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Objective: Diabetes is a well known risk factor for stroke, but the impact of diabetes on stroke incidence rates is not known. This study uses a population-based study to describe the epidemiology of ischemic stroke in diabetic patients.Research Design and Methods: Hospitalized cases were ascertained by ICD-9 discharge codes, prospective screening of emergency department admission logs, and review of coroner's cases. A sampling scheme was used to ascertain cases in the out-of-hospital setting. All potential cases underwent detailed chart abstraction by study nurses followed by physician review. Diabetes-specific incidence rates, case fatality rates, and population-attributable risks were estimated.Results: Ischemic stroke patients with diabetes are younger, more likely to be African American, and more likely to have hypertension, myocardial infarction, and high cholesterol than nondiabetic patients. Age-specific incidence rates and rate ratios show that diabetes increases ischemic stroke incidence at all ages, but this risk is most prominent before age 55 in African Americans and before age 65 in whites. One-year case fatality rates after ischemic stroke are not different between those patients with and without diabetes.Conclusions: Given the "epidemic" of diabetes, with substantially increasing diabetes prevalence each year across all age- and race/ethnicity groups, the significance of diabetes as a risk factor for stroke is becoming more evident. Diabetes is clearly one of the most important risk factors for ischemic stroke, especially in those patients less than 65 years of age. We estimate that 37-42% of all ischemic strokes in both African Americans and whites are attributable to the effects of diabetes alone or in combination with hypertension. [ABSTRACT FROM AUTHOR]

Background: Hypertension is a stroke risk factor with known disparities in prevalence and management between Black and White patients. We sought to identify if racial differences in presenting blood pressure (BP) during acute ischemic stroke exist., Methods and Results: Adults with acute ischemic stroke presenting to an emergency department within 24 hours of last known normal during study epochs 2005, 2010, and 2015 within the Greater Cincinnati/Northern Kentucky Stroke Study were included. Demographics, histories, arrival BP, National Institutes of Health Stroke Scale score, and time from last known normal were collected. Multivariable linear regression was used to determine differences in mean BP between Black and White patients, adjusting for age, sex, National Institutes of Health Stroke Scale score, history of hypertension, hyperlipidemia, smoking, stroke, body mass index, and study epoch. Of 4048 patients, 853 Black and 3195 White patients were included. In adjusted analysis, Black patients had higher presenting systolic BP (161 mm Hg [95% CI, 159-164] versus 158 mm Hg [95% CI, 157-159], P <0.01), diastolic BP (86 mm Hg [95% CI, 85-88] versus 83 mm Hg [95% CI, 82-84], P <0.01), and mean arterial pressure (111 mm Hg [95% CI, 110-113] versus 108 mm Hg [95% CI, 107-109], P <0.01) compared with White patients. In adjusted subanalysis of patients <4.5 hours from last known normal, diastolic BP (88 mm Hg [95% CI, 86-90] versus 83 mm Hg [95% CI, 82-84], P <0.01) and mean arterial pressure (112 mm Hg [95% CI, 110-114] versus 108 mm Hg [95% CI, 107-109], P <0.01) were also higher in Black patients., Conclusions: This population-based study suggests differences in presenting BP between Black and White patients during acute ischemic stroke. Further study is needed to determine whether these differences influence clinical decision-making, outcome, or clinical trial eligibility.

Background: Dysphagia after stroke is common and can impact morbidity and death. The purpose of this population-based study was to determine specific epidemiological and health risk factors that impact development of dysphagia after acute stroke., Methods and Results: Ischemic and hemorrhagic stroke cases from 2010 and 2015 were identified via chart review from the GCNKSS (Greater Cincinnati Northern Kentucky Stroke Study), a representative sample of ≈1.3 million adults from southwestern Ohio and northern Kentucky. Dysphagia status was determined on the basis of clinical assessments and necessity for alternative access to nutrition via nasogastric or percutaneous endoscopic gastrostomy tube placement. Comparisons between patients with and without dysphagia were made to determine differences in baseline characteristics and premorbid conditions. Multivariable logistic regression determined factors associated with increased risk of dysphagia. Dysphagia status was ascertained from 4139 cases (1709 with dysphagia). Logistic regression showed that increased age, Black race, higher National Institutes of Health Stroke Scale score at admission, having a hemorrhagic stroke (versus infarct), and right hemispheric stroke increased the risk of developing dysphagia after stroke. Factors associated with reduced risk included history of high cholesterol, lower prestroke modified Rankin Scale score, and white matter disease., Conclusions: This study replicated previous findings of variables associated with dysphagia (older age, worse stroke, right-sided hemorrhagic lesions), whereas other variables identified were without clear biological rationale (eg, Black race, history of high cholesterol, and presence of white matter disease) and should be investigated in future studies to determine biological relevance and potential influence in stroke recovery.

