Browsing by Author "Kissela, Brett M."
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Item C-reactive protein and risk of cognitive decline: The REGARDS study(PLOS, 2020-12-31) Rentería, Miguel Arce; Gillett, Sarah R.; McClure, Leslie A.; Wadley, Virginia G.; Glasser, Stephen P.; Howard, Virginia J.; Kissela, Brett M.; Unverzagt, Frederick W.; Jenny, Nancy S.; Manly, Jennifer J.; Cushman, Mary; Psychiatry, School of MedicineMarkers of systemic inflammation are associated with increased risk of cognitive impairment, but it is unclear if they are associated with a faster rate of cognitive decline and whether this relationship differs by race. Our objective was to examine the association of baseline C-reaction protein (CRP) with cognitive decline among a large racially diverse cohort of older adults. Participants included 21,782 adults aged 45 and older (36% were Black, Mean age at baseline 64) from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. CRP was measured at baseline and used as a continuous variable or a dichotomous grouping based on race-specific 90th percentile cutoffs. Cognitive measures of memory and verbal fluency were administered every 2 years for up to 12 years. Latent growth curve models evaluated the association of CRP on cognitive trajectories, adjusting for relevant demographic and health factors. We found that higher CRP was associated with worse memory (B = -.039, 95% CI [-.065,-.014]) and verbal fluency at baseline (B = -.195, 95% CI [-.219,-.170]), but not with rate of cognitive decline. After covariate adjustment, the association of CRP on memory was attenuated (B = -.005, 95% CI [-.031,-.021]). The association with verbal fluency at baseline, but not over time, remained (B = -.042, 95% CI [-.067,-.017]). Race did not modify the association between CRP and cognition. Findings suggest that levels of CRP at age 45+, are a marker of cognitive impairment but may not be suitable for risk prediction for cognitive decline.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 Deriving Place of Residence, Modified Rankin Scale, and EuroQol-5D Scores from the Medical Record for Stroke Survivors(Karger, 2021) Sucharew, Heidi; Kleindorfer, Dawn; Khoury, Jane C.; Alwell, Kathleen; Haverbusch, Mary; Stanton, Robert; Demel, Stacie; De Los Rios La Rosa, Felipe; Ferioli, Simona; Jasne, Adam; Mistry, Eva; Moomaw, Charles J.; Mackey, Jason; Slavin, Sabreena; Star, Michael; Walsh, Kyle; Woo, Daniel; Kissela, Brett M.; Neurology, School of MedicineIntroduction: We sought to determine the feasibility and validity of estimating post-stroke outcomes using information available in the electronic medical record (EMR) through comparison with outcomes obtained from telephone interviews. Methods: The Greater Cincinnati Northern Kentucky Stroke Study is a retrospective population-based epidemiology study that ascertains hospitalized strokes in the study region. As a sub-study, we identified all ischemic stroke patients who presented to a system of 4 hospitals during the study period 1/1/2015–12/31/2015 and were discharged alive. Enrolled subjects (or proxies for cognitively-disabled patients) were contacted by telephone at 3 and 6 months post-stroke to determine current place of residence and two functional outcomes—the modified Rankin Score (mRS) and the EuroQol (EQ-5D). Concurrently, the lead study coordinator, blinded to the telephone assessment outcomes, reviewed all available EMRs to estimate outcome status. Agreement between outcomes estimated from the EMR with “gold-standard” data obtained from telephone interviews was analyzed using the kappa statistic or interclass correlation (ICC), as appropriate. For each outcome, EMR-determined results were evaluated for added value beyond the information readily available from the stroke hospital stay. Results: Of 381 ischemic strokes identified, 294 (median [IQR] age 70 [60–79] years, 4% black, 52% female) were interviewed post-stroke. Agreement between EMR and telephone for 3-month residence was very good (kappa=0.84, 95% CI 0.74–0.94), good for mRS (weighted kappa=0.75, 95% CI 0.70–0.80), and good for EQ-5D (ICC=0.74, 95% CI 0.68–0.79). Similar results were observed at 6 months post stroke. At both 3 and 6 months post stroke, EMR-determined outcomes added value in predicting the gold standard telephone results beyond the information available from the stroke hospitalization; the added fraction of new information ranged from 0.25 to 0.59. Conclusions: Determining place of residence, mRS, and EQ-5D outcomes derived from information recorded in the EMR post-stroke, without patient contact, is feasible and has good agreement with data obtained from direct contact. However, we note that the level of agreement for mRS and EQ-5D was higher for proxy interviews and that the EMR often reflects health care providers’ judgments that tend to overestimate disability and underestimate quality of life.