Improvement in Delivery of Ischemic Stroke Treatments but Stagnation of Clinical Outcomes in Young Adults in South Korea.

BACKGROUND: There is limited information on the delivery of acute stroke therapies and secondary preventive measures and clinical outcomes over time in young adults with acute ischemic stroke. This study investigated whether advances in these treatments improved outcomes in this population. METHODS: Using a prospective multicenter stroke registry in Korea, young adults (aged 18-50 years) with acute ischemic stroke hospitalized between 2008 and 2019 were identified. The observation period was divided into 4 epochs: 2008 to 2010, 2011 to 2013, 2014 to 2016, and 2017 to 2019. Secular trends for patient characteristics, treatments, and outcomes were analyzed. RESULTS: A total of 7050 eligible patients (mean age, 43.1; men, 71.9%) were registered. The mean age decreased from 43.6 to 42.9 years (Ptrend=0.01). Current smoking decreased, whereas obesity increased. Other risk factors remained unchanged. Intravenous thrombolysis and mechanical thrombectomy rates increased over time from 2008 to 2010 to 2017 to 2019 (9.5%-13.8% and 3.2%-9.2%, respectively; Ptrend<0.01). Door-to-needle time improved (Ptrend <.001), but onset-to-door and door-to-puncture times remained constant. Secondary prevention, including dual antiplatelets for noncardioembolic minor stroke (26.7%-47.0%), direct oral anticoagulants for atrial fibrillation (0.0%-56.2%), and statins for large artery atherosclerosis (76.1%-95.3%) increased (Ptrend<0.01). Outcome data were available from 2011. One-year mortality (2.5% in 2011-2013 and 2.3% in 2017-2019) and 3-month modified Rankin Scale scores 0 to 1 (68.3%-69.1%) and 0 to 2 (87.6%-86.2%) remained unchanged. The 1-year stroke recurrence rate increased (4.1%-5.5%; Ptrend=0.04), although the difference was not significant after adjusting for sex and age. CONCLUSIONS: Improvements in the delivery of acute stroke treatments did not necessarily lead to better outcomes in young adults with acute ischemic stroke over the past decade, indicating a need for further progress.

Impact of prior use of antiplatelet agents and non-vitamin K antagonist oral anticoagulants on stroke outcomes among endovascular-treated patients with high pre-stroke CHA2DS2-VASc score.

BACKGROUND: We assessed the influence of prior non-vitamin K antagonist (NOAC) use on stroke outcomes after endovascular treatment (EVT) in patients at a high risk of stroke based on their pre-stroke CHA2DS2-VASc score, and compared them with those who did not use any antithrombotic (NAU) or antiplatelet (APT) agents. METHODS: Data were collected from a multicenter database comprising consecutive acute ischemic stroke patients who underwent EVT during a span of 103 months. We evaluated pre-stroke CHA2DS2-VASc scores in enrolled patients and measured instances of successful reperfusion and symptomatic hemorrhagic transformation (SHT) following EVT as the main outcome measures. RESULTS: Among 12 807 patients with acute ischemic stroke, 3765 (29.4%) had a history of atrial fibrillation. Of these, 418 patients with CHA2DS2-VASc scores ≥2 received EVT alone. The prior NOAC group showed higher successful reperfusion rates compared with the prior NAU and APT groups (p=0.04). Multivariate analysis revealed that prior NOAC use increased the likelihood of successful reperfusion after EVT (OR [95% CI] 2.54 [1.34 to 4.83], p=0.004) and improved stroke outcomes, while the prior APT group did not. Furthermore, the prior NOAC use group was not associated with SHT after EVT. Propensity score matching confirmed these findings. CONCLUSION: Prior use of NOAC is associated with improved outcomes in high-risk stroke patients (pre-stroke CHA2DS2-VASc score ≥2) undergoing EVT.

Prevalence of Mutations in Mendelian Stroke Genes in Early Onset Stroke Patients.