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 <0.001]). In the combined study year multivariable model, advanced imaging was associated with age and SES. Younger patients (≤55 years) were more likely to have advanced imaging compared with older patients (adjusted odds ratio, 1.85 [95% CI, 1.62-2.12]; P <0.01), and low SES patients were less likely to have advanced imaging compared with high SES (adjusted odds ratio, 0.83 [95% CI, 0.75-0.93]; P <0.01). A significant interaction was found between age and race. Stratified by age, the adjusted odds of advanced imaging were higher for Black patients compared with White patients among older patients (>55 years; adjusted odds ratio, 1.34 [95% CI, 1.15-1.57]; P <0.01), but no racial differences among the young., 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: 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 <0.001). Between 1993/1994 and 2015, documented substance use increased in all demographic subgroups. Adjusting for gender, comorbidities, and National Institutes of Health Stroke Scale, predictors of toxicology screens included Black race (adjusted odds ratio, 1.58 [95% CI, 1.02-2.45]), younger age (adjusted odds ratio, 0.70 [95% CI, 0.53-0.91], per 10 years), current smoking (adjusted odds ratio, 1.62 [95% CI, 1.06-2.46]), and treatment at an academic hospital (adjusted odds ratio, 1.80 [95% CI, 1.14-2.84]). After adding chart-reported substance use to the model, only chart-reported substance abuse and age were significant., 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: 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 <0.0001). Cohort site and National Institutes of Health Stroke Severity scale >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 (< 10) and 1 for moderate-to-severe EPVS (≥ 10). A three-dimensional residual network of 152 layers (3D-ResNet-152) was created to predict EPVS severity and 3D gradient class activation mapping (3DGradCAM) was used for visual interpretation of results. Our model achieved an accuracy 0.897 and area-under-the-curve of 0.879 on a hold-out test set of 15% of the total cohort (n = 39). 3DGradCAM showed areas of focus that were in physiologically valid locations, including other prevalent areas for EPVS. These maps also suggested that distribution of class activation values is indicative of the confidence in the model's decision. Potential clinical implications of our results include: (1) support for feasibility of automated of EPVS scoring using clinical-grade neuroimaging data, potentially alleviating rater subjectivity and improving confidence of visual rating scales, and (2) demonstration that explainable models are critical for clinical translation., (© 2022. The Author(s).)

Background and Purpose- Sex differences in stroke incidence over time were previously reported from the GCNKSS (Greater Cincinnati/Northern Kentucky Stroke Study). We aimed to determine whether these differences continued through 2015 and whether they were driven by particular age groups. Methods- Within the GCNKSS population of 1.3 million, incident (first ever) strokes among residents ≥20 years of age were ascertained at all local hospitals during 5 periods: July 1993 to June 1994 and calendar years 1999, 2005, 2010, and 2015. Out-of-hospital cases were sampled. Sex-specific incidence rates per 100 000 were adjusted for age and race and standardized to the 2010 US Census. Trends over time by sex were compared (overall and age stratified). Sex-specific case fatality rates were also reported. Bonferroni corrections were applied for multiple comparisons. Results- Over the 5 study periods, there were 9733 incident strokes (56.3% women). For women, there were 229 (95% CI, 215-242) per 100 000 incident strokes in 1993/1994 and 174 (95% CI, 163-185) in 2015 ( P <0.05), compared with 282 (95% CI, 263-301) in 1993/1994 to 211 (95% CI, 198-225) in 2015 ( P <0.05) in men. Incidence rates decreased between the first and last study periods in both sexes for IS but not for intracerebral hemorrhage or subarachnoid hemorrhage. Significant decreases in stroke incidence occurred between the first and last study periods for both sexes in the 65- to 84-year age group and men only in the ≥85-year age group; stroke incidence increased for men only in the 20- to 44-year age group. Conclusions- Overall stroke incidence decreased from the early 1990s to 2015 for both sexes. Future studies should continue close surveillance of sex differences in the 20- to 44-year and ≥85-year age groups, and future stroke prevention strategies should target strokes in the young- and middle-age groups, as well as intracerebral hemorrhage.

Objective: 1) To develop a machine learning approach for detecting stroke cases and subtypes from hospitalization data, 2) to assess algorithm performance and predictors on real-world data collected by a large-scale epidemiology study in the US; and 3) to identify directions for future development of high-precision stroke phenotypic signatures., Materials and Methods: We utilized 8,131 hospitalization events (ICD-9 codes 430-438) collected from the Greater Cincinnati/Northern Kentucky Stroke Study in 2005 and 2010. Detailed information from patients' medical records was abstracted for each event by trained research nurses. By analyzing the broad list of demographic and clinical variables, the machine learning algorithms predicted whether an event was a stroke case and, if so, the stroke subtype. The performance was validated on gold-standard labels adjudicated by stroke physicians, and results were compared with stroke classifications based on ICD-9 discharge codes, as well as labels determined by study nurses., Results: The best performing machine learning algorithm achieved a performance of 88.57%/93.81%/92.80%/93.30%/89.84%/98.01% (accuracy/precision/recall/F-measure/area under ROC curve/area under precision-recall curve) on stroke case detection. For detecting stroke subtypes, the algorithm yielded an overall accuracy of 87.39% and greater than 85% precision on individual subtypes. The machine learning algorithms significantly outperformed the ICD-9 method on all measures (P value<0.001). Their performance was comparable to that of study nurses, with better tradeoff between precision and recall. The feature selection uncovered a subset of predictive variables that could facilitate future development of effective stroke phenotyping algorithms., Discussion and Conclusions: By analyzing a broad array of patient data, the machine learning technologies held promise for improving detection of stroke diagnosis, thus unlocking high statistical power for subsequent genetic and genomic studies.

