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Jane C Khoury, Dawn Kleindorfer,
Kathleen Alwell,
Charles J Moomaw,
Daniel Woo,
Opeolu Adeoye,
Matthew L Flaherty,
Pooja Khatri,
Simona Ferioli,
Joseph P Broderick,
Brett M Kissela
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ABSTRACT: BACKGROUND AND PURPOSE: We previously reported increased incidence of ischemic stroke among both blacks and whites with diabetes mellitus, especially in those aged <55 years. With rising prevalence of diabetes mellitus in the past decade, we revisit the impact of diabetes mellitus on stroke incidence in the same population (≈1.3 million) 5 and 10 years later. METHODS: This is a population-based study. First ischemic strokes among black and white residents of the 5-county Greater Cincinnati/Northern Kentucky region, aged ≥20 years, for periods 7/1993 to 6/1994, 1999, and 2005, were included in this analysis. Incidence rates were adjusted for sex, race, and age, as appropriate, to the 2000 US population. RESULTS: History of diabetes mellitus among first ischemic strokes was reported for 493/1709 (28%) in 1993/1994, 522/1778 (29%) in 1999, and 544/1680 (33%) in 2005. Risk ratios (95% confidence interval) for rates of stroke in those with versus without diabetes mellitus for blacks reduced significantly from 5.6 in 1993/1994 to 3.2 in 2005; for whites the risk ratio remained stable at 3.8 in 1993/1994 and 2005. However, risk ratios varied with age, with an overall 5- to 14-fold increased risk observed in those aged 20 to 65 years. CONCLUSIONS: Those with diabetes mellitus remain at greatly increased risk for stroke at all ages, especially <65 years, regardless of race. The rates and risk ratios for 1999 and 2005, although similar to those previously reported for the mid-1990s, take on increased significance, given the epidemic of diabetes mellitus and metabolic syndrome throughout the US and the world.
Stroke 04/2013; · 5.73 Impact Factor
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Jason Mackey,
Robert D Brown,
Charles J Moomaw,
Richard Hornung,
Laura Sauerbeck,
Daniel Woo,
Tatiana Foroud,
Dheeraj Gandhi, Dawn Kleindorfer,
Matthew L Flaherty,
Irene Meissner,
Craig Anderson,
Guy Rouleau,
E Sander Connolly,
Ranjan Deka,
Daniel L Koller,
Todd Abruzzo,
John Huston,
Joseph P Broderick
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ABSTRACT: BACKGROUND AND PURPOSE: Previous studies have suggested that family members with intracranial aneurysms (IAs) often harbor IAs in similar anatomic locations. IA location is important because of its association with rupture. We tested the hypothesis that anatomic susceptibility to IA location exists using a family-based IA study. METHODS: We identified all affected probands and first-degree relatives (FDRs) with a definite or probable phenotype in each family. We stratified each IA of the probands by major arterial territory and calculated each family's proband-FDR territory concordance and overall contribution to the concordance analysis. We then matched each family unit to an unrelated family unit selected randomly with replacement and performed 1001 simulations. The median concordance proportions, odds ratios (ORs), and P values from the 1001 logistic regression analyses were used to represent the final results of the analysis. RESULTS: There were 323 family units available for analysis, including 323 probands and 448 FDRs, with a total of 1176 IAs. IA territorial concordance was higher in the internal carotid artery (55.4% versus 45.6%; OR, 1.54 [1.04-2.27]; P=0.032), middle cerebral artery (45.8% versus 30.5%; OR, 1.99 [1.22-3.22]; P=0.006), and vertebrobasilar system (26.6% versus 11.3%; OR, 2.90 [1.05-8.24], P=0.04) distributions in the true family compared with the comparison family. Concordance was also higher when any location was considered (53.0% versus 40.7%; OR, 1.82 [1.34-2.46]; P<0.001). CONCLUSIONS: In a highly enriched sample with familial predisposition to IA development, we found that IA territorial concordance was higher when probands were compared with their own affected FDRs than with comparison FDRs, which suggests that anatomic vulnerability to IA formation exists. Future studies of IA genetics should consider stratifying cases by IA location.
