Door-in-Door-out Times for Interhospital Transfer of Patients With Stroke.

Importance: Treatments for time-sensitive acute stroke are not available at every hospital, often requiring interhospital transfer. Current guidelines recommend hospitals achieve a door-in-door-out time of no more than 120 minutes at the transferring emergency department (ED). Objective: To evaluate door-in-door-out times for acute stroke transfers in the American Heart Association Get With The Guidelines-Stroke registry and to identify patient and hospital factors associated with door-in-door-out times. Design, Setting, and Participants: US registry-based, retrospective study of patients with ischemic or hemorrhagic stroke from January 2019 through December 2021 who were transferred from the ED at registry-affiliated hospitals to other acute care hospitals. Exposure: Patient- and hospital-level characteristics. Main Outcomes and Measures: The primary outcome was the door-in-door-out time (time of transfer out minus time of arrival to the transferring ED) as a continuous variable and a categorical variable (≤120 minutes, >120 minutes). Generalized estimating equation (GEE) regression models were used to identify patient and hospital-level characteristics associated with door-in-door-out time overall and in subgroups of patients with hemorrhagic stroke, acute ischemic stroke eligible for endovascular therapy, and acute ischemic stroke transferred for reasons other than endovascular therapy. Results: Among 108 913 patients (mean [SD] age, 66.7 [15.2] years; 71.7% non-Hispanic White; 50.6% male) transferred from 1925 hospitals, 67 235 had acute ischemic stroke and 41 678 had hemorrhagic stroke. Overall, the median door-in-door-out time was 174 minutes (IQR, 116-276 minutes): 29 741 patients (27.3%) had a door-in-door-out time of 120 minutes or less. The factors significantly associated with longer median times were age 80 years or older (vs 18-59 years; 14.9 minutes, 95% CI, 12.3 to 17.5 minutes), female sex (5.2 minutes; 95% CI, 3.6 to 6.9 minutes), non-Hispanic Black vs non-Hispanic White (8.2 minutes, 95% CI, 5.7 to 10.8 minutes), and Hispanic ethnicity vs non-Hispanic White (5.4 minutes, 95% CI, 1.8 to 9.0 minutes). The following were significantly associated with shorter median door-in-door-out time: emergency medical services prenotification (-20.1 minutes; 95% CI, -22.1 to -18.1 minutes), National Institutes of Health Stroke Scale (NIHSS) score exceeding 12 vs a score of 0 to 1 (-66.7 minutes; 95% CI, -68.7 to -64.7 minutes), and patients with acute ischemic stroke eligible for endovascular therapy vs the hemorrhagic stroke subgroup (-16.8 minutes; 95% CI, -21.0 to -12.7 minutes). Among patients with acute ischemic stroke eligible for endovascular therapy, female sex, Black race, and Hispanic ethnicity were associated with a significantly higher door-in-door-out time, whereas emergency medical services prenotification, intravenous thrombolysis, and a higher NIHSS score were associated with significantly lower door-in-door-out times. Conclusions and Relevance: In this US registry-based study of interhospital transfer for acute stroke, the median door-in-door-out time was 174 minutes, which is longer than current recommendations for acute stroke transfer. Disparities and modifiable health system factors associated with longer door-in-door-out times are suitable targets for quality improvement initiatives.

[Ethnic features of multipathology in elderly and senile patients of the Republic of Sakha suffering from chronic brain ischemia]. / Etnicheskie osobennosti mul'tipatologii u patsientov pozhilogo i starcheskogo vozrasta Respubliki Sakha (Yakutiya), stradayushchikh khronicheskoi ishemiei mozga.

OBJECTIVE: To study ethnic characteristics of multipathology in elderly and senile patients with chronic cerebral ischemia living in the Republic of Sakha (Yakutia). MATERIAL AND METHODS: The study included 522 inpatients, aged 60 to 89 years, who were divided into subgroups depending on the stage of chronic cerebral ischemia, ethnicity (Evens, Yakuts and Russians) and age (elderly and senile). RESULTS: In addition to vascular cerebral pathology, comorbidities were identified in patients of older age groups. At the same time, polymorbidity was less pronounced in the Evens, the indigenous inhabitants of the northern regions of Yakutia, than in the Yakuts and representatives of the non-indigenous population - Russians. CONCLUSION: The relatively rare occurrence of comorbid pathologies in Evens is presumably associated with greater adaptation to the extreme climatic conditions of the North.

Hyperglycemia, Ischemic Lesions, and Functional Outcomes After Intracerebral Hemorrhage.

