of IL-6 was 2.4 (1.6–3.4). HRs for the highest vs lowest quartiles of IL-8 and IL-10 were 1.5 (1.0–2.1) and 1.4 (1.0–1.9), respectively. After additional adjustment for stroke risk factors, only higher IL-6 remained associated with stroke risk (HR 2.0; 1.2–3.1). Associations did not differ by race. Mediation analyses showed that IL-6 mediated the black–white disparity in stroke risk, but mediation was via IL-6 associations with stroke risk factors.ConclusionsIn this biracial population-based sample, IL-6 was strongly associated with risk of incident stroke and mediated the racial disparity in stroke via inflammatory effects of risk factors. Further study on the clinical utility of IL-6 measurement in stroke risk assessment would be helpful.

Objective— Increased Lp(a) [lipoprotein(a)] is associated with coronary heart disease risk, but links with stroke are less consistent. Blacks have higher Lp(a) levels and stroke incidence than whites but have been underrepresented in studies. We hypothesized that Lp(a) is a risk factor for ischemic stroke and that risk differs by race. Approach and Results— REGARDS (Reasons for Geographic and Racial Differences in Stroke) recruited 30 239 black and white US adults aged ≥45 in 2003–2007 to study regional and racial differences in stroke mortality. We measured baseline Lp(a) by immunonephelometric assay in 572 cases of incident ischemic stroke and a 967-person cohort random sample. The hazard ratio of stroke by baseline Lp(a) was calculated using Cox proportional hazards models, stratified by race. Lp(a) was modeled in sex- and race-specific quartiles, given known differences in distributions by race and sex. Interactions were tested by including interaction terms in the proportional hazards models, with P P interaction=0.12. Lp(a) was lower in men than women, but associations with stroke in men and women were similar. Conclusions— We confirm that Lp(a) is a risk factor for ischemic stroke. Further research is needed to confirm the role of racial differences of the Lp(a) risk multiplier in ischemic stroke.

Aerobic exercise may acutely prime the brain to be more responsive to rehabilitation, thus facilitating neurologic recovery from conditions like stroke. This aerobic priming effect could occur through multiple mechanisms, including upregulation of circulating brain-derived neurotrophic factor (BDNF), increased corticospinal excitability, and decreased intracortical inhibition. However, optimal exercise parameters for targeting these mechanisms are poorly understood. This study tested the effects of exercise intensity on acute BDNF and neurophysiological responses. Sixteen ambulatory persons >6 mo poststroke performed three different 20-min exercise protocols in random order, approximately 1 wk apart, including the following: 1) treadmill high-intensity interval training (HIT-treadmill); 2) seated-stepper HIT (HIT-stepper); and 3) treadmill moderate-intensity continuous exercise (MCT-treadmill). Serum BDNF and transcranial magnetic stimulation measures of paretic lower limb excitability and inhibition were assessed at multiple time points during each session. Compared with MCT-treadmill, HIT-treadmill elicited significantly greater acute increases in circulating BDNF and corticospinal excitability. HIT-stepper initially showed BDNF responses similar to HIT-treadmill but was no longer significantly different from MCT-treadmill after decreasing the intensity in reaction to two hypotensive events. Additional regression analyses showed that an intensity sufficient to accumulate blood lactate appeared to be important for eliciting BDNF responses, that the interval training approach may have facilitated the corticospinal excitability increases, and that the circulating BDNF response was (negatively) related to intracortical inhibition. These findings further elucidate neurologic mechanisms of aerobic exercise and inform selection of optimal exercise-dosing parameters for enhancing acute neurologic effects. NEW & NOTEWORTHY Acute exercise-related increases in circulating BDNF and corticospinal excitability are thought to prime the brain for learning. Our data suggest that these responses can be obtained among persons with stroke using short-interval treadmill high-intensity interval training, that a vigorous aerobic intensity sufficient to generate lactate accumulation is needed to increase BDNF, that interval training facilitates increases in paretic quadriceps corticospinal excitability, and that greater BDNF response is associated with lesser intracortical inhibition response.

