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Background: Our primary objective was to evaluate if disparities in race, sex, age, and socioeconomic status (SES) exist in utilization of advanced neuroimaging in year 2015 in a population-based study. Our secondary objective was to identify the disparity trends and overall imaging utilization as compared with years 2005 and 2010. Methods: This was a retrospective, population-based study that utilized the GCNKSS (Greater Cincinnati/Northern Kentucky Stroke Study) data. Patients with stroke and transient ischemic attack were identified in the years 2005, 2010, and 2015 in a metropolitan population of 1.3 million. The proportion of imaging use within 2 days of stroke/transient ischemic attack onset or hospital admission date was computed. SES determined by the percentage below the poverty level within a given respondent’s US census tract of residence was dichotomized. Multivariable logistic regression was used to determine the odds of advanced neuroimaging use (computed tomography angiogram/magnetic resonance imaging/magnetic resonance angiogram) for age, race, gender, and SES. Results: There was a total of 10 526 stroke/transient ischemic attack events in the combined study year periods of 2005, 2010, and 2015. The utilization of advanced imaging progressively increased (48% in 2005, 63% in 2010, and 75% in 2015 [ P P P 55 years; adjusted odds ratio, 1.34 [95% CI, 1.15–1.57]; P Conclusions: Racial, age, and SES-related disparities exist in the utilization of advanced neuroimaging for patients with acute stroke. There was no evidence of a change in trend of these disparities between the study periods.

Background and ObjectivesThere is a rising incidence of infective endocarditis–related stroke (IERS) in the United States attributed to the opioid epidemic. A contemporary epidemiologic description is necessary to understand the impact of the opioid epidemic on clinical characteristics of IERS. We describe and analyze trends in the demographics, risk factors, and clinical features of IERS.MethodsThis is a retrospective cohort study within a biracial population of 1.3 million in the Greater Cincinnati/Northern Kentucky region. All hospitalized patients with hemorrhagic or ischemic stroke were identified and physician verified from the 2005, 2010, and 2015 calendar years using ICD-9 and ICD-10 codes. IERS was defined as an acute stroke attributed to infective endocarditis meeting modified Duke Criteria for possible or definite endocarditis. Unadjusted comparison of demographics, risk factors, outcome, and clinical characteristics was performed between each study period for IERS and non-IERS. An adjusted model to compare trends used the Cochran-Armitage test for categorical variables and a general linear model or Kruskal-Wallis test for numerical variables. Examination for interaction of endocarditis status in trends was performed using a general linear or logistic model.ResultsA total of 54 patients with IERS and 8,204 without IERS were identified during the study periods. Between 2005 and 2015, there was a decline in rates of hypertension (91.7% vs 36.0%;p= 0.0005) and increased intravenous drug users (8.3% vs 44.0%;p= 0.02) in the IERS cohort. The remainder of the stroke population demonstrated a significant rise in hypertension, diabetes, atrial fibrillation, and perioperative stroke. Infective endocarditis status significantly interacted with the trend in hypertension prevalence (p= 0.001).DiscussionFrom 2005 to 2015, IERS was increasingly associated with intravenous drug use and fewer risk factors, specifically hypertension. These trends likely reflect the demographics of the opioid epidemic, which has affected younger patients with fewer comorbidities.

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: Poorer socioeconomic status (SES) is associated with higher stroke incidence. Less is known about SES and stroke recurrence. We sought to obtain updated estimates of stroke incidence stratified by aggregate measures of SES, and to explore the association between SES and stroke recurrence. Methods: The Greater Cincinnati/Northern Kentucky region includes a population of 1.3 million, representative of the US population in terms of sociodemographics and percent black race. We ascertained all hospitalized strokes in the region in 2015 by screening ICD-9 codes 430-437 and ICD-10 codes I60-69, G45-46. Recurrent strokes were ascertained from 1/1/2015-12/31/2018. Patients’ home addresses were geocoded using DeGAUSS. Population estimates were obtained from the US Census Bureau using the 2015 5-year American Community Survey. Aggregate SES was estimated by percentage below poverty in each census tract. Regional incidence and recurrence rates were adjusted for age, sex, and race and calculated both with and without SES adjustment using Poisson regression models. Results: Stroke incidence and recurrence rates stratified by SES are shown in the Table. Poorer SES was associated with greater stroke incidence (p Conclusions: Poorer SES was associated with increased risk for both incident and recurrent stroke across races. Of the excess risk for stroke incidence among black individuals, 25.5% was accounted for by SES, while 35.1% of the excess risk for recurrence was accounted for by SES.

Background: Ischemic stroke is the 5 th leading cause of death in the US. As a measure of stroke severity, initial NIHSS has been used to predict clinical outcome. We sought to identify the optimal cut-points of NIHSS at initial presentation that are associated with higher 30-day mortality. Methods: In 2005, 2010, and 2015 all hospitalized, first acute ischemic stroke events occurring within the Greater Cincinnati area were ascertained. Potential ischemic stroke cases underwent chart abstraction and physician adjudication, including retrospective NIHSS score (range 0 - 42) based on clinical findings at initial presentation. Descriptive statistics for NIHSS were estimated by study year, demographics, and medical history. Data regarding mortality was obtained from the National Death Index. The Contal and O’Quigley method based on a modified log-rank test statistic was used to determine cut-points of the NIHSS score associated with 30-day mortality, and hazard ratios were obtained from Cox models with adjustment for sex, race, and age. Results: In 2005, 2010, and 2015 there were 1704, 1818 and 1852 ischemic stroke events with 30-day mortality rates of 10.5%, 9.6% and 9.0%, respectively. Optimal cut-points of NIHSS 16 were identified. Across all 3 periods, 3431 (84.5%) cases had NIHSS 0-8, 352 (8.7%) had NIHSS 9-16 and 274 (6.8%) >16. Kaplan Meier Survival Curves for the 3 NIHSS groups are shown in the Figure. Strokes with NIHSS >16 at initial presentation were associated with a 15-fold (HR with 95% CI: 13, 19) increase in the risk of death at 30-days compared to those with NIHSS Discussion: NIH Stroke Scale scores are a reliable predictor of mortality, with higher NIHSS scores having higher risk of death. The cut points reported identify subgroups of stroke patients with dramatically different prognoses. Future studies should assess if this excess mortality risk among severe strokes persists after the more widespread implementation of thrombectomy beyond 2015.