Stroke 11/2012; · 5.73 Impact Factor
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Matthew L Flaherty,
Brett Kissela,
Jane C Khoury,
Kathleen Alwell,
Charles J Moomaw,
Daniel Woo,
Pooja Khatri,
Simona Ferioli,
Opeolu Adeoye,
Joseph P Broderick, Dawn Kleindorfer
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ABSTRACT: Background: Population-based studies have estimated that about 15% of ischemic strokes are caused by large-vessel cerebrovascular disease. We determined the types of large-vessel atherosclerosis responsible for ischemic strokes in a population-based stroke study. Methods: Patients with first-ever or recurrent ischemic stroke in the Greater Cincinnati area were identified during 2005 at all local hospitals. Study physicians assigned ischemic stroke subtypes. Overall event rates and incidence rates for first-ever events were calculated, and age-, race- and sex-adjusted to the 2000 US population. Results: There were 2,204 ischemic strokes, including 365 strokes of large-vessel subtype (16.6% of all ischemic strokes). Extracranial internal carotid artery (ICA) stenosis was associated with 8.0% of all ischemic strokes, while extracranial ICA occlusion and intracranial atherosclerosis were each associated with 3.5% of strokes. The annual rate of first-ever and recurrent stroke attributed to extracranial ICA was 13.4 (11.4-15.4) per 100,000 persons. We conservatively estimate that about 41,000 strokes may be attributed to extracranial ICA stenosis annually in the United States. Conclusions: Large-vessel atherosclerosis is an important cause of stroke, with extracranial ICA stenosis being significantly more common than extracranial ICA occlusion or intracranial atherosclerotic disease.
Neuroepidemiology 10/2012; 40(1):36-41. · 2.31 Impact Factor
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Tatiana Foroud,
Daniel L Koller,
Dongbing Lai,
Laura Sauerbeck,
Craig Anderson,
Nerissa Ko,
Ranjan Deka,
Thomas H Mosley,
Myriam Fornage,
Daniel Woo, [......],
Guy Rouleau,
E Sander Connolly,
Bradford B Worrall, Dawn Kleindorfer,
Matthew L Flaherty,
Sharyl Martini,
Jason Mackey,
Felipe De Los Rios La Rosa,
Robert D Brown,
Joseph P Broderick
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ABSTRACT: Background- Genomewide association studies have identified novel genetic factors that contribute to intracranial aneurysm (IA) susceptibility. We sought to confirm previously reported loci, to identify novel risk factors, and to evaluate the contribution of these factors to familial and sporadic IA. Method- We utilized 2 complementary samples, one recruited on the basis of a dense family history of IA (discovery sample 1: 388 IA cases and 397 controls) and the other without regard to family history (discovery sample 2: 1095 IA cases and 1286 controls). Imputation was used to generate a common set of single nucleotide polymorphisms (SNP) across samples, and a logistic regression model was used to test for association in each sample. Results from each sample were then combined in a metaanalysis. RESULTS: There was only modest overlap in the association results obtained in the 2 samples. In neither sample did results reach genomewide significance. However, the metaanalysis yielded genomewide significance for SNP on chromosome 9p (CDKN2BAS; rs6475606; P=3.6 × 10(-8)) and provided further evidence to support the previously reported association of IA with SNP in SOX17 on chromosome 8q (rs1072737; P=8.7 × 10(-5)). Analyses suggest that the effect of smoking acts multiplicatively with the SNP genotype, and smoking has a greater effect on risk than SNP genotype. CONCLUSIONS: In addition to replicating several previously reported loci, we provide further evidence that the association on chromosome 9p is attributable to variants in CDKN2BAS (also known as ANRIL, an antisense noncoding RNA).