Introduction: Elevations in troponin (cTn) are common in patients with acute ischemic stroke, yet their significance remains uncertain. Hypothesis: Elevated cTn at the time of acute ischemic stroke is associated with ischemic stroke recurrence. Methods: We included all adult patients with acute ischemic stroke who were residents of the Greater Cincinnati/Northern Kentucky region and who presented to an emergency department (ED) in 2015 and who had a cTn measured within 24 hours of ED arrival. Our exposure variable was an elevated cTn, defined as a value exceeding the laboratory’s 99 th percentile. Our primary outcome was ischemic stroke recurrence, defined as a new ischemic stroke with radiographic confirmation in the 3 years following the index ischemic stroke event. Cox proportional hazards model was used to evaluate the association between elevated cTn and ischemic stroke recurrence while adjusting for demographics, vascular risk factors, and stroke severity. In a secondary analysis, we excluded patients with a concomitant adjudicated myocardial infarction (MI) at the time of the index ischemic stroke. Results: Among 2,334 patients with acute ischemic stroke, 1,992 (85%) had a cTn assay within 24 hours of ED arrival and were included in the analysis. 402 (20%) patients had an elevated cTn and 259 (13%) patients had a recurrent ischemic stroke. 66 (3%) patients had an elevated cTn and a concomitant acute MI and 336 (17%) patients had an elevated cTn without a concomitant acute MI. After adjustment for demographics, vascular risk factors, and stroke severity, we found an association between elevated cTn and recurrent ischemic stroke (hazards ratio [HR], 1.5; 95% CI, 1.1-2.0). Our results were unchanged after excluding patients with a concomitant adjudicated MI (HR 1.4; 95% CI, 1.03-2.0). Conclusions: Among patients with acute ischemic stroke, elevated cTn even in the absence of concomitant adjudicated MI, was associated with ischemic stroke recurrence. Further mechanistic studies are necessary to explore the underlying etiology of hypertroponinemia among patients with acute ischemic stroke in order to guide targeted therapies to reduce stroke recurrence.

Background: Hemorrhagic transformation (HT) of ischemic stroke can have devastating consequences, leading to longer hospitalizations, increased morbidity and mortality. We sought to identify the rate of HT in stroke patients not treated with tPA within a large, biracial population. Methods: The GCNKSS is a population-based stroke epidemiology study from five counties in the Greater Cincinnati region. During 2015, we captured all hospitalized strokes by screening ICD-9 codes 430-436 and ICD-10 codes I60-I68, and G45-46. Study nurses abstracted all potential cases and physicians adjudicated cases, including classifying the degree of HT. Patients treated with thrombolytics were excluded. Incidence rates per 100,000 and associated 95% confidence intervals (CI) were estimated for HT cases, age and sex adjusted to the 2000 US population. Multiple logistic regression was used to examine risk factors associated with HT. Results: In 2015, there were 2301 ischemic strokes included in the analysis. Of these 104 (4.5%) had HT; 23 (22.1%) symptomatic, 55 (52.9%) asymptomatic and 26 (25%) unknown. Documented reasons for not receiving tPA in these patients were: time (71, 68.3%), anticoagulant use (1, 1.0%), other (18,17.3%) and unknown (14, 13.5%), which were not significantly different compared to those without HT. Only 29/104 (18.3%) had HT classified as PH-1 or PH-2. The age, sex and race-adjusted rate of HT was 9.8 (7.9, 11.6) per 100,000. The table shows rates of potential risk factors and the adjusted odds of developing HT. 90 day all-cause case fatality for patients with HT was significantly higher, 27.9% vs. 15.7%, p Conclusion: We found that 4.5% of non-tPA treated IS patients had HT. These patients had more severe strokes, were more likely to have abnormal coagulation tests or anticoagulant use, and were more likely to die within 90 days. We also report the first population-based incidence rate of HT in non-tPA treated of 9.8/100,000, a rate similar to the incidence of SAH.