Background Ischemic lesions observed on diffusion-weighted imaging (DWI) magnetic resonance imaging are associated with poor outcomes after intracerebral hemorrhage (ICH). We evaluated the association between hyperglycemia, ischemic lesions, and functional outcomes after ICH. Methods and Results This was a retrospective observational analysis of 1167 patients who received magnetic resonance imaging in the ERICH (Ethnic and Racial Variations in Intracerebral Hemorrhage) study. A machine learning strategy using the elastic net regularization and selection procedure was used to perform automated variable selection to identify final multivariable logistic regression models. Sensitivity analyses with alternative model development strategies were performed, and predictive performance was compared. After covariate adjustment, white matter hyperintensity score, leukocyte count on admission, and non-Hispanic Black race (compared with non-Hispanic White race) were associated with the presence of DWI lesions. History of ICH and ischemic stroke, presence of DWI lesions, deep ICH location (versus lobar), ICH volume, age, lower Glasgow Coma Score on admission, and medical history of diabetes were associated with poor 6-month modified Rankin Scale outcome (4-6) after covariate adjustment. Inclusion of interactions between race and ethnicity and variables included in the final multivariable model for functional outcome improved model performance; a significant interaction between race and ethnicity and medical history of diabetes and serum blood glucose on admission was observed. Conclusions No measure of hyperglycemia or diabetes was associated with presence of DWI lesions. However, both medical history of diabetes and presence of DWI lesions were independently associated with poor functional outcomes after ICH.

No Racial Disparity in Outcome Measures After Endovascular Treatment for Stroke in the Elderly.

BACKGROUND AND PURPOSE: Despite the lower rates of good outcomes and higher mortality in elderly patients, age does not modify the treatment effect of mechanical thrombectomy for large vessel occlusion strokes. We aimed to study whether racial background influences the outcome after mechanical thrombectomy in the elderly population. METHODS: We reviewed a prospectively maintained database of patients with acute ischemic stroke treated with mechanical thrombectomy from October 2010 through June 2020 to identify all consecutive patients with age ≥80 years and anterior circulation large vessel occlusion strokes. The patients were categorized according to their race as Black and White. Univariable and multivariable analyses were performed to define the predictors of 90-day modified Rankin Scale and mortality in the overall population and in each race separately. RESULTS: Among 2241 mechanical thrombectomy, a total of 344 patients (median [interquartile range]; age 85 [82-88] years, baseline National Institutes of Health Stroke Scale score of 19 [15-23], Alberta Stroke Program Early CT Score 9 [7-9], 69.5% females) were eligible for the analysis. White patients (n=251; 73%) had significantly lower median body mass index (25.37 versus 26.89, P=0.04) and less frequent hypertension (78.9% versus 90.3%, P=0.01) but more atrial fibrillation (64.5% versus 44.1%, P=0.001) compared with African Americans (n=93; 27%). Other clinical, imaging, and procedural characteristics were comparable between groups. The rates of symptomatic intracerebral hemorrhage, 90-day modified Rankin Scale score of 0 to 2, and mortality were comparable among both groups. On multivariable analysis, race was neither a predictor of 90-day modified Rankin Scale score of 0 to 2 (White race: odds ratio, 0.899 [95% CI, 0.409-1.974], P=0.79) nor 90-day mortality (White race: odds ratio, 1.368; [95% CI, 0.715-2.618], P=0.34). CONCLUSIONS: In elderly patients undergoing mechanical thrombectomy for acute ischemic stroke, there was no racial difference in terms of outcome.

An Asian Perspective on Gender Differences in In-Hospital and Long-Term Outcome of Cardiac Mortality and Ischemic Stroke after Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction.

OBJECTIVES: Gender differences historically exist in cardiovascular disease, with women experiencing higher rates of major adverse cardiovascular events. We investigated these trends in a contemporary Asian cohort, examining the impact of gender differences on cardiac mortality and ischemic stroke after primary percutaneous coronary intervention (PPCI) for ST elevation myocardial infarction (STEMI). MATERIALS AND METHODS: We analysed 3971 consecutive patients who underwent primary PCI for STEMI retrospectively. The primary outcome was cardiac mortality and ischemic stroke in-hospital, at one year and on longer-term follow up (median follow up 3.62 years, interquartile range 1.03-6.03 years). RESULTS: There were 580 (14.6%) female patients and 3391 (85.4%) male patients. Female patients were older and had higher prevalence of hypertension, diabetes, previous strokes, and chronic kidney disease. Cardiac mortality was higher in female patients during in-hospital (15.5% vs. 6.2%), 1-year (17.4% vs. 7.0%) and longer term follow up (19.9% vs. 8.1%, log-rank test: p < 0.001). Similarly, females had higher incidence of ischemic stroke at in-hospital (2.6% vs. 1.0%), 1-year (3.6% vs. 1.4%) and in the longer-term (6.7% vs. 3.1%) as well (log-rank test: p < 0.001). Female gender remained an independent predictor of in-hospital cardiac mortality (HR 1.395, 95%CI 1.061-1.833, p=0.017) and on longer-term follow-up (HR 1.932 95%CI 1.212-3.080, p=0.006) even after adjusting for confounders. CONCLUSIONS: Females were at higher risk of in-hospital and long-term cardiac mortality and ischemic stroke after PPCI for STEMI. Future studies are warranted to investigate the role of aggressive management of cardiovascular risk factors and follow-up to improve outcomes in the females with STEMI.

