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Item Association of Prediabetes and Diabetes With Stroke Symptoms The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study(2012-09) Carson, April P; Muntner, Paul; Kissella, Brett M; Kleindorfer, Dawn O.; Howard, Virginia J; Meschia, James F; Williams, Linda S.; Prineas, Ronald J; Howard, George; Safford, Monika MOBJECTIVE Stroke symptoms among individuals reporting no physician diagnosis of stroke are associated with an increased risk of future stroke. Few studies have assessed whether individuals with diabetes or prediabetes, but no physician diagnosis of stroke, have an increased prevalence of stroke symptoms. RESEARCH DESIGN AND METHODS This study included 25,696 individuals aged ≥45 years from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study who reported no history of stroke or transient ischemic attack at baseline (2003–2007). Glucose measurements, medication use, and self-reported physician diagnosis were used to categorize participants into diabetes, prediabetes, or normal glycemia groups. The presence of six stroke symptoms was assessed using a validated questionnaire. RESULTS The prevalence of any stroke symptom was higher among participants with diabetes (22.7%) compared with those with prediabetes (15.6%) or normal glycemia (14.9%). In multivariable models, diabetes was associated with any stroke symptom (prevalence odds ratio [POR] 1.28 [95% CI 1.18–1.39]) and two or more stroke symptoms (1.26 [1.12–1.43]) compared with normal glycemia. In analyses of individual stroke symptoms, diabetes was associated with numbness (1.15 [1.03–1.29]), vision loss (1.52 [1.31–1.76]), half-vision loss (1.54 [1.30–1.84]), and lost ability to understand people (1.34 [1.12–1.61]) after multivariable adjustment. No association was present between prediabetes and stroke symptoms. CONCLUSIONS In this population-based study, almost one in four individuals with diabetes reported stroke symptoms, which suggests that screening for stroke symptoms in diabetes may be warranted.Item Depressive Symptoms and Risk of Stroke in a National Cohort of Black and White Participants From REGARDS(Wolters Kluwer, 2021) Ford, Cassandra D.; Gray, Marquita S.; Crowther, Martha R.; Wadley, Virginia G.; Austin, Audrey L.; Crowe, Michael G.; Pulley, LeaVonne; Unverzagt, Frederick; Kleindorfer, Dawn O.; Kissela, Brett M.; Howard, Virginia J.; Psychiatry, School of MedicineObjective: The purpose of this study was to examine depressive symptoms as a risk factor for incident stroke and determine whether depressive symptomatology was differentially predictive of stroke among Black and White participants. Methods: The study comprised 9,529 Black and 14,516 White stroke-free participants, aged 45 and older, enrolled in the REasons for Geographic and Racial Differences in Stroke (2003-2007). Incident stroke was the first occurrence of stroke. Association between baseline depressive symptoms (assessed via the 4-item Center for Epidemiologic Studies Depression Scale [CES-D-4]: 0, 1-3, or ≥4) and incident stroke was analyzed with Cox proportional hazards models adjusted for demographics, stroke risk factors, and social factors. Results: There were 1,262 strokes over an average follow-up of 9.21 (SD 4.0) years. Compared to participants with no depressive symptoms, after demographic adjustment, participants with CES-D-4 scores of 1-3 had 39% increased stroke risk (hazard ratio [HR] = 1.39, 95% confidence interval [CI] = 1.23-1.57), with slight attenuation after full adjustment (HR = 1.27, 95% CI = 1.11-1.43). Participants with CES-D-4 scores of ≥4 experienced 54% higher risk of stroke after demographic adjustment (HR = 1.54, 95% CI = 1.27-1.85), with risk attenuated in the full model similar to risk with 1-3 symptoms (HR = 1.25, 95% CI = 1.03-1.51). There was no evidence of a differential effect by race (p = 0.53). Conclusions: The association of depressive symptoms with increased stroke risk was similar among a national sample of Black and White participants. These findings suggest that assessment of depressive symptoms should be considered in primary stroke prevention for both Black and White participants.Item Gender and Time to Arrival among Ischemic Stroke Patients in the Greater Cincinnati/Northern Kentucky Stroke Study(Elsevier, 2016-03) Madsen, Tracy E.; Sucharew, Heidi; Katz, Brian; Alwell, Kathleen A.; Moomaw, Charles J.; Kissela, Brett M.; Flaherty, Matthew L.; Woo, Daniel; Khatri, Pooja; Ferioli, Simona; Mackey, Jason; Martini, Sharyl; De Los Rios La Rosa, Felipe; Kleindorfer, Dawn O.; Department of Neurology, IU School of MedicineBackground Some studies of stroke patients report longer pre-hospital 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 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, in the overall sample and then stratified by NIHSS and age. Results 1991 strokes (55% women) were included. Time to arrival was slightly longer in women (geometric mean 337 minutes [95%CI 307–369] vs. 297 [95%CI 268–329], p =0.05), and 24% of women vs. 27% of men arrived within 3 hours (p=0.15). 