Background and Purpose: Limited information is available regarding differences in neuroimaging use for acute stroke work-up. Our objective was to assess whether race, sex, or age differences exist in neuroimaging use and whether these differences depend on the care center type in a population-based study., Materials and Methods: Patients with stroke (ischemic and hemorrhagic) and transient ischemic attack were identified in a metropolitan, biracial population using the Greater Cincinnati/Northern Kentucky Stroke Study in 2005 and 2010. Multivariable regression was used to determine the odds of advanced imaging use (CT angiography/MR imaging/MR angiography) for race, sex, and age., Results: In 2005 and 2010, there were 3471 and 3431 stroke/TIA events, respectively. If one adjusted for covariates, the odds of advanced imaging were higher for younger (55 years or younger) compared with older patients, blacks compared with whites, and patients presenting to an academic center and those seen by a stroke team or neurologist. The observed association between race and advanced imaging depended on age; in the older age group, blacks had higher odds of advanced imaging compared with whites (odds ratio, 1.34; 95% CI, 1.12-1.61; P < .01), and in the younger group, the association between race and advanced imaging was not statistically significant. Age by race interaction persisted in the academic center subgroup ( P < .01), but not in the nonacademic center subgroup ( P = .58). No significant association was found between sex and advanced imaging., Conclusions: Within a large, biracial stroke/TIA population, there is variation in the use of advanced neuroimaging by age and race, depending on the care center type., (© 2017 by American Journal of Neuroradiology.)

Background: We examined practice patterns of inpatient testing to identify stroke etiologies and treatable risk factors for acute ischemic stroke recurrence., Methods and Results: We identified stroke cases and related diagnostic testing from four 1-year study periods (July 1993 to June 1994, 1999, 2005, and 2010) of the Greater Cincinnati/Northern Kentucky Stroke Study. Patients aged ≥18 years were included. We focused on evaluation of extracranial arteries for carotid stenosis and assessment of atrial fibrillation because randomized controlled trials supported treatment of these conditions for stroke prevention across all 4 study periods. In each study period, we also recorded stroke etiology, as determined by diagnostic testing and physician adjudication. An increasing proportion of stroke patients received assessment of both extracranial arteries and the heart over time (50%, 58%, 74%, and 78% in the 1993-1994, 1999, 2005, and 2010 periods, respectively; P <0.0001 for trend), with the most dramatic individual increases in echocardiography (57%, 63%, 77%, and 83%, respectively). Concurrently, we observed a decrease in strokes of unknown etiology (47%, 48%, 41%, and 38%, respectively; P <0.0001 for trend). We also found a significant increase in strokes of other known causes (32%, 25%, 45% and 59%, respectively; P <0.0001 for trend)., Conclusions: Stroke workup for treatable causes of stroke are being used more frequently over time, and this is associated with a decrease in cryptogenic strokes. Future study of whether better determination of treatable stroke etiologies translates to a decrease in stroke recurrence at the population level will be essential., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background and Purpose: Acute ischemic stroke (AIS) patients may have raised serum cardiac troponin levels on admission, although it is unclear what prognostic implications this has, and whether elevated levels are associated with cardiac causes of stroke or structural cardiac disease as seen on echocardiogram. We investigated the positivity of cardiac troponin and echocardiogram testing within a large biracial AIS population and any association with poststroke mortality., Methods: Within a catchment area of 1.3 million, we screened emergency department admissions from 2010 using International Classification of Diseases, Ninth Edition , discharge codes 430 to 436 and ascertained all physician-confirmed AIS cases by retrospective chart review. Hypertroponinemia was defined as elevation in cardiac troponin above the standard 99th percentile. Multiple logistic regression was performed, controlling for stroke severity, history of cardiac disease, and all other stroke risk factors., Results: Of 1999 AIS cases, 1706 (85.3%) had a cardiac troponin drawn and 1590 (79.5%) had echocardiograms. Hypertroponinemia occurred in 353 of 1706 (20.7%) and 160 of 1590 (10.1%) had echocardiogram findings of interest. Among 1377 who had both tests performed, hypertroponinemia was independently associated with echocardiogram findings (odds ratio, 2.9; 95% confidence interval, 2-4.2). When concurrent myocardial infarctions (3.5%) were excluded, hypertroponinemia was also associated with increased mortality at 1 year (35%; odds ratio, 3.45; 95% confidence interval, 2.1-5.6) and 3 years (60%; odds ratio, 2.91; 95% confidence interval, 2.06-4.11)., Conclusions: Hypertroponinemia in the context of AIS without concurrent myocardial infarction was associated with structural cardiac disease and long-term mortality. Prospective studies are needed to determine whether further cardiac evaluation might improve the long-term mortality rates seen in this group., (© 2017 American Heart Association, Inc.)

