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Background Despite good evidence that the prevalence of sleep-disordered breathing (SDB) is increasing in the general population, no data are available about trends in poststroke SDB. We therefore sought to assess changes in poststroke SDB over a 10-year period (2010-2019). Methods and Results Participants in the BASIC (Brain Attack Surveillance in Corpus Christi) project were offered a home sleep apnea test to assess for SDB after stroke. SDB assessment procedures remained unchanged throughout the study period. Respiratory event index was calculated as the sum of apneas and hypopneas per hour of recording. SDB was defined as respiratory event index ≥10/h for optimal sensitivity and specificity of the home sleep apnea test device compared with in-laboratory polysomnography. Regression models were used to test associations between SDB prevalence and severity and time, with adjustment for multiple potential confounders. Among the 1215 participants who completed objective sleep apnea testing, the prevalence of SDB grew from 61% in the first year of the study to 76% in the last, with 1.1 times higher odds each year (95% CI, 1.07-1.19), after adjustment. A linear association was identified between time and respiratory event index (average annual respiratory event index increase of 0.56/h; 95% CI, 0.20/h-0.91/h), after adjustment. There was no difference in time trends by sex or ethnicity. Conclusions The prevalence and severity of SDB after ischemic stroke has increased over the past 10 years in this population-based cohort. These data highlight the need to determine whether SDB treatment improves stroke outcomes.

Objective/background: Obstructive sleep apnea is a risk factor for stroke. This study sought to assess the relationship between obstructive sleep apnea (OSA) and wake-up strokes (WUS), that is, stroke symptoms that are first noted upon awakening from sleep., Patients/methods: In this analysis, 837 Brain Attack Surveillance in Corpus Christi (BASIC) project participants completed an interview to ascertain stroke onset during sleep (WUS) versus wakefulness (non-wake-up stroke, non-WUS). A subset of 316 participants underwent a home sleep apnea test (HSAT) shortly after ischemic stroke to assess for OSA. Regression models were used to test the association between OSA and WUS, stratified by sex., Results: Of 837 participants who completed the interview, 251 (30%) reported WUS. Among participants who underwent an HSAT, there was no significant difference in OSA severity [respiratory event index (REI)] among participants with WUS [median REI 17, interquartile range (IQR) 10, 29] versus non-WUS (median REI 18, IQR 9, 30; p = 0.73). OSA severity was not associated with increased odds of WUS among men [unadjusted odds ratio (OR) 1.011, 95% confidence interval (95% CI) 0.995, 1.027] or women (unadjusted OR 0.987, 95% CI 0.959, 1.015). These results remained unchanged after adjustment for age, congestive heart failure, body mass index, and pre-stroke depression in men (adjusted OR 1.011, 95% CI 0.994, 1.028) and women (adjusted OR 0.988, 95% CI 0.959, 1.018)., Conclusions: Although OSA is a risk factor for stroke, the onset of stroke during sleep is not associated with OSA in this large, population-based stroke cohort., (Copyright © 2021. Published by Elsevier B.V.)

Rationale: Obstructive sleep apnea is common among patients with acute ischemic stroke and is associated with reduced functional recovery and an increased risk for recurrent vascular events., Aims And/or Hypothesis: The Sleep for Stroke Management and Recovery Trial (Sleep SMART) aims to determine whether automatically adjusting continuous positive airway pressure (aCPAP) treatment for obstructive sleep apnea improves clinical outcomes after acute ischemic stroke or high-risk transient ischemic attack., Sample Size Estimate: A total of 3062 randomized subjects for the prevention of recurrent serious vascular events, and among these, 1362 stroke survivors for the recovery outcome., Methods and Design: Sleep SMART is a phase III, multicenter, prospective randomized, open, blinded outcome event assessed controlled trial. Adults with recent acute ischemic stroke/transient ischemic attack and no contraindication to aCPAP are screened for obstructive sleep apnea with a portable sleep apnea test. Subjects with confirmed obstructive sleep apnea but without predominant central sleep apnea proceed to a run-in night of aCPAP. Subjects with use (≥4 h) of aCPAP and without development of significant central apneas are randomized to aCPAP plus usual care or care-as-usual for six months. Telemedicine is used to monitor and facilitate aCPAP adherence remotely., Study Outcomes: Two separate primary outcomes: (1) the composite of recurrent acute ischemic stroke, acute coronary syndrome, and all-cause mortality (prevention) and (2) the modified Rankin scale scores (recovery) at six- and three-month post-randomization, respectively., Discussion: Sleep SMART represents the first large trial to test whether aCPAP for obstructive sleep apnea after stroke/transient ischemic attack reduces recurrent vascular events or death, and improves functional recovery.

