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1. Risk Factors Associated With Mortality and Neurologic Disability After Intracerebral Hemorrhage in a Racially and Ethnically Diverse Cohort.

Author

Woo D, Comeau ME, Venema SU, Anderson CD, Flaherty M, Testai F, Kittner S, Frankel M, James ML, Sung G, Elkind M, Worrall B, Kidwell C, Gonzales N, Koch S, Hall C, Birnbaum L, Mayson D, Coull B, Malkoff M, Sheth KN, McCauley JL, Osborne J, Morgan M, Gilkerson L, Behymer T, Coleman ER, Rosand J, Sekar P, Moomaw CJ, and Langefeld CD

Subjects
Cohort Studies, Female, Humans, Racial Groups, Risk Factors, Cerebral Hemorrhage, Stroke
Abstract

Introduction: Intracerebral hemorrhage (ICH) is the most severe subtype of stroke. Its mortality rate is high, and most survivors experience significant disability., Objective: To assess primary patient risk factors associated with mortality and neurologic disability 3 months after ICH in a large, racially and ethnically balanced cohort., Design, Setting, and Participants: This cohort study included participants from the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study, which prospectively recruited 1000 non-Hispanic White, 1000 non-Hispanic Black, and 1000 Hispanic patients with spontaneous ICH to study the epidemiological characteristics and genomics associated with ICH. Participants included those with uniform data collection and phenotype definitions, centralized neuroimaging review, and telephone follow-up at 3 months. Analyses were completed in November 2021., Exposures: Patient demographic and clinical characteristics as well as hospital event and imaging variables were examined, with characteristics meeting P < .20 considered candidates for a multivariate model. Elements included in the ICH score were specifically analyzed., Main Outcomes and Measures: Individual characteristics were screened for association with 3-month outcome of neurologic disability or mortality, as assessed by a modified Rankin Scale (mRS) score of 4 or greater vs 3 or less under a logistic regression model. A total of 25 characteristics were tested in the final model, which minimized the Akaike information criterion. Analyses were repeated removing individuals who had withdrawal of care., Results: A total of 2568 patients (mean [SD] age, 62.4 [14.7] years; 1069 [41.6%] women and 1499 [58.4%] men) had a 3-month outcome determination available, including death. The final logistic model had a significantly higher area under the receiver operating characteristics curve (C = 0.88) compared with ICH score alone (C = 0.76; P < .001). Among characteristics associated with neurologic disability and mortality were larger log ICH volume (OR, 2.74; 95% CI, 2.36-3.19; P < .001), older age (OR per 1-year increase, 1.04; 95% CI, 1.02-1.05; P < .001), pre-ICH mRS score (OR, 1.62; 95% CI, 1.41-1.87; P < .001), lobar location (OR, 0.22; 95% CI, 0.16-0.30; P < .001), and presence of infection (OR, 1.85; 95% CI, 1.42-2.41; P < .001)., Conclusions and Relevance: The findings of this cohort study validate ICH score elements and suggest additional baseline and interim patient characteristics were associated with variation in 3-month outcome.

Published
2022
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2. Pioglitazone after Ischemic Stroke or Transient Ischemic Attack.

Author

Kernan WN, Viscoli CM, Furie KL, Young LH, Inzucchi SE, Gorman M, Guarino PD, Lovejoy AM, Peduzzi PN, Conwit R, Brass LM, Schwartz GG, Adams HP Jr, Berger L, Carolei A, Clark W, Coull B, Ford GA, Kleindorfer D, O'Leary JR, Parsons MW, Ringleb P, Sen S, Spence JD, Tanne D, Wang D, and Winder TR

Subjects
Aged, Brain Ischemia drug therapy, Double-Blind Method, Female, Humans, Hypoglycemic Agents adverse effects, Male, Middle Aged, Peroxisome Proliferator-Activated Receptors metabolism, Pioglitazone, Secondary Prevention, Stroke prevention & control, Thiazolidinediones adverse effects, Weight Gain drug effects, Fractures, Bone chemically induced, Hypoglycemic Agents therapeutic use, Insulin Resistance, Ischemic Attack, Transient drug therapy, Myocardial Infarction prevention & control, Stroke drug therapy, Thiazolidinediones therapeutic use
Abstract

Background: Patients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease., Methods: In this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction., Results: By 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P=0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; P<0.001). There was no significant between-group difference in all-cause mortality (hazard ratio, 0.93; 95% CI, 0.73 to 1.17; P=0.52). Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg than was placebo (52.2% vs. 33.7%, P<0.001), edema (35.6% vs. 24.9%, P<0.001), and bone fracture requiring surgery or hospitalization (5.1% vs. 3.2%, P=0.003)., Conclusions: In this trial involving patients without diabetes who had insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00091949.).

Published
2016
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3. Shared genetic susceptibility of vascular-related biomarkers with ischemic and recurrent stroke.

Author

Williams SR, Hsu FC, Keene KL, Chen WM, Nelson S, Southerland AM, Madden EB, Coull B, Gogarten SM, Furie KL, Dzhivhuho G, Rowles JL, Mehndiratta P, Malik R, Dupuis J, Lin H, Seshadri S, Rich SS, Sale MM, and Worrall BB

Subjects
Aged, Brain Ischemia genetics, C-Reactive Protein genetics, Female, Fibrinogen genetics, Fibrinogen metabolism, Gene Expression, Genetic Loci, Humans, Male, Middle Aged, Oxidoreductases genetics, Polymorphism, Single Nucleotide, Randomized Controlled Trials as Topic, Recurrence, Stroke genetics, Biomarkers, Brain Ischemia metabolism, C-Reactive Protein metabolism, Genetic Predisposition to Disease, Genome-Wide Association Study, Stroke metabolism
Abstract

Objective: To investigate the genetic contributors to cerebrovascular disease and variation in biomarkers of ischemic stroke., Methods: The Vitamin Intervention for Stroke Prevention Trial (VISP) was a randomized, controlled clinical trial of B vitamin supplementation to prevent recurrent stroke, myocardial infarction, or death. VISP collected baseline measures of C-reactive protein (CRP), fibrinogen, creatinine, prothrombin fragments F1+2, thrombin-antithrombin complex, and thrombomodulin prior to treatment initiation. Genome-wide association scans were conducted for these traits and follow-up replication analyses were performed., Results: We detected an association between CRP single nucleotide polymorphisms (SNPs) and circulating CRP levels (most associated SNP, rs2592902, p = 1.14 × 10(-9)) in 2,100 VISP participants. We discovered a novel association for CRP level in the AKR1D1 locus (rs2589998, p = 7.3 × 10(-8), approaching genome-wide significance) that also is an expression quantitative trait locus for CRP gene expression. We replicated previously identified associations of fibrinogen with SNPs in the FGB and LEPR loci. CRP-associated SNPs and CRP levels were significantly associated with risk of ischemic stroke and recurrent stroke in VISP as well as specific stroke subtypes in METASTROKE. Fibrinogen levels but not fibrinogen-associated SNPs were also found to be associated with recurrent stroke in VISP., Conclusions: Our data identify a genetic contribution to inflammatory and hemostatic biomarkers in a stroke population. Additionally, our results suggest shared genetic contributions to circulating CRP levels measured poststroke and risk for incident and recurrent ischemic stroke. These data broaden our understanding of genetic contributors to biomarker variation and ischemic stroke risk, which should be useful in clinical risk evaluation., (© 2015 American Academy of Neurology.)

