Youngchai Ko

Case Characteristics, Hyperacute Treatment, and Outcome Information from the Clinical Research Center for Stroke-Fifth Division Registry in South Korea

Characteristics of stroke cases, acute stroke care, and outcomes after stroke differ according to geographical and cultural background. To provide epidemiological and clinical data on stroke care in South Korea, we analyzed a prospective multicenter clinical stroke registry, the Clinical Research Center for Stroke-Fifth Division (CRCS-5). Patients were 58% male with a mean age of 67.2±12.9 years and median National Institutes of Health Stroke Scale score of 3 [1-8] points. Over the 6 years of operation, temporal trends were documented including increasing utilization of recanalization treatment with shorter onset-to-arrival delay and decremental length of stay. Acute recanalization treatment was performed in 12.7% of cases with endovascular treatment utilized in 36%, but the proportion of endovascular recanalization varied across centers. Door-to-IV alteplase delay had a median of 45 [33-68] min. The rate of symptomatic hemorrhagic transformation (HT) was 7%, and that of any HT was 27% among recanalization-treated cases. Early neurological deterioration occurred in 15% of cases and were associated with longer length of stay and poorer 3-month outcomes. The proportion of mRS scores of 0-1 was 42% on discharge, 50% at 3 months, and 55% at 1 year after the index stroke. Recurrent stroke up to 1 year occurred in 4.5% of patients; the rate was higher among older individuals and those with neurologically severe deficits. The above findings will be compared with other Asian and US registry data in this article.

Current status of acute stroke management in Korea: a report on a multicenter, comprehensive acute stroke registry.

There are limited data on the utilization of diagnostics and the variation of treatments at the national level in acute stroke care. Clinical Research Center for Stroke – 5th division stroke registry aimed to describe stroke statistics and quality of care in Korea and to implement quality indicators. Clinical Research Center for Stroke – 5th division registry was established in April 2008 and covers pretreatment demographics, medical and stroke severity measures, diagnostic evaluation, hyperacute revascularization, in-hospital management, discharge disposition, quality indicators, and long-term functional outcomes. Consecutive stroke cases from 12 participating centers are registered to a web-based database. Meticulous data management and auditing policy were applied. A total of 14 792 ischemic stroke cases were enrolled from April 2008 to January 2012. The median National Institutes of Health Stroke Scale score was 4 at admission, with median delay of onset to arrival of 14 h. Rate of risk factor management before stroke exceeds more than 80% for hypertension and diabetes. Revascularization procedures were performed in 1736 subjects (12%), and 34% were endovascular (n = 598). Substantial variability was noted in the preferred modality of hyperacute revascularization (range of endovascular recanalization = 6–60%), use of computed tomography (30–93%), and perfusion imaging (2–96%). The Clinical Research Center for Stroke – 5th division registry documented that the current practice of acute stroke care in South Korea largely met the standard of guidelines, but variability of practice still remains. The registry would provide an opportunity to evaluate the quality of stroke care across South Korea and compare it with that of other countries.

MRI-based Algorithm for Acute Ischemic Stroke Subtype Classification

Background and Purpose In order to improve inter-rater reliability and minimize diagnosis of undetermined etiology for stroke subtype classification, using a stroke registry, we developed and implemented a magnetic resonance imaging (MRI)-based algorithm for acute ischemic stroke subtype classification (MAGIC). Methods We enrolled patients who experienced an acute ischemic stroke, were hospitalized in the 14 participating centers within 7 days of onset, and had relevant lesions on MR-diffusion weighted imaging (DWI). MAGIC was designed to reflect recent advances in stroke imaging and thrombolytic therapy. The inter-rater reliability was compared with and without MAGIC to classify the Trial of Org 10172 in Acute Stroke Treatment (TOAST) of each stroke patient. MAGIC was then applied to all stroke patients hospitalized since July 2011, and information about stroke subtypes, other clinical characteristics, and stroke recurrence was collected via a web-based registry database. Results The overall intra-class correlation coefficient (ICC) value was 0.43 (95% CI, 0.31-0.57) for MAGIC and 0.28 (95% CI, 0.18-0.42) for TOAST. Large artery atherosclerosis (LAA) was the most common cause of acute ischemic stroke (38.3%), followed by cardioembolism (CE, 22.8%), undetermined cause (UD, 22.2%), and small-vessel occlusion (SVO, 14.6%). One-year stroke recurrence rates were the highest for two or more UDs (11.80%), followed by LAA (7.30%), CE (5.60%), and SVO (2.50%). Conclusions Despite several limitations, this study shows that the MAGIC system is feasible and may be helpful to classify stroke subtype in the clinic.