Background and Purpose: Stroke incidence and mortality are declining rapidly in developed countries. Little data on ethnic-specific stroke recurrence trends exist. Fourteen-year stroke recurrence trend estimates were evaluated in Mexican Americans and non-Hispanic whites in a population-based study., Methods: Recurrent stroke was ascertained prospectively in the population-based BASIC (Brain Attack Surveillance in Corpus Christi) project in Texas, between 2000 and 2013. Incident cases were followed forward to determine 1- and 2-year recurrence. Fine & Gray subdistribution hazard models were used to estimate adjusted trends in the absolute recurrence risk and ethnic differences in the secular trends. The ethnic difference in the secular trend was examined using an interaction term between index year and ethnicity in the models adjusted for age, sex, hypertension, diabetes mellitus, smoking, atrial fibrillation, insurance, and cholesterol and relevant interaction terms., Results: From January 1, 2000 to December 31, 2013 (N=3571), the cumulative incidence of 1-year recurrence in Mexican Americans decreased from 9.26% (95% CI, 6.9%-12.43%) in 2000 to 3.42% (95% CI, 2.25%-5.21%) in 2013. Among non-Hispanic whites, the cumulative incidence of 1-year recurrence in non-Hispanic whites decreased from 5.67% (95% CI, 3.74%-8.62%) in 2000 to 3.59% (95% CI, 2.27%-5.68%) in 2013. The significant ethnic disparity in stroke recurrence existed in 2000 (risk difference, 3.59% [95% CI, 0.94%-6.22%]) but was no longer seen by 2013 (risk difference, -0.17% [95% CI, -1.96% to 1.5%]). The competing 1-year mortality risk was stable over time among Mexican Americans, while for non-Hispanic whites it was decreasing over time (difference between 2000 and 2013: -4.67% [95% CI, -8.72% to -0.75%])., Conclusions: Mexican Americans had significant reductions in stroke recurrence despite a stable death rate, a promising indicator. The ethnic disparity in stroke recurrence present early in the study was gone by 2013.

Intracerebral haemorrhage and small vessel ischaemic stroke (SVS) are the most acute manifestations of cerebral small vessel disease, with no established preventive approaches beyond hypertension management. Combined genome-wide association study (GWAS) of these two correlated diseases may improve statistical power to detect novel genetic factors for cerebral small vessel disease, elucidating underlying disease mechanisms that may form the basis for future treatments. Because intracerebral haemorrhage location is an adequate surrogate for distinct histopathological variants of cerebral small vessel disease (lobar for cerebral amyloid angiopathy and non-lobar for arteriolosclerosis), we performed GWAS of intracerebral haemorrhage by location in 1813 subjects (755 lobar and 1005 non-lobar) and 1711 stroke-free control subjects. Intracerebral haemorrhage GWAS results by location were meta-analysed with GWAS results for SVS from MEGASTROKE, using 'Multi-Trait Analysis of GWAS' (MTAG) to integrate summary data across traits and generate combined effect estimates. After combining intracerebral haemorrhage and SVS datasets, our sample size included 241 024 participants (6255 intracerebral haemorrhage or SVS cases and 233 058 control subjects). Genome-wide significant associations were observed for non-lobar intracerebral haemorrhage enhanced by SVS with rs2758605 [MTAG P-value (P) = 2.6 × 10-8] at 1q22; rs72932727 (P = 1.7 × 10-8) at 2q33; and rs9515201 (P = 5.3 × 10-10) at 13q34. In the GTEx gene expression library, rs2758605 (1q22), rs72932727 (2q33) and rs9515201 (13q34) are significant cis-eQTLs for PMF1 (P = 1 × 10-4 in tibial nerve), NBEAL1, FAM117B and CARF (P < 2.1 × 10-7 in arteries) and COL4A2 and COL4A1 (P < 0.01 in brain putamen), respectively. Leveraging S-PrediXcan for gene-based association testing with the predicted expression models in tissues related with nerve, artery, and non-lobar brain, we found that experiment-wide significant (P < 8.5 × 10-7) associations at three genes at 2q33 including NBEAL1, FAM117B and WDR12 and genome-wide significant associations at two genes including ICA1L at 2q33 and ZCCHC14 at 16q24. Brain cell-type specific expression profiling libraries reveal that SEMA4A, SLC25A44 and PMF1 at 1q22 and COL4A1 and COL4A2 at 13q34 were mainly expressed in endothelial cells, while the genes at 2q33 (FAM117B, CARF and NBEAL1) were expressed in various cell types including astrocytes, oligodendrocytes and neurons. Our cross-phenotype genetic study of intracerebral haemorrhage and SVS demonstrates novel genome-wide associations for non-lobar intracerebral haemorrhage at 2q33 and 13q34. Our replication of the 1q22 locus previous seen in traditional GWAS of intracerebral haemorrhage, as well as the rediscovery of 13q34, which had previously been reported in candidate gene studies with other cerebral small vessel disease-related traits strengthens the credibility of applying this novel genome-wide approach across intracerebral haemorrhage and SVS., (© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Obstructive sleep apnea (OSA) is highly prevalent in patients with ischemic stroke. Untreated OSA is associated with an increased risk of cardiovascular morbidity and OSA treatment may improve neurological recovery in stroke survivors, yet OSA in stroke patients remains poorly characterized. The goal of this study is to identify clinical phenotypes of ischemic stroke patients with OSA., Methods: Participants (n = 451) with ischemic strokes and OSA (respiratory-event-index, (REI) ≥ 10/hour based on home sleep apnea testing) were identified from the Brain Attack Surveillance in Corpus Christi (BASIC) project. Latent class analysis was performed based on the following variables: age, sex, race/ethnicity, REI, pre-stroke snoring, pre-stroke tiredness/fatigue, pre-stroke sleep duration, prior stroke history, NIHSS at presentation, body mass index (BMI), hypertension, diabetes, atrial fibrillation, coronary artery disease, and chronic heart failure., Results: A model with three phenotype clusters provided the best fit. Cluster 1 (n = 55, 12%) was defined by higher NIHSS scores. Participants in cluster 2 (n = 253, 56%) were younger and had relatively low NIHSS scores. Cluster 3 (n = 143, 32%) included participants with severe OSA and higher prevalence of medical comorbidities., Conclusion: Ischemic stroke survivors with OSA can be categorized into three clinical phenotype clusters characterized by differences in stroke severity, OSA severity, age and medical comorbidities. This highlights the heterogeneity of post-stroke OSA. Awareness of the different faces of OSA in patients with ischemic stroke may help clinicians identify OSA in their patients, and inform research concerning the pathophysiology, treatment and prognostic impact of post-stroke OSA., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Purpose- Limited data are available about the relationship between sleep-disordered breathing (SDB) and recurrent stroke and mortality, especially from population-based studies, large samples, or ethnically diverse populations. Methods- In the BASIC project (Brain Attack Surveillance in Corpus Christ), we identified patients with ischemic stroke (2010-2015). Subjects were offered screening for SDB with the ApneaLink Plus device, from which a respiratory event index (REI) score ≥10 defined SDB. Demographics and baseline characteristics were determined from chart review and interview. Recurrent ischemic stroke was identified through active and passive surveillance. Cause-specific proportional hazards models were used to assess the association between REI (modeled linearly) and ischemic stroke recurrence (as the event of interest), and all-cause poststroke mortality, adjusted for multiple potential confounders. Results- Among 842 subjects, the median age was 65 (interquartile range, 57-76), 47% were female, and 58% were Mexican American. The median REI score was 14 (interquartile range, 6-26); 63% had SDB. SDB was associated with male sex, Mexican American ethnicity, being insured, nonsmoking status, diabetes mellitus, hypertension, lower educational attainment, and higher body mass index. Among Mexican American and non-Hispanic whites, 85 (11%) ischemic recurrent strokes and 104 (13%) deaths occurred, with a median follow-up time of 591 days. In fully adjusted models, REI was associated with recurrent ischemic stroke (hazard ratio, 1.02 [hazard ratio for one-unit higher REI score, 95% CI, 1.01-1.03]), but not with mortality alone (hazard ratio, 1.00 [95% CI, 0.99-1.02]). Conclusions- Results from this large population-based study show that SDB is associated with recurrent ischemic stroke, but not mortality. SDB may therefore represent an important modifiable risk factor for poor stroke outcomes.