Multiple Chronic Conditions Explain Ethnic Differences in Functional Outcome Among Patients With Ischemic Stroke.

BACKGROUND AND PURPOSE: Mexican Americans (MAs) have worse stroke outcomes and a different profile of multiple chronic conditions (MCC) compared with non-Hispanic White people. MCC has implications for stroke treatment, complications, and poststroke care, which impact poststroke functional outcome (FO). We sought to assess the contribution of MCC to the ethnic difference in FO at 90 days between MAs and non-Hispanic White people. METHODS: In a prospective cohort of ischemic stroke patients (2008-2016) from Nueces County, Texas, data were collected from patient interviews, medical records, and hospital discharge data. MCC was assessed using a stroke-specific and function-relevant index (range, 0-35; higher scores greater MCC burden). Poststroke FO was measured by an average score of 22 activities of daily living (ADLs) and instrumental ADLs at 90 days (range, 1-4; higher scores worse FO). The contribution of MCC to the ethnic difference in FO was assessed using Tobit regression. Effect modification by ethnicity was examined. RESULTS: Among the 896 patients, 70% were MA and 51% were women. Mean age was 68±12.2 years; 33% of patients were dependent in ADL/instrumental ADLs (FO score >3, representing a lot of difficulty with ADL/instrumental ADLs) at 90 days. MAs had significantly higher age-adjusted MCC burden compared with non-Hispanic White people. Patients with high MCC score (at the 75th percentile) on average scored 0.70 points higher in the FO score (indicating worse FO) compared with those with low MCC score (at the 25th percentile) after adjusting for age, initial National Institutes of Health Stroke Scale, and sociodemographic factors. MCC explained 19% of the ethnic difference in FO, while effect modification by ethnicity was not statistically significant. CONCLUSIONS: MAs had a higher age-adjusted MCC burden, which partially explained the ethnic difference in FO. The prevention and treatment of MCC could potentially mitigate poststroke functional impairment and lessen ethnic disparities in stroke outcomes.

Racial, ethnic and socioeconomic disparities in patients undergoing left atrial appendage closure.

OBJECTIVE: This manuscript aims to explore the impact of race/ethnicity and socioeconomic status on in-hospital complication rates after left atrial appendage closure (LAAC). METHODS: The US National Inpatient Sample was used to identify hospitalisations for LAAC between 1 October 2015 to 31 December 2018. These patients were stratified by race/ethnicity and quartiles of median neighbourhood income. The primary outcome was the occurrence of in-hospital major adverse events, defined as a composite of postprocedural bleeding, cardiac and vascular complications, acute kidney injury and ischaemic stroke. RESULTS: Of 6478 unweighted hospitalisations for LAAC, 58% were male and patients of black, Hispanic and 'other' race/ethnicity each comprised approximately 5% of the cohort. Adjusted by the older Americans population, the estimated number of LAAC procedures was 69.2/100 000 for white individuals, as compared with 29.5/100 000 for blacks, 47.2/100 000 for Hispanics and 40.7/100 000 for individuals of 'other' race/ethnicity. Black patients were ~5 years younger but had a higher comorbidity burden. The primary outcome occurred in 5% of patients and differed significantly between racial/ethnic groups (p<0.001) but not across neighbourhood income quartiles (p=0.88). After multilevel modelling, the overall rate of in-hospital major adverse events was higher in black patients as compared with whites (OR: 1.60, 95% CI 1.22 to 2.10, p<0.001); however, the incidence of acute kidney injury was higher in Hispanics (OR: 2.19, 95% CI 1.52 to 3.17, p<0.001). No significant differences were found in adjusted overall in-hospital complication rates between income quartiles. CONCLUSION: In this study assessing racial/ethnic disparities in patients undergoing LAAC, minorities are under-represented, specifically patients of black race/ethnicity. Compared with whites, black patients had higher comorbidity burden and higher rates of in-hospital complications. Lower socioeconomic status was not associated with complication rates.

SNP rs2043211 (p.C10X) in CARD8 Is Associated with Large-Artery Atherosclerosis Stroke in a Chinese Population.