OBJECTIVE: Heritability of stroke is assumed not to be low, especially in the young stroke population. However, most genetic studies have been performed in highly selected patients with typical clinical or neuroimaging characteristics. We investigated the prevalence of 15 Mendelian stroke genes and explored the relationships between variants and the clinical and neuroimaging characteristics in a large, unselected, young stroke population. METHODS: We enrolled patients aged ≤55 years with stroke or transient ischemic attack from a prospective, nationwide, multicenter stroke registry. We identified clinically relevant genetic variants (CRGVs) in 15 Mendelian stroke genes (GLA, NOTCH3, HTRA1, RNF213, ACVRL1, ENG, CBS, TREX1, ABCC6, COL4A1, FBN1, NF1, COL3A1, MT-TL1, and APP) using a customized, targeted next generation sequencing panel. RESULTS: Among 1,033 patients, 131 (12.7%) had 28 CRGVs, most frequently in RNF213 (n = 59), followed by ABCC6 (n = 53) and NOTCH3 (n = 15). The frequency of CRGVs differed by ischemic stroke subtypes (p < 0.01): the highest in other determined etiology (20.1%), followed by large artery atherosclerosis (13.6%). It also differed between patients aged ≤35 years and those aged 51 to 55 years (17.1% vs 9.3%, p = 0.02). Only 27.1% and 26.7% of patients with RNF213 and NOTCH3 variants had typical neuroimaging features of the corresponding disorders, respectively. Variants of uncertain significance (VUSs) were found in 15.4% patients. INTERPRETATION: CRGVs in 15 Mendelian stroke genes may not be uncommon in the young stroke population. The majority of patients with CRGVs did not have typical features of the corresponding monogenic disorders. Clinical implications of having CRGVs or VUSs should be explored. ANN NEUROL 2023;93:768-782.

Frequency, management, and outcomes of early neurologic deterioration due to stroke progression or recurrence.

OBJECTIVE: The frequency, management, and outcomes of early neurologic deterioration (END) after ischemic stroke specifically due to stroke progression or stroke recurrence have not been well delineated. MATERIALS AND METHODS: In a multicenter, nationwide registry, data on END due to stroke progression or recurrence confirmed by imaging were collected prospectively between January 2019 and July 2020. Patient characteristics, management strategies, and clinical outcomes were analyzed. RESULTS: Among 14,828 consecutive ischemic stroke patients, 1717 (11.6%) experienced END, including 1221 (8.2%) with END due to stroke progression (SP) or stroke recurrence (SR). Active management after END was implemented in 64.2% of patients. Active management strategies included volume expansion (29.2%), change in antithrombotic regimen (26.1%), induced hypertension (8.6%), rescue reperfusion therapy (6.8%), intracranial pressure lowering with hyperosmolar agents (1.5%), bypass surgery (0.6%), and hypothermia (0.1%). Active management strategies that varied with patient features included volume expansion and induced hypertension, used more often in large artery atherosclerosis and small vessel occlusion, and rescue endovascular thrombectomy, more common in other (dissection), cardioembolism, and large artery atherosclerosis. Active management was associated with higher rates of freedom from disability (modified Rankin Scale, mRS, 0-1; 24.3% vs. 16.6%) and functional independence (mRS, 0-2; 41.6% vs. 27.7%) at 3 months. CONCLUSION: END specifically due to stroke progression or recurrence occurs in 1 in 12 acute ischemic stroke patients. In this observational study, active management, undertaken in two-thirds of patients, was most often hemodynamic or antithrombotic and was associated with improved functional outcomes.

Associations between migraine and major cardiovascular events in type 2 diabetes mellitus.

BACKGROUND: Migraine is one of the most common primary headache disorders and a well-known risk factor for cardiovascular disorders. We aimed to investigate the association between migraine and major cardiovascular outcomes, including myocardial infarction (MI), ischemic stroke (IS), and cardiovascular death (CVD) in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 2,229,598 people from the nationwide Korean National Health Insurance Service database with type 2 diabetes but without a previous history of MI and IS were included in this study. We identified patients over 20 years of age with migraine using the claim data of International Statistical Classification of Diseases Related Health Problems, Tenth Revision (ICD-10) code G43. The patients with migraine were divided according to their migraine aura status. RESULTS: Migraine was present in 6.3% of the study population. Cases observed for MI, IS, CVD, and all-cause death were 2.6%, 3.6%, 5.9%, and 7.9%, respectively. The diagnosis of migraine was significantly associated with an increased risk of MI, IS, and CVD. The results remained significant after adjusting for covariates, including age, sex, body mass index, alcohol intake, smoking habits, physical activity, economic status, hypertension history, dyslipidemia, and duration of type 2 diabetes (MI, adjusted hazard ratio [aHR]: 1.182, 95% confidence interval [CI]: 1.146-1.219; IS, aHR: 1.111, 95% CI 1.082-1.14; CVD, aHR: 1.143, 95% CI 1.12-1.167). In particular, the presence of aura was associated with a higher risk of MI development compared to the non-aura group. The difference became more prominent with progressing age. CONCLUSIONS: In this nationwide population-based study, people with type 2 diabetes and migraines were found to be at a significantly higher risk for major cardiovascular events, including MI, IS, and CVD. The risk of MI and CVD significantly increased with the presence of aura symptoms among patients with migraine.