Objective/background: Sleep-disordered breathing (SDB), an independent risk factor for stroke, is associated with worse post-stroke outcomes. Differences in the relationship between SDB and stroke may exist for women versus men. In this population-based study, we compared the prevalence of both pre- and post-stroke SDB by sex. We also explored whether menopausal status is related to post-stroke SDB., Patients/methods: We performed a cross-sectional study of subjects enrolled in the Brain Attack Surveillance in Corpus Christi (BASIC) project. Each subject (n = 1815) underwent a baseline interview including the Berlin Questionnaire to assess pre-stroke SDB risk and, if relevant, questions regarding menopausal status. Subjects were offered overnight SDB screening with a validated portable respiratory device (n = 832 with complete data). Log Poisson and linear regression models were used to assess the differences in SDB between men and women with adjustment for demographics, stroke risk factors, stroke severity, and other potential confounders., Results: Women were less likely than men to be at high risk for pre-stroke SDB (56.6% versus 61.9%) (prevalence ratio [PR] 0.87 for women; 95% confidence interval [CI], 0.81-0.95). A lower proportion of women than men (50.8% versus 70.2%) had post-stroke SDB by respiratory monitoring (PR 0.71; 95% CI, 0.63-0.80). SDB severity was higher for men than for women (mean difference in respiratory event index [REI] 6.5; 95% CI, 4.3-8.7). No significant association existed between post-stroke SDB and either menopausal status or age at menopause., Conclusions: After acute ischemic stroke, SDB was more prevalent and more severe in men than in women., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: The purpose of this study is to compare sleep-disordered breathing (SDB) prevalence and severity after stroke between Mexican Americans (MAs) and non-Hispanic whites (NHWs)., Patients/methods: Ischemic stroke (IS) patients within ∼30 days of onset were identified from the population-based BASIC Project (2010-2014) and offered screening with an overnight cardiopulmonary monitoring device, ApneaLink Plus™. The number of apneas and hypopneas per hour, as reflected by the apnea/hypopnea index (AHI), was used to measure SDB severity; SDB was defined as AHI ≥10. Ethnicity, demographics, and risk factors were collected from interviews and medical records. Log and negative-binomial regression models were used to determine prevalence ratios (PRs) and apnea/hypopnea event rate ratios (RRs) comparing MAs with NHWs after adjustment for demographics, risk factors, and stroke severity., Results: A total of 549 IS cases had AHI data. The median age was 65 years (interquartile range (IQR): 57-76), 55% were men, and 65% were MA. The MAs had a higher prevalence of SDB (68.5%) than NHWs (49.5%) in unadjusted (PR = 1.38; 95% confidence interval (CI): 1.14-1.67) and adjusted analyses (PR = 1.21; 95% CI: 1.01-1.46). The median AHI was 16 (IQR: 7-31) in MAs and nine (IQR: 5-24) in NHWs. The severity of SDB (rate of apneas/hypopneas) was higher in MAs than NHWs in unadjusted (RR = 1.31; 95% CI: 1.09-1.58) but not adjusted analysis (RR = 1.14; 95% CI: 0.95-1.38). There was no ethnic difference in severity among subjects with SDB., Conclusion: More than two-thirds of MA stroke patients had SDB, which was almost 40% more common among MAs than NHWs. Physicians treating MA patients after stroke should have a high index of suspicion for SDB, a treatable condition that could otherwise have adverse impact., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Little is known about the prevalence of sleep-disordered breathing (SDB) across ischemic stroke subtypes. Given the important implications for SDB screening, we tested the association between SDB and ischemic stroke subtype in a population-based study., Methods: Within the Brain Attack Surveillance in Corpus Christi Project, ischemic stroke patients were offered SDB screening with the ApneaLink Plus (n = 355). A neurologist assigned Trial of the ORG 10172 in Acute Stroke Treatment subtype (with an additional category for nonlacunar infarctions of unknown etiology) using hospital records. Unadjusted and adjusted (demographics, body mass index, National Institutes of Health Stroke Scale, diabetes, history of stroke/transient ischemic attack) logistic and linear regression models were used to test the association between subtype and SDB or apnea-hypopnea index (AHI)., Results: Median age was 65%, and 55% were men; 59% were Mexican American. Median time from stroke onset to SDB screen was 13 days (interquartile range [IQR] 6, 21). Overall, 215 (61%) had SDB (AHI ≥ 10). Median AHI was 13 (IQR 6, 27). Prevalence of SDB by subtype was cardioembolism, 66%; large-artery atherosclerosis, 57%; small-vessel occlusion, 68%; other determined, 50%; undetermined etiology, 58%; and nonlacunar stroke of unknown etiology, 63%. Ischemic stroke subtype was not associated with SDB in unadjusted (P = .72) or adjusted models (P = .91) models. Ischemic stroke subtype was not associated with AHI in unadjusted (P = .41) or adjusted models (P = .62)., Conclusions: In this population-based stroke surveillance study, ischemic stroke subtype was not associated with the presence or severity of SDB. Sleep-disordered breathing is likely to be present after ischemic stroke, and the subtype should not influence decisions about SDB screening., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Mexican Americans (MAs) were previously found to have lower mortality after ischemic stroke than non-Hispanic whites. We studied mortality trends in a population-based design., Methods: Active and passive surveillance were used to find all ischemic stroke cases from January 2000 to December 2011 in Nueces County, TX. Deaths were ascertained from the Texas Department of Health through December 31, 2012. Cumulative 30-day and 1-year mortality adjusted for covariates was estimated using log-binomial models with a linear term for year of stroke onset used to model time trends. Models used data from the entire study period to estimate adjusted mortality among stroke cases in 2000 and 2011 and to calculate projected ethnic differences., Results: There were 1974 ischemic strokes among non-Hispanic whites and 2439 among MAs. Between 2000 and 2011, model estimated mortality declined among non-Hispanic whites at 30 days (7.6% to 5.6%; P=0.24) and 1 year (20.8% to 15.5%; P=0.02). Among MAs, 30-day model estimated mortality remained stagnant at 5.1% to 5.2% (P=0.92), and a slight decline from 17.4% to 15.3% was observed for 1-year mortality (P=0.26). Although ethnic differences in 30-day (P=0.01) and 1-year (P=0.06) mortality were apparent in 2000, they were not so in 2011 (30-day mortality, P=0.63; 1-year mortality, P=0.92)., Conclusions: Overall, mortality after ischemic stroke has declined in the past decade, although significant declines were only observed for non-Hispanic whites and not MAs at 1 year. The survival advantage previously documented among MAs vanished by 2011. Renewed stroke prevention and treatment efforts for MAs are needed., (© 2014 American Heart Association, Inc.)

