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Background: Clinical trial enrollment and completion is challenging, with nearly half of all trials not being completed or not completed on time. In 2014, the National Institutes of Health StrokeNet in collaboration with stroke epidemiologists from GCNKSS (Greater Cincinnati/Northern Kentucky Stroke Study) began providing proposed clinical trials with formal trial feasibility assessments. Herein, we describe the process of prospective feasibility analyses using epidemiological data that can be used to improve enrollment and increase the likelihood a trial is completed., Methods: In 2014, DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) trialists, National Institutes of Health StrokeNet, and stroke epidemiologists from GCNKSS collaborated to evaluate the initial inclusion/exclusion criteria for the DEFUSE 3 study. Trial criteria were discussed and an assessment was completed to evaluate the percent of the stroke population that might be eligible for the study. The DEFUSE 3 trial was stopped early with the publication of DAWN (Thrombectomy 6 to 24 Hours After Stroke With a Mismatch Between Deficit and Infarct), and the Wilcoxon rank-sum statistic was used to analyze whether the trial would have been stopped had the proposed changes not been made, following the DEFUSE 3 statistical analysis plan., Results: After initial epidemiological analysis, 2.4% of patients with acute stroke in the GCNKSS population would have been predicted to be eligible for the study. After discussion with primary investigators and modifying 4 key exclusion criteria (upper limit of age increased to 90 years, baseline modified Rankin Scale broadened to 0-2, time since last well expanded to 16 hours, and decreased lower limit of National Institutes of Health Stroke Scale score to <6), the number predicted to be eligible for the trial increased to 4%. At the time of trial conclusion, 57% of the enrolled patients qualified only by the modified criteria, and the trial was stopped at an interim analysis that demonstrated efficacy. We estimated that the Wilcoxon rank-sum value for the unadjusted predicted enrollment would not have crossed the threshold for efficacy and the trial not stopped., Conclusions: Objectively assessing trial inclusion/exclusion criteria using a population-based resource in a collaborative and iterative process including epidemiologists can lead to improved recruitment and can increase the likelihood of successful trial completion.

Background: Though stroke risk factors such as substance use may vary with age, less is known about trends in substance use over time or about performance of toxicology screens in young adults with stroke., Methods: Using the Greater Cincinnati Northern Kentucky Stroke Study, a population-based study in a 5-county region comprising 1.3 million people, we reported the frequency of documented substance use (cocaine/marijuana/opiates/other) obtained from electronic medical record review, overall and by race/gender subgroups among physician-adjudicated stroke events (ischemic and hemorrhagic) in adults 20 to 54 years of age. Secondary analyses included heavy alcohol use and cigarette smoking. Data were reported for 5 one-year periods spanning 22 years (1993/1994-2015), and trends over time were tested. For 2015, to evaluate factors associated with performance of toxicology screens, multiple logistic regression was performed., Results: Overall, 2152 strokes were included: 74.5% were ischemic, mean age was 45.7±7.6, 50.0% were women, and 35.9% were Black. Substance use was documented in 4.4%, 10.4%, 19.2%, 24.0%, and 28.8% of cases in 1993/1994, 1999, 2005, 2010, and 2015, respectively ( P trend <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 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- Increased Lp(a) [lipoprotein(a)] is associated with coronary heart disease risk, but links with stroke are less consistent. Blacks have higher Lp(a) levels and stroke incidence than whites but have been underrepresented in studies. We hypothesized that Lp(a) is a risk factor for ischemic stroke and that risk differs by race. Approach and Results- REGARDS (Reasons for Geographic and Racial Differences in Stroke) recruited 30 239 black and white US adults aged ≥45 in 2003-2007 to study regional and racial differences in stroke mortality. We measured baseline Lp(a) by immunonephelometric assay in 572 cases of incident ischemic stroke and a 967-person cohort random sample. The hazard ratio of stroke by baseline Lp(a) was calculated using Cox proportional hazards models, stratified by race. Lp(a) was modeled in sex- and race-specific quartiles, given known differences in distributions by race and sex. Interactions were tested by including interaction terms in the proportional hazards models, with P<0.10 considered statistically significant. After adjustment for age, sex, and stroke risk factors, being in the fourth versus the first Lp(a) quartile was weakly associated with ischemic stroke overall, hazard ratio, 1.45 (95% CI, 0.96-2.19). In blacks, the hazard ratio was 1.96 (95% CI, 1.10-3.46), whereas in whites HR was 1.14 (95% CI, 0.64-2.04); P interaction=0.12. Lp(a) was lower in men than women, but associations with stroke in men and women were similar. Conclusions- We confirm that Lp(a) is a risk factor for ischemic stroke. Further research is needed to confirm the role of racial differences of the Lp(a) risk multiplier in ischemic stroke.