Risk of dementia according to the smoking habit change after ischemic stroke: a nationwide population-based cohort study.

There is a paucity of research regarding the association between the risk of incident dementia and changes in smoking habits in the acute ischemic stroke population. We aimed to investigate the effects of smoking habit change on the risk of incident dementia in an ischemic stroke population using data from the Korean National Health Insurance Services Database. This nationwide population-based cohort study included 197,853 patients with ischemic stroke. The patients were divided into never smokers, former smokers, smoking quitters, sustained smokers, and new smokers, based on the 2-year change in smoking status between the two consecutive health examinations before and after the index stroke. The patients were followed up from the index date to 2018 to assess the development of dementia. Dementia was further categorized into Alzheimer's, vascular, and other types of dementia according to the International Classification of Diseases, Tenth Revision diagnosis. Multivariable Cox proportional hazards models were used to assess the association between changes in smoking habits and the risk of dementia. After a median of 4.04 years of follow-up, 19,595 (9.9%) dementia cases were observed. Among them, 15,189 (7.7%) were diagnosed with Alzheimer's disease dementia and 2719 (1.4%) were diagnosed with vascular dementia. After adjusting for covariates, including age, sex, alcohol intake habits, cigarette pack-year, regular physical activity, income, history of hypertension, diabetes mellitus, dyslipidemia, and chronic kidney disease, new smokers, sustained smokers, and smoking quitters were significantly associated with a higher risk of all-cause dementia than never smokers (adjusted hazard ratio [aHR] 1.395, 95% confidence interval [CI] 1.254-1.552; aHR 1.324, 95% CI 1.236-1.418; and aHR 1.170, 95% CI 1.074-1.275, respectively). Similar trends were observed for both Alzheimer's dementia and vascular dementia, but the association between new smokers and vascular dementia was not significant. The impact of smoking habit change was more prominent in the 40-65-year-old group. New and sustained smokers had a substantially higher risk of incident dementia after ischemic stroke than never smokers. Smoking quitters also had an elevated risk of incident dementia, but the detrimental effects were lower than those in new and sustained smokers.

Stroke of Other Determined Etiology: Results From the Nationwide Multicenter Stroke Registry.

BACKGROUND: Stroke of other determined etiology (OE) includes patients with an uncommon cause of stroke. We described the general characteristics, management, and outcomes of stroke in OE and its subgroups. METHODS: This study is a retrospective analysis of a prospective, multicenter, nationwide registry, the Clinical Research Center for Stroke-Korea-National Institutes of Health registry. We classified OE strokes into 10 subgroups according to the literature and their properties. Each OE subgroup was compared according to clinical characteristics, sex, age strata, lesion locations, and management. Moreover, 1-year composites of stroke and all-cause mortality were investigated according to the OE subgroups. RESULTS: In total, 2119 patients with ischemic stroke with OE types (mean age, 55.6±16.2 years; male, 58%) were analyzed. In the Clinical Research Center for Stroke-Korea-National Institutes of Health registry, patients with OE accounted for 2.8% of all patients with stroke. The most common subtypes were arterial dissection (39.1%), cancer-related coagulopathy (17.3%), and intrinsic diseases of the arterial wall (16.7%). Overall, strokes of OE were more common in men than in women (58% versus 42%). Arterial dissection, intrinsic diseases of the arterial wall and stroke associated with migraine and drugs were more likely to occur at a young age, while disorders of platelets and the hemostatic system, cancer-related coagulopathy, infectious diseases, and hypoperfusion syndromes were more frequent at an old age. The composite of stroke and all-cause mortality within 1 year most frequently occurred in cancer-related coagulopathy, with an event rate of 71.8%, but least frequently occurred in stroke associated with migraine and drugs and arterial dissection, with event rates of 0% and 7.2%, respectively. CONCLUSIONS: This study presents the different characteristics, demographic findings, lesion locations, and outcomes of OE and its subtypes. It is characterized by a high proportion of arterial dissection, high mortality risk in cancer-related coagulopathy and an increasing annual frequency of cancer-related coagulopathy in patients with stroke of OE.