Background: Ascertaining self-reported information about the risk for pre-stroke obstructive sleep apnea (OSA) in the acute stroke period is challenging as many stroke patients have deficits that hinder communication. We examined agreement between stroke patients without communication limitations and family members (proxy) in the pre-stroke risk for OSA., Methods: Patient-proxy pairs (n=42) were interviewed independently as part of the Brain Attack Surveillance in Corpus Christi (BASIC) Project from May 2010 to April 2011. The Berlin questionnaire was used to measure a high risk for OSA defined as the presence of at least two of the following conditions: (1) snoring behaviors/witnessed apneas, (2) daytime sleepiness, and (3) hypertension or obesity. Patient-proxy agreement was assessed using a κ coefficient., Results: Forty-three percent of patients self-identified as being at high risk for sleep apnea, and 45% of proxies identified patients as high risk. Patient-proxy agreement for high risk for pre-stroke OSA was fair (κ=0.28) with better agreement for spouses and children proxies (κ=0.38) than for other family members. Agreement also was fair for most individual questions., Conclusions: Spouse and child proxy use of the Berlin questionnaire may be an option to assess a patient's pre-stroke likelihood of sleep apnea. Whereas prospective studies of incident stroke in patients with and without objectively confirmed sleep apnea would require formidable resources, our results suggest that an alternative strategy may involve proxy use of the Berlin questionnaire in a retrospective study design., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: To determine trends in ischemic stroke incidence among Mexican Americans and non-Hispanic whites., Methods: We performed population-based stroke surveillance from January 1, 2000 to December 31, 2010 in Corpus Christi, Texas. Ischemic stroke patients 45 years and older were ascertained from potential sources, and charts were abstracted. Neurologists validated cases based on source documentation blinded to ethnicity and age. Crude and age-, sex-, and ethnicity-adjusted annual incidence was calculated for first ever completed ischemic stroke. Poisson regression models were used to calculate adjusted ischemic stroke rates, rate ratios, and trends., Results: There were 2,604 ischemic strokes in Mexican Americans and 2,042 in non-Hispanic whites. The rate ratios (Mexican American:non-Hispanic white) were 1.94 (95% confidence interval [CI] = 1.67-2.25), 1.50 (95% CI = 1.35-1.67), and 1.00 (95% CI = 0.90-1.11) among those aged 45 to 59, 60 to 74, and 75 years and older, respectively, and 1.34 (95% CI = 1.23-1.46) when adjusted for age. Ischemic stroke incidence declined during the study period by 35.9% (95% CI = 25.9-44.5). The decline was limited to those aged ≥60 years, and happened in both ethnic groups similarly (p > 0.10), implying that the disparities seen in the 45- to 74-year age group persist unabated., Interpretation: Ischemic stroke incidence rates have declined dramatically in the past decade in both ethnic groups for those aged ≥60 years. However, the disparity between Mexican American and non-Hispanic white stroke rates persists in those <75 years of age. Although the decline in stroke is encouraging, additional prevention efforts targeting young Mexican Americans are warranted., (© 2013 American Neurological Association.)