Published
2016
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4. Identification of Barriers to Stroke Awareness and Risk Factor Management Unique to Hispanics.

Author

Martinez M, Prabhakar N, Drake K, Coull B, Chong J, Ritter L, and Kidwell C

Subjects
Adult, Aged, Aged, 80 and over, Arizona, Ethnicity statistics & numerical data, Female, Hispanic or Latino statistics & numerical data, Humans, Male, Middle Aged, Prospective Studies, Risk Factors, Risk Management, Socioeconomic Factors, Surveys and Questionnaires, White People psychology, White People statistics & numerical data, Attitude to Health, Ethnicity psychology, Health Services Accessibility statistics & numerical data, Hispanic or Latino psychology, Mass Screening psychology, Stroke diagnosis, Stroke prevention & control
Abstract

Barriers to risk factor control may differ by race/ethnicity. The goal of this study was to identify barriers to stroke awareness and risk factor management unique to Hispanics as compared to non-Hispanic whites (NHWs). We performed a prospective study of stroke patients from an academic Stroke Center in Arizona and surveyed members of the general community. Questionnaires included: the Duke Social Support Index (DSSI), the Multidimensional Health Locus of Control (MHLC) Scale, a stroke barriers questionnaire, and a Stroke Awareness Test. Of 145 stroke patients surveyed (72 Hispanic; 73 NHW), Hispanics scored lower on the Stroke Awareness Test compared to NHWs (72.5% vs. 79.1%, p = 0.029). Hispanic stroke patients also reported greater barriers related to medical knowledge, medication adherence, and healthcare access (p < 0.05 for all). Hispanics scored higher on the "powerful others" sub-scale (11.3 vs. 10, p < 0.05) of the MHLC. Of 177 members of the general public surveyed, Hispanics had lower stroke awareness compared to NHWs and tended to have lower awareness than Hispanic stroke patients. These results suggest that Hispanic stroke patients perceive less control over their health, experience more healthcare barriers, and demonstrate lower rates of stroke literacy. Interventions for stroke prevention and education in Hispanics should address these racial/ethnic differences in stroke awareness and barriers to risk factor control.

Published
2015
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5. Assessment of stroke risk in southern Arizona, the pairing of acculturation and stroke risk factor development.

Author

Nokes B, Sim Y, Gibson B, Byreddy S, Labiner DM, Coull B, and Chong J

Subjects
Adolescent, Adult, Aged, Arizona epidemiology, Community Health Centers, Diabetes Mellitus ethnology, Female, Humans, Hypertension ethnology, Incidence, Language, Male, Middle Aged, Obesity ethnology, Risk Factors, Socioeconomic Factors, White People statistics & numerical data, Young Adult, Acculturation, Hispanic or Latino statistics & numerical data, Stroke ethnology
Abstract

Stroke is a leading cause of mortality in the United States. Hispanics have the same incidence of stroke, but are more likely to have subsequent strokes than non-Hispanic whites. This difference in outcome may be attributable to differences in stroke risk factor awareness. Patients at a community health center in Tucson, AZ completed an anonymous survey regarding existing and perceived health issues. Patient responses were compared in terms of ethnicity and acculturation, as indicated by language preference. Patient responses (n = 301, Spanish: 150, English: 151) indicated that proportionately fewer non-acculturated Hispanics than acculturated Hispanic and non-Hispanic patients indicated that they were at risk for stroke. Acculturated Hispanics and non-Hispanics displayed similar morbidity trends, including increased obesity, hypertension, diabetes, heart problems, depression, and previous stroke. These findings suggest that Hispanics become less healthy and more at risk for stroke and stroke risk factors as they become acculturated.

Published
2015
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6. Role of EPI-FLAIR in patients with acute stroke: a comparative analysis with FLAIR.

Author

Meshksar A, Villablanca JP, Khan R, Carmody R, Coull B, and Nael K

Subjects
Adult, Aged, Aged, 80 and over, Brain Ischemia complications, Feasibility Studies, Female, Humans, Image Enhancement methods, Male, Middle Aged, Observer Variation, Reproducibility of Results, Sensitivity and Specificity, Stroke etiology, Brain pathology, Brain Ischemia pathology, Diffusion Tensor Imaging methods, Echo-Planar Imaging methods, Stroke pathology
Abstract

Background and Purpose: Further improvement in acquisition speed is needed, if MR imaging is to compete with CT for evaluation of patients with acute ischemic stroke. The purpose of this study was to evaluate the feasibility of implementing an echo-planar fluid-attenuated inversion recovery (EPI-FLAIR) sequence into an acute MR stroke protocol with potential reduction in scan time and to compare the results with conventional FLAIR images., Materials and Methods: Fifty-two patients (28 men and 24 women; age range, 32-96 years) with acute ischemic stroke were prospectively evaluated with an acute stroke MR protocol, which included both conventional FLAIR and EPI-FLAIR imaging with integration of parallel acquisition. The image acquisition time was 52 seconds for EPI-FLAIR and 3 minutes for conventional FLAIR. FLAIR and EPI-FLAIR studies were assessed by 2 observers independently for image quality and conspicuity of hyperintensity in correlation with DWI and were rated as concordant or discordant. Coregistered FLAIR and EPI-FLAIR images were evaluated for signal intensity ratio of the DWI-positive lesion to contralateral normal white matter., Results: An estimated 96% of all FLAIR and EPI-FLAIR studies were rated of diagnostic image quality by both observers, with interobserver agreements of κ = 0.82 and κ = 0.63 for FLAIR and EPI-FLAIR, respectively. In 36 (95%) of 38 patients with acute infarction, FLAIR and EPI-FLAIR were rated concordant regarding DWI lesion. The mean ± standard deviation of the signal intensity ratio values on EPI-FLAIR and FLAIR for DWI-positive lesions were 1.28 ± 0.16 and 1.25 ± 0.17, respectively (P = .47), and demonstrated significant correlation (r = 0.899, z value = 8.677, P < .0001)., Conclusions: In patients with acute stroke, EPI-FLAIR is feasible with comparable qualitative and quantitative results to conventional FLAIR and results in reduced acquisition time., (© 2014 by American Journal of Neuroradiology.)

Published
2014
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7. Transcobalamin 2 variant associated with poststroke homocysteine modifies recurrent stroke risk.