Blood pressure variability and the development of early neurological deterioration following acute ischemic stroke

Objectives: Early neurological deterioration (END) is a common condition associated with poor outcome after acute ischemic stroke. We studied association between blood pressure (BP) variability and development of END. Methods: In this retrospective observational study, we studied a consecutive series of patients hospitalized for acute ischemic stroke within 24 h of onset. The primary outcome of interest was the development of END according to predefined criteria within the first 72 h of stroke onset. During this period, the mean, maximum (max), and minimum (min) values for the SBP and DBP were measured. The following parameters of BP variability were calculated for the SBP and DBP: the difference between the maximum and minimum (max−min), the SD, and the coefficient of variation. Results: Of the 1161 patients enrolled in the study (mean age, 67.5 ± 13.3 years; 59.6% men), 210 (18.1%) developed END. All of the BP variability parameters were linearly associated with END independent of mean BP and potential clinical variables (P values < 0.05 on likelihood ratio tests for trend), except for SBPmax−min. Among the other BP parameters, SBPmean, SBPmax, DBPmax, and DBPmin were independently associated with END. After adjustments for potential confounders, the odds for END increased 14–21% with each increase of one standard deviation in the BP variability parameter. Conclusion: BP variability is independently and linearly associated with the development of neurologic deterioration in acute stage of ischemic stroke.

Low-Versus Standard-Dose Alteplase for Ischemic Strokes Within 4.5 Hours A Comparative Effectiveness and Safety Study

Background and Purpose— The low-dose (0.6 mg/kg) alteplase strategy to treat acute ischemic stroke patients became widespread in East Asian countries, without rigorous testing against standard-dose (0.9 mg/kg) alteplase treatment. Our aim was to investigate the comparative effectiveness and safety of the low-dose versus standard-dose intravenous alteplase strategy. Methods— A total of 1526 acute ischemic stroke patients who qualified for intravenous alteplase and treated within 4.5 hours were identified from a prospective, multicenter, and nationwide stroke registry database. Primary outcomes were a modified Rankin scale score of 0 to 1 at 3 months after stroke and occurrence of symptomatic hemorrhagic transformation. Inverse probability of low-dose alteplase weighting by propensity scores was used to remove baseline imbalances between the 2 groups, and variation among centers were also accounted using generalized linear mixed models with a random intercept. Results— Low-dose intravenous alteplase was given to 450 patients (29.5%) and standard-dose intravenous alteplase to 1076 patients (70.5%). Low-dose alteplase treatment was comparable to standard-dose therapy according to the following adjusted outcomes and odds ratios (95% confidence intervals): modified Rankin scale score 0 to 1 at 3 months and 0.95 (0.68–1.32); modified Rankin scale 0 to 2 at 3 months and 0.84 (0.62–1.15); symptomatic hemorrhagic transformation and 1.05 (0.65–1.70); and 3-month mortality and 0.54 (0.35–0.83). The associations were unchanged when the analysis was limited to those without endovascular recanalization. Conclusions— The low-dose alteplase strategy was comparable to the standard-dose treatment in terms of the effectiveness and safety.