Importance: Race-specific and sex-specific stroke risk varies across the lifespan, yet few reports describe sex differences in stroke risk separately in black individuals and white individuals., Objective: To examine incidence and risk factors for ischemic stroke by sex for black and white individuals., Design, Setting, and Participants: This prospective cohort study included participants 45 years and older who were stroke-free from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, enrolled from the continental United States 2003 through 2007 with follow-up through October 2016. Data were analyzed from March 2018 to September 2018., Exposures: Sex and race., Main Outcomes and Measures: Physician-adjudicated incident ischemic stroke, self-reported race/ethnicity, and measured and self-reported risk factors., Results: A total of 25 789 participants (14 170 women [54.9%]; 10 301 black individuals [39.9%]) were included. Over 222 120 person-years of follow-up, 939 ischemic strokes occurred: 159 (16.9%) in black men, 326 in white men (34.7%), 217 in black women (23.1%), and 237 in white women (25.2%). Between 45 and 64 years of age, white women had 32% lower stroke risk than white men (incidence rate ratio [IRR], 0.68 [95% CI, 0.49-0.94]), and black women had a 28% lower risk than black men (IRR, 0.72 [95% CI, 0.52-0.99]). Lower stroke risk in women than men persisted at age 65 through 74 years in white individuals (IRR, 0.71 [95% CI, 0.55-0.94]) but not in black individuals (IRR, 0.94 [95% CI, 0.68-1.30]); however, the race-sex interaction was not significant. At 75 years and older, there was no sex difference in stroke risk for either race. For white individuals, associations of systolic blood pressure (women: hazard ratio [HR], 1.13 [95% CI, 1.05-1.22]; men: 1.04 [95% CI, 0.97-1.11]; P = .099), diabetes (women: HR, 1.84 [95% CI, 1.35-2.52]; men: 1.13 [95% CI, 0.86-1.49]; P = .02), and heart disease (women: HR, 1.76 [95% CI, 1.30-2.39]; men, 1.26 [95% CI, 0.99-1.60]; P = .09) with stroke risk were larger for women than men, while antihypertensive medication use had a smaller association in women than men (women: HR, 1.17 [95% CI, 0.89-1.54]; men: 1.61 [95% CI, 1.29-2.03]; P = .08). In black individuals, there was no evidence of a sex difference for any risk factors., Conclusions and Relevance: For both races, at age 45 through 64 years, women were at lower stroke risk than men, and there was no sex difference at 75 years or older; however, the sex difference pattern may differ by race from age 65 through 74 years. The association of risk factors on stroke risk differed by race-sex groups. While the need for primordial prevention, optimal management, and control of risk factors is universal across all age, racial/ethnic, and sex groups, some demographic subgroups may require earlier and more aggressive strategies.