Association of ischemic stroke onset time with presenting severity, acute progression, and long-term outcome: A cohort study.

BACKGROUND: Preclinical data suggest circadian variation in ischemic stroke progression, with more active cell death and infarct growth in rodent models with inactive phase (daytime) than active phase (nighttime) stroke onset. We aimed to examine the association of stroke onset time with presenting severity, early neurological deterioration (END), and long-term functional outcome in human ischemic stroke. METHODS AND FINDINGS: In a Korean nationwide multicenter observational cohort study from May 2011 to July 2020, we assessed circadian effects on initial stroke severity (National Institutes of Health Stroke Scale [NIHSS] score at admission), END, and favorable functional outcome (3-month modified Rankin Scale [mRS] score 0 to 2 versus 3 to 6). We included 17,461 consecutive patients with witnessed ischemic stroke within 6 hours of onset. Stroke onset time was divided into 2 groups (day-onset [06:00 to 18:00] versus night-onset [18:00 to 06:00]) and into 6 groups by 4-hour intervals. We used mixed-effects ordered or logistic regression models while accounting for clustering by hospitals. Mean age was 66.9 (SD 13.4) years, and 6,900 (39.5%) were women. END occurred in 2,219 (12.7%) patients. After adjusting for covariates including age, sex, previous stroke, prestroke mRS score, admission NIHSS score, hypertension, diabetes, hyperlipidemia, smoking, atrial fibrillation, prestroke antiplatelet use, prestroke statin use, revascularization, season of stroke onset, and time from onset to hospital arrival, night-onset stroke was more prone to END (adjusted incidence 14.4% versus 12.8%, p = 0.006) and had a lower likelihood of favorable outcome (adjusted odds ratio, 0.88 [95% CI, 0.79 to 0.98]; p = 0.03) compared with day-onset stroke. When stroke onset times were grouped by 4-hour intervals, a monotonic gradient in presenting NIHSS score was noted, rising from a nadir in 06:00 to 10:00 to a peak in 02:00 to 06:00. The 18:00 to 22:00 and 22:00 to 02:00 onset stroke patients were more likely to experience END than the 06:00 to 10:00 onset stroke patients. At 3 months, there was a monotonic gradient in the rate of favorable functional outcome, falling from a peak at 06:00 to 10:00 to a nadir at 22:00 to 02:00. Study limitations include the lack of information on sleep disorders and patient work/activity schedules. CONCLUSIONS: Night-onset strokes, compared with day-onset strokes, are associated with higher presenting neurologic severity, more frequent END, and worse 3-month functional outcome. These findings suggest that circadian time of onset is an important additional variable for inclusion in epidemiologic natural history studies and in treatment trials of neuroprotective and reperfusion agents for acute ischemic stroke.

In-Hospital and Post-Discharge Recovery after Acute Ischemic Stroke: a Nationwide Multicenter Stroke Registry-base Study.

BACKGROUND: Using data from a large national stroke registry, we aimed to investigate the incidence and determinants of in-hospital and post-discharge recovery after acute ischemic stroke and the independence of their occurrence. METHODS: In-hospital recovery was defined as an improvement of 4 points or > 40% in the National Institutes of Health Stroke Scale (NIHSS) score from admission to discharge. Post-discharge recovery was defined as any improvement in the modified Rankin Scale (mRS) score from discharge to 3 months after stroke onset. Two analytic methods (multivariate and multivariable logistic regression) were applied to compare the effects of 18 known determinants of 3-month outcome and to verify whether in-hospital and post-discharge recovery occur independently. RESULTS: During 54 months, 11,088 patients with acute ischemic stroke meeting the eligibility criteria were identified. In-hospital and post-discharge recovery occurred in 36% and 33% of patients, respectively. Multivariate logistic regression with an equality test for odds ratios showed that 7 determinants (age, onset-to-admission time, NIHSS score at admission, blood glucose at admission, systolic blood pressure, smoking, recanalization therapy) had a differential effect on in-hospital and post-discharge recovery in the way of the opposite direction or of the same direction with different degree (all P values < 0.05). Both in-hospital and post-discharge recovery occurred in 12% of the study population and neither of them in 43%. The incidence of post-discharge recovery in those with in-hospital recovery was similar to that in those without (33.8% vs. 32.7%, respectively), but multivariable analysis showed that these 2 types of recovery occurred independently. CONCLUSION: Our findings suggest that, in patients with acute ischemic stroke, in-hospital and post-discharge recovery may occur independently and largely in response to different factors.