Stroke 09/2012; 43(11):2846-2852. · 5.73 Impact Factor
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ABSTRACT: Object Although decompressive hemicraniectomy has been shown to reduce death and improve functional outcome following malignant middle cerebral artery territory infarction, there is ongoing debate as to whether surgery should be routinely performed, considering the very high rates of disability and functional dependence in survivors. Through a systematic review of the literature, the authors sought to determine the outcome from a patient's perspective. Methods In September 2010, a MEDLINE search of the English-language literature was performed using various combinations of 12 key words. A total of 16 papers were reviewed and individual study data were extracted. Results There was significant variability in study design, patient eligibility criteria, timing of surgery, and methods of outcome assessment. There were 382 patients (59% male, 41% female) with a mean age of 50 years, 25% with dominant-hemisphere infarction. The mortality rate was 24% and the mean follow-up in survivors was 19 months (range 3-114 months). Of 156 survivors with available modified Rankin Scale (mRS) scores, 41% had favorable functional outcome (mRS Score ≤ 3), whereas 47% had moderately severe disability (mRS Score 4). Among 157 survivors with quality of life assessment, the mean overall reduction was 45%: 67% for physical aspect and 37% for psychosocial aspect. Of 114 screened survivors, depression affected 56% and was moderate or severe in 25%. Most patients and/or caregivers (77% of the 209 interviewed) were satisfied and would give consent again for the procedure. Conclusions Despite high rates of physical disability and depression, the vast majority of patients are satisfied with life and do not regret having undergone surgery.
Journal of Neurosurgery 08/2012; 117(4):749-54. · 2.96 Impact Factor
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Ralph Rahme,
Lincoln Jimenez,
Umair Bashir,
Opeolu M Adeoye,
Todd A Abruzzo,
Andrew J Ringer,
Brett M Kissela,
Jane Khoury,
Charles J Moomaw,
Heidi Sucharew,
Simona Ferioli,
Matthew L Flaherty,
Daniel Woo,
Pooja Khatri,
Kathleen Alwell, Dawn Kleindorfer
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ABSTRACT: PURPOSE: Malignant middle cerebral artery (MCA) infarctions are thought to be rare in children. In a recent hospital-based study, only 1.3 % of pediatric ischemic strokes were malignant MCA infarctions. However, population-based rates have not been published. We performed subgroup analysis of a population-based study to determine the rate of malignant MCA infarctions in children. METHODS: In 2005 and 2010, all ischemic stroke-related emergency visits and hospital admissions among the 1.3 million residents of the five-county Greater Cincinnati/Northern Kentucky area were ascertained. Cases that occurred in patients 18 years and younger were reviewed in detail, and corresponding clinical and neuroimaging findings were recorded. Infarctions were considered malignant if they involved 50 % or more of the MCA territory and resulted in cerebral edema and mass effect. RESULTS: In 2005, eight pediatric ischemic strokes occurred in the study population, none of which were malignant infarctions. In 2010, there were also eight ischemic strokes. Of these, two malignant MCA infarctions were identified: (1) a 7-year-old boy who underwent hemicraniectomy and survived with moderate disability at 30 days and (2) a 17-year-old girl with significant prestroke disability who was not offered hemicraniectomy and died following withdrawal of care. Thus, among 16 children over 2 years, there were two malignant MCA infarctions (12.5 %, 95 % CI 0-29). CONCLUSIONS: Malignant MCA infarctions in children may not be as rare as previously thought. Given the significant survival and functional outcome benefit conferred by hemicraniectomy in adults, future studies focusing on its potential role in pediatric patients are warranted.
Child s Nervous System 08/2012; · 1.54 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
Stroke 07/2012; 43(8):2055-9. · 5.73 Impact Factor
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Jason Mackey,
Robert D Brown,
Charles J Moomaw,
Laura Sauerbeck,
Richard Hornung,
Dheeraj Gandhi,
Daniel Woo, Dawn Kleindorfer,
Matthew L Flaherty,
Irene Meissner,
Craig Anderson,
E Sander Connolly,
Guy Rouleau,
David F Kallmes,
James Torner,
John Huston,
Joseph P Broderick
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ABSTRACT: Familial predisposition is a recognized nonmodifiable risk factor for the formation and rupture of intracranial aneurysms (IAs). However, data regarding the characteristics of familial IAs are limited. The authors sought to describe familial IAs more fully, and to compare their characteristics with a large cohort of nonfamilial IAs.
