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Item Acute Ischemic Stroke, Depressed Left Ventricular Ejection Fraction, and Sinus Rhythm: Prevalence and Practice Patterns(American Heart Association, 2022) Baker, Anna D.; Schwamm, Lee H.; Sanborn, Danita Y.; Furie, Karen; Stretz, Christoph; Grory, Brian Mac; Yaghi, Shadi; Kleindorfer, Dawn; Sucharew, Heidi; Mackey, Jason; Walsh, Kyle; Flaherty, Matt; Kissela, Brett; Alwell, Kathleen; Khoury, Jane; Khatri, Pooja; Adeoye, Opeolu; Ferioli, Simona; Woo, Daniel; Martini, Sharyl; De Los Rios La Rosa, Felipe; Demel, Stacie L.; Madsen, Tracy; Star, Michael; Coleman, Elisheva; Slavin, Sabreena; Jasne, Adam; Mistry, Eva A.; Haverbusch, Mary; Merkler, Alexander E.; Kamel, Hooman; Schindler, Joseph; Sansing, Lauren H.; Faridi, Kamil F.; Sugeng, Lissa; Sheth, Kevin N.; Sharma, Richa; Neurology, School of MedicineBackground: 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%; I2, 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.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 Genome-wide association study of intracranial aneurysm identifies a new association on chromosome 7(Ovid Technologies Wolters Kluwer – American Heart Association, 2014-11) Foroud, Tatiana; Lai, Dongbing; Koller, Daniel; van’t Hof, Femke; Kurki, Mitja I.; Anderson, Craig S.; Brown, Robert D.; Connolly, E. Sander; Eriksson, Johan G.; Flaherty, Matthew; Fornage, Myriam; von und zuFraunberg, Mikael; Gaál, Emília I.; Laakso, Aki; Hernesniemi, Juha; Huston, John; Jääskeläinen, Juha E.; Kiemeney, Lambertus A.; Kivisaari, Riku; Kleindorfer, Dawn; Ko, Nerissa; Lehto, Hanna; Mackey, Jason; Meissner, Irene; Moomaw, Charles J.; Mosley, Thomas H.; Moskala, Marek; Niemelä, Mika; Palotie, Aarno; Pera, Joanna; Rinkel, Gabriel; Ripke, Stephan; Rouleau, Guy; Ruigrok, Ynte; Sauerbeck, Laura; Słowik, Agnieszka; Vermeulen, Sita H.; Woo, Daniel; Worrall, Bradford B.; Broderick, Joseph; Department of Medical & Molecular Genetics, IU School of MedicineBACKGROUND AND PURPOSE: Common variants have been identified using genome-wide association studies which contribute to intracranial aneurysms (IA) susceptibility. However, it is clear that the variants identified to date do not account for the estimated genetic contribution to disease risk. METHODS: Initial analysis was performed in a discovery sample of 2617 IA cases and 2548 controls of white ancestry. Novel chromosomal regions meeting genome-wide significance were further tested for association in 2 independent replication samples: Dutch (717 cases; 3004 controls) and Finnish (799 cases; 2317 controls). A meta-analysis was performed to combine the results from the 3 studies for key chromosomal regions of interest. RESULTS: Genome-wide evidence of association was detected in the discovery sample on chromosome 9 (CDKN2BAS; rs10733376: P<1.0×10(-11)), in a gene previously associated with IA. A novel region on chromosome 7, near HDAC9, was associated with IA (rs10230207; P=4.14×10(-8)). This association replicated in the Dutch sample (P=0.01) but failed to show association in the Finnish sample (P=0.25). Meta-analysis results of the 3 cohorts reached statistical significant (P=9.91×10(-10)). CONCLUSIONS: We detected a novel region associated with IA susceptibility that was replicated in an independent Dutch sample. This region on chromosome 7 has been previously associated with ischemic stroke and the large vessel stroke occlusive subtype (including HDAC9), suggesting a possible genetic link between this stroke subtype and IA.Item Health Factors Associated With Development and Severity of Poststroke Dysphagia: An Epidemiological Investigation(American Heart Association, 2024) Krekeler, Brittany N.; Schieve, Heidi J. P.; Khoury, Jane; Ding, Lili; Haverbusch, Mary; Alwell, Kathleen; Adeoye, Opeolu; Ferioloi, Simona; Mackey, Jason; Woo, Daniel; Flaherty, Matthew; De Los Rios La Rosa, Felipe; Demel, Stacie; Star, Michael; Coleman, Elisheva; Walsh, Kyle; Slavin, Sabreena; Jasne, Adam; Mistry, Eva; Kleindorfer, Dawn; Kissela, Brett; Neurology, School of MedicineBackground: 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.Item Screening