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.

Smoking is Not a Good Prognostic Factor following First-Ever Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: There is evidence that smoking increases stroke risk; however, the effect of smoking on functional outcome after stroke is unclear. The aim of this study was to explore the effect of smoking status on outcome following acute ischemic stroke. METHODS: We assessed 1,117 patients with first-ever acute cerebral infarction and no prestroke disability whose functional outcome was measured after three months. A poor outcome was defined as a modified Rankin Scale score of ≥2. Smoking within one month prior to admission was defined as current smoking. Our analysis included demographics, vascular risk factors, initial National Institutes of Health Stroke Scale (NIHSS) score, stroke subtype, onset-to-admission time, thrombolytic therapy, initial blood pressure, and prognostic blood parameters as covariates. RESULTS: At baseline, current smokers were predominantly male, approximately 10 years younger than non-smokers (mean age, 58.6 vs. 68.3 years), and less likely to have hypertension and atrial fibrillation (53.9% vs. 65.4% and 8.7% vs. 25.9%, respectively), with a lower mean NIHSS score (4.6 vs. 5.7). The univariate analyses revealed that current smokers had a better functional outcome and significantly fewer deaths at three months follow-up when compared with non-smokers (functional outcome: 64.0% vs. 58.4%, P=0.082; deaths: 3.0% vs. 8.4%, P=0.001); however, these effects disappeared after adjusting for covariates (P=0.168 and P=0.627, respectively). CONCLUSIONS: In this study, smoking was not associated with a good functional outcome, which does not support the paradoxical benefit of smoking on functional outcome following acute ischemic stroke.

Clinical practice guidelines for the medical and surgical management of primary intracerebral hemorrhage in Korea.

The purpose of this clinical practice guideline (CPG) is to provide current and comprehensive recommendations for the medical and surgical management of primary intracerebral hemorrhage (ICH). Since the release of the first Korean CPGs for stroke, evidence has been accumulated in the management of ICH, such as intracranial pressure control and minimally invasive surgery, and it needs to be reflected in the updated version. The Quality Control Committee at the Korean Society of cerebrovascular Surgeons and the Writing Group at the Clinical Research Center for Stroke (CRCS) systematically reviewed relevant literature and major published guidelines between June 2007 and June 2013. Based on the published evidence, recommendations were synthesized, and the level of evidence and the grade of the recommendation were determined using the methods adapted from CRCS. A draft guideline was scrutinized by expert peer reviewers and also discussed at an expert consensus meeting until final agreement was achieved. CPGs based on scientific evidence are presented for the medical and surgical management of patients presenting with primary ICH. This CPG describes the current pertinent recommendations and suggests Korean recommendations for the medical and surgical management of a patient with primary ICH.

Internet-based control recruitment for a case-control study of major risk factors for stroke in Korea: lessons from the experience.

BACKGROUND: This study aimed to estimate the population-attributable risks (PARs) of 9 major risk factors for stroke in Korea through a case-control study and to test the feasibility and validity of internet-based control recruitment. METHODS: From April 2008 to September 2009, controls were enrolled via internet after providing consent for participation through a web-based survey. The cases included patients who were admitted to the participating centers due to acute stroke or transient ischemic attack within 7 days of onset during the study period. Each control was age- and sex-matched with 2 cases. Adjusted odd ratios, age-standardized prevalence, and PARs were estimated for the 9 major risk factors using the prevalence of risk factors in the control group and the age and sex characteristics from Korea's national census data. RESULTS: In total, 1041 controls were matched to 2082 stroke cases. Because of a shortage of elderly controls in the internet-based recruitment, 248 controls were recruited off-line. The PARs were 23.44%, 10.95%, 51.32%, and 6.35% for hypertension, diabetes, smoking, and stroke history, respectively. Hypercholesterolemia, atrial fibrillation, obesity, coronary heart disease, and a family history of stroke were not associated with stroke. Comparison with education and religion of the control group with that mentioned in the national census data showed a notable difference. CONCLUSIONS: The study results imply that internet-based control recruitment for a case-control study requires careful selection of risk factors with high self-awareness and effective strategies to facilitate the recruitment of elderly participants.