Background: Hypertension is an important risk factor in the development of acute ischemic stroke (AIS). African American (AA) race is strongly associated with both hypertension and uncontrolled hypertension despite treatment, yet little is known about racial differences in presenting blood pressure (BP) in AIS. This study sought to describe differences in presenting BP and acute antihypertensive treatment between AA and white AIS patients who received and did not receive alteplase within a population. Methods: Using the Greater Cincinnati/Northern Kentucky Stroke Study (GCNKSS) database for years 2005, 2010 and 2015, we selected patients with a diagnosis of AIS using ICD-9/10 codes in adults ≥ 18 yrs of age presenting to a local ED within 4.5 hrs of symptom onset. Candidates were stratified by race and alteplase use. Socio-demographics, stroke risk factors, stroke severity, BP on arrival, and acute BP treatment were compared using chi-square, t-tests or Wilcoxon rank sum test, as appropriate. Results (Table 1): Of 1838 AIS patients included in the analysis, 392 (21%) received IV alteplase. AA patients were younger in both groups who received and did not receive alteplase. On presentation, AA stroke patients had higher diastolic BP. AA patients were more likely to receive 2 or more BP lowering medications compared to white patients in the alteplase treated group and the untreated group. Conclusion: AA patients presenting within 4.5 hours of AIS symptom onset are more likely to have elevated diastolic BP and to receive multiple BP lowering medications compared to white patients. These findings were significant regardless of alteplase treatment. To our knowledge, we report the first population-based distribution of BP, and medical treatment of BP, upon presentation to an ED in AIS. Further study is needed to determine if these racial differences in elevated BP and refractoriness of BP and/or aggressive treatment contribute to outcome differences.

Introduction: Patients without prior functional deficits who suffer mild stroke (NIHSS Methods: Hospitalized strokes from the Greater Cincinnati Northern Kentucky Stroke Study were used. Included patients had an initial NIHSS Results: Of 1268 ischemic strokes, 353 (28%) were functionally dependent at discharge. Increased baseline NIHSS was associated with worse outcome on the mRS. Leg, LOC questions, and sensation NIHSS subscores were the best predictors of outcome. Multivariable analysis identified age, race, hypertension, chronic kidney disease, heart failure, and post-stroke dysphagia as independently associated with discharge mRS ≥3. Discussion: Our results agree with and complement the results of prior studies. They are not limited by inclusion/exclusion criteria or referral bias. Rather, our major limitation is the retrospective estimation of NIHSS and mRS based on physician descriptive documentation rather than direct score assessment. Our results may allow for modeling to better predict outcome which in turn can inform clinical decision making and trial design.

Introduction: A main goal for hospital admission following acute ischemic stroke (AIS) is to establish the mechanism of stroke (MoS) allowing for patient specific secondary prevention of stroke interventions. We previously reported on diagnostic testing trends and MoS determination from 1993 through 2010. We updated this analysis with 2015 data to better understand the effects of trends in diagnostic testing on MoS determination. Methods: Patients with AIS aged > 20 years from all study time periods (Table) of the population based GCNKSS were included. Charts were abstracted in a systematic way for tests performed during the hospital stay. Only first-ever ischemic stroke cases, evaluated in an emergency department were used for this analysis. Stroke experts reviewed these events and adjudicated the mechanism of stroke according to modified TOAST criteria. We looked at and compared trends for testing and MoS. Results: Our analysis included 7226 patients. Basic patient demographics, MoS categories and tests across study periods are detailed in the Table. There were significant increases in EKG (7%), TTE (35%), TEE (7%), HCT (4%), brain MRI (65%), MRA (30%) and CTA (28%). Across study periods, cardioembolic (4.1%), small vessel disease (3%), large artery disease (0.9%) and other (1.5%) MoS increased while unknown MoS decreased (-9.5%). Discussion: From 1993/1994 to 2015 there has been a significant increase of in-hospital testing in AIS and decreases in undetermined MoS. Cardioembolic and small vessel disease MoS categories increased the most. Despite a significant increase in vessel imaging, large artery disease and “other determined” MoS categories are largely unchanged. Further research is required to elucidate the occult MoS underlying the undetermined category. Based on our analysis it appears unlikely to be significantly associated with our current definition of stroke associated with large artery disease defined as ≥ 50% ipsilateral stenosis.