SNP rs2043211 in CARD8 was found to have significant association with ischemic stroke. This study aimed to explore the possible association between rs2043211 and large-artery atherosclerosis stroke in Chinese and explain the possible mechanism. In total, 716 large-artery atherosclerosis stroke patients and 1088 controls were included in the study. Co-dominant, dominant, and recessive genetic models were constructed to evaluate the relationship between rs2043211 and large-artery atherosclerosis stroke risk by odds ratios with 95% confidence intervals. Stratified and interaction analyses were also done. We selected another 111 large-artery atherosclerosis stroke patients and measured the CARD8 levels in their plasma samples by enzyme-linked immunosorbent assay. Participants who carry T/T genotype have a higher risk of large-artery atherosclerosis stroke compared with those carry A/T or A/A genotypes (odds ratio = 1.35, 95% confidence intervals 1.03-1.77, P = 0.029). The higher risk for the T/T genotype is still notable in female, people with hypertension, and people without diabetes. In the interaction analysis, compared to the non-hypertensive participants with the wild homozygote type A/A, the hypertensive participants with the A/T+T/T homozygote had 3.27-fold increased risk (odds ratio = 3.27, 95% confidence intervals 2.33-4.60). The A/A group had lower CARD8 levels in plasma than the A/T and T/T group (P < 0.001). Further bioinformatics prediction indicated that the rs2043211 could significantly influence the mRNA secondary structure and protein expression of CARD8 (eQTL P = 9.8 × 10-198). The rs2043211 is probably a novel biomarker for large-artery atherosclerosis stroke in Chinese.

Non-vitamin K antagonist oral anticoagulants in very elderly east Asians with atrial fibrillation: A nationwide population-based study.

BACKGROUND: The evidence of effectiveness and safety of the non-vitamin K antagonist oral anticoagulants (NOACs) among elderly East Asians is limited. OBJECTIVES: We aimed to describe the effectiveness and safety outcomes associated with NOACs and warfarin among elderly Koreans aged ≥80 years. METHODS: Using the Korean Health Insurance Review and Assessment service database, patients with atrial fibrillation (AF) who were naïve to index oral anticoagulant between 2015 and 2017 were included in this study (20,573 for NOACs and 4086 for warfarin). Two treatment groups were balanced using the inverse probability of treatment weighting (IPTW) method. The clinical outcomes including ischemic stroke, major bleeding including intracranial hemorrhage (ICH) and gastrointestinal bleeding (GIB), and a composite of these outcomes were evaluated. RESULTS: Compared to warfarin, NOACs were associated with lower risks of ischemic stroke (hazard ratio 0.74 [95% confidence interval 0.62-0.89]), and composite outcome (0.78 [0.69-0.90]). NOACs showed nonsignificant trends towards to lower risks of GIB and major bleeding than warfarin. The risk of ICH of NOAC group was comparable with the warfarin group. Among NOACs, apixaban and edoxaban showed better composite outcomes than warfarin. Among the clinical outcomes, only ischemic stroke and the composite outcome had a significant interaction with age subgroups (80-89 years and ≥90 years, P-for-interaction = .097 and .040, respectively). CONCLUSION: NOACs were associated with lower risks of ischemic stroke and the composite outcome (ischemic stroke and major bleeding) compared to warfarin in elderly East Asians. Physicians should be more confident in prescribing NOACs to elderly East Asians with AF.

Ischemic stroke in COVID-19: An urgent need for early identification and management.

OBJECTIVE: In the setting of the Coronavirus Disease 2019 (COVID-19) global pandemic caused by SARS-CoV-2, a potential association of this disease with stroke has been suggested. We aimed to describe the characteristics of patients who were admitted with COVID-19 and had an acute ischemic stroke (AIS). METHODS: This is a case series of PCR-confirmed COVID-19 patients with ischemic stroke admitted to an academic health system in metropolitan Atlanta, Georgia (USA) between March 24th, 2020 and July 17th, 2020. Demographic, clinical, and radiographic characteristics were described. RESULTS: Of 396 ischemic stroke patients admitted during this study period, 13 (2.5%) were also diagnosed with COVID-19. The mean age of patients was 61.6 ± 10.8 years, 10 (76.9%) male, 8 (61.5%) were Black Americans, mean time from last normal was 4.97 ± 5.1 days, and only one received acute reperfusion therapy. All 13 patients had at least one stroke-associated co-morbidity. The predominant pattern of ischemic stroke was embolic with 4 explained by atrial fibrillation. COVID-19 patients had a significantly higher rate of cryptogenic stroke than non-COVID-19 patients during the study period (69% vs 17%, p = 0.0001). CONCLUSIONS: In our case series, ischemic stroke affected COVID-19 patients with traditional stroke risk factors at an age typically seen in non-COVID populations, and mainly affecting males and Black Americans. We observed a predominantly embolic pattern of stroke with a higher than expected rate of cryptogenic strokes, a prolonged median time to presentation and symptom recognition limiting the use of acute reperfusion treatments. These results highlight the need for increased community awareness, early identification, and management of AIS in COVID-19 patients.

Sex and racial disparity in utilization and outcomes of t-PA and thrombectomy in acute ischemic stroke.