The Familial Intracranial Aneurysm (FIA) study is a multicenter international study with the goal of identifying genetic and other risk factors for formation and rupture of IAs in a highly enriched population. The authors compared the FIA study cohort with the International Study of Unruptured Intracranial Aneurysms (ISUIA) cohort with regard to patient demographic data, IA location, and IA multiplicity. To improve comparability, all patients in the ISUIA who had a family history of IAs or subarachnoid hemorrhage were excluded, as well as all patients in both cohorts who had a ruptured IA prior to study entry.
Of 983 patients enrolled in the FIA study with definite or probable IAs, 511 met the inclusion criteria for this analysis. Of the 4059 patients in the ISUIA study, 983 had a previous IA rupture and 657 of the remainder had a positive family history, leaving 2419 individuals in the analysis. Multiplicity was more common in the FIA patients (35.6% vs 27.9%, p<0.001). The FIA patients had a higher proportion of IAs located in the middle cerebral artery (28.6% vs 24.9%), whereas ISUIA patients had a higher proportion of posterior communicating artery IAs (13.7% vs 8.2%, p=0.016).
Heritable structural vulnerability may account for differences in IA multiplicity and location. Important investigations into the underlying genetic mechanisms of IA formation are ongoing.
Journal of Neurosurgery 04/2012; 117(1):60-4. · 2.96 Impact Factor
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ABSTRACT: The purpose of this study was to examine the association between prolongation of QT interval corrected for heart rate (QTc) with incident stroke.
Unlike cardiovascular morbidity and mortality, little is known about the relationship between QTc and risk of stroke.
A total of 27,411 participants age 45 years and older without previous stroke from the REGARDS (REasons for Geographic and Racial Differences in Stroke) study were included in this analysis. QTc was calculated using Framingham formula (QTc(Fram)). Stroke cases were identified and adjudicated during up to 8.2 years of follow-up (median, 5.1 years).
The risk of incident stroke in study participants with prolonged QTc(Fram) was almost 3 times the risk in those with normal QTc(Fram) (hazard ratio [HR] [95% confidence interval (CI)]: 2.88 [2.12 to 3.92], p < 0.0001). After adjustment for demographics (age, race, and sex), traditional stroke risk factors (antihypertensive medication use, systolic blood pressure, current smoking, diabetes, left ventricular hypertrophy, atrial fibrillation, and previous cardiovascular disease), warfarin use, aspirin use, QRS duration and use of QTc-prolonging drugs, the risk of stroke remained significantly high (HR [95% CI]: 1.67 [1.16 to 2.41], p = 0.0061) and was consistent across several subgroups of REGARDS study participants. Similar results were obtained when the risk of stroke was estimated per 1-SD increase in QTc(Fram), (HR [95% CI]: 1.12 [1.03 to 1.21], p = 0.0053 in multivariable-adjusted model) and when other QTc correction formulas including those of Hodge, Bazett, and Fridericia were used.
QTc prolongation is associated with a significantly increased risk of incident stroke independent of traditional stroke risk factors. Examining the risk of stroke associated with QTc-prolonging drugs may be warranted.
Journal of the American College of Cardiology 04/2012; 59(16):1460-7. · 14.16 Impact Factor
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Virginia Culyer,
Erin McDonough,
Christopher J Lindsell,
Kathleen Alwell,
Charles J Moomaw,
Brett M Kissela,
Matthew L Flaherty,
Pooja Khatri,
Daniel Woo,
Simona Ferioli,
Joseph P Broderick, Dawn Kleindorfer,
Opeolu Adeoye
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ABSTRACT: Elevated blood pressure is common in patients with acute subarachnoid hemorrhage (SAH). American Heart Association guidelines do not specify a blood pressure target, but limited data suggest that systolic blood pressure (SBP) ≥160 mmHg is associated with increased risk of rebleeding and neurologic decline. In a population-based study, we determined the frequency of antihypertensive therapy in emergency department (ED) patients with SAH and the proportion of those patients with SBP ≥160 mmHg who received this therapy. In 2005, nontraumatic SAH cases were retrospectively ascertained at 16 hospitals in our region by screening for International Classification of Diseases Ninth Revision diagnostic codes 430-436. Blood pressure was recorded at ED presentation and also before and after any treatment with antihypertensives. Hypotension was defined as SBP <100 mmHg. The Mann-Whitney U test and χ(2) test were used for comparisons. Our cohort comprised 82 patients with SAH presenting to an ED; 4 patients were excluded. The median age of the included patients was 54 years, 74.4% were female, 29.5% were black, and 31 (39.7%) had SBP ≥160 mmHg. Antihypertensive therapy was given to 22 of 31 patients (70.9%) with SBP ≥160 mmHg and to 4 of 47 patients (8.5%) with SBP <160 mmHg. No patients became hypotensive after receiving treatment. Age, sex, Glascow Coma Scale score, and National Institutes of Health Stroke Scale score were similar between treated and untreated patients. In the absence of definitive evidence, current blood pressure management in local EDs appears reasonable. Further studies of blood pressure management in acute SAH are warranted.
Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 04/2012;
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Erin McDonough Grise,
Opeolu Adeoye,
Christopher Lindsell,
Kathleen Alwell,
Charles Moomaw,
Brett Kissela,
Dan Woo,
Matthew Flaherty,
Simona Ferioli,
Pooja Khatri,
Joseph Broderick, Dawn Kleindorfer
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ABSTRACT: Severely elevated blood pressure (BP) and aggressive BP reduction are both associated with poor outcome in acute ischemic stroke (AIS). In nontissue-type plasminogen activator patients, the American Heart Association recommends antihypertensive therapy only if BP is ≥ 220/120 mm Hg with a goal of 15% to 25% reduction in the first 24 hours. We hypothesized that patients with AIS often receive antihypertensives in the emergency department below the recommended threshold and that BP reduction is often >20%.
In 2005, AIS cases were ascertained at all 16 hospitals in Greater Cincinnati. BP was recorded at emergency department presentation and before and after antihypertensive treatment. Hypertension was defined as BP ≥ 220/120 mm Hg. Chi-square and Mann-Whitney U tests were used for comparisons.
A total of 1739 patients with AIS met inclusion criteria. Median age was 72 years with 43% male and 25% black. Of 218 treated with antihypertensives, 65 (30.0%) met treatment criteria immediately before treatment. Treated patients were younger (66 versus 73 years, P<0.001) with greater stroke severity than untreated patients (National Institutes of Health Stroke Scale score 4 versus 3, P=0.028). Median change in systolic BP was -25 mm Hg (range, -96 to 25 mm Hg). Median percentage change in systolic BP was -12.3% (range, -49.2% to 16.1%). Systolic BP decreased > 20% in 52 treated patients (23.7%).
Only one third of patients with AIS treated with antihypertensives met American Heart Association-recommended treatment criteria, and the rate of change of BP was frequently greater than recommended. Further studies are warranted to determine the impact of practice patterns on AIS outcomes.
Stroke 02/2012; 43(2):557-9. · 5.73 Impact Factor
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Ralph Rahme,
Richard Curry, Dawn Kleindorfer,
Jane C Khoury,
Andrew J Ringer,
Brett M Kissela,
Kathleen Alwell,
Charles J Moomaw,
Matthew L Flaherty,
Pooja Khatri,
Daniel Woo,
Simona Ferioli,
Joseph Broderick,
Opeolu Adeoye
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ABSTRACT: 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.
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.
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.
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.