Author

Hsu FC, Sides EG, Mychaleckyj JC, Worrall BB, Elias GA, Liu Y, Chen WM, Coull BM, Toole JF, Rich SS, Furie KL, and Sale MM

Subjects
Adult, Aged, Female, Genetic Association Studies, Humans, Male, Middle Aged, Homocysteine blood, Polymorphism, Single Nucleotide genetics, Stroke blood, Stroke genetics, Transcobalamins genetics
Abstract

Objectives: The Vitamin Intervention for Stroke Prevention trial found an association between baseline poststroke homocysteine (Hcy) and recurrent stroke. We investigated genes for enzymes and cofactors in the Hcy metabolic pathway for association with Hcy and determined whether associated single nucleotide polymorphisms (SNPs) influenced recurrent stroke risk., Methods: Eighty-six SNPs in 9 candidate genes (BHMT1, BHMT2, CBS, CTH, MTHFR, MTR, MTRR, TCN1, and TCN2) were genotyped in 2,206 subjects (83% European American). Associations with Hcy measures were assessed using linear regression models assuming an additive genetic model, adjusting for age, sex, and race and additionally for baseline Hcy when postmethionine load change was assessed. Associations with recurrent stroke were evaluated using survival analyses., Results: Five SNPs in the transcobalamin 2 (TCN2) gene were associated with baseline Hcy (false discovery rate [FDR]-adjusted p = 0.049). TCN2 SNP rs731991 was associated with recurrent stroke risk in the low-dose arm of the trial under a recessive model (log-rank test p = 0.009, hazard ratio 0.34). Associations with change in postmethionine load Hcy levels were found with 5 SNPs in the cystathionine β-synthase (CBS) gene (FDR-adjusted p < 0.031)., Conclusions: TCN2 variants contribute to poststroke Hcy levels, whereas variants in the CBS gene influence Hcy metabolism. Variation in the TCN2 gene also affects recurrent stroke risk in response to cofactor therapy.

Published
2011
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8. Awareness, treatment, and control of vascular risk factors among stroke survivors.

Author

Brenner DA, Zweifler RM, Gomez CR, Kissela BM, Levine D, Howard G, Coull B, and Howard VJ

Subjects
Black or African American, Aged, Aged, 80 and over, Diabetes Mellitus, Type 2 therapy, Dyslipidemias therapy, Female, Humans, Hypertension therapy, Longitudinal Studies, Male, Middle Aged, Prevalence, Risk Factors, Stroke epidemiology, White People, Diabetes Mellitus, Type 2 epidemiology, Dyslipidemias epidemiology, Health Knowledge, Attitudes, Practice, Hypertension epidemiology, Stroke prevention & control, Survivors
Abstract

Introduction: Stroke survivors should recognize and control vascular risk factors to prevent recurrent strokes. We therefore assessed the prevalence, treatment, and control of hypertension, diabetes, and dyslipidemia among stroke survivors versus stroke-free control subjects., Methods: We conducted cross-sectional analysis from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study cohort, which includes oversampling from the Stroke Belt and African Americans. Patients were interviewed by telephone then visited for blood pressure, glucose, and lipid measurements. There were 2830 participants reporting a past stroke or transient ischemic attack (TIA) (stroke survivors) and 24,886 participants without past stroke or TIA (control subjects). Outcome measures included the recognition, treatment, and control of hypertension, diabetes, and dyslipidemia., Results: Stroke survivors were more likely to have unrecognized hypertension (18.7% v 13.5%, P < .0003), unrecognized stage 2 hypertension (4.4% v 2.2%, P < .0006), and unrecognized diabetes (4.2% v 3.2%, P < .026) versus control subjects. Stroke survivors were more likely to be treated for hypertension (92.4% v 89.0%, P < .0001), diabetes (88.3% v 81.4%, P < .0001), and dyslipidemia (76.3% v 61.9%, P < .0001). However, despite treatment, stroke survivors were more likely to have hypertension (33.3% v 30.4%, P=.0074) and stage 2 hypertension (9.1% v 7.6%, P=.017). Predictors of unrecognized and undertreated risk factors in stroke survivors include increasing body mass index, black race, and lower education., Conclusion: Despite having a past stroke or TIA, stroke survivors had higher rates of unrecognized hypertension, unrecognized diabetes, and undertreated hypertension. Better efforts are needed to help stroke survivors recognize and control vascular risk factors to prevent recurrent stroke., (Copyright (c) 2010 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Published
2010
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9. Antithrombotic therapy for stroke in young adults.

Author

Payne JR and Coull B

Subjects
Adolescent, Adult, Age Factors, Anticoagulants therapeutic use, Blood Coagulation Factors genetics, Carotid Artery, Internal, Dissection complications, Clinical Trials as Topic, Heart Septal Defects, Atrial complications, Humans, Migraine Disorders complications, Platelet Aggregation Inhibitors therapeutic use, Risk Factors, Secondary Prevention, Sinus Thrombosis, Intracranial complications, Stroke etiology, Thrombophilia complications, Thrombophilia genetics, Vertebral Artery Dissection complications, Fibrinolytic Agents therapeutic use, Stroke prevention & control
Abstract

Stroke in young adults is a markedly heterogeneous disease, and remains an understudied phenomenon. While advances are being made in our understanding of the pathophysiology of its underlying conditions, treatment concerns are controversial, and clinical trials are sorely lacking. This review presents an overview of some of the relevant management issues in hypercoagulable states, migraine, patent foramen ovale, vascular dissection and venous sinus thrombosis.

Published
2005
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10. Cryptogenic stroke in relation to genetic variation in clotting factors and other genetic polymorphisms among young men and women.

Author

Austin H, Chimowitz MI, Hill HA, Chaturvedi S, Wechsler LR, Wityk RJ, Walz E, Wilterdink JL, Coull B, Sila CA, Mitsias P, Evatt B, and Hooper WC

Subjects
Adult, Black People genetics, Case-Control Studies, Causality, DNA Mutational Analysis, Female, Gene Frequency, Humans, Male, Middle Aged, Odds Ratio, Prevalence, Risk Assessment, Risk Factors, Stroke blood, Stroke classification, Stroke epidemiology, Tissue Plasminogen Activator genetics, United States epidemiology, White People genetics, Black or African American, Blood Coagulation Factors genetics, Genetic Variation, Polymorphism, Genetic genetics, Stroke diagnosis, Stroke genetics
Abstract

Background and Purpose: The purpose of the present study was to compare the prevalences of genetic polymorphisms in persons with cryptogenic stroke with those among stroke patients with evidence of large-artery occlusive disease or an unequivocal cardioembolic source (noncryptogenic stroke)., Methods: We compared the prevalences of genetic polymorphisms thought to be related to thrombi formation in young stroke patients with evidence of large-artery occlusive disease or an unequivocal cardioembolic source (noncryptogenic stroke; controls; n=79) with those in young stroke patients without such sources (cryptogenic stroke; cases; n=67). Common variations in the genes encoding factor V, prothrombin, angiotensin I-converting enzyme, 5,10-methylenetetrahydrofolate reductase, endothelial cell nitric oxide synthase, tissue plasminogen activator, plasminogen activator inhibitor-1, and fibrinogen were evaluated. We also compared the allele prevalence of these genes among all stroke patients with those among a large pool of historical controls assayed for these genes., Results: None of these genetic polymorphisms was statistically significantly related to cryptogenic stroke. With respect to a comparison of all ischemic stroke with historical controls, only the prevalence of tissue plasminogen activator D allele among stroke subjects was statistically significantly higher than that of the historical controls (P=0.0014)., Conclusions: These findings generally do not support the hypothesis that genes associated with a prothrombotic state are risk factors among a subgroup of young people with stroke of undetermined cause. Except for the D tissue plasminogen activator allele, the findings also indicated that these genetic factors are unrelated, or only weakly related, to all ischemic stroke.

Published
2002
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11. Anticoagulants and antiplatelet agents in acute ischemic stroke: report of the Joint Stroke Guideline Development Committee of the American Academy of Neurology and the American Stroke Association (a division of the American Heart Association).