BACKGROUND/PURPOSE: Racial/ethnic and sex disparity may occur in stroke throughout the continuum of care. Endovascular therapy (EVT) became standard of care in 2015 for eligible patients with acute ischemic stroke (AIS). We evaluated for racial and sex differences in t-PA and EVT utilization and outcomes in 2016 in the National Inpatient Sample. METHODS: Treatment rates for t-PA, EVT, and t-PA+EVT and outcomes including home discharge, in-hospital mortality and prolonged length of stay (pLOS) were evaluated by sex and race. Multivariate survey-logistic regression was performed to evaluate outcomes. RESULTS: The study had 468,630 patients - 49.3% men, 50.7% women; 69.3% whites, and 30.7% non-whites. There was no difference in treatment utilization by sex, women vs men for t-PA (7.65% vs 7.76%; aOR:1.02; 95% CI:0.97-1.07), EVT (1.74% vs 1.67%; aOR:1.09; 95% CI:0.99-1.20) and t-PA+EVT (0.57% vs 0.57%; aOR:1.01; 95% CI:0.85-1.21); and by race, non-white vs white for t-PA (7.62% vs 7.74%; aOR:0.98; 95% CI:0.93-1.05), EVT (1.62% vs 1.74%; aOR:0.91; 95% CI:0.78-1.07), and t-PA+EVT(0.59% vs 0.56%; aOR:1.05; 95% CI:0.84-1.30). Compared to men, women treated with t-PA had less home discharge (37.2% vs 46.3%; aOR:0.81; 95% CI:0.72-0.90), more in-hospital mortality (5.7% vs 3.9%; aOR:1.37; 95% CI:1.06-1.77) and less pLOS (8.3% vs 9.6%; aOR:0.82; 95% CI:0.69-0.98); women treated with EVT had less home discharge (15.8% vs 23.7%; aOR:0.69; 95% CI:0.52-0.91). Compared to whites, non-whites treated with t-PA had lower odds of home discharge (42.1% vs 41.6%; aOR:0.79; 95% CI:0.69-0.90), less in-hospital mortality (3.7% vs 5.3%; aOR:0.65; 95% CI:0.49-0.87), and higher pLOS (11.4% vs 7.9%; aOR:1.3; 95% CI:1.07-1.56); non-whites treated with EVT had less home discharge (18%vs 20.2%; aOR:0.70; 95% CI:0.51-0.97) and higher pLOS (35.1% vs 24%; aOR:1.52; 95% CI:1.16-1.99). CONCLUSION: Sex and racial disparity exists for outcomes of t-PA and EVT despite no difference in utilization rates.

Nomogram for predicting delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage in the Chinese population.

BACKGROUND: Delayed cerebral ischemia is a serious complication of aneurysmal subarachnoid hemorrhage with debilitating and fatal consequences. Lack of well-established risk factors impedes early identification of high-risk patients with delayed cerebral ischemia. A nomogram provides personalized, evidence-based, and accurate risk estimation. To offset the lack of a predictive tool, we developed a nomogram to predict delayed cerebral ischemia before performing surgical interventions for aneurysmal subarachnoid hemorrhage to aid surgical decision-making. METHODS: We retrospectively collected data from 887 consecutive eligible Chinese patients who underwent surgical clipping or endovascular coiling for aneurysmal subarachnoid hemorrhage. Patients who previously underwent surgery formed the training cohort (n = 621) for nomogram development; those who underwent surgery later formed the validation cohort (n = 266) to confirm the performance of the model. A multivariate logistic regression analysis identified the independent risk factors associated with delayed cerebral ischemia, which were then incorporated into the nomogram. RESULTS: Delayed cerebral ischemia was identified in 158/621 patients (25.4%) in the training cohort and in 66/266 patients (24.8%) in the validation cohort. Preoperative factors associated with delayed cerebral ischemia were age > 65 years, modified Fisher grade of 3-4, ruptured aneurysm in the anterior circulation, Hunt-Hess grade of 4-5, high blood pressure on admission, and plasma homocysteine level ≥ 10 µmol/L. Incorporating these six factors in the nomogram achieved efficient concordance indices of 0.73 (95% confidence interval, 0.68-0.77) and 0.65 (95% confidence interval, 0.57-0.72) in predicting delayed cerebral ischemia in the training and validation cohorts, respectively. CONCLUSIONS: Our model can help determine an individual's risk of developing delayed cerebral ischemia in the Chinese population, and thereby, facilitate reasonable treatment-related decision-making.

Trends in Stroke Recurrence in Mexican Americans and Non-Hispanic Whites.

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.

Racial disparities in post-stroke functional outcomes in young patients with ischemic stroke.