Stroke statistics in Korea: part I. Epidemiology and risk factors: a report from the korean stroke society and clinical research center for stroke.

The aim of the Part I of Stroke Statistics in Korea is to summarize nationally representative data of the epidemiology and risk factors of stroke in a single document. Every year, approximately 105,000 people experience a new or recurrent stroke and more than 26,000 die of stroke, which indicates that every 5 minutes stroke attacks someone and every 20 minutes stroke kills someone in Korea. Stroke accounts for roughly 1 of every 10 deaths. The estimated stroke prevalence is about 795,000 in people aged ≥30 years. The nationwide total cost for stroke care was 3,737 billion Korean won (US$3.3 billion) in 2005. Fortunately, the annual stroke mortality rate decreased substantially by 28.3% during the first decade of the 21th century (53.2/100,000 in 2010). Among OECD countries, Korea had the lowest in-hospital 30-day case-fatality rate for ischemic stroke and ranked third lowest for hemorrhagic stroke in 2009. The proportion of ischemic stroke has steadily increased and accounted for 76% of all strokes in 2009. According to hospital registry studies, the 90-day mortality rate was 3-7% for ischemic stroke and 17% for intracerebral hemorrhage. For risk factors, among Korean adults ≥30 years of age, one in 3-4 has hypertension, one in 10 diabetes, and one in 7 hypercholesterolemia. One in 3 Korean adults ≥19 years of age is obese. Over the last 10 years, the prevalence of hypertension slightly decreased, but the prevalence of diabetes, hypercholesterolemia, and obesity increased. Smoking prevalence in men has decreased, but is still as high as 48%. This report could be a valuable resource for establishing health care policy and guiding future research directions.

Secular trends in ischemic stroke characteristics in a rapidly developed country: results from the Korean Stroke Registry Study (secular trends in Korean stroke).

BACKGROUND: A dynamic change in industry, lifestyle, and healthcare structure brings a corresponding change in disease patterns. Limited data exist with respect to secular trends in stroke epidemiology in Korea, a rapidly developed country. METHODS AND RESULTS: We analyzed individual patient data registered the Korean Stroke Registry, a nationwide hospital-based stroke database, between January 2002 and November 2010. Mortality data were obtained from a national death certificate system. Linear or logistic regression analyses were performed to assess secular trends. A total of 46 098 patients were included in this study. Mean ± SD age was 66.1 ± 12.3 years, and 57.6% of the patients were men. Over the 9-year period, patient ages steadily increased by 0.24 year annually (P<0.001). Risk factor proportions of hypertension, diabetes, smoking, and prior stroke declined slightly (P<0.05 for all). However, dyslipidemia frequency showed a complex pattern of an initial decline and then an increase. For relative proportions of subtypes, cardioembolism increased, small vessel occlusion decreased, and large artery atherosclerosis remained stable. Still, intracranial stenosis overwhelms extracranial stenosis, but extracranial stenosis is on the rise. Arrival within 3 hours increased from 20% to 29%, and reperfusion therapy increased from 5.3% to 7.0%. Age-adjusted all-cause mortality did not decrease at 30 days but decreased at 1 year over time. CONCLUSIONS: During the first decade of 21st century, stroke characteristics in Korea changed, likely because of increased lifespan, westernized lifestyle, and improved public awareness. Stroke experts need to cope with these distinguishing trends to establish a better strategy for prevention and acute therapy.

Nonaspirin nonsteroidal anti-inflammatory drugs and hemorrhagic stroke risk: the Acute Brain Bleeding Analysis study.