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 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 Sex-specific stroke incidence over time in the Greater Cincinnati/Northern Kentucky Stroke Study(Wolters Kluwer, 2017-09-05) Madsen, Tracy E.; Khoury, Jane; Alwell, Kathleen; Moomaw, Charles J.; Rademacher, Eric; Flaherty, Matthew L.; Woo, Daniel; Mackey, Jason; La Rosa, Felipe De Los Rios; Martini, Sharyl; Ferioli, Simona; Adeoye, Opeolu; Khatri, Pooja; Broderick, Joseph P.; Kissela, Brett M.; Kleindorfer, Dawn; Neurology, School of MedicineOBJECTIVE: Recent data suggest stroke incidence is decreasing over time, but it is unknown whether incidence is decreasing in women and men to the same extent. METHODS: Within our population of 1.3 million, all incident strokes among residents ≥20 years old were ascertained at all hospitals during July 1993-June 1994 and calendar years 1999, 2005, and 2010. A sampling scheme was used to ascertain out-of-hospital cases. Sex-specific incidence rates per 100,000 among black and white participants, age- and race-adjusted, were standardized to the 2000 US Census population. Trends over time by sex were compared; a Bonferroni correction was applied for multiple comparisons. RESULTS: Over the 4 study periods, there were 7,710 incident strokes; 57.2% (n = 4,412) were women. Women were older than men (mean ± SE 72.4 ± 0.34 vs 68.2 ± 0.32, p < 0.001). Incidence of all strokes decreased over time in men (263 [confidence interval 246-281] to 192 [179-205], p < 0.001) but not in women (217 [205-230] to 198 [187-210], p = 0.15). Similar sex differences were seen for ischemic stroke (men, 238 [223-257] to 165 [153-177], p < 0.01; women, 193 [181-205] to 173 [162-184], p = 0.09). Incidence of all strokes and of ischemic strokes was similar between women and men in 2010. Incidence of intracerebral hemorrhage and subarachnoid hemorrhage were stable over time in both sexes. CONCLUSIONS: Decreases in stroke incidence over time are driven by a decrease in ischemic stroke in men. Contrary to previous study periods, stroke incidence rates were similar by sex in 2010. Future research is needed to understand why the decrease in ischemic stroke incidence is more pronounced in men.Item Stable incidence but declining case-fatality rates of subarachnoid hemorrhage in a population(American Academy of Neurology, 2016-11-22) Mackey, Jason; Khoury, Jane C.; Alwell, Kathleen; Moomaw, Charles J.; Kissela, Brett M.; Flaherty, Matthew L.; Adeoye, Opeolu; Woo, Daniel; Ferioli, Simona; De Los Rios La Rosa, Felipe; Martini, Sharyl; Khatri, Pooja; Broderick, Joseph P.; Zuccarello, Mario; Kleindorfer, Dawn; Neurology, School of MedicineObjective: To characterize temporal trends in subarachnoid hemorrhage (SAH) incidence and outcomes over 5 time periods in a large population-based stroke study in the United States. Methods: All SAHs among residents of the Greater Cincinnati/Northern Kentucky region at least 20 years of age were identified and verified via study physician review in 5 distinct year-long study periods between 1988 and 2010. We abstracted demographics, care patterns, and outcomes, and we compared incidence and case-fatality rates across the study periods. Results: The incidence of SAH in the 5 study periods (age-, race-, and sex-adjusted to the 2000 US population) was 8.8 (95% confidence interval 6.8–10.7), 9.2 (7.2–11.2), 10.0 (8.0–12.0), 9.0 (7.1–10.9), and 7.7 (6.0–9.4) per 100,000, respectively; the trend in incidence rates from 1988 to 2010 was not statistically significant (p = 0.22). Advanced neurovascular imaging, endovascular coiling, and neurologic intensive care unit availability increased significantly over time. All-cause 5-day (32%–18%, p = 0.01; for trend), 30-day (46%–25%, p = 0.001), and 90-day (49%–29%, p = 0.001) case-fatality rates declined from 1988 to 2010. When we included only proven or highly likely aneurysmal SAH, the declines in case-fatality were no longer statistically significant. Conclusions: Although the incidence of SAH remained stable in this population-based region, 5-day, 30-day, and 90-day case-fatality rates declined significantly. Advances in surgical and medical management, along with systems-based changes such as the emergence of neurocritical care units, are potential explanations for the reduced case-fatality.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.