BACKGROUND AND PURPOSE: Recent studies show rising incidence of stroke in the young, for which risk factors are not well characterized. There is evidence of increased risk in certain racial and ethnic groups. We assessed racial differences in risk factors, stroke etiology, and outcomes among young stroke patients. METHODS: Using data from our inpatient registry for ischemic stroke, we reviewed patients aged 18-50 who were admitted 01/2013 to 04/2018. Race/ethnicity were characterized as non-Hispanic White (NHW), non-Hispanic Black (NHB), Hispanic (HIS). For univariate comparisons Chi-square and Kruskal-Wallis tests were performed as appropriate. Multivariable logistic regression was used to assess impact of race on day seven modified Rankin score (mRS). RESULTS: Among 810 patients with race and outcome data who were admitted in the study period, median age was 43, 57.1% were male, and 36.5% NHW, 43.2% NHB, 20.2% HIS. History of hypertension (HTN), type II diabetes (DM II), smoking, heart failure (CHF), prior stroke, and end-stage renal disease varied significantly by race. Compared to NHW, NHB had higher odds of HTN (OR 2.28, 1.65-3.15), CHF (OR 2.17, 1.06-4.46), and DM II 1.92 (1.25-2.94) while HIS had higher odds of DM II (OR 2.52, 1.55-4.10) and lower odds of smoking (OR 0.56, 0.35-0.90). Arrival NIHSS was higher in NHB, but etiology and rates of tpA treatment and thrombectomy did not vary by race. Compared to NHW patients, NHB (OR 0.50 CI (0.31-0.78)) and HIS (OR 0.37 CI (0.21-0.67)) were less likely to have good functional outcome (mRS <2) at day 7 in adjusted analyses. CONCLUSIONS: In this study, there was a higher prevalence of several modifiable risk factors in NHB and HIS young stroke patients and early functional outcome was worse in these groups. Our study suggests a need for targeted prevention efforts for younger populations at highest risk for stroke.

Combined polymorphisms in genes encoding the inflammasome components NLRP3 and CARD8 confer risk of ischemic stroke in men.

INTRODUCTION: Previous studies have reported the involvement of nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome in the inflammatory activation and pathophysiology of Ischemic Stroke (IS). Variations in genes encoding the constituent proteins of NLRP3 inflammasome can alter the risk of IS. OBJECTIVE: We investigated the role of the NLRP3 inflammasome in the pathogenesis of IS by establishing associations between combined polymorphisms of caspase recruitment domain-containing protein 8 (CARD8) rs2043211 and NLRP3 rs10754558 and the susceptibility to IS in a Chinese population. METHODS: Single nucleotide polymorphisms (SNPs) in CARD8 rs2043211 and NLRP3 rs10754558 were analyzed using TaqMan SNP genotyping assays in patients with IS (n=234) and healthy controls (n=115). Logistic regression analysis was carried out to evaluate potential interactions between CARD8 and NLRP3. RESULTS: Compared with healthy controls, there were no significant differences in the minor allele frequency (MAF) and the genotype frequency of NLRP3 rs10754558 or CARD8 rs2043211 in patients with IS(P>0.05). After stratification by gender, there was an increased risk for IS in men carrying heterozygous CARD8 rs2043211 when a co-dominant genetic model was applied (P=0.021, OR=3.83[1.22-12.03]). Logistic regression analysis indicated that men carrying both CARD8 rs2043211 AT and NLRP3 rs10754558 CG had a significantly higher risk of IS (P=0.046, OR=7.116[1.033-49.044]). CONCLUSIONS: Nucleotide variations in the genes encoding NLRP3 inflammasome proteins may be important to IS, and men carrying CARD8 rs2043211 and NLRP3 rs10754558, both heterozygous, confer a higher risk of IS.

Pioglitazone for primary stroke prevention in Asian patients with type 2 diabetes and cardiovascular risk factors: a retrospective study.

BACKGROUND: Studies assessing the efficacy of pioglitazone solely for primary stroke prevention in Asian patients with type 2 diabetes mellitus (DM) and present multiple cardiovascular (CV) risk factors are rare. Thus, we aimed to assess the effect of pioglitazone on primary stroke prevention in Asian patients with type 2 DM without established CV diseases but with risk factors for CV diseases. METHODS: Between 2000 and 2012, we enrolled patients aged ≥ 18 years, who were newly diagnosed with type 2 diabetes and had at least one of the following CV risk factors: hypertension and hyperlipidemia. Patients with a history of stroke and those using insulin or glucagon-like peptide-1 agonist for more than 3 months were excluded. Patients were divided into the pioglitazone and non-pioglitazone groups based on their receipt of pioglitazone during the follow-up period. Propensity-score matching (1:1) was used to balance the distribution of the baseline characteristics and medications. Follow-up was terminated upon ischemic stroke development, withdrawal from the insurance system, or on December 31, 2013, whichever occurred first. The overall incidence of new-onset ischemic stroke in the two groups was subsequently compared. The subgroup analyses of ischemic stroke were conducted using different baseline features. Additionally, the effect of pioglitazone exposure dose on the occurrence of ischemic stroke was evaluated. Chi square test, Student's t-test, competing risk regression models, Kaplan-Meier method, and log-rank test were some of the statistical tests conducted. RESULTS: A total of 13 078 patients were included in the pioglitazone and non-pioglitazone groups. Compared with patients who did not receive pioglitazone, those administered pioglitazone had a lower risk of developing ischemic stroke (adjusted hazard ratio: 0.78; 95% confidence interval: 0.62-0.95). The subgroup analyses defined by different baseline features did not reveal significant alterations in the observed effect of pioglitazone. Moreover, a significant decreasing trend in ischemic stroke risk with an increase in pioglitazone dose (p-value for trend = 0.04) was observed. CONCLUSION: Pioglitazone use decreased the risk of new-onset ischemic stroke in Asian patients with type 2 DM and CV risk factors. Trial registration number CMUH104-REC2-115-CR4.