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:There are significant racial disparities in stroke in the United States, with Black individuals having a higher risk of incident stroke even when adjusted for traditional stroke risk factors. It is unknown whether Black individuals are also at a higher risk of recurrent stroke.Methods:Over an 18-month period spanning 2014-2015, we ascertained index stroke cases within the Greater Cincinnati/Northern Kentucky population of 1.3 million. We then followed all patients for 3 years and determined the risk of recurrence. Multivariable survival analysis was performed to determine the effect of Black race on recurrence.Results:There were 3816 patients with index stroke/TIA events in our study period, and 476 patients had a recurrent event within three years. The Kaplan-Meier estimate of 3-year recurrence rate was 15.4%. Age- and sex-adjusted stroke recurrence rate was higher in Black individuals (HR 1.34, 95% CI 1.1-1.6; p=0.003); however, when adjusted for traditional stroke risk factors including hypertension, diabetes, smoking status, age, and left ventricular hypertrophy, the association between Black race and recurrence was significantly attenuated and became nonsignificant (HR 1.1, 95% CI 0.9-1.36, p=0.32). At younger ages, Black race was more strongly associated with recurrence and this effect may not be fully attenuated by traditional stroke risk factors.Conclusions:Recurrent stroke was more common among Black individuals, but the magnitude of the racial difference was substantially attenuated and became nonsignificant when adjusted for traditional stroke risk factors. Interventions targeting these risk factors could reduce disparities in stroke recurrence.

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.

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: Stroke patients with a pre-existing disability are less likely to receive acute stroke treatments compared to those without a pre-existing disability. Using the Greater Cincinnati Northern Kentucky (GCNK) Stroke Study, we aimed to understand the disparities in inpatient and outpatient continuum of stroke care according to the patients’ pre-stroke functional status. Methods: We ascertained all hospitalized stroke patients ≥18 years old in year 2015 using ICD-9 430-436; ICD-10 I60-I67, G45-G46 within GCNK population; all cases were physician-reviewed. Per-stroke functional status was ascertained by trained research nurses during medical record review. We compared rates of in-hospital rehabilitative therapies, initiation of stroke prevention treatments, inpatient stroke workup (cardiac/vessel imaging), in-hospital and post-discharge rehabilitative therapies between ischemic stroke patients with pre-stroke modified Rankin score (mRS) 0-1 vs ≥2. Logistic regression was used to evaluate the association between pre-stroke mRS and these outcomes adjusting for age, presenting NIHSS, and insurance status. Results: Of 2476 patients with ischemic stroke in the GCNK population during 2015, 1326 (53%) had a pre-stroke mRS ≥2. Compared to those with pre-stroke mRS 0-1, these patients were less likely to receive complete stroke workup (aOR 0.86 [0.71-1.04]) and certain stroke prevention treatments (aOR 0.46[0.26-0.81], p Conclusions: Ischemic stroke patients with pre-stroke disability were less likely to receive complete in-hospital stroke workup and initiation of certain stroke preventive treatments. Further research into factors driving medical decision-making for stroke patients with a pre-stroke disability is urgently needed to ensure optimal continuum of stroke care.

Background: Acute ischemic stroke (AIS) is a leading cause of disability worldwide, with up to 30% of cases preceded by transient ischemic attack (TIA). Urgent evaluation of TIA symptoms is recommended to reduce risk of stroke, but not all patients with TIA symptoms seek evaluation. Our goal was to assess temporal trends in the demographics of such patients. Methods: Using the Greater Cincinnati/Northern Kentucky Stroke Study (GCNKSS) for years 2005, 2010, and 2015, we selected patients with a diagnosis of AIS using ICD-9/10 codes in adults ≥18yrs of age presenting to the ED. We identified patients who had a preceding TIA based on symptoms within 60 days of presentation, as judged by an adjudicating physician. Demographics, histories, and proportion of patients with TIA were compared across study years using Wilcoxon rank sum test or chi-square test. Results: We identified 5977 patients presenting with AIS across three epochs. Of these 207 (3%) had prior suspected TIA and did not seek immediate medical attention; 56/1790 (3%) in 2005, 62/1993 (3%) in 2010, and 70/2194 (3%) in 2015 (p-value=0.99). Patients with suspected TIA had increasing rates of previously diagnosed HLD and DM over the three time periods. No other risk factors or demographics showed a change over time. Known HTN was consistently prevalent across epochs (Table 2). Conclusion: Over the three epochs, 3% of AIS patients consistently did not seek emergent medical attention for a recent preceding TIA. A substantial proportion of these patients were increasingly already diagnosed with DM and HLD over the study periods, and the majority were persistently diagnosed with HTN. This is an opportune cohort for future targeted outreach.

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.

