Stroke subtypes and risk factors in patients living in Southern Seoul, Korea: The impact of hypertension control on stroke subtypes.

Background and Purpose: The prevalence of hypertension (HT) does not explain the relatively high incidence of hemorrhagic stroke in Korea and other Asian countries, and whether HT has a greater impact on development of the intracerebral hemorrhage (ICH) than cerebral infarction (CI) remains unclear. It may be speculated that the adequacy of HT control is related to the subtype differences. The present study was aimed to elucidate (1) whether various risk factors exert a different impact on stroke subtypes and (2) whether the adequacy of HT control in patients with a previous history of HT is related to different subtypes in stroke patients from southern Seoul, Korea. Methods: We prospectively studied 602 consecutive patients with acute stroke (CI and ICH) admitted to the Asan Medical Center and analyzed their stroke subtypes and risk factors. The mode of HT treatment before the stroke onset was specifically asked. We examined whether various risk factors were related to subtype differences in these patients. We also attempted, in patients with a prior history of HT, to see whether the mode of HT control was related to the subtype differences. Results: 75.8% of the patients had CI (large vessel infarction 33.8%, small vessel infarction 22.1%) and 24.2% had ICH; 75% of the patients had HT of whom the presence of HT was previously unidentified in 8%. Previous treatment of HT was considered adequate in 32.4% and inadequate in the others. On multiple logistic analysis, diabetes mellitus and alcohol drinking were independently related to CI (v ICH), whereas HT did not favor any stroke subtypes. However, in patients with a prior history of HT, previous mode of HT control was a significant factor related to subtype differences in a way that inadequate treatment favored ICH. There were no specific risk factors that independently discriminate large vessel infarction versus small vessel infarction. Conclusions: Apparently, HT was not a risk factor that preferentially favors any specific stroke subtypes in patients from southern Seoul. However, in patients with HT, previous mode of HT control was an important factor influencing the subtypes. Inadequate treatment of HT may play a role, at least in part, on the relatively prevalent ICH and hence the greater significance of stroke as a cause of death in Korea compared with Western countries.     

Delirium in acute stroke: a preliminary study of the role of anticholinergic medications

The pathogenesis of delirium in acute stroke is incompletely understood. The use of medications with anticholinergic (ACH) activity is associated with an increased frequency of delirium. We hypothesized that the intake of medications with ACH activity is associated with delirium in acute stroke patients. Delirium was assessed using the DSM-IV-TR criteria and the Delirium Rating Scale, in a sample of consecutive patients with an acute (< or =4 days) cerebral infarct or intracerebral haemorrhage (ICH). We performed a gender and age matched case-control study. Twenty-two delirious stroke patients (cases) and 52 non-delirious patients (controls) were compared concerning the intake of ACH medications (i) before stroke, (ii) during hospitalization but before the assessment. The variables associated with delirium on bivariate analysis were entered in a stepwise logistic regression analysis. The final regression model (Nagelkerke R2 = 0.65) retained non-neuroleptics ACH medication during hospitalization (OR = 24.4; 95% CI = 2.18-250), medical complications (OR = 20.8; 95% CI = 3.46-125), ACH medication taken before stroke (OR = 17.5; 95% CI = 1.00-333.3) and ICH (OR = 16.9; 95% CI = 2.73-100) as independent predictors of delirium. This preliminary result indicates that drugs with subtle ACH activity play a role in the pathogeneses of delirium in acute stroke. Medication with ACH activity should be avoided in acute stroke patients.     