A Promoter Polymorphism (Rs57137919) of ABCG1 Gene Influence on Blood Lipoprotein in Chinese Han Population.

BACKGROUND: Adenosine triphosphate-binding cassette subfamily G member 1 (ABCG1) has the function of transporting free intracellular cholesterol to extracellular high-density lipoprotein (HDL) particles, which play a crucial role in atherosclerosis. The goal of this study is to examine the relationship between the polymorphisms of the ABCG1 gene promoter region and ischemic stroke. METHODS: In the present study, a case-control association study was designed to identify 3 single-nucleotide polymorphisms (SNPs; rs5713919, rs1378577, and rs1893590), which were located in the promoter region of ABCG1 gene by kompetitive allele-specific polymerase chain reaction genotyping approach. The in vitro luciferase assay was done to estimate the effect of rs5713919 on gene expression. Finally, the relationships of 3 SNPs of ABCG1 gene with plasma lipids and lipoproteins were investigated in this Chinese cohort. RESULTS: The correlation analysis between lipids and genotypes showed that the rs57137919 locus genotype was significantly associated with HDL cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels (P = 0.021 and P = 0.017, respectively), and the GA and AA genotypes had higher HDL-C levels than the GG genotype. CONCLUSIONS: Our study provides evidence that ABCG1 promoter region polymorphism rs57137919 has an influence on plasma HDL-C and LDL-C levels in Chinese Han population.

Safety and Efficacy of Prasugrel in Elderly/Low Body Weight Japanese Patients with Ischemic Stroke: Randomized PRASTRO-II.

INTRODUCTION: The safety of prasugrel in elderly and/or low body weight Japanese patients with ischemic stroke who have a relatively high bleeding risk with antiplatelet therapy remains unknown. OBJECTIVE: We aimed to investigate the safety and efficacy of long-term prasugrel monotherapy for stroke prevention compared with clopidogrel in elderly and/or low body weight Japanese patients with non-cardioembolic ischemic stroke. METHODS: In this randomized, double-blind, comparative, phase III study, elderly (age ≥75 years) and/or low body weight (≤50 kg) Japanese patients with a previous history of non-cardioembolic ischemic stroke were assigned to a prasugrel 3.75 mg (PRA3.75) group, a prasugrel 2.5 mg (PRA2.5) group, or a clopidogrel 50 mg (CLO50) group and followed up for 48 weeks. The primary safety endpoint was the combined incidence of primary safety events, defined as life-threatening, major, and other clinically relevant bleeding. The efficacy endpoint was a composite of ischemic stroke, myocardial infarction, and death from other vascular causes. RESULTS: A total of 654 patients (age 76.4 ± 7.3 years, body weight 55.6 ± 9.3 kg, women 43.9%) from 74 medical institutions within Japan were enrolled. The combined incidence (95% CI) of primary safety events was 4.2% (1.9-7.8%), 1.9% (0.5-4.7%), and 3.6% (1.6-6.9%) in the PRA3.75 group (n = 216), PRA2.5 group (n = 215), and CLO50 group (n = 223), respectively (hazard ratios [HR] PRA3.75/CLO50, 1.13 [0.44-2.93]; PRA2.5/CLO50, 0.51 [0.15-1.69]). The incidences of bleeding leading to treatment discontinuation (95% CI) were 2.3% (0.8-5.3%), 0.9% (0.1-3.3%), and 2.2% (0.7-5.2%) in the PRA3.75, PRA2.5, and CLO50 groups, respectively (HRs PRA3.75/CLO50, 1.01 [0.29-3.48]; PRA2.5/CLO50, 0.41 [0.08-2.12]). There was no significant difference in all bleeding events between groups. The incidence of ischemic stroke, myocardial infarction, and death from other vascular causes was lower, but not significantly so, in patients treated with prasugrel than in patients treated with clopidogrel: PRA3.75, 0.0% (0/216); PRA2.5, 3.3% (7/215); and CLO50, 3.6% (8/223; HRs PRA3.75/CLO50, 0.00 [0.00-0.00]; PRA2.5/CLO50, 0.90 [0.32-2.47]). CONCLUSIONS: Elderly and/or low body weight -Japanese patients with previous non-cardioembolic ischemic stroke who received PRA3.75 showed similar results in terms of primary safety endpoint, and a numerically lower incidence of ischemic stroke, myocardial infarction, and death from other vascular causes, compared with those who received CLO50.