Author

Coull BM, Williams LS, Goldstein LB, Meschia JF, Heitzman D, Chaturvedi S, Johnston KC, Starkman S, Morgenstern LB, Wilterdink JL, Levine SR, and Saver JL

Subjects
Acute Disease, Humans, Anticoagulants therapeutic use, Brain Ischemia drug therapy, Platelet Aggregation Inhibitors therapeutic use, Stroke drug therapy
Published
2002
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12. Leukocyte accumulation and hemodynamic changes in the cerebral microcirculation during early reperfusion after stroke.

Author

Ritter LS, Orozco JA, Coull BM, McDonagh PF, and Rosenblum WI

Subjects
Animals, Blood Flow Velocity, Disease Models, Animal, Leukocyte Count, Leukocytes pathology, Male, Rats, Rats, Sprague-Dawley, Stroke blood, Stroke pathology, Stroke therapy, Cerebrovascular Circulation, Reperfusion, Stroke physiopathology
Abstract

Background and Purpose: Leukocytes contribute to cerebral ischemia-reperfusion injury. However, few experimental models examine both in vivo behavior of leukocytes and microvascular rheology after stroke. The purpose of the present study was to characterize patterns of leukocyte accumulation in the cerebral microcirculation and to examine the relationship between leukocyte accumulation and microcirculatory hemodynamics after middle cerebral artery occlusion and reperfusion (MCAO-R)., Methods: Male rats (250 to 350 g) were anesthetized and ventilated. Tail catheters were inserted for measurement of arterial blood gases and administration of drugs. Body temperature was maintained at 37 degrees C. Animals were subjected to 2 hours of MCAO by the filament method. A cranial-window preparation was performed, and the brain was superfused with warm, aerated artificial cerebrospinal fluid. Reperfusion was initiated by withdrawing the filament, and the pial microcirculation was observed by use of intravital fluorescence microscopy. Leukocyte accumulation in venules, arterioles, and capillaries; leukocyte rolling in venules; and leukocyte venular shear rate were assessed during 1 hour of reperfusion., Results: We found significant leukocyte adhesion in cerebral venules during 1 hour of reperfusion after 2 hours of MCAO. Leukocyte trapping in capillaries and adhesion to arterioles after MCAO-R tended to increase compared with controls, but the increase was not significant. We also found that shear rate was significantly reduced in venules during early reperfusion after MCAO., Conclusions: A model using the filament method of stroke and fluorescence microscopy was used to examine white-cell behavior and hemodynamics in the cerebral microcirculation after MCAO-R. We observed a significant increase in leukocyte rolling and adhesion in venules and a significant decrease in blood shear rate in the microcirculation of the brain during early reperfusion. Leukocytes may activate and damage the blood vessels and surrounding brain cells, which contributes to an exaggerated inflammatory component to reperfusion. The model described can be used to examine precisely blood cell-endothelium interactions and hemodynamic changes in the microcirculation during postischemic reperfusion. Information from these and similar experiments may contribute to our understanding of the early inflammatory response in the brain during reperfusion after stroke.

Published
2000
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13. Role of EPI-FLAIR in Patients with Acute Stroke: A Comparative Analysis with FLAIR

Author

Meshksar, A, Villablanca, JP, Khan, R, Carmody, R, Coull, B, and Nael, K

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Stroke, Neurosciences, Brain Disorders, Clinical Research, Biomedical Imaging, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Adult, Aged, Aged, 80 and over, Brain, Brain Ischemia, Diffusion Tensor Imaging, Echo-Planar Imaging, Feasibility Studies, Female, Humans, Image Enhancement, Male, Middle Aged, Observer Variation, Reproducibility of Results, Sensitivity and Specificity, Clinical Sciences, Nuclear Medicine & Medical Imaging, Clinical sciences, Physical chemistry
Abstract

Background and purposeFurther improvement in acquisition speed is needed, if MR imaging is to compete with CT for evaluation of patients with acute ischemic stroke. The purpose of this study was to evaluate the feasibility of implementing an echo-planar fluid-attenuated inversion recovery (EPI-FLAIR) sequence into an acute MR stroke protocol with potential reduction in scan time and to compare the results with conventional FLAIR images.Materials and methodsFifty-two patients (28 men and 24 women; age range, 32-96 years) with acute ischemic stroke were prospectively evaluated with an acute stroke MR protocol, which included both conventional FLAIR and EPI-FLAIR imaging with integration of parallel acquisition. The image acquisition time was 52 seconds for EPI-FLAIR and 3 minutes for conventional FLAIR. FLAIR and EPI-FLAIR studies were assessed by 2 observers independently for image quality and conspicuity of hyperintensity in correlation with DWI and were rated as concordant or discordant. Coregistered FLAIR and EPI-FLAIR images were evaluated for signal intensity ratio of the DWI-positive lesion to contralateral normal white matter.ResultsAn estimated 96% of all FLAIR and EPI-FLAIR studies were rated of diagnostic image quality by both observers, with interobserver agreements of κ = 0.82 and κ = 0.63 for FLAIR and EPI-FLAIR, respectively. In 36 (95%) of 38 patients with acute infarction, FLAIR and EPI-FLAIR were rated concordant regarding DWI lesion. The mean ± standard deviation of the signal intensity ratio values on EPI-FLAIR and FLAIR for DWI-positive lesions were 1.28 ± 0.16 and 1.25 ± 0.17, respectively (P = .47), and demonstrated significant correlation (r = 0.899, z value = 8.677, P < .0001).ConclusionsIn patients with acute stroke, EPI-FLAIR is feasible with comparable qualitative and quantitative results to conventional FLAIR and results in reduced acquisition time.