BACKGROUND AND PURPOSE: The relationship between nonaspirin nonsteroidal anti-inflammatory drugs (NANSAIDs) and hemorrhagic stroke (HS) remains unclear. We examined the risk of HS associated with the use of NANSAIDs in Koreans. METHODS: We performed a nationwide, multicenter case-control study from 2002 to 2004. This study included 940 nontraumatic acute HS cases in patients aged 30 to 84 years, with an absence of a history of stroke or hemorrhage-prone brain lesions, alongside 940 community controls, matched to each case by age and sex. Pretrained interviewers obtained information on prescription drugs as well as over-the-counter drugs taken within 14 days before the onset of stroke. We adjusted potential confounders, including family histories of stroke, histories of hypertension, smoking, alcohol consumption, high salt intake, and laborious work hours. The adjusted ORs and their 95% CIs were calculated by conditional logistic regression. RESULTS: The proportion of NANSAIDs exposure within 14 days was 2.9% for HS patients and 2.0% for the controls. The adjusted odds ratios of stroke in NANSAIDs users compared with nonusers was 1.12 (95% CI, 0.77 to 1.65) for all HS, 1.03 (95% CI, 0.49 to 2.18) for subarachnoid hemorrhage, and 1.19 (95% CI, 0.76 to 1.87) for intracerebral hemorrhage. CONCLUSIONS: No increased risk of HS either subarachnoid hemorrhage or intracerebral hemorrhage was found among NANSAIDs users.

Klotho is a genetic risk factor for ischemic stroke caused by cardioembolism in Korean females.

An aging-suppressor gene, klotho, is a candidate factor for vascular disease because its deficiency leads to impaired endothelium-dependent vasodilation and impaired angiogenesis. We investigated the association of polymorphisms in klotho with ischemic stroke. We searched for sequence variants in promoter and exons of klotho gene. For the association study, selected variants were genotyped in control subjects and in patients with ischemic stroke and vascular dementia. The association with ischemic stroke was further investigated with its subtypes classified based on Trial of Org 10172 in Acute Stroke Treatment (TOAST). No significant association was observed for both G-395A and C1818T with ischemic stroke and vascular dementia (P>0.05). The analysis with subtypes of ischemic stroke revealed the associations that the A allele of G-395A increased the risk of cardioembolic stroke (CE, OR=2.60; P=0.006), and subjects carrying the A allele were susceptible to CE in both of dominant (AA+GA versus GG; OR=2.50; P=0.046) and recessive (AA versus GA+GG; OR=6.52; P=0.007) models. Further analysis of data partitioned by gender showed that the associations of G-395A with CE only existed in women (A versus G; OR=4.33; P=0.002), AA+GA versus GG; OR=5.68; P=0.014, and AA versus GA+GG; OR=9.07; P=0.012), but the significance disappeared in men (P>0.05). The sequence variant of G-395A in klotho might be a genetic risk factor for CE in females.

The Hallym Stroke Registry: a web-based stroke data bank with an analysis of 1,654 consecutive patients with acute stroke.

OBJECTIVES: In Korea, stroke ranks as one of the leading causes of death along with cancer and ischemic heart disease. The purpose of this study was to better understand clinical characteristics, risk factors and subtypes of acute stroke among Korean people. METHOD: 1,654 acute stroke patients within 7 days of onset were consecutively enrolled in the Hallym Stroke Registry (HSR). The study was a prospective hospital-based registry aided with a web-based, computerized data bank system. The project began in January 1996 and the data obtained until September 2002 were analyzed. The analysis was basically carried out regarding demographic features, risk factors, time elapsed before coming to the hospitals after the symptom onset, duration of hospitalization, and 30-day mortality rate. RESULTS: 1,567 patients had ischemic stroke and 87 patients had hemorrhagic stroke. The mean age of the patients was 63.6 +/- 11.8 years, and 815 patients (56.8%) were men. The estimated time interval between stroke onset and hospital visit was 1.3 days on average and the mean duration of hospital stay was 12.1 days. Only a small fraction (12%) of patients reached the hospital within 3 h after the symptom onset. As for the risk factors, hypertension topped for both ischemic and hemorrhagic strokes followed by smoking and prior history of stroke, diabetes, hyperlipidemia and cardioembolism. With respect to subtype classification of ischemic stroke, large-artery atherosclerosis was most frequent (42.0%), followed by small-vessel occlusion (31.0%), cardioembolism (8.7%), other determined etiology (1.9%), and undetermined etiology (16.4%). The 30-day mortality rate was 7.2%. CONCLUSION: In the HSR, demographic features were essentially comparable with other major registries. However, the data analysis varies from registry to registry. This may in part be due to a different study design, racial-ethnic differences and patient selection methods.