Long-term trends in death and dependence after ischaemic strokes: A retrospective cohort study using the South London Stroke Register (SLSR).

BACKGROUND: There have been reductions in stroke mortality over recent decades, but estimates by aetiological subtypes are limited. This study estimates time trends in mortality and functional dependence by ischaemic stroke (IS) aetiological subtype over a 16-year period. METHODS AND FINDINGS: The study population was 357,308 in 2011; 50.4% were males, 56% were white, and 25% were of black ethnic backgrounds. Population-based case ascertainment of stroke was conducted, and all participants who had their first-ever IS between 2000 and 2015 were identified. Further classification was concluded according to the underlying mechanism into large-artery atherosclerosis (LAA), cardio-embolism (CE), small-vessel occlusion (SVO), other determined aetiologies (OTH), and undetermined aetiologies (UND). Temporal trends in survival rates were examined using proportional-hazards survival modelling, adjusted for demography, prestroke risk factors, case mix variables, and processes of care. We carried out additional regression analyses to explore patterns in case-fatality rates (CFRs) at 30 days and 1 year and to explore whether these trends occurred at the expense of greater functional dependence (Barthel Index [BI] < 15) among survivors. A total of 3,128 patients with first-ever ISs were registered. The median age was 70.7 years; 50.9% were males; and 66.2% were white, 25.5% were black, and 8.3% were of other ethnic groups. Between 2000-2003 and 2012-2015, the adjusted overall mortality decreased by 24% (hazard ratio [HR] per year 0.976; 95% confidence interval [CI] 0.959-0.993). Mortality reductions were equally noted in both sexes and in the white and black populations but were only significant in CE strokes (HR per year 0.972; 95% CI 0.945‒0.998) and in patients aged ≥55 years (HR per year 0.975; 95% CI 0.959‒0.992). CFRs within 30 days and 1 year after an IS declined by 38% (rate ratio [RR] per year 0.962; 95% CI 0.941‒0.984) and 37% (RR per year 0.963; 95% CI 0.949‒0.976), respectively. Recent IS was independently associated with a 23% reduced risk of functional dependence at 3 months after onset (RR per year 0.983; 95% CI 0.968-0.998; p = 0.002 for trend). The study is limited by small number of events in certain subgroups (e.g., LAA), which could have led to insufficient power to detect significant trends. CONCLUSIONS: Both mortality and 3-month functional dependence after IS decreased by an annual average of around 2.4% and 1.7%, respectively, during 2000‒2015. Such reductions were particularly evident in strokes of CE origins and in those aged ≥55 years.

Race and Ethnic Disparities in Stroke Incidence in the Northern Manhattan Study.

Background and Purpose- An excess incidence of strokes among blacks versus whites has been shown, but data on disparities related to Hispanic ethnicity remain limited. This study examines race/ethnic differences in stroke incidence in the multiethnic, largely Caribbean Hispanic, NOMAS (Northern Manhattan Study), and whether disparities vary by age. Methods- The study population included participants in the prospective population-based NOMAS, followed for a mean of 14±7 years. Multivariable-adjusted Cox proportional hazards models were constructed to estimate the association between race/ethnicity and incident stroke of any subtype and ischemic stroke, stratified by age. Results- Among 3298 participants (mean baseline age 69±10 years, 37% men, 24% black, 21% white, 52% Hispanic), 460 incident strokes accrued (400 ischemic, 43 intracerebral hemorrhage, 9 subarachnoid hemorrhage). The most common ischemic subtype was cardioembolic, followed by lacunar infarcts, then cryptogenic. The greatest incidence rate was observed in blacks (13/1000 person-years), followed by Hispanics (10/1000 person-years), and lowest in whites (9/1000 person-years), and this order was observed for crude incidence rates until age 75. By age 85, the greatest incidence rate was in Hispanics. Blacks had an increased risk of stroke versus whites overall in multivariable models that included sociodemographics (hazard ratio, 1.51 [95% CI, 1.13-2.02]), and stratified analyses showed that this disparity was driven by women of age ≥70. The increased rate of stroke among Hispanics (age/sex-adjusted hazard ratio, 1.48 [95% CI, 1.13-1.93]) was largely explained by education and insurance status (a proxy for socieoeconomic status; hazard ratio after further adjusting for these variables, 1.17 [95% CI, 0.85-1.62]) but remained significant for women age ≥70. Conclusions- This study provides novel data regarding the increased stroke risk among Caribbean Hispanics in this elderly population. Results highlight the need to create culturally tailored campaigns to reach black and Hispanic populations to reduce race/ethnic stroke disparities and support the important role of low socioeconomic status in driving an elevated risk among Caribbean Hispanics.