Background and Purpose: Computed tomographic angiography and conventional angiography provide timely vascular anatomic information in patients with stroke. However, iodinated contrast dye may cause acute kidney injury (AKI). Within a large, biracial population, we examined in-hospital incidence of new or worsening kidney disease in patients with stroke and its association with administration of intravenous dye., Methods: All adult residents of the Greater Cincinnati/Northern Kentucky region with acute ischemic stroke or intracerebral hemorrhage who presented to an emergency department in 2010 were included. Prevalence of unsuspected kidney disease at the time of emergency department presentation and the incidence of AKI after admission in 2 groups of patients-those who did and those who did not receive intravenous dye-were determined., Results: In 2010, 2299 patients met inclusion criteria (89% ischemic stroke and 11% intracerebral hemorrhage); mean age 69 years (SD 15), 22% black, and 54% women. Among these patients, 37% had kidney disease at baseline, including 22% (516/2299) in whom this was unsuspected. Two percent (2%; 15/853) of patients with baseline kidney disease developed AKI during the hospital stay. Of those with no baseline kidney disease, 1% (14/14 467) developed AKI. There was no association between dye administration and new or worsening kidney disease., Conclusions: Although 22% of patients in the Greater Cincinnati/Northern Kentucky stroke population had unsuspected kidney disease, the incidence of new or worsening kidney disease was low, and AKI was not associated with dye administration. These findings confirm single-center reports that the risk of severe renal complications after contrast dye is small., (© 2017 American Heart Association, Inc.)

The incidence of stroke among younger adults in the United States is increasing. Few studies have investigated the prevalence of depressive symptoms after stroke among different age groups or the extent to which subjective stress at the time of stroke interacts with age to contribute to post-stroke depression. The present study examined whether there exists an age gradient in survivors' level of depressive symptoms and explored the extent to which financial, family, and health-related stress may also impact on depression. Bivariate analyses (N = 322) indicated significant differences in depression and stress by age group, as well as differences in age and stress by 3-month depression status. Linear regression analyses indicated that survivors between the ages of 25-54 and 55-64 years old had, on average, significantly higher depressive symptom scores. Those with financial, family, and health-related stress at the time of stroke, irrespective of age, also had significantly higher scores.

Background: Spasticity often leads to symptomatic and functional problems that can cause disability for stroke survivors. We studied whether spasticity has a negative impact on health-related quality of life (HRQoL)., Methods: As part of the Greater Cincinnati/Northern Kentucky Stroke Study (NCT00642213), 460 ischemic stroke patients were interviewed during hospitalization and then followed over time. HRQoL was measured by the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores of the Short Form-12 (SF-12), EuroQol-5 dimension (EQ-5D), and Stroke-Specific Quality of Life (SSQOL) instruments, with lower scores indicating worse health. HRQoL differences between stroke survivors with and without spasticity were compared, adjusting for age, race, stroke severity, pre-stroke function, and comorbidities., Results: Of the 460 ischemic stroke patients, 328 had spasticity data available 3 months after their stroke (mean age of 66 years, 49% were female, and 26% were black). Of these patients, 54 (16%) reported having spasticity. Three months following their stroke, patients who reported spasticity had lower mean scores on the PCS (29.6 ± 1.4 vs 37.3 ± 0.6; P < .001), EQ-5D (0.59 ± 0.03 vs 0.71 ± 0.01; P < .001), and SSQOL (3.57 ± 0.08 versus 3.78 ± 0.03; P = .03) compared with patients who did not report spasticity. Lower HRQoL scores were also observed at the 1-year (PCS, EQ-5D, and SSQOL) and 2-year (EQ-5D and SSQOL) interviews in those with spasticity compared with those without spasticity., Conclusions: Statistically and clinically meaningful differences in HRQoL exist between stroke survivors with and without spasticity.

Background: There are several situations in which magnetic resonance imaging (MRI) might impact whether an cerebrovascular event is considered a new stroke. These include clinically non-focal events with positive imaging for acute cerebral infarction, and worsening of older symptoms without evidence of new infarction on MRI. We sought to investigate the impact of MRI on stroke detection and stroke incidence, by describing agreement between a strictly clinical definition of stroke and a definition based on physician opinion, including MRI imaging findings., Methods: All hospitalized strokes that occurred in five Ohio and Northern Kentucky counties (population 1.3 million) in the calendar year of 2005 were identified using ICD-9 discharge codes 430-436. The two definitions used were: "clinical case definition" which included sudden onset focal neurologic symptoms referable to a vascular territory for >24 h, compared to the "best clinical judgment of the physician definition", which considers all relevant information, including neuroimaging findings. The 95% confidence intervals (CI) for the incidence rates were calculated assuming a Poisson distribution. Rates were standardized to the 2000 U.S. population, adjusting for age, race, and sex, and included all age groups., Results: There were 2403 ischemic stroke events in 2269 patients; 1556 (64%) had MRI performed. Of the events, 2049 (83%) were cases by both definitions, 185 (7.7%) met the clinical case definition but were non-cases in the physician's opinion and 169 (7.0%) were non-cases by clinical definition but were cases in the physician's opinion. There was no significant difference in the incidence rates of first-ever or total ischemic strokes generated by the two different definitions, or when only those with MRI imaging were included., Conclusions: We found that MRI findings do not appear to substantially change stroke incidence estimates, as the strictly clinical definition of stroke did not significantly differ from a definition that included imaging findings. Including MRI in the case definition "rules out" almost the same number of strokes as it "rules in".