Published
2014

14. Rivaroxaban for stroke prevention after embolic stroke of undetermined source

Author

Hart, Robert G, Sharma, Mukul, Mundl, Hardi, Kasner, Scott E, Bangdiwala, Shrikant I, Berkowitz, Scott D, Swaminathan, Balakumar, Lavados, Pablo, Wang, Yongjun, Wang, Yilong, Davalos, Antonio, Shamalov, Nikolay, Mikulik, Robert, Cunha, Luis, Lindgren, Arne, Arauz, Antonio, Lang, Wilfried, Czlonkowska, Anna, Eckstein, Jens, Gagliardi, Rubens J, Amarenco, Pierre, Ameriso, Sebastian F, Tatlisumak, Turgut, Veltkamp, Roland, Hankey, Graeme J, Toni, Danilo, Bereczki, Daniel, Uchiyama, Shinichiro, Ntaios, George, Yoon, Byung-Woo, Brouns, Raf, Endres, Matthias, Muir, Keith W, Bornstein, Natan, Ozturk, Serefnur, O'Donnell, Martin J, De Vries Basson, Matthys M, Pare, Guillaume, Pater, Calin, Kirsch, Bodo, Sheridan, Patrick, Peters, Gary, Weitz, Jeffrey I, Peacock, W Frank, Shoamanesh, Ashkan, Benavente, Oscar R, Joyner, Campbell, Themeles, Ellison, Connolly, Anderson DC, Stuart J., Demets, Dl, Kaste, M, Norrving, B, Wyse, Dg, Alet, M, Allende, G, Beinlich, A, Berrios, W, Bruera, G, Castro, D, Chialvo, L, Claverie, S, Contardo, L, Couto, J, Deganutto, R, Diaz, R, Dossi, D, Esnaola, M, Falco, M, Fernandez Pirrone, P, Ferrari, J, Firstenfeld, A, Galli Giqueauk, E, Gilli, M, Gonzalez, L, Gonzalez Toledo, M, Grecco, M, Halac, B, Hawkes, M, Ioli, P, Jure, L, Klein, F, Lepera, S, Lujan, S, Mackinnon, F, Marroquin, M, Martin, J, Parisi, V, Perez Leguizamon, P, Persi, G, Povedano, P, Povedano, G, Pujol Lereis, V, Radrizzani, L, Reich, E, Repetto, M, Rodriguez Lucci, F, Romano, M, Saredo, G, Schneider, M, Simonsini, C, Sumay, G, Thomson, A, Toledo, W, Torres, C, Vila, A, Abdul Rasheed, N, Anderson, C, Bailey, P, Blacker, D, Carcel, C, Clissold, B, Delcourt, C, Field, D, Gangadharan, S, Ghia, D, Kleinig, T, Leyden, J, Ly, J, Ma, H, Mackey, E, Mishra, S, Moey, A, Musuka, T, Pepper, E, Phan, T, Sabet, A, Saw, J, Singh, B, Tryambake, D, Tu, H, Wijeratne, T, Wong, A, Augustin, S, Esterbauer, M, Garnauf, M, Gasiorek, K, Gasser, S, Gaugg, M, Greisenegger, S, Harrasser, M, Heine, M, Huber, 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S, Gunathilagan, G, Gutierrez, R, Guyler, P, Hargroves, D, Harkness, K, Harvey, M, Hayhoe, H, Hicken, L, Hussain, M, Kelly, S, Lam, M, Lindert, R, Louw, S, Luder, R, Macleod, M, Majid, A, Mangion, D, Markova, S, Markus, H, Marsh, R, Mcarthur, K, Menon, N, Metcalf, K, Minhas, J, Minns, M, Mistri, A, Moreton, F, Mpelembue, M, Muddegowda, G, Mudhar, O, Musarrat, K, Myint, M, Natarajan, I, Naylor, D, Ngeh, J, Papavasileiou, V, Perry, R, Piechowski-Jozwiak, B, Pradhan, M, Rani, A, Rashed, K, Robinson, T, Roffe, C, Saksena, R, Sattar, N, Sekaran, L, Selvarajah, J, Shah, S, Sinha, D, Sivakumar, R, Sztriha, L, Walters, D, Webb, T, Werring, D, Whiteley, W, Whiting, R, Abdelhamid, N, Abdul Rahman, D, Amin, H, Androulakis, M, Babikian, V, Baker, M, Barker Trejo, S, Benjamin, A, Birnbaum, L, Burke, J, Chen, S, Clark, W, Coull, B, De Havenon, A, Dearborn, J, Degeorgia, M, Essa, B, Fares, M, Favate, A, Furlan, A, Gebreyohanns, M, Goddeau, R, Green, D, Greer, D, Haralur Sreekantaiah, Y, Hasan, R, Hedna, V, Henninger, N, Holmstedt, C, Ishida, K, Jagolino, A, Johnson, M, Jun-Oconnell, A, Kaur, S, Khanna, A, Kirshner, H, Kittner, S, Kleindorfer, D, Leira, E, Loomis, C, Lord, A, Lowenkopf, T, Lutsep, H, Magadan, A, Majjhoo, A, Maud, A, Mayasi, Y, Mccullough, L, Mckinney, J, Mehta, S, Mehta, D, Mehta, B, Messe, S, Miller, B, Milling, T, Moonis, M, Navaratnam, D, Okpala, M, Patel, N, Pettigrew, L, Phinney, T, Ramos-Estebanez, C, Rasmussen, J, Rodriguez, G, Rybinnik, I, Santiago, P, Sarraj, A, Savitz, S, Sawyer, R, Scandura, T, Schindler, J, Sen, S, Shang, T, Sharrief, A, Sila, C, Simpkins, A, Sundararajan, S, Talahma, M, Tayal, A, Thaler, D, Tirschwell, D, Torres, J, Vora, N, Warnack, W, Waters, M, Wilson, C, Xiong, W, Zweifler, R, Zanferrari, C., St Marys Development Trust, Servicio de Neurologia (SANTIAGO - Neurologie), Universidad del Desarrollo, Department of Neurology (Dep Neuro - BEIJING), Tiantan Hospital, Neurology department, Universidade de Coimbra [Coimbra], Department of Internal Medicine, University Hospital Basel [Basel], Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Neurological Sciences, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Department of Neurology, Seoul National University Hospital, Institute of Neurosciences and Psychology [Glasgow], University of Glasgow, Neurology Department, Ichilov Medical Center, CIC Brest, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, Yperzeele, Laetitia, NAVIGATE ESUS Investigators, and Selçuk Üniversitesi

Subjects
Stroke/etiology, Male, [SDV]Life Sciences [q-bio], Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Brain Ischemia, Brain ischemia, 0302 clinical medicine, DESIGN, Rivaroxaban, Hemorrhage/chemically induced, Secondary Prevention, Medicine, Factor Xa Inhibitors/adverse effects, Stroke, Rivaroxaban/adverse effects, ComputingMilieux_MISCELLANEOUS, 11 Medical and Health Sciences, Aspirin, Atrial fibrillation, General Medicine, FORAMEN OVALE CLOSURE, Middle Aged, TRIALS, Intracranial Embolism, SAFETY, Aged, Factor Xa Inhibitors, Female, Hemorrhage, Humans, Platelet Aggregation Inhibitors, Medicine (all), Cardiology, Foramen ovale closure, Platelet aggregation inhibitor, Settore MED/26 - Neurologia, Life Sciences & Biomedicine, medicine.drug, medicine.medical_specialty, Platelet Aggregation Inhibitors/adverse effects, ANTITHROMBOTIC THERAPY, Aspirin/adverse effects, WARFARIN, 03 medical and health sciences, Secondary Prevention/methods, Medicine, General & Internal, Internal medicine, Intracranial Embolism/drug therapy, General & Internal Medicine, NAVIGATE ESUS Investigators, METAANALYSIS, Science & Technology, CRYPTOGENIC STROKE, business.industry, Warfarin, medicine.disease, EFFICACY, ATRIAL-FIBRILLATION, Human medicine, business, Brain Ischemia/prevention & control, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

WOS: 000434263000007, PubMed: 29766772, BACKGROUND Embolic strokes of undetermined source represent 20% of ischemic strokes and are associated with a high rate of recurrence. Anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, may result in a lower risk of recurrent stroke than aspirin. METHODS We compared the efficacy and safety of rivaroxaban (at a daily dose of 15 mg) with aspirin (at a daily dose of 100 mg) for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism but without arterial stenosis, lacune, or an identified cardioembolic source. The primary efficacy outcome was the first recurrence of ischemic or hemorrhagic stroke or systemic embolism in a time-to-event analysis; the primary safety outcome was the rate of major bleeding. RESULTS A total of 7213 participants were enrolled at 459 sites; 3609 patients were randomly assigned to receive rivaroxaban and 3604 to receive aspirin. Patients had been followed for a median of 11 months when the trial was terminated early because of a lack of benefit with regard to stroke risk and because of bleeding associated with rivaroxaban. The primary efficacy outcome occurred in 172 patients in the rivaroxaban group (annualized rate, 5.1%) and in 160 in the aspirin group (annualized rate, 4.8%) (hazard ratio, 1.07; 95% confidence interval [CI], 0.87 to 1.33; P=0.52). Recurrent ischemic stroke occurred in 158 patients in the rivaroxaban group (annualized rate, 4.7%) and in 156 in the aspirin group (annualized rate, 4.7%). Major bleeding occurred in 62 patients in the rivaroxaban group (annualized rate, 1.8%) and in 23 in the aspirin group (annualized rate, 0.7%) (hazard ratio, 2.72; 95% CI, 1.68 to 4.39; P, BayerBayer AG; Janssen Research and Development, Supported by Bayer and Janssen Research and Development.