Introduction: Disparities exist in acute ischemic stroke care according to patients’ pre-stroke functional status. However, the effects of baseline disability on the presentation and care of patients with intracerebral hemorrhage (ICH) are unknown. We aimed to understand this using the Greater Cincinnati Northern Kentucky (GCNK) Stroke Study. Methods: We ascertained all hospitalized ICH patients ≥18 years old in 2015 using ICD-9 430-436; ICD-10 I60-I67, G45-G46 GCNK) population; all cases were physician-reviewed. Per-stroke functional status was ascertained by medical record review. Baseline NIHSS, Glasgow coma scale (GCS), imaging modalities (CT/MRI), in-hospital rehabilitative therapies (rate and frequency), initiation of antihypertensive treatment, and discharge disposition between patients with pre-ICH mRS 0-1 vs ≥2 were compared using Wilcoxon rank-sum or chi-square tests. Logistic regression was used to evaluate the association between pre-stroke mRS and in-hospital therapy, post-discharge therapy, and ICH workup adjusting for age, Glasgow score, insurance status, and ICH location. Results: Of 350 patients with ICH, 187 (53%) had a pre-ICH mRS ≥2. Compared to those with pre-stroke mRS 0-1, these patients had more severe clinical presentation as measured by NIHSS and GCS (table). Among patients who were not made comfort care, no association between pre-ICH mRS and performance of inpatient MRI or in-hospital and post-discharge rehabilitative therapies was found in adjusted analyses. Conclusions: Patients with pre-ICH mRS >2 were made comfort care at a higher rate, but for those not made comfort care there were no post-ICH disparities of care seen in the 2015 GCNK population-based cohort of 350 patients.

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: Anticoagulant-associated intracerebral hemorrhage (AA-ICH) quintupled in the Greater Cincinnati/Northern Kentucky (GC/NK) region from 1988 to 1999 in association with increasing warfarin use. Direct-acting oral anticoagulants (DOACs), available in 2010, have evidence of less bleeding risk, while atrial fibrillation detection rates have increased. We sought to determine if rates of AA-ICH continued to increase in the last decade within a large, bi-racial population. Methods: We identified all patients, 20 years or older, hospitalized with first-ever intracerebral hemorrhage (ICH) in GC/NK region in 1993/4, 1999, 2005, 2010 and 2015. AA-ICH was defined as ICH in patients prescribed warfarin, heparin or low molecular weight heparin, or a DOAC at the time of their ICH. Incidence rates were age-, sex- and race-adjusted to the 2010 US population. Change over time was tested using regression. All-cause case fatality was adjusted for age, sex and race and trend over time evaluated using a general linear model. Results: There was no significant change over time in the incidence rate for total ICH or AA-ICH from 1993 through 2015 (Table). As compared to ICH patients without anticoagulant use, patients with AA-ICH were more likely to be older, white, have hypertension, diabetes mellitus, hyperlipidemia, prior ischemic stroke and atrial fibrillation, but less likely to smoke. The age-, sex- and race-adjusted 30-day case fatality for ICH overall and AA-ICH also did not change significantly from 1993/4 to 2015 (Table). Warfarin utilization increased in our ICH population from 1993/4 (7.6%) to 2005 (17.7%), then decreased through 2015 (11.8%/DOAC 6.4%); p Conclusion: Despite increased incidence rates of AA-ICH in the late 1980s to 1990s, we observed no overall change in incidence or case-fatality rate from AA-ICH over the full 20-year period despite higher rates of atrial fibrillation detection which may be explained by higher rates of DOAC (vs warfarin) use.

Introduction: Endovascular (EVT) eligibility estimates using population-based, NIH-funded Greater Cincinnati Northern Kentucky (GCNK) Stroke Study 2010 data have been reported. Given the evolving EVT landscape, we present updated estimates of annual EVT eligibility using the 2015 GCNK epidemiological data and extrapolate to the 2021 US census. We project the potential increase in eligible patients in the US for each possible expanded indication with a randomized trial currently planned/underway. Methods: We ascertained all hospitalized AIS patients ≥18 years old in 2015 using ICD-9 430-436; ICD-10 I60-I67, G45-G46 within GCNK population; all cases were physician-reviewed. Patients presenting within 0-5 hrs of last known well (LKW) were considered EVT eligible if they had a pre-stroke mRS1 (for 0-5 hrs) or ≥2 (for 5-23 hrs), or larger core. Estimates of vessel occlusion and favorable imaging were applied based on literature review and expert opinions. The derived estimates were age, race and sex-adjusted to the 2015 US adult population and extrapolated to 2021 population. Results: Among the 1.3 million total (1.05m adult) GCNK population in 2015, 2741 adults had an ischemic stroke and 2176 had data available for this analysis. A total of 1978 presented within 23 hrs of LKW, and 1233 within 0-5 hrs of LKW. Further results are outlined in the figure. Conclusions: It is estimated 18,484 adult patients in the US in 2021 meet strict EVT eligibility criteria. An estimated 15,699 patients with low NIHSS, 9621 with unfavorable imaging, and 28,107 with pre-stroke disability may become eligible for EVT in the future annually. US stroke systems should be optimized to handle all EVT-eligible stroke patients both now and in the future.

Background: Posterior circulation strokes (PCS) make up 20% of all strokes, yet there is poor understanding of what factors contribute to poor clinical outcomes. We investigated clinical and demographic characteristics associated with poor clinical outcomes in PCS using a population-based biracial cohort. Methods: Greater Cincinnati Northern Kentucky Stroke Study (GSNKSS) 2010 and 2015 data was utilized to identify 1842 patients who were >20 years old with MRI-proven PCS. Eligible patients were then stratified based on functional outcomes (modified Rankin Scale/= 3, with >= 3 considered poor) according to demographics, stroke risk factors, tPA treatment, stroke location, and stroke mechanism. A multivariable logistic model was used to identify the predictors for poor functional outcomes. Results: Age, higher NIHSS, higher baseline mRS, hypertension, temporal, thalamus, and brainstem location, and cardioembolic mechanism were associated with poor clinical outcomes (Table). After multivariable analysis, age, higher NIHSS, higher baseline mRS, hypertension, temporal, thalamus, and brainstem location, and cardioembolic mechanism remained associated with poor outcomes. Conclusion: Understanding these factors associated with poor prognosis after posterior circulation stroke will allow for better prognostication and family counseling.