Background: Transesophageal echocardiography (TEE) is the standard for evaluating cardioembolic sources of stroke, although many strokes remain cryptogenic after TEE. Cardiac magnetic resonance (CMR) imaging may have advantages over TEE. We performed a prospective pilot study comparing CMR to TEE after stroke to assist in planning future definitive studies., Methods: Individuals with nonlacunar stroke within 90 days of undergoing clinical TEE were prospectively identified and underwent a 1.5 Tesla research CMR scan. Exclusion criteria included >50% relevant cervical vessel stenosis and inability to undergo nonsedated CMR. A descriptive comparison of cardioembolic source (intracardiac thrombus/mass, aortic atheroma ≥ 4 mm, or patent foramen ovale [PFO]) by study type was performed., Results: Twenty patients underwent CMR and TEE a median of 6 days apart. The median age was 51 years (interquartile range [IQR] 40, 63.5), 40% had hypertension, 15% had diabetes, 25% had a previous stroke/transient ischemic attack, 5% had atrial fibrillation, and none had coronary disease or heart failure. No patient had intracardiac thrombus or mass detected on either study. Aortic atheroma ≥ 4 mm thick was identified by TEE in 1 patient. CMR identified aortic atheroma as <4 mm in this patient (3 mm on CMR compared with 5 mm on TEE). PFO was identified in 6 of 20 patients on TEE; CMR found only 1 of these., Conclusions: In this pilot study, TEE identified more potential cardioembolic sources than CMR imaging. Future studies comparing TEE and CMR after stroke should focus on older subjects at higher risk for cardiac disease to determine whether TEE, CMR, or both can best elucidate potential cardioembolic sources., (Copyright © 2012 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Stroke outcome studies often combine cases of intracerebral hemorrhage (ICH) and ischemic stroke (IS). These studies of mixed stroke typically ignore computed tomography (CT) findings for ICH cases, though the impact of omitting these traditional predictors of ICH mortality is unknown. We investigated the incremental impact of ICH CT findings on mortality prediction model performance., Methods: Cases of ICH and IS (2000-2003) were identified from the Brain Attack Surveillance in Corpus Christi (BASIC) project. Base models predicting 30-day mortality included demographics, stroke type, and clinical findings (National Institutes of Health Stroke Scale (NIHSS) +/- Glasgow Coma Scale (GCS)). The impact of adding CT data (volume, intraventricular hemorrhage, infratentorial location) was assessed with the area under the curve (AUC), unweighted sum of squared residuals (Ŝ), and integrated discrimination improvement (IDI). The model assessment was performed first for the mixed case of IS and ICH, and then repeated for ICH cases alone to determine whether any lack of improvement in model performance with CT data for mixed stroke type was due to IS cases naturally forming a larger proportion of the total sample than ICH., Results: A total of 1,256 cases were included (86% IS, 14% ICH). Thirty-day mortality was 16% overall (11% for IS; 43% for ICH). When both clinical scales (NIHSS and GCS) were included, none of the model performance measures showed improvement with the addition of CT findings whether considering IS and ICH together (ΔAUC: 0.002, 95% CI -0.01, 0.02; ΔŜ: -3.0, 95% CI -9.1, 2.6; IDI: 0.017, 95% CI -0.004, 0.05) or considering ICH cases alone (ΔAUC: 0.02, 95% CI -0.02, 0.08; ΔŜ: -2.0, 95% CI -9.7, 3.4; IDI 0.065, 95% CI -0.03, 0.21). If NIHSS was the only clinical scale included, there was still no improvement in AUC or Ŝ when CT findings were added for the sample with IS/ICH combined (ΔAUC: 0.005, 95% CI -0.01, 0.02; ΔŜ: -5.0, 95% CI -11.6, 1.0) or for ICH cases alone (ΔAUC: 0.05, 95% CI -0.002, 0.11; ΔŜ: -4.2, 95% CI -11.5, 2.3). However, IDI was improved when NIHSS was the only clinical scale for IS/ICH combined (IDI: 0.029, 95% CI 0.002, 0.065) and ICH alone (IDI: 0.12, 95% CI 0.005, 0.26)., Conclusions: Excluding ICH CT findings had only minimal impact on mortality prediction model performance whether examining ICH and IS together or ICH alone. These findings have important implications for the design of clinical studies involving ICH patients., (Copyright © 2012 S. Karger AG, Basel.)