Trial of ORG 10172 in Acute Stroke Treatment (TOAST) Classification and Vascular Territory of Ischemic Stroke Lesions Diagnosed by Diffusion-Weighted Imaging

Background The association between the location and the mechanism of a stroke lesion remains unclear. A diffusion‐weighted imaging study may help resolve this lack of clarity. Methods and Results We studied a consecutive series of 2702 acute ischemic stroke patients whose stroke lesions were confirmed by diffusion‐weighted imaging and who underwent a thorough etiological investigation. The vascular territory in which an ischemic lesion was situated was identified using standard anatomic maps of the dominant arterial territories. Stroke subtype was based on the Trial of ORG 10172 in Acute Stroke Treatment, or TOAST, classification. Large‐artery atherosclerosis (37.3%) was the most common stroke subtype, and middle cerebral artery (49.6%) was the most frequently involved territory. Large‐artery atherosclerosis was the most common subtype for anterior cerebral, middle cerebral, vertebral, and anterior and posterior inferior cerebellar artery territory infarctions. Small vessel occlusion was the leading subtype in basilar and posterior cerebral artery territories. Cardioembolism was the leading cause in superior cerebellar artery territory. Compared with carotid territory stroke, vertebrobasilar territory stroke was more likely to be caused by small vessel occlusion (21.4% versus 30.1%, P<0.001) and less likely to be caused by cardioembolism (23.2% versus 13.8%, P<0.001). Multiple‐vascular‐territory infarction was frequently caused by cardioembolism (44.2%) in carotid territory and by large‐artery atherosclerosis (52.1%) in vertebrobasilar territory. Conclusions Information on vascular territory of a stroke lesion may be helpful in timely investigation and accurate diagnosis of stroke etiology.

Identifying Target Risk Factors Using Population Attributable Risks of Ischemic Stroke by Age and Sex

Background and Purpose Estimating age- and sex-specific population attributable risks (PARs) of major risk factors for stroke may be a useful strategy to identify risk factors for targeting preventive strategies. Methods For this case-control matched study, consecutive patients aged 18-90 years and admitted to nine nationwide hospitals with acute ischemic stroke between December 2008 and June 2010, were enrolled as cases. Controls, individually matched by age and sex, were chosen from the 4th Korean National Health & Nutrition Examination Survey (2008-2010). Based on odds ratios and prevalence, standardized according to the age and sex structure of the Korean population, PARs of major risk factors were estimated according to age (young, ≤ 45; middle-aged, 46-65; and elderly, ≥ 66 years) and sex subgroups. Results In 4,743 matched case-control sets, smoking (PAR, 45.1%) was the greatest contributing risk factor in young men, followed by hypertension (28.5%). In middle-aged men, the greatest contributing factors were smoking (37.4%), hypertension (22.7%), and diabetes (14.6%), whereas in women the greatest factors were hypertension (22.7%) and stroke history (10.6%). In the elderly, hypertension was the leading factor in men (23.7%) and women (23.4%). Other noticeable factors were stroke history (men, 19.7%; women, 17.3%) and diabetes (men, 12.5%; women, 15.1%). In young women, risk factors with a PAR greater than 10% were not found. Conclusions Smoking cessation in young people and hypertension and diabetes control in older people may be effective in reducing the burden of stroke on the population. In the elderly, secondary prevention could also be emphasized.

Gender differences in the age-stratified prevalence of risk factors in Korean ischemic stroke patients: a nationwide stroke registry-based cross-sectional study

Background Although ethnic or cultural differences affect prevalence of cardiovascular risk factors, limited information is available about the age- and gender-stratified prevalence of the risk factors in Asian stroke population. Aims and hypothesis We assessed gender- and age-stratified prevalences of major risk factors in Korean stroke patients, and assumed that the gender differences are attenuated by adjustment with lifestyle factors. Methods Using the nationwide hospital-based stroke registry, we identified 9417 ischemic stroke patients admitted between April 2008 and January 2011. Prevalence of hypertension, diabetes, hyperlipidemia, atrial fibrillation, prior stroke, and coronary heart disease was assessed in both genders by age groups. We analyzed gender differences of the prevalence among the age groups by calculating prevalence ratio, and further explored the influence of lifestyle factors on the gender difference in multivariable analyses. Results Hypertension and hyperlipidemia were more common in men until middle age, but after that more common in women, whereas diabetes was more common in women after 65 years of age. Atrial fibrillation increased steadily with age in both genders but was more common in women through all age groups. Prior stroke and coronary heart disease showed inconsistent gender differences. Gender differences in hypertension and diabetes among the age groups were attenuated by adjustment with accompanying risk factors including lifestyle factors. Conclusion Korean women with stroke had more hypertension and hyperlipidemia after middle age, more diabetes after 65 years, and more atrial fibrillation throughout all ages. Strategies to control risk factors in women at risk for stroke are eagerly needed.