Published
2018

15. Effect of atorvastatin in elderly patients with a recent stroke or transient ischemic attack

Author

Chaturvedi, S, Zivin, J, Breazna, A, Amarenco, P, Callahan, A, Goldstein, LB, Hennerici, M, Sillesen, H, Rudolph, A, Welch, MA, SPARCL Investigators, Crimmins D, Davis S, Dimmitt S, Donnan G, Frayne J, Freilich D, Zagami A, Mikocki J, Schmidauer C, Schmidt R, De Bleecker J, Deceuninck F, Tack P, Thijs V, Gomes Fernandes J, Beaudry M, Cote R, Hoyte K, Lebrun LH, Mackey A, Sahlas D, Selchen D, Shuaib A, Spence JD, Teal P, Winger M, Matamala G, Cifkova R, Kalita Z, Rektor I, Rosolova H, Stipal R, Vaclavik D, Boysen G, Klingenberg H, Iversen, Sillesen H, Hillbom M, Kaste M, Numminen H, Pilke A, Salmivaara A, Sivenius J, Alamowitch S, Amarenco P, Boulliat J, De Broucker T, Chollet F, Mahagne MH, Milandre L, Moulin T, Bogdahn U, Diener HC, Dichgans M, Glahn J, Haberl R, Harms L, Hennerici MG, Knecht S, Kroczek G, Lichy C, Sander D, Schneider D, Kazis A, Karageorgiou C, Milonas I, Stathis P, Vogiatzoglou D, Bornstein N, Honigman S, Lampl Y, Streifler J, Capurso A, Comi G, Gandolfo C, Poloni M, Senin U, Rangel Guerra R, Boon AM, De Keyser JH, De Kort PL, Haas JA, Kamphuis DJ, Koudstaal PJ, Anderson N, Scott R, Singh G, Czlonkowska A, Drozdowski W, Gralewski Z, Kozubski W, Kuczynska Zardzewialy A, Podemski R, Stelmasiak Z, Szczudlik A, Da Costa Correia C, Ferro J, Salgueiro e. Cunha L, Lietava J, Raslova K, Carr J, Gardiner J, Kruger A, Alvarez Sabin J, Chamorro A, Diez Tejedor E, Fernández O, Trejo Gabriel y. Galán J, González Marcos J, Egido Herrero J, Jiménez Martínez M, Lago Martin A, Mostacero Miguel E, Vivancos Mora J, Moltó J, Viguera Romero J, Cuartero Rodriguez E, Rodriguez F, Serena J, Laska AC, Leijd B, Strand T, Terent A, Waegner A, Wallén T, Baumgartner R, Bogousslavsky J, Hungerbühler H, Lyrer P, Mattle H, Bath PM, Ekpo EB, Freeman A, Lees KR, MacLeod MJ, MacWalter RS, Sharma AK, Shetty HG, Albers G, Altafullah I, Benavente O, Book D, Broderick J, Callahan A. 3rd, Calder C, Carlini W, Chaturvedi S, Chippendale T, Clark W, Coull B, Davis P, Devlin T, Dick A, Dooneief G, Duff R, Estronza N, Forteza A, Frankel M, Frey J, Friday G, Graham G, Goldstein J, Hammer M, Harris J, Harper W, Hendin B, Hendin D, Hinton R, Hollander J, Hughes R, Kasner S, Kent T, Kim L, Kirshner H, LaMonte M, Ledbetter L, Lee Kwen P, Levin K, Libman R, Matlock J, McDowell P, McGee F. Jr, Meyer B, Minagar A, Moussouttas M, Munson R, Nash M, Nassief A, Orr S, Ratinov G, Salanga V, Silliman S, Singer R, Smith D, Sullivan H, Tietjen G, Thaler D, Tuchman M, Uskavitch D, Verro P, Vicari R, Weinstein R, Wilterdink J, Zweifler R, De Bastos M., FERRARESE, CARLO, Chaturvedi, S, Zivin, J, Breazna, A, Amarenco, P, Callahan, A, Goldstein, L, Hennerici, M, Sillesen, H, Rudolph, A, Welch, M, Sparcl, I, Crimmins, D, Davis, S, Dimmitt, S, Donnan, G, Frayne, J, Freilich, D, Zagami, A, Mikocki, J, Schmidauer, C, Schmidt, R, De Bleecker, J, Deceuninck, F, Tack, P, Thijs, V, Gomes Fernandes, J, Beaudry, M, Cote, R, Hoyte, K, Lebrun, L, Mackey, A, Sahlas, D, Selchen, D, Shuaib, A, Spence, J, Teal, P, Winger, M, Matamala, G, Cifkova, R, Kalita, Z, Rektor, I, Rosolova, H, Stipal, R, Vaclavik, D, Boysen, G, Klingenberg, H, Iversen, Hillbom, M, Kaste, M, Numminen, H, Pilke, A, Salmivaara, A, Sivenius, J, Alamowitch, S, Boulliat, J, De Broucker, T, Chollet, F, Mahagne, M, Milandre, L, Moulin, T, Bogdahn, U, Diener, H, Dichgans, M, Glahn, J, Haberl, R, Harms, L, Knecht, S, Kroczek, G, Lichy, C, Sander, D, Schneider, D, Kazis, A, Karageorgiou, C, Milonas, I, Stathis, P, Vogiatzoglou, D, Bornstein, N, Honigman, S, Lampl, Y, Streifler, J, Capurso, A, Comi, G, Ferrarese, C, Gandolfo, C, Poloni, M, Senin, U, Rangel Guerra, R, Boon, A, De Keyser, J, De Kort, P, Haas, J, Kamphuis, D, Koudstaal, P, Anderson, N, Scott, R, Singh, G, Czlonkowska, A, Drozdowski, W, Gralewski, Z, Kozubski, W, Kuczynska Zardzewialy, A, Podemski, R, Stelmasiak, Z, Szczudlik, A, Da Costa Correia, C, Ferro, J, Salgueiro e., C, Lietava, J, Raslova, K, Carr, J, Gardiner, J, Kruger, A, Alvarez Sabin, J, Chamorro, A, Diez Tejedor, E, Fernández, O, Trejo Gabriel y., G, González Marcos, J, Egido Herrero, J, Jiménez Martínez, M, Lago Martin, A, Mostacero Miguel, E, Vivancos Mora, J, Moltó, J, Viguera Romero, J, Cuartero Rodriguez, E, Rodriguez, F, Serena, J, Laska, A, Leijd, B, Strand, T, Terent, A, Waegner, A, Wallén, T, Baumgartner, R, Bogousslavsky, J, Hungerbühler, H, Lyrer, P, Mattle, H, Bath, P, Ekpo, E, Freeman, A, Lees, K, Macleod, M, Macwalter, R, Sharma, A, Shetty, H, Albers, G, Altafullah, I, Benavente, O, Book, D, Broderick, J, Callahan A., 3, Calder, C, Carlini, W, Chippendale, T, Clark, W, Coull, B, Davis, P, Devlin, T, Dick, A, Dooneief, G, Duff, R, Estronza, N, Forteza, A, Frankel, M, Frey, J, Friday, G, Graham, G, Goldstein, J, Hammer, M, Harris, J, Harper, W, Hendin, B, Hendin, D, Hinton, R, Hollander, J, Hughes, R, Kasner, S, Kent, T, Kim, L, Kirshner, H, Lamonte, M, Ledbetter, L, Lee Kwen, P, Levin, K, Libman, R, Matlock, J, Mcdowell, P, McGee F., J, Meyer, B, Minagar, A, Moussouttas, M, Munson, R, Nash, M, Nassief, A, Orr, S, Ratinov, G, Salanga, V, Silliman, S, Singer, R, Smith, D, Sullivan, H, Tietjen, G, Thaler, D, Tuchman, M, Uskavitch, D, Verro, P, Vicari, R, Weinstein, R, Wilterdink, J, Zweifler, R, and De Bastos, M