Importance: Get With The Guidelines-Stroke (GWTG-Stroke) is an American Heart Association/American Stroke Association stroke-care quality-improvement program; however, to our knowledge, there has not been a direct comparison of the quality of care between patients hospitalized at participating hospitals and those at nonparticipating hospitals., Objective: To contrast quality of stroke care measures for patients admitted to hospitals participating and not participating in GWTG-Stroke., Design, Setting, and Participants: Subpopulation of 546 participants with ischemic stroke occurring during a 9-year follow-up of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study, a population-based cohort study of 30 239 randomly selected black and white participants 45 years and older recruited between 2003 and 2007. Of those with stroke, 207 (36%) were treated in a hospital participating in GWTG-Stroke and 339 in a nonparticipating hospital. Data were analyzed between July 29, 2017, and April 17, 2018., Main Outcomes and Measures: Quality of care measures including use of tissue plasminogen activator, performance of swallowing evaluation, antithrombotic use in first 48 hours, lipid profile assessment, discharge receiving antithrombotic therapy, discharge receiving a statin, neurologist evaluation, providing weight loss and exercise counseling, education on stroke risk factors and warning signs, and assessment for rehabilitation., Results: Participants treated at participating hospitals had a mean (SD) age of 74 (8) years and 100 of 207 were men (48%), while those seen at nonparticipating hospitals had a mean (SD) age of 73 (9) years, and 161 of 339 were men (48%). Those seen in participating hospitals were more likely to receive 5 of 10 evidence-based interventions recommended for patients hospitalized with ischemic stroke, including receiving tissue plasminogen activator (RR, 3.74; 95% CI, 1.65-8.50), education on risk factors (RR, 1.54; 95% CI, 1.16-2.05), having an evaluation for swallowing (RR, 1.25; 95% CI, 1.04-1.50), a lipid evaluation (RR, 1.18; 95% CI, 1.05-1.32), and an evaluation by a neurologist (RR, 1.12; 95% CI, 1.05-1.20). Those seen in participating hospitals received a mean of 5.4 (95% CI, 5.2-5.6) interventions compared with 4.8 (95% CI, 4.6-5.0) in nonparticipating hospitals (P < .001)., Conclusions and Relevance: These data collected independently of the GWTG-Stroke program document improved stroke care for patients with ischemic stroke hospitalized at participating hospitals.

Background: The aim of the present study was to compare sex-specific associations between cardiovascular risk factors and diabetes mellitus (DM) among patients with acute ischemic stroke (AIS) in the Greater Cincinnati/Northern Kentucky Stroke Study (GCNKSS)., Methods: The GCNKSS ascertained AIS cases in 2005 and 2010 among adult (age ≥ 20 years) residents of a biracial population of 1.3 million. Past and current stroke risk factors were compared between those with and without DM using Chi-squared tests and multiple logistic regression analysis to examine sex-specific profiles., Results: There were 3515 patients with incident AIS; 1919 (55%) were female, 697 (20%) were Black, and 1146 (33%) had DM. Among both women and men with DM, significantly more were obese and had hypertension, high cholesterol, and coronary artery disease (CAD) compared with those without DM. For women with AIS, multivariable sex-specific adjusted analyses revealed that older age was associated with decreased odds of having DM (adjusted odds ratio [aOR] 0.88, 95% confidence interval [CI] 0.80-0.98). For women with CAD, the odds of DM were increased (aOR 1.76, 95% CI 1.33-2.32). Age and CAD were not significant factors in differentiating the profiles of men with and without DM., Conclusions: Women with DM had strokes at a younger age, whereas no such age difference existed in men. Compared with men, women with DM were also more likely to have CAD than those without DM, suggesting a sex difference in the association between DM and vascular disease. These findings may suggest a need for more aggressive risk factor management in diabetic women., (© 2017 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

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.)

Background Although statin therapy is associated with reduced stroke and mortality risk, some studies report that higher lipid levels are associated with improved outcomes following ischemic stroke. Aims We examined the association of hyperlipidemia (HLD) combined with statin therapy on all-cause mortality in stroke patients. Methods All stroke patients in the Greater Cincinnati Northern Kentucky region of ∼1.3 million were identified using ICD-9 discharge codes in 2005 and 2010. Stroke patients with and without HLD were categorized based on their reported statin use at baseline or discharge into three groups: no-HLD/no-statins, HLD/no-statins, and HLD/on-statins. Cox proportional hazards model was used to estimate the risk of mortality at 30 days, 1 year, and 3 years poststroke. Results Overall, 77% (2953) of the 3813 ischemic stroke patients were diagnosed with HLD and 72% ( n = 2123) of those patients were on statin medications. The mean age was 70.0 ± 14.6 years, 56% were women, and 21% were black. In adjusted analyses, the HLD/no-statins group showed 35% (adjusted hazard ratio (aHR) = 0.65, 95% CI: 0.46-0.92), 27% (aHR = 0.73, 95% CI: 0.59-0.90), and 17% (aHR = 0.83, 95% CI: 0.70-0.97) reduced risk of mortality at 30 days, 1 year, and 3 years, respectively, poststroke, compared with no-HLD/no-statins group. The HLD/on-statins group showed an additional 17% significant survival benefit at 3 years poststroke compared with HLD/no-statins group. Conclusions A diagnosis of HLD in ischemic stroke patients is associated with reduced short- and long-term mortality, irrespective of statin use. Statin therapy is associated with significant, additional long-term survival benefit.