Stroke 02/2012; 43(2):550-2. · 5.73 Impact Factor
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Matthew L Flaherty,
Brett Kissela,
Heidi Sucharew,
Kathleen Alwell,
Charles J Moomaw,
Daniel Woo,
Pooja Khatri,
Simona Ferioli,
Opeolu Adeoye,
Jason Mackey,
Joseph P Broderick, Dawn Kleindorfer
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ABSTRACT: Carotid endartectomy (CEA) and carotid artery stenting (CAS) reduce the risk of stroke when performed with acceptable perioperative morbidity and mortality. Studies from the 1980s in the greater Cincinnati/northern Kentucky population showed that perioperative risk after CEA exceeded the recommended boundaries of 3.0% for asymptomatic stenosis and 6.0% for symptomatic stenosis. We investigated the indications and outcomes for CEA and CAS in the same population during 2005. We identified all residents of the greater Cincinnati/northern Kentucky region who underwent CEA or CAS at any local hospital during 2005. Identified cases of transient ischemic attack or stroke occurring before or after CEA or CAS were abstracted by study nurses and reviewed by a study physician. The main outcome of interest was 30-day risk of stroke or death after CEA or CAS. Events were analyzed using Kaplan-Meier statistics. Among approximately 1.3 million greater Cincinnati/northern Kentucky residents, 525 CEAs were performed, 343 (65%) for asymptomatic stenosis and 182 (35%) for symptomatic stenosis. There were 43 CAS procedures, 23 (53%) for asymptomatic stenosis and 20 (47%) for symptomatic stenosis. The 30-day perioperative risk of stroke or death after CEA was 3.3% (95% confidence interval [CI], 1.8%-5.9%) for asymptomatic stenosis and 6.3% (95% CI, 3.5%-11.1%) for symptomatic stenosis. The 30-day perioperative risk of stroke or death after CAS was 4.6% (95% CI, 0.7%-28.1%) for asymptomatic stenosis and 21.1% (95% CI, 8.5%-46.8%) for symptomatic stenosis. Point estimates for perioperative risk after CEA were improved from previous studies but remained above the recommended benchmarks. The number of CAS procedures was low, but the perioperative risk was significant.
Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 11/2011;
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ABSTRACT: Previously in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort, we found 18% of the stroke/transient ischemic attack-free study population reported ≥1 stroke symptom at baseline. We sought to evaluate the additional impact of these stroke symptoms on risk for subsequent stroke.
REGARDS recruited 30,239 US blacks and whites, aged 45+ years in 2003 to 2007 who are being followed every 6 months for events. All stroke events are physician-verified; those with prior diagnosed stroke or transient ischemic attack are excluded from this analysis. At baseline, participants were asked 6 questions regarding stroke symptoms. Measured stroke risk factors were components of the Framingham Stroke Risk Score.
After excluding those with prior stroke or missing data, there were 24,412 participants in this analysis with a median follow-up of 4.4 years. Participants were 39% black, 55% female, and had median age of 64 years. There were 381 physician-verified stroke events. The Framingham Stroke Risk Score explained 72.0% of stroke risk; individual components explained between 0.2% (left ventricular hypertrophy) and 5.7% (age+race) of stroke risk. After adjustment for Framingham Stroke Risk Score factors, stroke symptoms were significantly related to stroke risk: for each stroke symptom reported, the risk of stroke increased by 21% per symptom.
Among participants without self-reported stroke or transient ischemic attack, prior stroke symptoms are highly predictive of future stroke events. Compared with Framingham Stroke Risk Score factors, the impact of stroke symptom on the prediction of future stroke was almost as large as the impact of smoking and hypertension and larger than the impact of diabetes and heart disease.
Stroke 09/2011; 42(11):3122-6. · 5.73 Impact Factor
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ABSTRACT: 'Exception from informed consent for research' (EFIC) is a rigorous procedure regulated by the FDA that requires community assent but allows enrollment without patient or family consent. Recently, several acute stroke trials have explored the use of EFIC to improve enrollment. We obtained ischemic stroke survivors' opinions regarding hypothetical enrollment into a clinical trial at the time of their stroke without personal or proxy consent.
During 2005, 460 ischemic stroke patients (or their proxy) who met case criteria were prospectively interviewed and followed. After 2 years, patients were asked to think back to the time of their stroke and indicate whether they would have wished to be enrolled in an acute stroke research study before individual or proxy consent could be obtained, understanding that consent would be sought as soon as possible thereafter, and they rated how agreeable they would have been to acute stroke research with different levels of invasiveness. Predictors of a positive opinion regarding the hypothetical research were analyzed using logistic regression. Variables included in the model were age, race, sex, education, initial NIHSS, modified Rankin Scale prior to stroke and 30 days after stroke, and proxy versus patient responder.