Introduction: The availability of rapid tissue and vessel imaging for TIA has increased, but the utilization rates of these and other diagnostic and management strategies for TIA over time are unknown. Objective: To investigate trends in TIA diagnostic and management strategies over time in the Greater Cincinnati Northern Kentucky Stroke Study (GCNKSS). Methods: The GCNKSS is a population-based study of 1.3 million people living in a 5-county area of southern Ohio and Northern Kentucky. For this study, all physician-adjudicated, first-ever cases of TIA (defined clinically as sudden onset of focal symptoms lasting < 24 hours) presenting to an emergency department over five study periods (1993/4, 1999, 2005, 2010, 2015) were included. Use of AHA-recommended aspects of TIA management as well as disposition of TIA patients (admission to hospital or discharge from ED) and length of stay were compared across study periods. Rates of acute infarct on MRI were also reported. Trends were examined using the Cochran-Armitage test for trend. Results: In total, over all study periods, there were 2251 first-ever TIAs. Overall, 14% (n=311) occurred in Black individuals, and 57% (n=1275) occurred in women. Utilization of diagnostic modalities [non-contrast CT brain, vascular imaging (CTA, MRA, or carotid dopplers), tissue imaging (MRI), and echocardiogram] increased significantly over time (all p Conclusions: The management of TIA has changed significantly over time. Utilization of tissue and vessel imaging as well as echocardiogram during the hospital stay has increased; in 2015, the vast majority of patients with TIA in this population-based study received each of these testing modalities and were admitted to a hospital for TIA work-up. Further work is needed to understand the best practices for work-up of suspected TIA.

Background: Substantial practice variability exists with respect to the diagnostic workup and disposition of patients with TIA. Identifying the workup needed to prevent adverse outcomes is critical. We aimed to determine whether there is an association between specific elements of TIA management and outcomes. Methods: The GCNKSS is a population-based study of 1.3 million people living in a 5-county area of southern Ohio/ Northern Kentucky. For this study, all physician adjudicated, first-ever TIAs (clinically defined as sudden onset, focal neurologic symptoms lasting < 24 hours, with or without MRI correlate) presenting to the ED during 2015 were included; those with prior stoke or TIA were excluded. Multivariable logistic regression was performed to investigate associations between specific aspects of TIA management and an adverse outcome, defined as stroke, recurrent TIA, or all-cause mortality within 30 days, adjusted for demographics, co-morbidities, and symptom type and length as classified in the ABCD2 score. Results: In 2015, there were 477 adjudicated first ever TIA events presenting to the ED. Overall, 13% (n=62) occurred in Black individuals and 51% (n=243) in women. Regarding outcomes, 3% (n=16) had a stroke within 30 days, 6% (n=30) had a recurrent TIA within 30 days, and 1% (n=4) died within 30 days (all-cause mortality). 16.4% had acute infarct on MRI. In multivariable analysis, having an MRI was associated with reduced risk of adverse outcome, while performance of vessel imaging, echocardiogram, or admission to hospital were not significantly associated with outcomes (Table). Conclusions: Among common diagnostic and management strategies for TIA, only performance of MRI was associated with a lower likelihood of having an adverse outcome within 30 days. Possible contributors include variability in care between hospitals with differing MRI performance rates and changes in management of risk factors based on MRI results, though further work is needed.

Background: Functional outcomes are improved when AIS patients receive faster treatment. The first medical contact for many AIS patients is with emergency medical services (EMS) providers. We hypothesize that AIS treatment is faster when EMS providers suspect stroke. Methods: We performed a retrospective analysis of the Greater Cincinnati/Northern Kentucky Stroke Study, a comprehensive study of stroke patients in a large geographical area with 1.3 million inhabitants whose demographics are representative of the United States. We compared AIS patients age ≥18 years transported by EMS in 2015 with an EMS impression of “stroke” or “weakness/numbness” to those with other EMS impressions. Primary outcome was thrombolysis rate, and secondary outcomes were times from EMS scene arrival to ED arrival, CT, and treatment and times from ED arrival to CT and treatment. Chi-square and Mann-Whitney U-tests were used to compare treatment rates and times, respectively. Logistic regression (for rates) and median regression (for times) adjusted for NIHSS, GCS, age, sex, race, and prior stroke history. Results: Among 2,486 confirmed AIS patients from 1/1/2015-12/31/2015, 868 were transported by EMS, including 595 (69%) with EMS suspected stroke. Compared to EMS non-suspected strokes, patients with EMS suspected stroke patients were more likely to receive thrombolysis (18% vs 8%; OR 2.67, 95% CI 1.63-4.47) and had faster prehospital transport (30 vs 32 min, p=0.02), ED arrival to CT (27 vs 46 min, p Conclusions: In a large population-based study, EMS stroke identification is associated with a higher rate of and faster thrombolysis. Efforts to increase accuracy of EMS stroke identification is likely to have significant clinical impact by shortening treatment times.