Background: Some studies of stroke patients report longer prehospital delays in women, but others conflict; studies vary in their inclusion of factors including age and stroke severity. We aimed to investigate the relationship between gender and time to emergency department (ED) arrival and the influence of age and stroke severity on this relationship., Methods: Ischemic stroke patients 20 years old or older who presented to 15 hospitals within a 5-county region of Greater Cincinnati/Northern Kentucky during 2010 were included. Time from symptom onset to ED arrival and covariates were abstracted by study nurses and reviewed by study physicians. Data were analyzed using logistic regression with time to arrival dichotomized at 3 hours or less in the overall sample and then stratified by National Institutes of Health Stroke Scale (NIHSS) and age., Results: 1991 strokes (55% women) were included. Time to arrival was slightly longer in women (geometric mean 337 minutes [95% confidence interval {CI} 307-369] versus 297 [95% CI 268-329], P = .05), and 24% of women versus 27% of men arrived within 3 hours (P = .15). After adjusting for age, race, NIHSS, living situation, and other covariates, gender was not associated with delayed time to arrival (OR = 1.00, 95% CI .78-1.28). This did not change across age or NIHSS categories., Conclusions: After adjusting for factors including age, NIHSS score, and living alone, women and men with ischemic stroke had similar times to arrival. Arrival time is not likely a major contributor to differences in outcome between men and women., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

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: Sex differences in recombinant tissue-type plasminogen activator (r-tPA) administration are present in some populations. It is unknown whether this is because of eligibility differences or the modifiable exclusion criterion of severe hypertension. Our aim was to investigate sex differences in r-tPA eligibility, in individual exclusion criteria, and in the modifiable exclusion criterion, hypertension., Methods: We included all ischemic stroke patients ≥18 years among residents of the Greater Cincinnati/Northern Kentucky region who presented to 16-area emergency departments in 2005. Eligibility for r-tPA and individual exclusion criteria were determined using 2013 American Heart Association (AHA) and European Cooperative Acute Stroke Study (ECASS) III guidelines., Results: Of 1837 ischemic strokes, 58% were women, 24% were black. Mean age in years was 72.2 for women and 66.1 for men. Eligibility for r-tPA was similar by sex (6.8% men and 6.1% women; P=0.55), even after adjusting for age (7.0% and 5.9%; P=0.32). Similar proportions of women and men arrived beyond 3- and 4.5-hour time windows, but more women had severe hypertension. There were no sex differences in blood pressure treatment rates among those with severe hypertension (14.6% women and 20.8% men; P=0.21). More women were >80 years and had National Institutes of Health Stroke Scale (NIHSS) >25., Conclusions: Within a large, biracial population, eligibility for r-tPA was similar by sex. Women were more likely to have the modifiable exclusion criterion of severe hypertension but were not more likely to be treated. Women were more likely to have 2 of the 5 ECASS III exclusion criteria. Undertreatment of hypertension in women is a potentially modifiable contributor to reported differences in r-tPA administration., (© 2015 American Heart Association, Inc.)

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: Approximately 5% of strokes occur in adults aged 18 to 44 years. Substance abuse is a prevalent risk factor for stroke in young adults. We sought to identify trends in substance abuse detection among stroke patients., Methods: Using a population-based design, we sought to identify all patients aged 18 to 54 years experiencing a stroke (ischemic or hemorrhagic) in the Greater Cincinnati and Northern Kentucky Study region during 1993 to 1994, 1999, and 2005. Demographic and clinical characteristics and substance use data were obtained retrospectively from chart review and adjudicated by physicians., Results: The number of young patients identified with a stroke increased from 1993 to 1994 (297) to 2005 (501). Blacks (61% vs 51%; P<0.02) and men (61% vs 47%; P<0.002) reported substance abuse (current smoking, alcohol, or illegal drug use) more frequently than did whites and women. Overall use of substances increased across study periods, 45% in 1993 versus 62% in 2005 (P=0.003). The trend was significant for illegal drug use (3.8% in 1993 vs 19.8% in 2005) and ever smoking (49% in 1993 vs 66% in 2005). Documentation of both cocaine and marijuana use increased over time. In 2005, half of young adults with a stroke were current smokers, and 1 in 5 abused illegal drugs., Conclusions: Substance abuse is common in young adults experiencing a stroke. The observed increase in substance abuse is contributing to the increased incidence of stroke in young adults. Patients aged younger than 55 years who experience a stroke should be routinely screened and counseled regarding substance abuse.