Background: Acute ischemic stroke (AIS) remains a leading cause of mortality and disability worldwide, with stroke etiology having an important role in work-up, management, and prognosis. The current AHA/ASA guidelines cite routine echocardiography as reasonable but not mandatory for the work-up of ischemic stroke. We sought to identify how often transthoracic echocardiogram (TTE) results would show a potentially treatment-altering finding. Methods: Using the Greater Cincinnati/Northern Kentucky Stroke Study (GCNKSS) for years 2005, 2010, and 2015, we selected patients with a new diagnosis of AIS using ICD-9/10 codes in adults ≥18yrs of age presenting to the emergency department and who had a TTE with stroke etiology of Cardioembolic, Small Vessel, or Large Vessel. All cases were physician reviewed and stroke etiology determined based on our epidemiologic criteria. Demographic information, medical history, electrocardiograms with atrial fibrillation (Afib), and TTE features were collected for each patient and compared across stroke etiology groups using Wilcoxon rank sum test and chi-square test, or Fisher’s exact test, as appropriate. Results: There were 5,490 patients presenting with AIS in the GCNKSS in 2005, 2010, and 2015 and 3,984 (73%) had a TTE performed. Of those with TTE, 2,422 (61%) had a presumed etiology of Small Vessel, Large Artery Atherosclerosis (LAA), or Cardioembolic (120 identified as “Other,” 1442 identified as “Undetermined”). Potential findings of TTE that could change management were 1% in Small Vessel, 2% in LAA, and 7% in Cardioembolic etiology strokes. Conclusion: In patients presenting with Small Vessel or LAA stroke etiologies, routine inpatient TTE rarely had management-changing findings. Future studies are needed in order to assess cost effective use of TTE in patients with established stroke etiology.

Background: There are limited data about the epidemiology and secondary stroke prevention strategies used for patients with depressed left ventricular ejection fraction (LVEF) and sinus rhythm following an acute ischemic stroke (AIS). We sought to describe the prevalence of LVEF ≤40% and sinus rhythm among patients with AIS and antithrombotic treatment practice in a multi-center cohort from 2002 to 2018. Methods: This was a multi-center, retrospective cohort study comprised of patients with AIS hospitalized in the Greater Cincinnati Northern Kentucky Stroke Study and 4 academic, hospital-based cohorts in the United States. A 1-stage meta-analysis of proportions was undertaken to calculate a pooled prevalence. Univariate analyses and an adjusted multivariable logistic regression model were performed to identify demographic, clinical, and echocardiographic characteristics associated with being prescribed an anticoagulant upon AIS hospitalization discharge. Results: Among 14 338 patients with AIS with documented LVEF during the stroke hospitalization, the weighted pooled prevalence of LVEF ≤40% and sinus rhythm was 5.0% (95% CI, 4.1–6.0%; I 2 , 84.4%). Of 524 patients with no cardiac thrombus and no prior indication for anticoagulant who survived postdischarge, 200 (38%) were discharged on anticoagulant, 289 (55%) were discharged on antiplatelet therapy only, and 35 (7%) on neither. There was heterogeneity by site in the proportion discharged with an anticoagulant (22% to 45%, P 8 (odds ratio, 2.0 [95% CI, 1.1–3.8]) were significant, independent predictors of being discharged with an anticoagulant in an adjusted analysis. Conclusions: Nearly 5% of patients with AIS have a depressed LVEF and are in sinus rhythm. There is significant variation in the clinical practice of antithrombotic therapy prescription by site and stroke severity. Given this clinical equipoise, further study is needed to define optimal antithrombotic treatment regimens for secondary stroke prevention in this patient population.

Enlarged perivascular spaces (EPVS), specifically in stroke patients, has been shown to strongly correlate with other measures of small vessel disease and cognitive impairment at 1 year follow-up. Typical grading of EPVS is often challenging and time consuming and is usually based on a subjective visual rating scale. The purpose of the current study was to develop an interpretable, 3D neural network for grading enlarged perivascular spaces (EPVS) severity at the level of the basal ganglia using clinical-grade imaging in a heterogenous acute stroke cohort, in the context of total cerebral small vessel disease (CSVD) burden. T2-weighted images from a retrospective cohort of 262 acute stroke patients, collected in 2015 from 5 regional medical centers, were used for analyses. Patients were given a label of 0 for none-to-mild EPVS (

Objectives Population-level estimates of the median intracerebral hemorrhage (ICH) volume would allow for the evaluation of clinical trial external validity and determination of temporal trends. We previously reported the median ICH volume in 1988. However, differences in risk factor management, neuroimaging, and demographics may have affected ICH volumes. The goal of this study is to determine the median volume of ICH within a population-based cross-sectional study, including whether it has changed over time. Methods The Genetic and Environmental Risk Factors for Hemorrhagic Stroke study was a population-based study of ICH among residents of the Greater Cincinnati/Northern Kentucky region from 2008 through 2012. This study utilizes those data and compares with ICH cases from the same region in 1988. Initial computed tomography images of the head were reviewed, and ICH volumes were calculated using consistent methodology. Results From 2008 through 2012, we identified 1117 cases of ICH. The median volume of ICH was 14.0 mL and was lower in black (11.6) than in white (15.5) patients. Median volumes of lobar and deep ICH were 28.8 mL and 9.8 mL, respectively. Median ICH volume changed significantly from 1988 to 2008–2012, with age-and-race-adjusted volume decreasing from 18.3 mL to 13.76 mL (p = 0.025). Conclusions Median volume of ICH was 13.76 mL, and this should be considered in clinical trial design. Median ICH volume has apparently decreased from 1988 to 2008–2012.