At 2 years after stroke, after excluding patient deaths, missing data or refusals, there were 194 patient/proxy responses included in this analysis. Overall, 72-79% of responses were favorable for chart review or blood draw without consent. The proportions answering agreeably to questions about medications or invasive strategies were smaller (62.9 and 59.8%). Older subjects were less likely to offer an agreeable response regarding use of medications [OR 0.97 per year (95% CI 0.94-0.99)] and invasive procedures [OR 0.97 per year (95% CI 0.94-0.99)]. Nonblacks tended to be more agreeable than blacks to invasive procedures. Men had twice the odds of being agreeable to blood draws than women.
We found that the majority of interviewed ischemic stroke patients were agreeable to being enrolled in acute stroke research with exception from informed consent, although the rates of agreement were lower than we expected among a cohort of patients who had already agreed to research. Older subjects, black race, and women were less likely to agree to blood draws or treatment strategies.
Cerebrovascular Diseases 09/2011; 32(4):321-6. · 2.72 Impact Factor
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Neurology 06/2011; 76(23):1956-7. · 8.31 Impact Factor
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ABSTRACT: Recombinant tissue-type plasminogen activator (rtPA) is the only approved therapy for acute ischemic stroke (AIS). In 2004, 1.8% to 2.1% of AIS patients in the United States received rtPA. Given incentives from regulatory agencies and payors to increase rtPA use, we hypothesized that rtPA use in the United States would increase from 2005 to 2009.
AIS cases were defined by exclusion of hemorrhagic stroke and transient ischemic attack International Classification of Diseases 9th revision codes (430, 431, 432, and 435) from diagnosis-related groups 14, 15, 524, and 559 discharges. Patients receiving thrombolytics were identified using International Classification of Diseases 9th revision code 99.10 (Medicare Provider and Analysis Review and Premier databases) and pharmacy billing records (Premier). Change over time and differences between databases were tested using negative binomial regression.
Within Medicare Provider and Analysis Review, thrombolytic use increased from 1.1% in 2005 to 3.4% in 2009 (P<0.001 for trend). Within Premier, thrombolytic use increased from 1.4% in 2005 to 3.7% in 2009 for all cases (P<0.001). Analysis of pharmacy billing records in Premier for 50-mg or 100-mg doses of rtPA showed that 3.4% of AIS cases were treated in 2009. Inclusion of patients with transient ischemic attack or hemorrhagic stroke International Classification of Diseases 9th revision codes who received any thrombolytic as "ischemic stroke patients receiving rtPA" changed the rate of thrombolysis to 5.2%.
In 2009, 3.4% to 5.2% of AIS patients in the United States received thrombolytics, approximately double the rate of treatment in 2005. Rapid recognition and transport and quick treatment in the emergency department remain goals for further improving treatment rates.
Stroke 06/2011; 42(7):1952-5. · 5.73 Impact Factor
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ABSTRACT: Early deterioration is common in intracerebral hemorrhage (ICH). Treatment at tertiary care centers has been associated with lower ICH mortality. Guidelines recommend aggressive care for 24 hours irrespective of the initial outlook. We examined the frequency of and factors associated with transfer to tertiary centers in ICH patients who initially presented at nontertiary emergency departments (EDs). We also compared observed with expected mortality in transferred and nontransferred patients using published short-term mortality predictors for ICH.
Adult patients who resided in a 5-county region and presented to nontertiary EDs with nontraumatic ICH in 2005 were identified. Intracerebral hemorrhage score and ICH Grading Scale (ICH-GS) were determined. Of 16 local hospitals, 2 were designated tertiary care centers. Logistic regression was used to assess factors associated with transfer.
Of 205 ICH patients who presented to nontertiary EDs, 80 (39.0%) were transferred to a tertiary center. In multivariate regression, better baseline function (modified Rankin scale 0-2 versus 3-5; odds ratio, 0.42, 95% confidence interval, 0.21-0.85, P = .016) and black race (odds ratio, 2.28, 95% confidence interval 1.01-5.12, P = .046) were associated with transfer. A trend toward higher 30-day mortality was observed in nontransferred patients (32.5% versus 45.6%, P = .06). The ICH-GS overestimated mortality for all patients, while the ICH Score adequately predicted mortality.