for brain aneurysm in the Familial Intracranial Aneurysm study: frequency and predictors of lesion detection(Journal of Neurosurgery Publishing Group (JNSPG), 2008-06) Brown, Robert D., Jr.; Huston, John, III; Hornung, Richard; Foroud, Tatiana; Kallmes, David F.; Kleindorfer, Dawn; Meissner, Irene; Woo, Daniel; Sauerbeck, Laura; Broderick, Joseph; Department of Medical & Molecular Genetics, School of Medicine,Object Approximately 20% of patients with an intracranial saccular aneurysm report a family history of intracranial aneurysm (IA) or subarachnoid hemorrhage. A better understanding of predictors of aneurysm detection in familial IA may allow more targeted aneurysm screening strategies. Methods The Familial Intracranial Aneurysm (FIA) study is a multicenter study, in which the primary objective is to define the susceptibility genes related to the formation of IA. First-degree relatives (FDRs) of those affected with IA are offered screening with magnetic resonance (MR) angiography if they were previously unaffected, are ≥ 30 years of age, and have a history of smoking and/or hypertension. Independent predictors of aneurysm detection on MR angiography were determined using the generalized estimating equation version of logistic regression. Results Among the first 303 patients screened with MR angiography, 58 (19.1%) had at least 1 IA, including 24% of women and 11.7% of men. Ten (17.2%) of 58 affected patients had multiple aneurysms. Independent predictors of aneurysm detection included female sex (odds ratio [OR] 2.46, p = 0.001), pack-years of cigarette smoking (OR 3.24 for 20 pack-years of cigarette smoking compared with never having smoked, p < 0.001), and duration of hypertension (OR 1.26 comparing those with 10 years of hypertension to those with no hypertension, p = 0.006). Conclusions In the FIA study, among the affected patients’ FDRs who are > 30 years of age, those who are women or who have a history of smoking or hypertension are at increased risk of suffering an IA and should be strongly considered for screening.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 Temporal Trends of Sex Differences in Transient Ischemic Attack Incidence Within a Population(Elsevier, 2019-07-01) Madsen, Tracy E.; Khoury, Jane C.; Alwell, Kathleen; Moomaw, Charles J.; Rademacher, Eric; Flaherty, Matthew L.; Woo, Daniel; De Los Rios La Rosa, Felipe; Mackey, Jason; Martini, Sharyl; Ferioli, Simona; Adeoye, Opeolu; Khatri, Pooja; Broderick, Joseph P.; Kissela, Brett M.; Kleindorfer, Dawn; Neurology, School of MedicineObjective: Previously we reported that ischemic stroke incidence is declining over time for men but not women. We sought to describe temporal trends of sex differences in incidence of transient ischemic attack (TIA) within the same large, biracial population. Methods: Among the population of 1.3 million in the Greater Cincinnati Northern Kentucky Stroke Study (GCNKSS) region, TIAs among area residents (≥20 years old) were identified at all local hospitals. Out of hospital cases were ascertained using a sampling scheme. First-ever cases and first within each study period for a patient were included in incidence rates. All cases were physician-adjudicated. Incidence rates (during 7/93-6/94 and calendar years 1999, 2005, and 2010) were calculated using the age-, race-, and sex-specific number of TIAs divided by the GCNKSS population in that group; rates were standardized to the 2010 U.S. population. T-tests with Bonferroni correction were used to compare rates over time. Results: There were a total of 4746 TIA events; 53% were female, and 12% were black. In males, incidence decreased from 153 (95%CI 139-167) per 100,000 in 1993/4 to 117 (95%CI 107-128) in 2010 (p<0.05 for trend test) but was similar over time among females (107 (95%CI 97-116) to 102 (95%CI 94-111), p>0.05). Conclusions: Within the GCNKSS population, TIA incidence decreased significantly over time in males but not females, data which parallels trends in ischemic stroke in the GCNKSS over the same time period. Future research is needed to determine if these sex differences in incidence over time continue past 2010.