Objectives: We describe temporal trends in stroke incidence stratified by age from our population-based stroke epidemiology study. We hypothesized that stroke incidence in younger adults (age 20-54) increased over time, most notably between 1999 and 2005., Methods: The Greater Cincinnati/Northern Kentucky region includes an estimated population of 1.3 million. Strokes were ascertained in the population between July 1, 1993, and June 30, 1994, and in calendar years 1999 and 2005. Age-, race-, and gender-specific incidence rates with 95 confidence intervals were calculated assuming a Poisson distribution. We tested for differences in age trends over time using a mixed-model approach, with appropriate link functions., Results: The mean age at stroke significantly decreased from 71.2 years in 1993/1994 to 69.2 years in 2005 (p < 0.0001). The proportion of all strokes under age 55 increased from 12.9% in 1993/1994 to 18.6% in 2005. Regression modeling showed a significant change over time (p = 0.002), characterized as a shift to younger strokes in 2005 compared with earlier study periods. Stroke incidence rates in those 20-54 years of age were significantly increased in both black and white patients in 2005 compared to earlier periods., Conclusions: We found trends toward increasing stroke incidence at younger ages. This is of great public health significance because strokes in younger patients carry the potential for greater lifetime burden of disability and because some potential contributors identified for this trend are modifiable.

Background and Purpose: Initial stroke severity is one of the strongest predictors of eventual stroke outcome. However, predictors of initial stroke severity have not been well-described within a population. We hypothesized that poorer patients would have a higher initial stroke severity on presentation to medical attention., Methods: We identified all cases of hospital-ascertained ischemic stroke occurring in 2005 within a biracial population of 1.3 million. "Community" socioecomic status was determined for each patient based on the percentage below poverty in the census tract in which the patient resided. Linear regression was used to model the effect of socioeconomic status on stroke severity. Models were adjusted for race, gender, age, prestroke disability, and history of medical comorbidities., Results: There were 1895 ischemic stroke events detected in 2005 included in this analysis; 22% were black, 52% were female, and the mean age was 71 years (range, 19-104). The median National Institutes of Health Stroke Scale was 3 (range, 0-40). The poorest community socioeconomic status was associated with a significantly increased initial National Institutes of Health Stroke Scale by 1.5 points (95% confidence interval, 0.5-2.6; P<0.001) compared with the richest category in the univariate analysis, which increased to 2.2 points after adjustment for demographics and comorbidities., Conclusions: We found that increasing community poverty was associated with worse stroke severity at presentation, independent of other known factors associated with stroke outcomes. Socioeconomic status may impact stroke severity via medication compliance, access to care, and cultural factors, or may be a proxy measure for undiagnosed disease states.

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: 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.

Background: The Joint Commission (JC) certifies primary stroke centers in the United States. Whether certification promotes enrollment of study subjects into stroke research studies is not known. We examined whether enrollment performance of centers was related to JC certification status., Methods: The 51 US Siblings with Ischemic Stroke Study (SWISS) centers were characterized by JC certification status, year of certification, year initiated into SWISS, center location, and whether the center had a vascular/stroke neurology fellowship program accredited by the Accreditation Council for Graduate Medical Education. Performance measures included days elapsed from initiation to first enrollment, total enrollments within 12 months after initiation, and annual rate of enrollment thereafter., Results: In all, 36 of 51 SWISS sites (71%) were JC certified. A total of 32 (63%) were initiated into the study from 2000 through 2002, and 19 (37%) were initiated from 2005 through May 2008. Comparison of certified and noncertified sites showed no significant difference in the time to first enrollment (median, 77.5 v 115 days; P = .90), total enrollees in the first year (median, 3 v 2 probands; P = .69), or annual enrollment rate (median, 1.9 v 1.8 probands; P = .72). The rate of enrollment or time to first enrollment was not different between 2000-to-2002 and 2005-to-2008 sites. Early-initiated centers tended to have better year-1 enrollment than later-initiated centers (3 v 2 probands; P = .056)., Conclusions: JC certification did not have a significant effect on SWISS center enrollment. The JC should encourage the research mission among certified stroke centers.