Subjects
Male, medicine.medical_specialty, Atorvastatin, medicine.medical_treatment, Coronary Disease, Pyrrole, Revascularization, Risk Assessment, Cohort Studies, Coronary artery disease, Internal medicine, Anticholesteremic Agent, Myocardial Revascularization, medicine, Clinical endpoint, Humans, Pyrroles, Age Factor, cardiovascular diseases, Stroke, Aged, Cerebral infarction, business.industry, Anticholesteremic Agents, Hazard ratio, Age Factors, Cholesterol, LDL, Middle Aged, medicine.disease, Surgery, Heptanoic Acid, Heptanoic Acids, Ischemic Attack, Transient, Cohort, Cardiology, Female, Hydroxymethylglutaryl-CoA Reductase Inhibitor, Neurology (clinical), Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cohort Studie, business, Human, medicine.drug
Abstract

BACKGROUND: It is unclear whether patients age 65 years and over with a recent stroke or TIA benefit from statin treatment to a similar degree as younger patients. METHODS: The 4,731 patient cohort in the SPARCL study was divided into an elderly group (65 and over) and a younger group. The primary endpoint (fatal or nonfatal stroke) and secondary endpoints were analyzed, with calculation of the hazard ratio (HR) and p values from a Cox regression model. RESULTS: There were 2,249 patients in the elderly group and 2,482 in the younger group. The baseline LDL (133 mg/dL) and total cholesterol were comparable in the two groups. The elderly and younger groups had a 61.4 mg/dL and 58.7 mg/dL decrease in mean LDL during the trial. The primary endpoint was reduced by 26% in younger patients (HR 0.74, 0.57-0.96, p = 0.02) and by 10% in elderly subjects (HR 0.90, 0.73-1.11, p = 0.33). A test of heterogeneity for a treatment-age interaction was not significant (p = 0.52). The risk of stroke or TIA (HR 0.79, p = 0.01), major coronary events (HR 0.68, p = 0.035), any coronary heart disease event (HR 0.61, p = 0.0006), and revascularization procedures (HR 0.55, p = 0.0005) was reduced in the elderly group. CONCLUSIONS: There was no heterogeneity in the stroke reduction seen with atorvastatin in the elderly and younger groups. Cardiac events and revascularization procedures were also lower in both the elderly and younger subgroups treated with atorvastatin. These results support the use of atorvastatin in elderly patients with recent stroke or TIA.

Published
2008

16. Relative effects of statin therapy on stroke and cardiovascular events in men and women: secondary analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Study