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.

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.

Introduction: After WARCEF, there is limited data about the epidemiology and treatment strategies for patients after an acute ischemic stroke (AIS) with existing or new left ventricular cardiomyopathy (CM) and sinus rhythm (SR). We aim to estimate prevalence, describe treatment practice, and analyze antithrombotic strategies. Methods: We calculated the prevalence of CM (ejection fraction or EF ≤40%) and SR among AIS patients with EF measurements and the frequency of anticoagulation upon discharge at Massachusetts General Hospital (MGH), Rhode Island Hospital (RIH), Yale-New Haven Hospital (YNHH), and the Greater Cincinnati/Northern Kentucky Stroke Study (GCNKSS). We collected longitudinal outcome data for patients with AIS, CM, and SR at RIH and YNHH spanning 2014-2018 and computed the hazard of a combined outcome of AIS, intracranial hemorrhage, major hemorrhage, myocardial infarction, and death up to 12 months after AIS by anticoagulation status. Results: Of 11,996 AIS patients with documented EF at the 4 sites, 693 had CM and SR (MGH N=333/5481, GCNKSS N=250/3284, RIH N=30/1549, YNHH N=80/1682). The pooled percentage of AIS patients with CM and SR was 5% (95% C.I. 3-7%, I 2 =96.5%). Mean age was 67 years (SD 14.2), 47.1% were female, 31.9% had pre-stroke CM, and mean NIHSS was 7.1 (SD 7.1). Among survivors, 241 were discharged on anticoagulation, 326 on antiplatelet, and 38 on neither. There was heterogeneity by site in the proportion discharged with an anticoagulant versus an antiplatelet only (MGH 49.8%, GCNKSS 29.6%, RIH 32.3%, YNHH 36.7%, p Conclusions: AIS patients have concomitant cardiomyopathy and post-stroke antithrombotic prescription practice varies. Further study is needed to determine the association between post-stroke anticoagulation and subsequent ischemic and hemorrhagic events.

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: Intracerebral hemorrhage (ICH) has the highest morbidity and mortality rate of the major stroke subtypes. Volume is a well-established predictor of outcome. Theoretically, ICH should expand more in areas of less resistance. We hypothesize that 1) expansion perpendicular to neural tracts (axially) will be less great than expansion parallel to tracts (vertically) and 2) differing effect on outcome will occur based on axial and vertical areas of hemorrhage. Methods: The Genetic and Environmental Risk Factors of Hemorrhagic Stroke (GERFHS) study is a population-based case-control study. Each case of ICH within the 5 county region of Greater Cincinnati was evaluated for volume of hemorrhage with a subset completing 3 month telephone follow-up to obtain data including modified Rankin Scale (mRS). Baseline variables were assessed for poor outcome, defined as mRS greater than or equal to 3 at 90 days. Results: From July 2009 to December 2012, 1205 cases of ICH were identified, of which 304 had 3-month follow up. The table presents univariate association with outcome. More than 86% of hemorrhages had greater vertical area than axial area. On multivariable analysis controlling for ICH score variables, vertical area showed a trend toward worse outcome (OR 1.09, p= 0.06) vs axial area (OR 0.97, p=0.69) which was not found to have a significant effect on outcome independent of total volume. Conclusion: Most patients have greater vertical expansion of ICH than axial expansion. This pattern of hemorrhage growth is consistent with neural tracts having less resistance vertically. If the greater impact on outcome is confirmed, improved outcome and trial inclusion criteria may be determined.

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: About 21% of acute ischemic stroke (AIS) patients present to medical attention with an elevated cardiac troponin (cTn). Previously, we described that elevated cTn is associated with an increased case-fatality at 1 year. However, it is not clear if there is a dose-dependent relationship between cTn and case-fatality, or if this effect is related to causes of death. Methods: Within a catchment area of 1.3 million we screened local hospital admissions using ICD-9/10 codes 430-436/I60-I68, G45-46 in 2014/2015, and ascertained all physician-confirmed AIS cases by retrospective chart review. Positive cTn was defined by the standard 99th percentile. To account for by hospital variance in cTn results in machine brands and normal ranges, cTn values were log-transformed and centered. Case fatality at 1 year and cause of death was obtained from the National Death Index database. Logistic regression evaluated the impact of cTn on case fatality, and included demographic and clinical risk factors in the model. The percentage with all-cause and cardiac/non-cardiac case-fatality was computed by quartiles of centered cTn levels and compared using the chi-square test. Results: In 2014/2015, there were 2989 AIS cases ascertained, which were 53% female, 30% black, with a mean age of 70 (SD 14). 441 patients with hypertropinemia were included in the analysis. See Table for case fatality at 1 year by quartile of centered cTn levels. There was no association between cTN and non-cardiac case-fatality. After adjustment for demographic and clinical characteristics, every 0.5 point increase in the centered cTn level increased the cardiac case-fatality by OR 1.19 (1.09, 1.31), p Discussion: We found that the impact of hypertropinemia on case fatality after AIS appears to be a dose-dependent association: as cTn increases, so does the cardiac case-fatality. This suggests that the degree of cTn elevation is likely an important prognostic marker for cardiac death in AIS patients.