Background: A recent meta-analysis suggested that racial/ethnic status is not a major determinant of willingness to participate in observational studies or treatment trials. However, little is known about the predictors of enrollment in family-based observational genetic studies. We tested the hypothesis that proband race/ethnicity is a significant predictor of enrolling a pedigree., Methods: Univariable and multivariable logistic regression modeling was used to determine proband characteristics that predict DNA donation from both members of an affected sibling pair. A total of 619 adult male and female probands with first-time or recurrent ischemic stroke and a positive sibling history of stroke enrolled across 53 hospitals and clinics in the United States and Canada into the Siblings with Ischemic Stroke Study, a family-based prospective genomics study., Results: In univariable analysis, probands with siblings who agreed to a blood draw for DNA analyses were more likely to be male and less likely to be nonwhite. In multivariable analysis, only race/ethnicity was significantly associated with likelihood of a proband's having a sibling who agreed to a blood draw., Conclusions: Contrary to observational studies that are not family based, the willingness of family members to participate in observational genetics studies may be influenced by race/ethnicity. This result reinforces the need for improving methods for recruiting diverse populations into genetic studies of stroke.

Background and Purpose: Hyperglycemia may worsen brain injury during acute cerebral infarction. We tested the feasibility and tolerability of aggressive hyperglycemia correction with intravenous insulin compared with usual care during acute cerebral infarction., Methods: We conducted a randomized, multicenter, blinded pilot trial for patients with cerebral infarction within 12 hours after onset, a baseline glucose value >or=8.3 mmol/L (>or=150 mg/dL), and a National Institutes of Health Stroke Scale score of 3 to 22. Patients were randomized 2:1 to aggressive treatment with continuous intravenous insulin or subcutaneous insulin QID as needed (usual care). Target glucose levels were <7.2 mmol/L (<130 mg/dL) in the aggressive-treatment group and <11.1 mmol/L (<200 mg/dL) in the usual-care group. Glucose was monitored every 1 to 2 hours, and the protocol treatments continued for up to 72 hours. Final clinical outcomes were assessed at 3 months., Results: We randomized 46 patients (31 to aggressive treatment and 15 to usual care). All patients in the aggressive-treatment group and 11 (73%) in the usual-care group had diabetes (P=0.008). Glucose levels were significantly lower in the aggressive-treatment group throughout protocol treatment (7.4 vs 10.5 mmol/L [133 vs 190 mg/dL], P<0.001). Hypoglycemia <3.3 mmol/L (<60 mg/dL) occurred only in the aggressive-treatment group (11 patients, 35%), 4 (13%) of whom had brief symptoms, including only 1 (3%) neurologic. Final clinical outcomes were nonsignificantly better in the aggressive-treatment group., Conclusions: The intravenous insulin protocol corrected hyperglycemia during acute cerebral infarction significantly better than usual care without major adverse events and should be investigated in a clinical efficacy trial.

Introduction: Only 8% of ischemic stroke (IS) patients are eligible for rt-PA, and the largest exclusion criterion is delayed time of presentation to the ED. We sought to investigate whether patients are arriving to the ED more quickly in 1999 than in 1993/94 within our large biracial population of 1.3 million., Methods: Using ICD-9 codes 430-436, we ascertained all stroke events that presented to a local ED within our population in 7/93-6/94 and again in 1999. Times were recorded as documented in the medical record., Results: There were 1,792 IS patients that presented to an ED in 1993/94 and 1,973 in 1999. The percentage of patients with documented times arriving in under 3 h improved slightly in 1999 (26% vs. 23% in 93/94, P = 0.03), however, the percentage arriving in under 2 h did not. Blacks significantly improved in arrivals under 3 h: 26% in 1999 compared to 17% in 1993/94 (P = 0.01), while whites did not (26% vs. 25%, P = 0.29). In 1999, only 9% of patients arrived from 3-8 h after symptom onset, the large majority of times were either estimated, unknown, or >8 h., Discussion: We found only marginal improvement in arrival times during the 1990s. In our population, blacks improved in early arrival after symptom onset, while whites did not. Very few patients arrive 3-8 h after onset; therefore expansion of the acute treatment time window to 8 h is unlikely to dramatically affect acute treatment of ischemic stroke.

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.