Author

Goldstein, LB, Amarenco, P, Lamonte, M, Gilbert, S, Messig, M, Callahan, A, Hennerici, M, Sillesen, H, Welch, KMA, SPARCL investigators, Bogousslavsky J, Goldstein LB, Zivin J, Clark W, Dávalos A, Kaste M, Leiter L, Altafullah I, Graham G, Glahn J, Jiménez Hernández D, MacWalter R, Scott R, Shuaib A, Sivenius J, Stipal R, Hart R, Marsh J, Norrving B, Pocock S, Sacco R, Easton J, Brown M, Nagy Z, Whisnant J, O'Neill B, Kleber F, LaBlanche JM, Welty F, Crimmins D, Davis S, Dimmitt S, Donnan G, Frayne J, Freilich D, Zagami A, Mikocki J, Schmidauer C, Schmidt R, De Bleecker J, Deceuninck F, Tack P, Thijs V, Gomes Fernandes J, Beaudry M, Cote R, Hoyte K, Lebrun LH, Mackey A, Sahlas D, Selchen D, Spence JD, Teal P, Winger M, Matamala G, Cifkova R, Kalita Z, Rektor I, Rosolova H, Vaclavik D, Boysen G, Klingenberg H, Sillesen H, Hillbom M, Numminen H, Pilke A, Salmivaara A, Alamowitch S, Amarenco P, Boulliat J, De Broucker T, Chollet F, Mahagne MH, Milandre L, Moulin T, Milonas I, Stathis P, Vogiatzoglou D, Bornstein N, Honigman S, Lampl Y, Streifler J, Capurso A, Comi G, Gandolfo C, Poloni M, Senin U, Rangel Guerra R, Boon AM, De Keyser JH, De Kort PL, Haas JA, Kamphuis DJ, Koudstaal PJ, Anderson N, Singh G, Czlonkowska A, Drozdowski W, Gralewski Z, Kozubski W, Kuczynska Zardzewialy A, Podemski R, Stelmasiak Z, Szczudlik A, Da Costa Correia C, Ferro J, Salgueiro e. Cunha L, Lietava J, Raslova K, Carr J, Gardiner J, Kruger A, Alvarez Sabin J, Chamorro A, Diez Tejedor E, Fernández O, Trejo Gabriel y. Galán J, González Marcos J, Egido Herrero J, Jiménez Martínez M, Lago Martin A, Mostacero Miguel E, Vivancos Mora J, Moltó J, Viguera Romero J, Cuartero Rodriguez E, Rubio F, Serena J, Laska AC, Leijd B, Strand T, Terent A, Waegner A, Wallén T, Baumgartner R, Hungerbühler H, Lyrer P, Mattle H, Bath PM, Ekpo EB, Freeman A, Lees KR, MacLeod MJ, MacWalter RS, Sharma AK, Shetty HG, Albers G, Benavente O, Book D, Broderick J, Calder C, Carlini W, Chaturvedi S, Chippendale T, Coull B, Davis P, Devlin T, Dick A, Dooneief G, Duff R, Estronza N, Forteza A, Frankel M, Frey J, Friday G, Goldstein J, Hammer M, Harris J, Harper W, Hendin B, Hess D, Hinton R, Hollander J, Hughes R, Kasner S, Kent T, Kim L, Kirshner H, LaMonte M, Ledbetter L, Lee Kwen P, Levin K, Libman R, Matlock J, McDowell P, McGee F. Jr, Meyer B, Minagar A, Moussouttas M, Munson R, Nash M, Nassief A, Orr S, Ratinov G, Salanga V, Silliman S, Singer R, Smith D, Sullivan H, Tietjen G, Thaler D, Tuchman M, Uskavitch D, Verro P, Vicari R, Weinstein R, Wilterdink J, Zweifler R, De Bastos M., FERRARESE, CARLO, Goldstein, L, Amarenco, P, Lamonte, M, Gilbert, S, Messig, M, Callahan, A, Hennerici, M, Sillesen, H, Welch, K, Sparcl, I, Bogousslavsky, J, Zivin, J, Clark, W, Dávalos, A, Kaste, M, Leiter, L, Altafullah, I, Graham, G, Glahn, J, Jiménez Hernández, D, Macwalter, R, Scott, R, Shuaib, A, Sivenius, J, Stipal, R, Hart, R, Marsh, J, Norrving, B, Pocock, S, Sacco, R, Easton, J, Brown, M, Nagy, Z, Whisnant, J, O'Neill, B, Kleber, F, Lablanche, J, Welty, F, Crimmins, D, Davis, S, Dimmitt, S, Donnan, G, Frayne, J, Freilich, D, Zagami, A, Mikocki, J, Schmidauer, C, Schmidt, R, De Bleecker, J, Deceuninck, F, Tack, P, Thijs, V, Gomes Fernandes, J, Beaudry, M, Cote, R, Hoyte, K, Lebrun, L, Mackey, A, Sahlas, D, Selchen, D, Spence, J, Teal, P, Winger, M, Matamala, G, Cifkova, R, Kalita, Z, Rektor, I, Rosolova, H, Vaclavik, D, Boysen, G, Klingenberg, H, Hillbom, M, Numminen, H, Pilke, A, Salmivaara, A, Alamowitch, S, Boulliat, J, De Broucker, T, Chollet, F, Mahagne, M, Milandre, L, Moulin, T, Milonas, I, Stathis, P, Vogiatzoglou, D, Bornstein, N, Honigman, S, Lampl, Y, Streifler, J, Capurso, A, Comi, G, Ferrarese, C, Gandolfo, C, Poloni, M, Senin, U, Rangel Guerra, R, Boon, A, De Keyser, J, De Kort, P, Haas, J, Kamphuis, D, Koudstaal, P, Anderson, N, Singh, G, Czlonkowska, A, Drozdowski, W, Gralewski, Z, Kozubski, W, Kuczynska Zardzewialy, A, Podemski, R, Stelmasiak, Z, Szczudlik, A, Da Costa Correia, C, Ferro, J, Salgueiro e., C, Lietava, J, Raslova, K, Carr, J, Gardiner, J, Kruger, A, Alvarez Sabin, J, Chamorro, A, Diez Tejedor, E, Fernández, O, Trejo Gabriel y., G, González Marcos, J, Egido Herrero, J, Jiménez Martínez, M, Lago Martin, A, Mostacero Miguel, E, Vivancos Mora, J, Moltó, J, Viguera Romero, J, Cuartero Rodriguez, E, Rubio, F, Serena, J, Laska, A, Leijd, B, Strand, T, Terent, A, Waegner, A, Wallén, T, Baumgartner, R, Hungerbühler, H, Lyrer, P, Mattle, H, Bath, P, Ekpo, E, Freeman, A, Lees, K, Macleod, M, Sharma, A, Shetty, H, Albers, G, Benavente, O, Book, D, Broderick, J, Calder, C, Carlini, W, Chaturvedi, S, Chippendale, T, Coull, B, Davis, P, Devlin, T, Dick, A, Dooneief, G, Duff, R, Estronza, N, Forteza, A, Frankel, M, Frey, J, Friday, G, Goldstein, J, Hammer, M, Harris, J, Harper, W, Hendin, B, Hess, D, Hinton, R, Hollander, J, Hughes, R, Kasner, S, Kent, T, Kim, L, Kirshner, H, Ledbetter, L, Lee Kwen, P, Levin, K, Libman, R, Matlock, J, Mcdowell, P, McGee F., J, Meyer, B, Minagar, A, Moussouttas, M, Munson, R, Nash, M, Nassief, A, Orr, S, Ratinov, G, Salanga, V, Silliman, S, Singer, R, Smith, D, Sullivan, H, Tietjen, G, Thaler, D, Tuchman, M, Uskavitch, D, Verro, P, Vicari, R, Weinstein, R, Wilterdink, J, Zweifler, R, and De Bastos, M

Subjects
Male, Atorvastatin, Blood Pressure, Sex Factor, Pyrrole, Triglyceride, law.invention, Randomized controlled trial, law, Stroke, Sex Characteristics, Middle Aged, Heptanoic Acid, Cholesterol, Treatment Outcome, Data Interpretation, Statistical, Hypertension, Population study, Female, Cardiology and Cardiovascular Medicine, Human, medicine.drug, medicine.medical_specialty, Randomization, Logistic Model, Reproducibility of Result, Placebo, Sex Factors, Internal medicine, medicine, Humans, Pyrroles, Triglycerides, Advanced and Specialized Nursing, Apolipoprotein A-I, Proportional hazards model, business.industry, Reproducibility of Results, Sex Characteristic, medicine.disease, Surgery, Blood pressure, Logistic Models, Heptanoic Acids, Hydroxymethylglutaryl-CoA Reductase Inhibitor, Neurology (clinical), Hydroxymethylglutaryl-CoA Reductase Inhibitors, business
Abstract

Background and Purpose— In SPARCL, treatment with atorvastatin 80 mg daily reduced stroke risk in patients with recent stroke or TIA and no known coronary heart disease by 16% versus placebo over 4.9 years of follow-up. The purpose of this secondary analysis was to determine whether men and women similarly benefited from randomization to statin treatment. Methods— The effect of sex on treatment-related reductions in stroke and other cardiovascular outcomes were analyzed with Cox regression modeling testing for sex by treatment interactions. Results— Women (n=1908) constituted 40% of the SPARCL study population. At baseline, men (n=2823) were younger (62.0±0.21versus 63.9±0.27 years), had lower systolic BPs (138.1±0.35 versus 139.5±0.47 mm Hg), higher diastolic BPs (82.2±0.20 versus 81.0±0.25 mm Hg), more frequently had a history of smoking (73% versus 38%), and had lower total cholesterol (207.0±0.54 versus 218.9±0.67 mg/dL) and LDL-C levels (132±0.45 versus 134±0.57 mg/dL) than women. Use of antithrombotics and antihypertensives were similar. After prespecified adjustment for region, entry event, time since event, and age, there were no sex by treatment interactions for the combined risk of nonfatal and fatal stroke (treatment Hazard Ratio, HR=0.84, 95% CI 0.68, 1.02 in men versus HR=0.84, 95% CI 0.63, 1.11 in women; treatment×sex interaction P =0.99), major cardiac events (HR=0.61, 95% CI 0.42, 0.87 in men versus HR=0.76, 95% CI 0.48, 1.21 in women; P =0.45), major cardiovascular events (HR=0.78, 95% CI 0.65, 0.93 in men versus HR=0.84, 95% CI 0.65, 1.07 in women; P =0.63), revascularization procedures (HR=0.50, 95% CI 0.37, 0.67 in men versus HR=0.76, 95% CI 0.46, 1.24 in women; P =0.17), or any CHD event (HR=0.54, 95% CI 0.41, 0.72 in men versus 0.67 95% CI 0.46, 0.98 in women; P =0.40). Conclusion— Stroke and other cardiovascular events are similarly reduced with atorvastatin 80 mg/d in men and women with recent stroke or TIA.

Published
2008

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