Background: Data from the Greater Cincinnati Northern Kentucky Stroke Study (GCNKSS) have demonstrated stable or increasing stroke incidence rates in young adults with differences by sex and race, suggesting the need for targeted approaches to stroke prevention in the young. We aimed to describe trends over time in prevalence of stroke risk factors among adults ages 20-54 with stroke by sex and race. Methods: Cases of incident stroke (IS, ICH, SAH) occurring in those 20-54 years old and living in a 5-county area of southern Ohio/northern Kentucky were ascertained during 5 study periods (1993-1994, 1999, 2005, 2010, 2015). All physician-adjudicated inpatient events and a sampling of outpatient events were included, excluding nursing home events. Data on risk factors (hypertension, diabetes, obesity (BMI≥30), and high cholesterol) diagnosed prior to stroke were abstracted from medical records, and prevalence of each risk factor was reported over time in race/sex groups. Trends over time were examined using the Cochran-Armitage test. Results: Over the 5 study periods, 1204 incident strokes were included; 49% were women, 33% were black, and mean age was 46 (SD 7) years. Premorbid hypertension increased over time in Black women (48% in 1993/4 to 76% in 2015, p=0.005) but not in any other race/sex group (all p>0.05). Premorbid high cholesterol increased significantly in all race/sex groups (Figure, all p Conclusions: Among patients aged 20-54 with incident stroke in a large population-based study, the change in the prevalence of hypertension and high cholesterol differed by sex and race, while obesity and diabetes were stable over time in all race/sex groups. Future research is needed to address risk factor control at a population level and to understand the role of undiagnosed pre-stroke risk factors in the young.

Background and Purpose— Patients with intracerebral hemorrhage (ICH) and atrial fibrillation (AF) are at risk for ischemic events. While risk calculators (CHA 2 DS 2 -VASc and HAS-BLED) have been validated to assess risk for ischemic stroke and major bleeding in AF patients, decisions about anticoagulation must consider the net clinical benefit of anticoagulation. Furthermore, stroke and bleeding risk are highly correlated, making decisions more difficult. Methods— We examined patients in the GERFHS III study (Genetic and Environmental Risk Factors for Hemorrhagic Stroke)—a population-based retrospective study of spontaneous ICH patients without a structural or traumatic cause in the Greater Cincinnati/Northern Kentucky region between July 2008 and December 2012. CHA 2 DS 2 -VASc and HAS-B(L)ED (minus L because labile international normalized ratio was unavailable) scores were calculated for ICH patients with AF. Using a Markov state transition model, we estimated net clinical benefit of anticoagulation relative to no treatment in quality-adjusted life years (QALYs). We defined minimal clinically relevant benefit as 0.1 QALYs. Results— Among 1186 cases of spontaneous ICH, 95 cases had AF and met our survival criteria. Within 1 year, 8 of 95 (8%) would be expected to have a major bleeding event on anticoagulation, and 5 of 95 (5%) of patients would be expected to have an ischemic stroke off anticoagulation. Sixty-eight of 95 (71%) patients would have higher risk for major bleeding than for ischemic stroke. Anticoagulation with directly acting anticoagulants would result in no clinically significant gain or loss in 73%. Roughly 12% would gain >0.1 QALYs, and 15% would lose >0.1 QALYs. Among patients receiving aspirin, most have no significant net clinical benefit or loss. Overall, anticoagulation of the entire cohort would result in an aggregate loss of 0.92 QALYs. Conclusions— Our analysis suggests that universal anticoagulation after ICH would be associated with a net loss of QALY. Additional factors should be considered before anticoagulating patients with AF after ICH. Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT00930280.

Background: Both intraventricular hemorrhage (IVH) and white matter lesion (WML) severity are associated with higher rates of death and disability among cases of intracerebral hemorrhage (ICH). Prior reports suggest higher WML burden is associated with propensity of IVH. However, those analyses were not stratified by location. Our objective was to investigate the hypothesis that a higher degree of WML would be associated with a higher risk of IVH after controlling for ICH location. Methods: The Genetic and Environmental Risk Factors for Hemorrhagic Stroke (GERFHS) III study was a prospective study of hemorrhagic stroke in the Greater Cincinnati/Northern Kentucky region. We utilized the interviewed cohort from the study and systematically graded WML using the Van Swieten Scale (0-4) and presence or absence of IVH in baseline head CT scans. Additional variables included ICH volume, location of ICH and vascular risk factors. We used multiple logistic regression with backward elimination to adjust for relevant covariates. Results: Among the included 426 ICH patients (mean± SD age 71.2± 13.8; 49% females), 161 (38%) had presence of IVH. In patients with IVH, the proportion of severe WML (39.7%) was significantly higher compared with patients without IVH (27.2%) (p=0.0044). The median volume of ICH was 14.4 mL (IQR, 4.9-46.3) in patients with IVH as compared with 8.9 ml (IQR, 2.6-20.8) in patients without IVH (p Conclusion: Moderate to severe white matter lesions are a risk for intraventricular hemorrhage. Further studies are needed to determine if greater severity of IVH or subsequent rupture into IVH are associated with higher grades of WML.