Background and Purpose: Little is known about the distribution of National Institutes of Health Stroke Scale (NIHSS) scores from patients with ischemic stroke sampled from population-based studies. We describe the distribution of NIHSS in ischemic stroke cases from the Cincinnati/Northern Kentucky Stroke Study., Methods: Within a biracial population of 1.3 million, all strokes among area residents in 2005 were ascertained by screening discharge records at local hospitals and outpatient clinics. A sampling scheme was developed to ascertain additional cases presenting to physician offices and nursing homes, not identified through the other sources. All confirmed ischemic stroke cases underwent chart abstraction, and a retrospective NIHSS (rNIHSS) score (range, 0-42) was generated on the basis of initial physician examination findings., Results: There were 2233 ischemic stroke cases identified during the 12-month study. The overall median rNIHSS score was 3 (interquartile range, 1-7). Median rNIHSS score was 3, 7, and 1, respectively, for stroke cases ascertained through the admitted, in-hospital, and out-of-hospital sources. Median rNIHSS was significantly higher in subjects ≥80 years compared with younger cases (4 versus 3)., Conclusions: More than half of all ischemic stroke cases have mild symptom severity on initial presentation (ie, rNIHSS≤3). Monitoring trends in NIHSS represents a legitimate target for population-based surveillance efforts.

Background and Purpose: Initial National Institutes of Health Stroke Scale (NIHSS) score is highly predictive of outcome after ischemic stroke. We examined whether grouping strokes by presence of individual NIHSS symptoms could provide prognostic information additional or alternative to the NIHSS total score., Methods: Ischemic strokes from the Greater Cincinnati Northern Kentucky Stroke Study in 2005 were used to develop the model. Latent class analysis was implemented to form groups of patients with similar retrospective NIHSS (rNIHSS) item responses. Profile group was then used as an independent predictor of discharge modified Rankin and mortality, using logistic regression and Cox proportional hazards model., Results: A total of 2112 stroke patients were identified in 2005. Six distinct profiles were characterized. Consistent with the profile patterns, the median rNIHSS total score decreased from profile A "most severe" (median [interquartile range], 20 [15-25]) to profile F "mild" (1[1-2]). Two profiles falling between these extremes, C and D, both had median rNIHSS total score of 5, but different survival rates. Compared with A, C was associated with 59% risk reduction for death, whereas D with 70%. C patients were more likely to have decreased level of consciousness and abnormal language, whereas D patients were more likely to have abnormal right arm and right leg motor function., Conclusions: Six rNIHSS profiles were identifiable using latent class analysis. In particular, 2 symptom profiles with identical median rNIHSSS were observed with widely disparate outcomes, which may prove useful both clinically and for research studies as an enhancement to the overall NIHSS score.

Background and Purpose: We previously reported increased incidence of ischemic stroke among both blacks and whites with diabetes mellitus, especially in those aged <55 years. With rising prevalence of diabetes mellitus in the past decade, we revisit the impact of diabetes mellitus on stroke incidence in the same population (≈1.3 million) 5 and 10 years later., Methods: This is a population-based study. First ischemic strokes among black and white residents of the 5-county Greater Cincinnati/Northern Kentucky region, aged ≥ 20 years, for periods 7/1993 to 6/1994, 1999, and 2005, were included in this analysis. Incidence rates were adjusted for sex, race, and age, as appropriate, to the 2000 US population., Results: History of diabetes mellitus among first ischemic strokes was reported for 493/1709 (28%) in 1993/1994, 522/1778 (29%) in 1999, and 544/1680 (33%) in 2005. Risk ratios (95% confidence interval) for rates of stroke in those with versus without diabetes mellitus for blacks reduced significantly from 5.6 in 1993/1994 to 3.2 in 2005; for whites the risk ratio remained stable at 3.8 in 1993/1994 and 2005. However, risk ratios varied with age, with an overall 5- to 14-fold increased risk observed in those aged 20 to 65 years., Conclusions: Those with diabetes mellitus remain at greatly increased risk for stroke at all ages, especially <65 years, regardless of race. The rates and risk ratios for 1999 and 2005, although similar to those previously reported for the mid-1990s, take on increased significance, given the epidemic of diabetes mellitus and metabolic syndrome throughout the US and the world.