Air pollution is associated with ischemic stroke via cardiogenic embolism

Background and Purpose— The aim of the study was to assessed the impact of short-term exposure to air pollution on ischemic stroke subtype, while focusing on stroke caused via cardioembolism. Methods— From a nationwide, multicenter, prospective, stroke registry database, 13 535 patients with acute ischemic stroke hospitalized to 12 participating centers were enrolled in this study. Data on the hourly concentrations of particulate matter <10 &mgr;m, nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and carbon monoxide (CO) were collected from 181 nationwide air pollution surveillance stations. The average values of these air pollutants over the 7 days before stroke onset from nearest air quality monitoring station in each patient were used to determine association with stroke subtype. The primary outcome was stroke subtype, including large artery atherosclerosis, small-vessel occlusion, cardioembolism, and stroke of other or undetermined cause. Results— Particulate matter <10 &mgr;m and SO2 concentrations were independently associated with an increased risk of cardioembolic stroke, as compared with large artery atherosclerosis and noncardioembolic stroke. In stratified analyses, the proportion of cases of cardioembolic stroke was positively correlated with the particulate matter <10 &mgr;m, NO2, and SO2 quintiles. Moreover, seasonal and geographic factors were related to an increased proportion of cardioembolic stroke, which may be attributed to the high levels of air pollution. Conclusions— Our findings suggest that the short-term exposure to air pollutants is associated with cardioembolic stroke, and greater care should be taken for those susceptible to cerebral embolism during peak pollution periods. Public and environmental health policies to reduce air pollution could help slow down global increasing trends of cardioembolic stroke.

Grading and Interpretation of White Matter Hyperintensities Using Statistical Maps

Background and Purpose— We aimed to generate rigorous graphical and statistical reference data based on volumetric measurements for assessing the relative severity of white matter hyperintensities (WMHs) in patients with stroke. Methods— We prospectively mapped WMHs from 2699 patients with first-ever ischemic stroke (mean age=66.8±13.0 years) enrolled consecutively from 11 nationwide stroke centers, from patient (fluid-attenuated-inversion-recovery) MRIs onto a standard brain template set. Using multivariable analyses, we assessed the impact of major (age/hypertension) and minor risk factors on WMH variability. Results— We have produced a large reference data library showing the location and quantity of WMHs as topographical frequency-volume maps. This easy-to-use graphical reference data set allows the quantitative estimation of the severity of WMH as a percentile rank score. For all patients (median age=69 years), multivariable analysis showed that age, hypertension, atrial fibrillation, and left ventricular hypertrophy were independently associated with increasing WMH (0–9.4%, median=0.6%, of the measured brain volume). For younger (⩽69) hypertensives (n=819), age and left ventricular hypertrophy were positively associated with WMH. For older (≥70) hypertensives (n=944), age and cholesterol had positive relationships with WMH, whereas diabetes mellitus, hyperlipidemia, and atrial fibrillation had negative relationships with WMH. For younger nonhypertensives (n=578), age and diabetes mellitus were positively related to WMH. For older nonhypertensives (n=328), only age was positively associated with WMH. Conclusions— We have generated a novel graphical WMH grading (Kim statistical WMH scoring) system, correlated to risk factors and adjusted for age/hypertension. Further studies are required to confirm whether the combined data set allows grading of WMH burden in individual patients and a tailored patient-specific interpretation in ischemic stroke-related clinical practice.