Background: Obstructive sleep apnea (OSA) has been associated with cardiac abnormalities. Whether any cardiac dysfunction is present in ischemic stroke patients with OSA is not known. The purpose of this study was to compare echocardiographic findings in ischemic stroke patients with and without OSA., Methods: Nocturnal polysomnography was performed on 28 ischemic stroke subjects within 7 days of symptom onset. OSA was defined as an apnea-hypopnea index of ≥10. Echocardiographic variables were compared between the OSA and non OSA groups using Wilcoxon signed-rank, chi-square, or Fisher's exact tests., Results: The 14 (50%) subjects with OSA had comparable cardiac function and structure to those without OSA (n=14). Left ventricular (LV) mass index, LV ejection fraction, LV diastolic function, left atrial area, and right ventricular systolic function were not different between groups. Ischemic stroke subjects, regardless of their OSA status, had LV diastolic dysfunction with preserved systolic function., Conclusions: Subjects with and without OSA, based on polysomnography in the first 7 days after stroke, have comparable right and left ventricular function., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Aspirin is used to prevent ischemic stroke and other types of cardiovascular disease. Seven trials of aspirin focusing on the effectiveness of primary prevention of stroke and other cardiovascular events have been performed, but three of these did not include women. Data from these trials, and one meta-analysis, suggest that aspirin prevents myocardial infarction in men and stroke in women, although the findings in women were driven by the results of a single large study, and a subsequent meta-analysis did not find a gender difference. The reasons for the possible gender differences in aspirin's effectiveness are not entirely clear.

Background: Obstructive sleep apnea (OSA) is common in stroke patients and is associated with poor functional outcome. The effects of positional therapy in ischemic stroke patients with OSA have not been investigated. We tested the hypothesis that ischemic stroke patients have less severe OSA during positional therapy that promotes nonsupine positioning., Methods: We conducted a randomized, controlled, cross-over study. Sleep apnea screening studies were performed on two consecutive nights, using a portable respiratory monitoring system, on 18 subjects within the first 14days of ischemic stroke. An apnea-hypopnea index (AHI) ⩾5 established the diagnosis of OSA. Subjects were randomized to positional therapy that included the use of a therapeutic pillow on either the first or second night. On the control night, subjects used the hospital pillow and were positioned ad lib. Treatment effect on AHI was estimated using a repeated measures model., Results: All ischemic stroke subjects studied had OSA. The predominantly male group had a median age of 58years, BMI of 29kg/m(2), NIH Stroke Scale score of 3, and a median AHI on the nontherapeutic night of 39 (interquartile range: 21-54). Positional therapy reduced the amount of supine positioning by 36% (95% CI: 18-55% (P<0.001)). The AHI was reduced by 19.5% (95% CI: 4.9-31.9% (P=0.011)), when using positional therapy compared to sleeping ad lib., Conclusions: Positional therapy to avoid supine positioning modestly reduces sleep apnea severity after ischemic stroke, and may therefore improve outcomes., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background and Purpose: Intravenous alteplase (rtPA) remains the only approved treatment for acute ischemic stroke, but its use remains limited. In a previous pilot dose-escalation study, intravenous tenecteplase showed promise as a potentially safer alternative. Therefore, a Phase IIB clinical trial was begun to (1) choose a best dose of tenecteplase to carry forward; and (2) to provide evidence for either promise or futility of further testing of tenecteplase versus rtPA. If promise was established, then the trial would continue as a Phase III efficacy trial comparing the selected tenecteplase dose to standard rtPA., Methods: The trial began as a small, multicenter, randomized, double-blind, controlled clinical trial comparing 0.1, 0.25, and 0.4 mg/kg tenecteplase with standard 0.9 mg/kg rtPA in patients with acute stroke within 3 hours of onset. An adaptive sequential design used an early (24-hour) assessment of major neurological improvement balanced against occurrence of symptomatic intracranial hemorrhage to choose a "best" dose of tenecteplase to carry forward. Once a "best" dose was established, the trial was to continue until at least 100 pairs of the selected tenecteplase dose versus standard rtPA could be compared by 3-month outcome using the modified Rankin Scale in an interim analysis. Decision rules were devised to yield a clear recommendation to either stop for futility or to continue into Phase III., Results: The trial was prematurely terminated for slow enrollment after only 112 patients had been randomized at 8 clinical centers between 2006 and 2008. The 0.4-mg/kg dose was discarded as inferior after only 73 patients were randomized, but the selection procedure was still unable to distinguish between 0.1 mg/kg and 0.25 mg/kg as a propitious dose at the time the trial was stopped. There were no statistically persuasive differences in 3-month outcomes between the remaining tenecteplase groups and rtPA. Symptomatic intracranial hemorrhage rates were highest in the discarded 0.4-mg/kg tenecteplase group and lowest (0 of 31) in the 0.1-mg/kg tenecteplase group. Neither promise nor futility could be established., Conclusion: This prematurely terminated trial has demonstrated the potential efficiency of a novel design in selecting a propitious dose for future study of a new thrombolytic agent for acute stroke. Given the truncation of the trial, no convincing conclusions can be made about the promise of future study of tenecteplase in acute stroke.

Background and Purpose: Women have increased lifetime stroke risk and more disabling strokes compared with men. Insights into the association between menopause and stroke could lead to new prevention strategies for women. The objective of this study was to examine the association of age at natural menopause with ischemic stroke risk in the Framingham Heart Study., Methods: Participants included women who survived stroke-free until age 60, experienced natural menopause, did not use estrogen before menopause, and who had complete data (n=1430). Participants were followed until first ischemic stroke, death, or end of follow-up (2006). Age at natural menopause was self-reported. Cox proportional hazards models were used to examine the association between age at natural menopause (<42, 42 to 54, >or=55) and ischemic stroke risk adjusted for age, systolic blood pressure, atrial fibrillation, diabetes, current smoking, cardiovascular disease and estrogen use., Results: There were 234 ischemic strokes identified. Average age at menopause was 49 years (SD=4). Women with menopause at ages 42 to 54 (hazard ratio=0.50; 95% CI: 0.29 to 0.89) and at ages >or=55 (hazard ratio=0.31; 95% CI: 0.13 to 0.76) had lower stroke risk compared with those with menopause <42 years adjusted for covariates. Women with menopause before age 42 had twice the stroke risk compared to all other women (hazard ratio=2.03; 95% CI: 1.16 to 3.56)., Conclusions: In this prospective study, age at natural menopause before age 42 was associated with increased ischemic stroke risk. Future stroke studies with measures of endogenous hormones are needed to inform the underlying mechanisms so that novel prevention strategies for midlife women can be considered.