BACKGROUND: Intraventricular hemorrhage (IVH) and white matter lesion (WML) severity are associated with higher rates of death and disability in intracerebral hemorrhage (ICH). A prior report identified an increased risk of IVH with greater WML burden but did not control for location of ICH. We sought to determine whether a higher degree of WML is associated with a higher risk of IVH after controlling for ICH location. METHODS: Utilizing the patient population from two large ICH studies; the Genetic and Environmental Risk Factors for Hemorrhagic Stroke (GERFHS III) Study and the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) Study, we graded WML using the Van Swieten Scale (0-1 for mild, 2 for moderate, and 3-4 for severe WML) and presence or absence of IVH in baseline CT scans. We used multivariable regression models to adjust for relevant covariates. RESULTS: Among 3023 ICH patients, 1260 (41.7%) had presence of IVH. In patients with IVH, the proportion of severe WML (28.6%) was higher compared with patients without IVH (21.8%) (p

Objective: Patients on antiplatelet (AP) or anticoagulant (AC) agents cause more alarm when they develop intracerebral hemorrhage (ICH) compared with non-users. This analysis aimed to quantitatively evaluate the differences in the hospital course of ICH patients based on underlying AP and/or AC use, using a population-based cohort. Methods: Genetic and Environmental Risk Factors for Hemorrhagic Stroke (GERFHS III) was a population-based study of spontaneous ICH among residents of the five-county Greater Cincinnati/Northern Kentucky region between July 2008 and December 2012. Baseline demographics, medications, hospital course, and discharge disposition were collected. Initial and subsequent computed tomography (CT) images of the head were reviewed to assess ICH location, volume, and presence of intraventricular hemorrhage (IVH). Change in ICH volume was calculated when repeat CT image was available. Results: There were 1121 cases of ICH during the study period. A higher proportion of white patients were on AP or AC than other races (56.4% vs. 39.7%, p Conclusion: Pre-ICH AC use was associated with greater ICH volume increase and inpatient death. There was no significant difference in number of IVH, rate of surgical treatment, or length of stay. Inpatient mortality did not differ between AP users and non-users.

Introduction: There is a trend towards ischemic stroke (IS) occurring at younger ages. We sought to better characterize outcomes and mortality over 3 years by age at time of stroke within a large, biracial population. Methods: Incident IS were ascertained during the 2005 and 2010 study periods of our population based epidemiology study via ICD-9 codes 430-436. Research nurse coordinators performed medical record abstraction on all potential events, which were then adjudicated by study physicians as case/not a case. Abstractions included discharge or 30-day outcomes (if available) as measured by modified Rankin scale (mRS). Mortality for IS events out to 3 years was determined via all available information including the Social Security Death Index. We compared the outcomes and post-stroke mortality by 20-55 (young stroke) versus >55 years, and by decade. Descriptive statistics are reported as n (%), and mean (SD) or median (25 th and 75 th %ile) as appropriate. The primary analysis examined the effect of age, race and sex using regression, life table and proportional hazards models. Results: Results are shown in the table. IS in the young occurred more frequently among black cases. The median rNIHSS was 3 although the NIHSS distribution trended towards more severe IS in the older age group. Young strokes had lower baseline and 30-day mRS. The mortality rate was greater in the older ages, at each time point and overall. After adjusting for race, sex and stroke severity the hazard ratio for lower survival in the strokes >55 years old was 4.03 (95% CI 3.15, 5.17). Conclusion: IS patients < 55 years old are less likely to die after stroke. Young stroke occurs in demographically different populations than older strokes and this group would benefit from further study.

Background: Patients with intracerebral hemorrhage (ICH) and atrial fibrillation (a-fib) are at risk for having future ischemic events after stopping anticoagulation. Risk calculators (CHA 2 DS 2 -VASc and HAS-BLED) have been validated to assess risk for ischemic stroke and for major bleeding in a-fib patients. We sought to compare the distribution of these scores among ICH patients with a-fib within a large biracial population. Methods: The Genetic and Environmental Risk Factors for Hemorrhagic Stroke (GERFHS III) Study included a population-based retrospective chart review of spontaneous ICH among residents of the five-county Greater Cincinnati/Northern Kentucky region between 7/2008 and 12/2012. CHA 2 DS 2 -VASc (risk of ischemic stroke) and HAS-BED (risk of bleeding with anticoagulation; minus “L” because “labile INR” was unavailable) scores were calculated for all ICH patients with a-fib who survived the hospital stay. Published risk coefficients for each score were used to calculate predicted ischemic and bleeding events within one year of onset. Results: Among 1186 cases of spontaneous ICH, 232 had a-fib, of which 123 patients were excluded due to inpatient death or discharge to hospice. Among the remaining 109 cases, 7-8 would be expected to have a major bleeding event (on anticoagulation), and about 6 patients would be expected to have an ischemic stroke within one year (off anticoagulation), with 73 of the 109 patients having higher risk for major bleeding than for ischemic stroke. The correlation between the two scores was weak (Spearman r=.220, p=.021). Discussion: Comparison of CHA 2 DS 2 -VASc and HAS-BED scores suggest a higher CHA 2 DS 2 -VASc threshold for considering anticoagulation is needed for ICH a-fib patients to balance their higher risk of major bleeding. Further evaluation of the consequences of ischemic stroke and major bleeding would be needed to better understand the best treatment strategies for our patients.

Background: While patients (pts) with atrial fibrillation (AF) face a risk of ischemic events, AF pts with intracerebral hemorrhage (ICH) are at increased risk of bleeding with anticoagulation (AC). Optimal decision-making must weigh the tradeoffs between these competing risks. Our goal was to analyze the impact of AC decisions on projected quality-adjusted life years (QALYs) pts with both ICH and AF within a population. Methods: The Genetic and Environmental Risk Factors for Hemorrhagic Stroke (GERFHS III) Study is a population-based evaluation of spontaneous ICH among residents of the five-county Greater Cincinnati/Northern Kentucky study region. The study period was 7/08-12/12. Pts with ICH and AF surviving the hospital stay were included. Medical history and demographics were entered into the Atrial Fibrillation Decision Support Tool, which is a 29-state Markov decision analytic model that projects patient-level QALYs for 7 thromboprophylaxis treatment strategies, using published event rates from CHADSVASC, HAS-B(L)ED, the Friberg ICH prediction model and clinical trials of anticoagulants (including warfarin and direct anticoagulants, DOACs), as well as published rates of outcomes for each possible event. Results: In the study period, there were 1186 cases of spontaneous ICH, 232 with a-fib, of which 123 were excluded because of inpatient death/discharge to hospice. Among the 109 cases, the aggregate net loss for AC was 16.9 QALYs; however there were 10 cases (9%) that gained > 0.1 QALYs with AC. The table displays a heat map showing aggregate gain/loss of QALYs with AC (compared with no treatment) for the cohort, displayed by their CHADSVASC and HASBED scores. Conclusion: We found that 91% of our ICH pts with AF would have either no change or a loss of QALYs with AC. However, given lower bleeding rates with DOACs, anticoagulation may be beneficial in a very select subset of AF pts with ICH. Thresholds for AC treatment should be considered carefully in this population.