We found no significant difference in mortality between transferred and nontransferred patients, but the trend toward higher mortality in nontransferred patients suggests that further evaluation of ED disposition decisions for ICH patients is warranted. Expected ICH mortality may be overestimated by published tools.
The American journal of emergency medicine 05/2011; 29(4):391-5. · 1.54 Impact Factor
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Opeolu Adeoye,
Arthur Pancioli,
Jane Khoury,
Charles J Moomaw,
Pamela Schmit,
Irene Ewing,
Kathleen Alwell,
Matthew L Flaherty,
Daniel Woo,
Simona Ferioli,
Pooja Khatri,
Joseph P Broderick,
Brett M Kissela, Dawn Kleindorfer
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ABSTRACT: BACKGROUND: Recruitment challenges are common in acute stroke clinical trials. In a population-based study, we determined eligibility and actual enrollment for a successful, phase II acute stroke clinical trial. We hypothesized that missed opportunities for enrollment of eligible patients occurred frequently, despite the success of the trial. METHODS: In 2005, acute ischemic stroke (AIS) cases in our region were identified at all 17 local hospitals as part of an epidemiologic study. The Combined Approach to Lysis Utilizing Eptifibatide and Recombinant Tissue Plasminogen Activator (CLEAR) trial assessed the safety of this combination in AIS patients within 3 hours of symptom onset. In 2005, we determined the proportion of AIS patients who were eligible for CLEAR and the proportion that were actually enrolled. RESULTS: At 8 participating hospitals, 33 (2.8%) of 1175 AIS patients were eligible for CLEAR. Of 33 eligible patients, 18 (54.5%) were approached for enrollment, 4 (12.1%) refused, 1 (3.0%) was not consentable, and 13 (39.4%) were enrolled. Of the 15 not approached for enrollment in the trial, 10 were evaluated by the stroke team; 7 received recombinant tissue plasminogen activator. Enrollment was not associated with night or weekend presentation. CONCLUSIONS: Although the CLEAR trial was successful in meeting its delineated recruitment goals, our findings suggest enrollment could have been more efficient. Three out of 4 patients approached for enrollment participated in the trial. Eligible patients who were not approached and those treated with recombinant tissue plasminogen activator but not enrolled represent targets for improving enrollment rates.
Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 04/2011;
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Opeolu Adeoye,
Laura Heitsch,
Charles J Moomaw,
Kathleen Alwell,
Jane Khoury,
Daniel Woo,
Matthew L Flaherty,
Simona Ferioli,
Pooja Khatri,
Joseph P Broderick,
Brett M Kissela, Dawn Kleindorfer
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ABSTRACT: The American Heart Association recently redefined TIA to exclude patients with infarction on neuroimaging. Given its advantages, MRI/diffusion-weighted imaging (DWI) was recommended as the preferred imaging modality. We determined how frequently MRI/DWI was performed for TIA and ascertained the proportion of clinically defined TIA patients who had ischemic lesions on DWI in our community in 2005.
All clinically defined TIA cases among residents of a 5-county region around Cincinnati who presented to emergency departments were identified during 2005. Demographics and medical history, whether MRI/DWI was performed, and DWI findings were recorded. Generalized estimating equations were used to compare groups to account for the design of the study and multiple events per patient.
Of 834 TIA events in 799 patients, 323 events (40%) had MRI/DWI performed. Patients who had MRI/DWI were younger (mean, 66 vs 70 years; P=0.03), had less severe prestroke disability (baseline modified Rankin Scale score, 0; 44% vs 34%; P=0.02), were less likely to have previous stroke or TIA (42% vs 56%; P=0.002), and were less likely to have atrial fibrillation (10% vs 16%; P=0.01). Of the 323 events with DWI, 51 (15%) had evidence of acute infarction. Patients with positive DWI were older (75 vs 64 years; P=0.0001) and more likely to have atrial fibrillation (21% vs 7%; P=0.002).
Performing MRI/DWI on all clinically defined TIA patients in our community would reveal more cases of actual infarction but would more than double current use. Future studies should assess whether MRI/DWI is warranted for all TIA patients.
Stroke 10/2010; 41(10):2218-22. · 5.73 Impact Factor