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 0.78–1.28). This did not change across age or NIHSS categories. Conclusions After adjusting for factors including age, NIHSS, 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.Item Prehospital neurological deterioration in stroke(BMJ Publishing Group, 2018-08) Slavin, Sabreena J.; Sucharew, Heidi; Alwell, Kathleen; Moomaw, Charles J.; Woo, Daniel; Adeoye, Opeolu; Flaherty, Matthew L.; Ferioli, Simona; McMullan, Jason; Mackey, Jason; De Los Rios La Rosa, Felipe; Martini, Sharyl; Kissela, Brett M.; Kleindorfer, Dawn O.; Neurology, School of MedicineBACKGROUND AND PURPOSE: Patients with stroke can experience neurological deterioration in the prehospital setting. We evaluated patients with stroke to determine factors associated with prehospital neurological deterioration (PND). METHODS: Among the Greater Cincinnati/Northern Kentucky region (population ~1.3 million), we screened all 15 local hospitals' admissions from 2010 for acute stroke and included patients aged ≥20. The GCS was compared between emergency medical services (EMS) arrival and hospital arrival, with decrease ≥2 points considered PND. Data obtained retrospectively included demographics, medical history and medication use, stroke subtype (eg, ischaemic stroke (IS), intracerebral haemorrhage (ICH), subarachnoid haemorrhage (SAH)) and IS subtype (eg, small vessel, large vessel, cardioembolic), seizure at onset, time intervals between symptom onset, EMS arrival and hospital arrival, EMS level of training, and blood pressure and serum glucose on EMS arrival. RESULTS: Of 2708 total patients who had a stroke, 1092 patients (median (IQR) age 74 (61-83) years; 56% women; 21% black) were analysed. PND occurred in 129 cases (12%), including 9% of IS, 24% of ICH and 16% of SAH. In multivariable analysis, black race, atrial fibrillation, haemorrhagic subtype and ALS level of transport were associated with PND. CONCLUSION: Haemorrhage and atrial fibrillation is associated with PND in stroke, and further investigation is needed to establish whether PND can be predicted. Further studies are also needed to assess whether preferential transport of patients with deterioration to hospitals equipped with higher levels of care is beneficial, identify why race is associated with deterioration and to test therapies targeting PND.Item Racial Differences in Atrial Cardiopathy Phenotypes in Patients With Ischemic Stroke(Wolters Kluwer, 2021-02-22) Kamel, Hooman; Alwell, Kathleen; Kissela, Brett M.; Sucharew, Heidi J.; Woo, Daniel; Flaherty, Matthew; Ferioli, Simona; Demel, Stacie L.; Moomaw, Charles J.; Walsh, Kyle; Mackey, Jason; De Los Rios La Rosa, Felipe; Jasne, Adam; Slavin, Sabreena; Martini, Sharyl; Adeoye, Opeolu; Baig, Tehniyat; Chen, Monica L.; Levitan, Emily B.; Soliman, Elsayed Z.; Kleindorfer, Dawn O.; Neurology, School of MedicineObjective: To test the hypothesis that thrombogenic atrial cardiopathy may be relevant to stroke-related racial disparities, we compared atrial cardiopathy phenotypes between Black vs White patients with ischemic stroke. Methods: We assessed markers of atrial cardiopathy in the Greater Cincinnati/Northern Kentucky Stroke Study, a study of stroke incidence in a population of 1.3 million. We obtained ECGs and reports of echocardiograms performed during evaluation of stroke during the 2010/2015 study periods. Patients with atrial fibrillation (AF) or flutter (AFL) were excluded. Investigators blinded to patients' characteristics measured P-wave terminal force in ECG lead V1 (PTFV1), a marker of left atrial fibrosis and impaired interatrial conduction, and abstracted left atrial diameter from echocardiogram reports. Linear regression was used to examine the association between race and atrial cardiopathy markers after adjustment for demographics, body mass index, and vascular comorbidities. Results: Among 3,426 ischemic stroke cases in Black or White patients without AF/AFL, 2,391 had a left atrial diameter measurement (mean, 3.65 ± 0.70 cm). Black race was associated with smaller left atrial diameter in unadjusted (β coefficient, -0.11; 95% confidence interval [CI], -0.17 to -0.05) and adjusted (β, -0.15; 95% CI, -0.21 to -0.09) models. PTFV1 measurements were available in 3,209 patients (mean, 3,434 ± 2,525 μV*ms). Black race was associated with greater PTFV1 in unadjusted (β, 1.59; 95% CI, 1.21-1.97) and adjusted (β, 1.45; 95% CI, 1.00-1.80) models. Conclusions: We found systematic Black-White racial differences in left atrial structure and pathophysiology in a population-based sample of patients with ischemic stroke. Classification