Introduction: Immediate post-stroke discharge destination is easily determined. Long-term disposition and healthcare utilization is more difficult to study due to the variability in outcomes, including multiple transitions for many patients. We sought to longitudinally determine place of residence and physician follow-up in a defined population. Methods: Our population-based stroke epidemiology study retrospectively ascertains hospitalized ischemic and hemorrhagic strokes via ICD-9/10 codes within 5 counties in the greater Cincinnati metropolitan region. For this study, post-stroke dispositions and physician encounters for ischemic strokes that presented to one healthcare system of 4 community hospitals from 1/1/15 to 12/31/15 were analyzed by mining patient electronic medical records (EMRs). Disposition was analyzed at discharge, 3, and 6 months post-stroke, and outpatient and emergency department (ED) visits, and hospital admissions, were tabulated at 3, 6, and 12 months. The first post-discharge physician encounter was also assessed, and time to encounter was considered. Previous analysis has shown that this network is relatively self-contained with few transfers to other health systems, making it ideal for this study. Results: See figure for details. Only 17% of the cohort saw a neurologist within 1 year, whereas 73% saw a primary care provider (PCP) and 37% saw a cardiologist. PCPs accounted for 56% of the first post-stroke encounters. Over 24% of the cohort visited the ED or were re-hospitalized before having their first outpatient visit. Conclusions: In a community setting, PCPs are responsible for the majority of post-stroke care, and fewer than one in five patients sees a neurologist post-stroke. Future work will include additional analysis to determine whether the results from this health system are consistent with others in our region.

Background: We previously followed a cohort of survivors longitudinally with direct interview for outcomes. We then proved that we could obtain similar outcomes by tracking people in a health information exchange followed by first phone call contact at 3 months, thus minimizing contact. This study sought to determine the feasibility of estimating population-based post-stroke outcomes using information available in the electronic medical record (EMR) without any patient contact. Methods: Our study is a retrospective population-based epidemiology project that ascertains hospitalized strokes via ICD-discharge codes (ICD-9 430-436, ICD-10 I60-I67, G45-G46). Our study region encompasses 5 greater Cincinnati counties; study period 1/1/15-12/31/15. For this pilot outcomes study, we identified all ischemic strokes that presented to a system of 4 hospitals and performed phone calls at 3 and 6 months to determine current place of residence and functional outcomes including the modified Rankin Score (mRS) and the Euroqol (EQ-5D). Simultaneously, our lead Study Coordinator reviewed all available EMR records and used this information to estimate outcome status blinded to phone call results. We compared the “gold-standard” of interview-determined place of residence, mRS and EQ-5D to those estimated from EMR using the either the Kappa statistic or interclass correlation (ICC), as appropriate. Results: See Table for details. Using standard definitions of Kappa/ICC, estimation of 3- and 6-mo place of residence was “almost perfect” and estimation of mRS grade and EQ-5D was “substantial”. Censoring observations where no EMR information was available did not reduce Kappa/ICC. Conclusion: This work shows promise in using EMR information to accurately estimate post-stroke outcomes without patient contact, to allow a population-based estimation of outcome. Future work will involve machine-learning to improve our accuracy in outcomes estimation from EMR information.

Intracerebral hemorrhage (ICH) is the stroke subtype with the worst prognosis and has no established acute treatment. ICH is classified as lobar or nonlobar based on the location of ruptured blood vessels within the brain. These different locations also signal different underlying vascular pathologies. Heritability estimates indicate a substantial genetic contribution to risk of ICH in both locations. We report a genome-wide association study of this condition that meta-analyzed data from six studies that enrolled individuals of European ancestry. Case subjects were ascertained by neurologists blinded to genotype data and classified as lobar or nonlobar based on brain computed tomography. ICH-free control subjects were sampled from ambulatory clinics or random digit dialing. Replication of signals identified in the discovery cohort with p < 1 × 10(-6) was pursued in an independent multiethnic sample utilizing both direct and genome-wide genotyping. The discovery phase included a case cohort of 1,545 individuals (664 lobar and 881 nonlobar cases) and a control cohort of 1,481 individuals and identified two susceptibility loci: for lobar ICH, chromosomal region 12q21.1 (rs11179580, odds ratio [OR] = 1.56, p = 7.0 × 10(-8)); and for nonlobar ICH, chromosomal region 1q22 (rs2984613, OR = 1.44, p = 1.6 × 10(-8)). The replication included a case cohort of 1,681 individuals (484 lobar and 1,194 nonlobar cases) and a control cohort of 2,261 individuals and corroborated the association for 1q22 (p = 6.5 × 10(-4); meta-analysis p = 2.2 × 10(-10)) but not for 12q21.1 (p = 0.55; meta-analysis p = 2.6 × 10(-5)). These results demonstrate biological heterogeneity across ICH subtypes and highlight the importance of ascertaining ICH cases accordingly.