Background and Purpose: Sleep apnea is very common after stroke and is associated with poor outcome. Supine sleep is known to exacerbate apneas in the general sleep apnea population. We therefore investigated the pattern of sleep positions in the acute stroke period., Methods: Inpatients with acute ischemic stroke underwent full polysomnography that included continuous monitoring of sleep positions. Sleep apnea severity was measured using the apnea-hypopnea index (AHI). Stroke severity was measured by the NIH Stroke Scale (NIHSS) at the time of study enrollment by certified study personnel. Percent total sleep time spent in the supine position was calculated and compared by stroke severity based on a median split of NIHSS using a Wilcoxon rank-sum test., Results: Of the 30 patients, the median age was 67. The median AHI was 23 (IQR: 6, 47). Twenty-two patients (73%) had sleep apnea with an AHI >/=5. The vast majority of sleep time among the stroke cases was spent supine, with a median percent sleep time spent supine of 100 (IQR: 62, 100). The majority (63%) of subjects spent no time asleep in any of the nonsupine positions (prone, left, right). Median percent sleep time supine was 100 (IQR: 100, 100) in those with a higher NIHSS and 63 (IQR: 51, 100) in those with a lower NIHSS (P<0.01)., Conclusions: Given the high prevalence of supine sleep identified, research into positional therapy for stroke patients with sleep apnea seems warranted.

Background: Little data exist on stroke burden in Mexican-American (MA) women. The objective of this study was to characterize the burden of stroke in MA and non-Hispanic white (NHW) women and to compare this burden across ethnic groups., Methods: Cases of ischemic stroke and intracerebral hemorrhage among women (January 2000-December 2006) were identified as part of the Brain Attack Surveillance in Corpus Christi (BASIC) Project, a stroke surveillance study in a biethnic Texas community. Cumulative incidence of stroke among women was compared by ethnicity and age. Logistic regression was used to compare risk factors and age-adjusted use of antihypertensives between MA and NHW female stroke cases., Results: MA women had elevated stroke risk compared with NHW women at younger ages (ages 45-59: relative risk (RR) = 2.00 (95% confidence interval (CI): 1.54-2.58); ages 60-74: RR = 1.57 (95% CI: 1.31-1.87); ages > or =75: RR = 1.13 (95% CI: 0.98-1.29)). Stroke severity and stroke type did not differ between ethnic groups. MA female stroke cases were more likely to have hypertension (odds ratio (OR) = 1.41 (95% CI: 1.11-1.80)), diabetes (OR = 3.54 (95% CI: 2.82-4.45)), and the presence of both risk factors (OR = 3.31 (95% CI: 2.61-4.21)) compared with NHW female stroke cases and were more likely to report use of antihypertensives (OR = 1.51 (95% CI: 1.10-2.06)). There was a trend toward greater hypertension awareness among MA female stroke cases (OR = 1.37 (95% CI: 0.98-1.91))., Conclusions: MA women have increased risk of stroke at younger ages compared with NHW women. Reasons for this ethnic disparity, including an increased prevalence of hypertension and diabetes, should be explored.

Objective: Data on the association between air pollution and cerebrovascular disease in the United States are limited. The objective of this study was to investigate the association between short-term exposure to ambient air pollution and risk for ischemic cerebrovascular events in a US community., Methods: Daily counts of ischemic strokes/transient ischemic attacks (TIAs) (2001-2005) were obtained from the population-based Brain Attack Surveillance in Corpus Christi (BASIC) Project. Daily particulate matter less than 2.5microm in diameter (PM(2.5)), ozone (O(3)), and meteorological data were obtained from Texas Commission on Environmental Quality. To examine the association between PM(2.5) and stroke/TIA risk, we used Poisson regression. Separate models included same-day PM(2.5), PM(2.5) lagged 1 to 5 days, and an averaged lag effect. All models were adjusted for temperature, day of week, and temporal trends in stroke/TIA. The effects of O(3) were also investigated., Results: Median PM(2.5) was 7.0microg/m(3) (interquartile range, 4.8-10.0microg/m(3)). There were borderline significant associations between same-day (relative risk [RR], 1.03; 95% confidence interval [CI], 0.99-1.07 for an interquartile range increase in PM(2.5)) and previous-day (RR, 1.03; 95% CI, 1.00-1.07) PM(2.5) and stroke/TIA risk. These associations were independent of O(3), which demonstrated similar associations with stroke/TIA risk (same-day RR, 1.02; 95% CI, 0.97-1.08; previous-day RR, 1.04; 95% CI, 0.99-1.09)., Interpretation: We observed associations between recent PM(2.5) and O(3) exposure and ischemic stroke/TIA risk even in this community with relatively low pollutant levels. This study provides data on environmental exposures and stroke risk in the United States, and suggests future research on ambient air pollution and stroke is warranted.