Background and Purpose: The publication of the European Cooperative Acute Stroke Study (ECASS III) expanded the treatment time to thrombolysis for acute ischemic stroke from 3 to 4.5 hours from symptom onset. The impact of the expanded time window on treatment rates has not been comprehensively evaluated in a population-based study., Methods: All patients with an ischemic stroke presenting to an emergency department during calendar year 2005 in the 17 hospitals that compromise the large 1.3 million Greater Cincinnati/Northern Kentucky population were included in the analysis. Criteria for exclusion from thrombolytic therapy are analyzed retrospectively for both the standard and expanded timeframes with varying door-to-needle times., Results: During the study period, 1838 ischemic strokes presenting to an emergency department were identified. A small proportion of them arrived in the expanded time window (3.4%) compared with the standard time window (22%). Only 0.5% of those who arrived in this timeframe met eligibility criteria for thrombolysis compared with 5.9% using standard eligibility criteria in the standard timeframe. These results did not vary significantly by repeated analysis varying the door-to-needle time or the expanded time window's exclusion criteria., Conclusions: In reality, the expanded time window for thrombolysis in acute ischemic stroke benefits few patients. If we are to improve recombinant tissue-type plasminogen activator administration rates, our focus should be on improving stroke awareness, transport to facilities with ability to administer thrombolysis, and familiarity of physicians with acute stroke treatment guidelines.

Background and Purpose: Severely elevated blood pressure (BP) and aggressive BP reduction are both associated with poor outcome in acute ischemic stroke (AIS). In nontissue-type plasminogen activator patients, the American Heart Association recommends antihypertensive therapy only if BP is ≥ 220/120 mm Hg with a goal of 15% to 25% reduction in the first 24 hours. We hypothesized that patients with AIS often receive antihypertensives in the emergency department below the recommended threshold and that BP reduction is often >20%., Methods: In 2005, AIS cases were ascertained at all 16 hospitals in Greater Cincinnati. BP was recorded at emergency department presentation and before and after antihypertensive treatment. Hypertension was defined as BP ≥ 220/120 mm Hg. Chi-square and Mann-Whitney U tests were used for comparisons., Results: A total of 1739 patients with AIS met inclusion criteria. Median age was 72 years with 43% male and 25% black. Of 218 treated with antihypertensives, 65 (30.0%) met treatment criteria immediately before treatment. Treated patients were younger (66 versus 73 years, P<0.001) with greater stroke severity than untreated patients (National Institutes of Health Stroke Scale score 4 versus 3, P=0.028). Median change in systolic BP was -25 mm Hg (range, -96 to 25 mm Hg). Median percentage change in systolic BP was -12.3% (range, -49.2% to 16.1%). Systolic BP decreased > 20% in 52 treated patients (23.7%)., Conclusions: Only one third of patients with AIS treated with antihypertensives met American Heart Association-recommended treatment criteria, and the rate of change of BP was frequently greater than recommended. Further studies are warranted to determine the impact of practice patterns on AIS outcomes.

Background and Purpose: Malignant middle cerebral artery infarction is estimated to occur in 10% of ischemic strokes, but few patients undergo decompressive hemicraniectomy, a proven therapy. We determined the proportion of patients with ischemic stroke without significant baseline disability with large middle cerebral artery infarction who would have been potentially eligible for hemicraniectomy in an era before publication of recent hemicraniectomy trials., Methods: Ischemic stroke cases that occurred in 2005 among residents of the 5-county Greater Cincinnati/Northern Kentucky area were ascertained. Two study physicians reviewed all clinical and neuroimaging data for patients with baseline modified Rankin Scale score < 2, age ≥ 18 years with National Institutes of Health Stroke Scale score ≥ 10. Large middle cerebral artery infarction was defined as >50% of the middle cerebral artery territory or >145 mL on diffusion-weighted MRI. Other eligibility criteria for hemicraniectomy, based on the pooled analysis of recent clinical trials, were age 18 to 60 years and National Institutes of Health Stroke Scale score > 15., Results: Of 2227 ischemic strokes, 39 (1.8%) with baseline modified Rankin Scale score < 2 had large middle cerebral artery infarction. None underwent hemicraniectomy, and 16 (41.0%) died within 30 days. Six patients (0.3% of all ischemic strokes) were potentially eligible for hemicraniectomy; 1 died within 30 days., Conclusions: Based on criteria from clinical trials, only 0.3% of cases were eligible for hemicraniectomy. Given the survival and functional outcome benefit in treated patients, future studies should determine whether additional subgroups of patients with ischemic stroke may benefit from hemicraniectomy.

Background and Purpose: Antithrombotic medications (anticoagulants and antiplatelets) are often withheld in the periprocedural period and after bleeding complications to limit the risk of new or recurrent bleeding. These medications are also stopped by patients for various reasons such as cost, side effects, or unwillingness to take medication., Methods: Patient records from the population-based Greater Cincinnati/Northern Kentucky Stroke Study were reviewed to identify cases of ischemic stroke in 2005 and determine the temporal association of strokes with withdrawal of antithrombotic medication. Ischemic strokes and reasons for medication withdrawal were identified by study nurses for subsequent physician review., Results: In 2005, 2197 cases of ischemic stroke among residents of the region were identified through hospital discharge records. Of the 2197 ischemic strokes, 114 (5.2%) occurred within 60 days of an antithrombotic medication withdrawal, 61 (53.5%) of these after stoppage of warfarin and the remainder after stoppage of an antiplatelet medication. Of the strokes after withdrawal, 71 (62.3%) were first-ever and 43 (37.7%) were recurrent; 54 (47.4%) occurred after withdrawal of medication by a physician in the periprocedural period., Conclusions: The withdrawal of antiplatelet and antithrombotic medications in the 60 days preceding an acute ischemic stroke was associated with 5.2% of ischemic strokes in our study population. This finding emphasizes the need for thoughtful decision-making concerning antithrombotic medication use in the periprocedural period and efforts to improve patient compliance.