Ischemia-modified albumin in acute stroke

BACKGROUND: Ischemia-modified albumin (IMA)is a new biological marker of ischemia. Previous studies have found increased serum IMA levels after myocardial ischemia, but no study has investigated the possibility that stroke modifies IMA blood levels. MATERIALS AND METHODS: We studied 118 consecutive patients presenting within 3 h of the onset of an acute neurological deficit [84 brain infarctions (BI), 18 brain hemorrhages (ICH) and 16 transient ischemic attacks lasting less than 1 h or epileptic seizures]. Serum samples were obtained for all patients at initial presentation and repeated only in patients with stroke at 6, 12 and 24 h. IMA was measured by the albumin-cobalt-binding test (Ischemia Technologies, Denver, Colo., USA). RESULTS: The initial median IMA (bootstrap 95% confidence interval, CI) was 83 U/ml (79-86) and 86 U/ml (75-90) in patients with BI and ICH, respectively (p = 0.76), and was 73 U/ml (58-79) in others (p = 0.003 compared with BI, and p = 0.017 with ICH). Baseline IMA levels correlated with the National Institutes of Health Stroke Scale [Spearman correlation coefficient: 0.34 (p = 0.002) in BI, 0.61 (p = 0.008) in ICH]. During the first 24 h, IMA levels increased in BI patients (median, 9.1%; bootstrap 95% CI, 5.2-11.5), whereas no change was observed in ICH patients (median, 1.2%; bootstrap 95% CI, -7.8 to 6.8). CONCLUSIONS: IMA blood levels may be a biomarker for early identification of acute stroke. Further studies are required to investigate the role of IMA in the early detection of acute stroke.     

急性缺血性与出血性脑卒中危险因素的对比研究

目的 探讨各种危险因素在脑卒中患者中的构成比,并对脑梗死与脑出血的危险因素进行比较,为脑卒中防治提供依据.方法 收集1995-2002年福建医科大学附属第一医院急性脑卒中住院病例1875例,其中缺血性脑卒中1504例,出血性脑卒中371例;男1216例,女659例;平均年龄(73.42±10.35)岁,对两种脑卒中类型的多种危险因素进行描述性对比分析研究.结果 高血压、脉压增大是本组脑卒中患者突出的危险因素.相对于脑出血,与脑梗死相关更密切的危险因素依次是房颤(OR=3.942)、糖尿病(OR=3.674)、肥胖(OR=3.647)、高纤维蛋白原(OR=2.781)、高血压家族史(OR=2.573)、高LDL-C(OR=2.167)、高甘油三酯(OR=1.976)、吸烟(OR=1.849)、年龄增大(OR=1.588)、低Apo A(OR=1.460)(P＜0.05).相对脑梗死,仅高血压(OR=0.545)和饮酒(OR=0.662)与脑出血有更显著的相关性(P＜0.05).除共同危险因素外,高尿酸血症和低HDL-C血症与男性脑梗死关系更密切,而肥胖、高LDL-C及高纤维蛋白原血症与女性脑梗死相关性更强.结论 高血压、饮酒是脑出血患者主要的危险因素.相对于脑出血,与脑梗死相关密切的危险因素除了高血压外,依次为房颤、糖尿病、肥胖、高纤维蛋白原、高血压家族史、高LDL-C等.不同危险因素对男女脑梗死的影响不同.     

Polymorphisms at the osteoprotegerin and interleukin-6 genes in relation to first-ever stroke