of evidence: This study provides Class II evidence that atrial cardiopathy phenotypes differ in Black people with acute stroke compared to White people.Item Racial Disparities in Stroke Recurrence: A Population-Based Study(Wolters Kluwer, 2022) Robinson, David Joseph; Stanton, Robert; Sucharew, Heidi; Alwell, Kathleen; Haverbusch, Mary; De Los Rios La Rosa, Felipe; Ferioli, Simona; Coleman, Elisheva; Jasne, Adam; Mackey, Jason; Star, Michael; Mistry, Eva A.; Demel, Stacie; Slavin, Sabreena; Walsh, Kyle; Woo, Daniel; Kissela, Brett; Kleindorfer, Dawn O.; Neurology, School of MedicineBackground and objective: There are significant racial disparities in stroke in the United States, with Black individuals having a higher risk of incident stroke even when adjusted for traditional stroke risk factors. It is unknown whether Black individuals are also at a higher risk of recurrent stroke. Methods: Over an 18-month period spanning 2014-2015, we ascertained index stroke cases within the Greater Cincinnati/Northern Kentucky population of 1.3 million. We then followed up all patients for 3 years and determined the risk of recurrence. Multivariable survival analysis was performed to determine the effect of Black race on recurrence. Results: There were 3,816 patients with index stroke/TIA events in our study period, and 476 patients had a recurrent event within 3 years. The Kaplan-Meier estimate of 3-year recurrence rate was 15.4%. Age-adjusted and sex-adjusted stroke recurrence rate was higher in Black individuals (HR 1.34, 95% CI 1.1-1.6; p = 0.003); however, when adjusted for traditional stroke risk factors including hypertension, diabetes, smoking status, age, and left ventricular hypertrophy, the association between Black race and recurrence was significantly attenuated and became nonsignificant (HR 1.1, 95% CI 0.9-1.36, p = 0.32). At younger ages, Black race was more strongly associated with recurrence, and this effect may not be fully attenuated by traditional stroke risk factors. Discussion: Recurrent stroke was more common among Black individuals, but the magnitude of the racial difference was substantially attenuated and became nonsignificant when adjusted for traditional stroke risk factors. Interventions targeting these risk factors could reduce disparities in stroke recurrence.Item Sex differences in cardiovascular risk profiles of ischemic stroke patients with diabetes in the Greater Cincinnati/Northern Kentucky Stroke Study(Wiley, 2017) Madsen, Tracy E.; Khoury, Jane C.; Alwell, Kathleen A.; Moomaw, Charles J.; Demel, Stacie L.; Flaherty, Matthew L.; Woo, Daniel; Mackey, Jason; De Los Rios La Rosa, Felipe; Martini, Sharyl; Ferioli, Simona; Adeoye, Opeolu; Khatri, Pooja; Kissela, Brett M.; Kleindorfer, Dawn O.; Department of Neurology, School of MedicineBackground 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.Item Substance Use and Performance of Toxicology Screens in the Greater Cincinnati Northern Kentucky Stroke Study(American Heart Association, 2022-10) Madsen, Tracy E.; Cummings, Olivia W.; De Los Rios La Rosa, Felipe; Khoury, Jane C.; Alwell, Kathleen; Woo, Daniel; Ferioli, Simona; Martini, Sharyl; Adeoye, Opeolu; Khatri, Pooja; Flaherty, Matthew L.; Mackey, Jason; Mistry, Eva A.; Demel, Stacie L.; Coleman, Elisheva; Jasne, Adam S.; Slavin, Sabreena J.; Walsh, Kyle; Star, Michael; Broderick, Joseph P.; Kissela, Brett M.; Kleindorfer, Dawn O.; Neurology, School of MedicineBackground 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 20–54 years old. Secondary analyses included heavy alcohol use and cigarette smoking. Data were reported for 5 one-year periods spanning 22 years (1993/4–2015), 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 1993/4, 1999, 2005, 2010 and 2015, respectively (ptrend<0.001). Between 1993/4 and 2015, documented substance use increased in all demographic subgroups. Adjusting for gender, comorbidities, and NIHSS, predictors of toxicology screens included Black race (aOR 1.58, 95%CI 1.02–2.45), younger age (aOR 0.70, 95%CI 0.53–0.91, per 10 years), current smoking (aOR 1.62, 95%CI 1.06–2.46) and treatment at an academic hospital (aOR 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.Item Temporal Trends in Stroke Incidence over Time by Sex and Age in the Greater Cincinnati Northern Kentucky Stroke Study(American Heart Association, 2020-04) Madsen, Tracy E.; Khoury, Jane C.; Leppert, Michelle; Alwell, Kathleen; Moomaw, Charles J.; Sucharew, Heidi; Woo, Daniel; Ferioli, Simona; Martini, Sharyl; Adeoye, Opeolu; Khatri, Pooja; Flaherty, Matthew; De Los Rios La Rosa, Felipe; Mackey, Jason; Mistry, Eva; Demel, Stacie L.; Coleman, Elisheva; Jasne, Adam; Slavin, Sabreena J.; Walsh, Kyle; Star, Michael; Broderick, Joseph P.; Kissela, Brett M.; Kleindorfer, Dawn O.; Neurology, School of MedicineBackground 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.