Stroke mortality is an important national health statistic and represents a frequent endpoint for epidemiologic studies. Several methods have been used to determine cause of death after stroke, but their agreement and reliability are unknown. Two hundred consecutive deaths of transient ischemic attack or ischemic stroke patients were identified (January 2000-September 2001) from an ongoing population-based stroke surveillance study in Texas, The Brain Attack Surveillance in Corpus Christi Project. Two neurologists independently recorded the cause of death based on two methods: 1) determining the underlying cause of death as defined by the World Health Organization, and 2) determining whether the death was stroke related. Kappa statistics with 95% confidence intervals were calculated by comparing agreement between methods within reviewers and between reviewers within methods. Agreement between the two cause-of-death-determination methods for each neurologist was 0.41 (95% confidence interval (CI): 0.31, 0.51) and 0.47 (95% CI: 0.38, 0.58), respectively. Agreement between neurologists for the underlying-cause-of-death method was 0.46 (95% CI: 0.32, 0.60); for the stroke-related method, it was 0.63 (95% CI: 0.52, 0.75). Accurate, reliable determinations of cause of death after stroke/transient ischemic attack are not currently feasible. More research is needed to identify a reliable process for coding cause of death from stroke.

Studies that accurately identify myocardial infarction (MI) and stroke within populations would provide valuable epidemiological information as well as data on vascular disease prevention. We performed a pilot study to assess the feasibility of adding MI surveillance to an ongoing population-based stroke surveillance study, the Brain Attack Surveillance in Corpus Christi (BASIC) Project. We also tested two screening methods for MI ascertainment: discharge International Classification of Diseases, Ninth Revision (ICD-9) codes and cardiac biomarker screening. This pilot study suggests that the addition of MI surveillance to community-based stroke surveillance studies is feasible. Screening for abnormal cardiac biomarkers to identify potential MI cases may be more accurate and efficient than using ICD-9 codes., ((c) 2007 S. Karger AG, Basel.)

Purpose: To estimate ethnic-specific all-cause mortality risk following ischemic stroke and to compare mortality risk by ethnicity., Methods: DATA from the Brain Attack Surveillance in Corpus Christi Project, a population-based stroke surveillance study, were used. Stroke cases between January 1, 2000 and December 31, 2002 were identified from emergency department (ED) and hospital sources (n = 1,234). Deaths for the same period were identified from the surveillance of stroke cases, the Texas Department of Health, the coroner, and the Social Security Death Index. Ethnic-specific all-cause cumulative mortality risk was estimated at 28 days and 36 months using Kaplan Meier analysis. Cox proportional hazards regression was used to compare mortality risk by ethnicity., Results: Cumulative 28-day all-cause mortality risk for Mexican Americans (MAs) was 7.8% and for non-Hispanic whites (NHWs) was 13.5%. Cumulative 36-month all-cause mortality risk was 31.3% in MAs and 47.2% in NHWs. MAs had lower 28-day (RR = 0.58; 95% CI: 0.41, 0.84) and 36-month all-cause mortality risk (RR = 0.79, 95% CI: 0.64, 0.98) compared with NHWs, adjusted for confounders., Conclusions: Better survival after stroke in MAs is surprising considering their similar stroke subtype and severity compared with NHWs. Social or psychological factors, which may explain this difference, should be explored.

Background: Sixty-two percent of all stroke deaths in the United States occur in women. We compared diagnostic evaluations by gender in ischemic stroke patients in a biethnic, population-based study., Methods: A random sample of patients with ischemic stroke identified between 2000 and 2002 by BASIC (Brain Attack Surveillance in Corpus Christi Project) were selected for this study (n = 381). Gender differences in the use of stroke diagnostic tests were assessed. Separate multivariable logistic regression models predicting diagnostic test use were constructed, adjusted for age, ethnicity, hypertension, atrial fibrillation, diabetes, history of stroke, coronary artery disease, having a primary care provider, discharge disposition, modified Rankin Scale score at discharge, and insurance status., Results: The study population consisted of 161 men and 220 women. Median age was 74.3 years. The respective proportions of males and females receiving any carotid artery evaluation were 71% and 62%; brain MRI, 43% and 41%; echocardiography, 57% and 48%; and EKG, 90% and 86%. Multivariable logistic models found that women were less likely to undergo echocardiography (odds ratio [OR] 0.64, CI: 0.42 to 0.98) and carotid evaluation (OR 0.57, CI: 0.36 to 0.91). There was no association of ischemic stroke subtype and gender to explain these results (p = 0.76)., Conclusions: Despite controlling for explanatory variables, women with stroke were less likely to receive standard diagnostic tests vs men. Intervention is needed to increase access to quality stroke care for women.

To plan a multisite, ischemic stroke genetic study, stroke patients were surveyed about the availability and characteristics of a convenience sample of spouse/friend controls. 65% of all stroke-affected probands reported a living spouse. A more detailed survey was conducted at the University of Virginia, Charlottesville, Va., USA: 51% of stroke patients reported a living, stroke-free spouse who would be willing to serve as a control, and 49% reported having a stroke-free friend who would be willing to serve as a control. Overall, 75% of stroke patients reported at least 1 individual willing to participate as a control. Cases without an identified control were more likely to be non-white (48%) than were cases with a control (13%; p = 0.00004). Cases were older than controls (67.3 vs. 59.2 years; p = 0.000002), and a greater proportion of cases than controls were male (57 vs. 33%; p = 0.0002). Without proper attention to matching, the use of a spouse/friend convenience sample would result in imbalances in basic demographic characteristics., (Copyright 2003 S. Karger AG, Basel)