Objectives: The American Heart Association recently redefined TIA to exclude patients with infarction on neuroimaging. Given its advantages, MRI/diffusion-weighted imaging (DWI) was recommended as the preferred imaging modality. We determined how frequently MRI/DWI was performed for TIA and ascertained the proportion of clinically defined TIA patients who had ischemic lesions on DWI in our community in 2005., Methods: All clinically defined TIA cases among residents of a 5-county region around Cincinnati who presented to emergency departments were identified during 2005. Demographics and medical history, whether MRI/DWI was performed, and DWI findings were recorded. Generalized estimating equations were used to compare groups to account for the design of the study and multiple events per patient., Results: Of 834 TIA events in 799 patients, 323 events (40%) had MRI/DWI performed. Patients who had MRI/DWI were younger (mean, 66 vs 70 years; P=0.03), had less severe prestroke disability (baseline modified Rankin Scale score, 0; 44% vs 34%; P=0.02), were less likely to have previous stroke or TIA (42% vs 56%; P=0.002), and were less likely to have atrial fibrillation (10% vs 16%; P=0.01). Of the 323 events with DWI, 51 (15%) had evidence of acute infarction. Patients with positive DWI were older (75 vs 64 years; P=0.0001) and more likely to have atrial fibrillation (21% vs 7%; P=0.002)., Conclusions: Performing MRI/DWI on all clinically defined TIA patients in our community would reveal more cases of actual infarction but would more than double current use. Future studies should assess whether MRI/DWI is warranted for all TIA patients.

Purpose: The incidence of seizures within 24 h of acute stroke has not been studied extensively. We aimed to establish the incidence of acute poststroke seizures in a biracial cohort and to determine whether acute seizure occurrence differs by race/ethnicity, stroke subtype, and/or stroke localization., Methods: We identified all stroke cases between July 1993 and June 1994 and in 1999 within the population of the Greater Cincinnati metropolitan region. Patients with a prior history of seizures/epilepsy were excluded from analysis., Results: A total of 6044 strokes without a history of seizure(s) were identified; 190 (3.1%) had seizures within the first 24 h of stroke onset. Of ICH/SAH patients, 8.4% had a seizure within the first 24 h of stroke onset (p or=1. Race/ethnicity or localization of the ischemic stroke did not influence the risk for seizure development in the studied population., Discussion: The overall incidence of acute seizures after stroke was 3.1%, with a higher incidence seen in hemorrhagic stroke, younger patients, and those presenting with higher prestroke Rankin scores. Acute seizures were associated with a higher mortality at 30 days after stroke.

Background and Purpose: Previous studies have shown poor public knowledge of stroke warning signs. The current public education message adopted by the American Heart Association lists 5 stroke warning signs ("suddens"). Another message called FAST (face, arm, speech, time) could be easier to remember, but it does not contain as many stroke symptoms. We sought to assess the percentage of stroke/transient ischemic attack (TIA) patients identified by both public awareness messages by examining presenting symptoms of all stroke/TIA patients from a large, biracial population in 1999., Methods: Cases of stroke who presented to an emergency department or were directly admitted were ascertained at all local hospitals by screening of ICD-9 codes 430 to 436, and prospective screening of emergency department admission logs, in 1999. Study nurses abstracted initial presenting symptoms from the medical record. All-cause 30-day case-fatality was calculated., Results: During 1999, 3498 stroke/TIA patients (17% black, 56% female) presented to an emergency department. Of these events, 11.1% had presenting symptoms not included in FAST, whereas 0.1% had presenting symptoms not included in the suddens. The FAST message performed much better for ischemic stroke and TIA than for hemorrhage, missing 8.9% of the ischemic strokes and 8.2% of the TIAs, versus 30.6% of intracerebral hemorrhage/subarachnoid hemorrhage cases. Case-fatality in patients missed by FAST was similar to patients with FAST symptoms (9.0% versus 11.6%, P=0.15)., Conclusions: Within our population, we found that the FAST message identified 88.9% of stroke/TIA patients. The FAST message performed better for ischemic stroke and TIA than for hemorrhagic stroke. Whether the FAST message is easier to recall for the public than the "suddens" message has yet to be determined.

Arachidonate 5-lipoxygenase activating protein (ALOX5AP) has been reported to demonstrate linkage and association with ischemic stroke and myocardial infarction. However, replication studies have been conflicting and to date, a significant proportion of blacks have not been studied. We prospectively recruited cases of ischemic stroke from all 16 hospitals in the Greater Cincinnati/Northern Kentucky region and demographically matched them to stroke-free population-based controls. Single nucleotide polymorphisms (SNPs) were selected based on association with ischemic stroke in prior studies. Allelic, genotypic and haplotypic association testing was performed using HAPLOVIEW. Multiple logistic regression was used to control for the presence of traditional risk factors including hypertension, diabetes, hypercholesterolemia and smoking. A total of 357 cases and 482 controls were genotyped. The SNPs, rs9579646 and rs4769874 were found to be significantly associated at both allelic (P=0.019 and P<10(-4), respectively) and genotypic level with ischemic stroke among whites after correction for multiple testing. Haplotype association was identified with ischemic stroke as well as ischemic stroke subtypes among whites. Although an overall haplotype association with ischemic stroke was identified among blacks no evidence of association among individual haplotypes, alleles or genotypes were observed. Allele frequencies for the SNPs examined were markedly different among whites and blacks. In conclusion, we report significant association of variants of ALOX5AP with ischemic stroke and ischemic stroke subtypes among whites. No significant association was identified among blacks.

Background and Purpose: Transient ischemic attacks (TIAs) have been shown to be a strong predictor of subsequent stroke and death. We present the incidence and short-term prognosis of TIA within a large population with a significant proportion of minorities with out-of-hospital TIA., Methods: TIA cases were identified between July 1, 1993 and June 30, 1994 from the Greater Cincinnati/Northern Kentucky population of 1.3 million inhabitants by previously published surveillance methods, including inpatient and out-of-hospital events. Incidence rates were adjusted to the 1990 population, and life-table analyses were used for prognosis., Results: The overall race, age, and gender-adjusted incidence rate for TIA within our population was 83 per 100,000, with age, race, and gender adjusted to the 1990 US population. Blacks and men had significantly higher rates of TIA than whites and women. Risk of stroke after TIA was 14.6% at 3 months, and risk of TIA/stroke/death was 25.2%. Age, race, and sex were not associated with recurrent TIA or subsequent stroke in our population, but age was associated with mortality., Conclusions: Using our incidence rates for TIA in blacks and whites, we conservatively estimate that approximately 240 000 TIAs occurred in 2002 in the United States. Our incidence rate of TIA is slightly higher than previously reported, which may be related to the inclusion of blacks and out-of-hospital events. There are racial and gender-related differences in the incidence of TIA. We found a striking risk of adverse events after TIA; however, there were no racial or gender differences predicting these events. Further study is warranted in interventions to prevent these adverse events after TIA.

Background and Purpose: Blacks have an excess burden of stroke compared with whites; however, data comparing ischemic stroke subtypes among the 2 groups are limited and typically involve relative frequencies. The objective of this study is to compare the incidence rates of ischemic stroke subtypes between blacks and whites within a large, representative, biracial population., Methods: The Greater Cincinnati/Northern Kentucky Stroke Study is designed to measure incidence rates and trends of all strokes within a well-defined, large, biracial population. Hospitalized cases were ascertained by International Classification of Disease (9th revision; ICD-9) discharge codes. Out-of-hospital events were ascertained by prospective screening of emergency department admission logs, review of coroners' cases, and monitoring all public health and hospital-based primary care clinics. A sampling scheme was used to ascertain events from nursing homes and all other primary care physician offices. All potential cases underwent detailed chart abstraction and confirmed by physician review. Based on all available clinical, laboratory, and radiographic information, ischemic stroke cases were subtyped into the following categories: cardioembolic, large-vessel, small-vessel, other, and stroke of undetermined cause. Race-specific incidence rates were calculated and compared after adjusting for age and gender, and standardizing to the 1990 US population., Results: Between July 1, 1993, and June 30, 1994, 1956 first-ever ischemic strokes occurred among blacks and whites in the study population. Small-vessel strokes and strokes of undetermined cause were nearly twice as common among blacks. Large-vessel strokes were 40% more common among blacks than whites, and there was a trend toward cardioembolic strokes being more common among blacks., Conclusions: The excess burden of ischemic strokes among blacks compared with whites is not uniformly spread across the different subtypes. Large-vessel strokes are more common and cardioembolic stroke are as common among blacks, traditionally thought to be more common among whites.

Background and Purpose: Acute ischemic stroke patients are infrequently treated with recombinant tissue plasminogen activator (rtPA). We present unique population-based data regarding the eligibility of ischemic stroke patients for rtPA treatment., Methods: All ischemic strokes presenting to an emergency department (ED) within a biracial population of 1.3 million were identified. The patient was considered eligible for rtPA on the basis of exclusion criteria from the National Institute of Neurological Disorders and Stroke rtPA trial., Results: Of 2308 ischemic strokes, 1849 presented to an ED. Only 22% of all ischemic strokes in the population arrived in the ED in <3 hours from symptom onset; of these, 209 (51%) were ineligible for rtPA on the basis of mild stroke severity, medical and surgical history, or blood tests., Conclusions: In our population in 1993 to 1994, 8% of all ischemic stroke patients presented to an ED within 3 hours and met other eligibility criteria for rtPA. Even if time were not an exclusion for rtPA, only 29% of all ischemic strokes in our population would have otherwise been eligible for rtPA.