BACKGROUND: Arterial calcification and osteoporosis often coexist, especially in postmenopausal women. Osteoporosis associates with a substantially increased risk of stroke in elderly women, suggesting that impaired estrogen signaling may link stroke and osteoporosis. Osteoprotegerin (OPG, TNFRSF11B) and interleukin-6 (IL-6, IL6) are putative target genes for estrogen signaling and have been implicated in both cardiovascular diseases and osteoporosis. We hypothesized that specific polymorphisms in these genes may be associated with increased risk of ischemic stroke or intracerebral hemorrhage (ICH). METHODS: We performed a population-based prospective nested case-control study, in which the relationships between polymorphisms (OPG-1181G/C, OPG-950T/C and IL6-174G/C) and ischemic stroke and ICH were examined. Definitive first-ever stroke events (n = 388), i.e. ischemic stroke (n = 320), ICH (n = 61) and unspecified stroke (n = 7) cases, and controls without cardiovascular disease (n = 773), matched for age, sex and geographical region were studied. Univariate and multivariate models using conditional logistic regression, which included traditional risk factors, were used to test for association. RESULTS: Carriers of the OPG-1181C/C genotype had a significantly (p = 0.018) increased risk of ICH (OR, 2.69; 95% CI, 1.19-6.12) in the univariate analysis. After adjustments (hypertension, diabetes, BMI and triglycerides), this genotype remained significantly (p = 0.005) associated with ICH (OR, 6.04; 95% CI, 1.71-21.29). By contrast, no correlations were found between this genotype and ischemic stroke, nor between the OPG-950T/C or IL6-174G/C polymorphisms and stroke subtypes. CONCLUSIONS: In this population, the OPG-1181C/C genotype associates with first-ever ICH, implying that alterations in OPG-mediated signaling in the vasculature may be involved in the pathophysiology of this disease.     

Cerebral hemorrhage after intra-arterial thrombolysis for ischemic stroke: the PROACT II trial.

OBJECTIVE: To analyze the frequency, clinical characteristics, and predictors of symptomatic intracerebral hemorrhage (ICH) after intraarterial (IA) thrombolysis with recombinant pro-urokinase (r-proUK) in acute ischemic stroke. METHOD: The authors conducted an exploratory analysis of symptomatic ICH from a randomized, controlled clinical trial of IA thrombolysis with r-proUK for patients with angiographically documented occlusion of the middle cerebral artery within 6 hours from stroke onset. Patients (n = 180) were randomized in a ratio of 2:1 to either 9 mg IA r-proUK over 120 minutes plus IV fixed-dose heparin or IV fixed-dose heparin alone. As opposed to intention to treat, this analysis was based on "treatment received" and includes 110 patients given r-proUK and 64 who did not receive any thrombolytic agent. The remaining six patients received out-of-protocol urokinase and were excluded from analysis. The authors analyzed centrally adjudicated ICH with associated neurologic deterioration (increase in NIH Stroke Scale [NIHSS] score of > or =4 points) within 36 hours of treatment initiation. RESULTS: Symptomatic ICH occurred in 12 of 110 patients (10.9%) treated with r-proUK and in two of 64 (3.1%) receiving heparin alone. ICH symptoms in r-proUK-treated patients occurred at a mean of 10.2 +/- 7.4 hours after the start of treatment. Mortality after symptomatic ICH was 83% (10/12 patients). Only blood glucose was significantly associated with symptomatic ICH in r-proUK-treated patients based on univariate analyses of 24 variables: patients with baseline glucose >200 mg/dL experienced a 36% risk of symptomatic ICH compared with 9% for those with < or =200 mg/dL (p = 0.022; relative risk, 4.2; 95% CI, 1.04 to 11.7). CONCLUSIONS: Symptomatic ICH after IA thrombolysis with r-proUK for acute ischemic stroke occurs early after treatment and has high mortality. The risk of symptomatic ICH may be increased in patients with a blood glucose >200 mg/dL at stroke onset.     

Family history of stroke in stroke types and subtypes

Many studies have provided data showing that family history of stroke (FHS) is associated with an increased risk of stroke. The association of the FHS with the various stroke subtypes has not been adequately studied. The purpose of this study was to assess the association of the FHS with the two major stroke types (cerebral haematomas and ischaemic strokes) and the four stroke subtypes (cardioembolic, large artery disease, small artery disease, and undetermined) in a Greek population.The FHS was obtained from 421 consecutive acute stroke patients and from 239 matched control subjects. Positive FHS was observed in 49% of all stroke patients compared with 28% of the control subjects [adjusted OR=2.06 (95% confidence intervals (CI) 1.42-3.00)]. Haematomas, ischaemic strokes, and from the ischaemic strokes, both large and small artery disease strokes were strongly associated with positive FHS compared with the control subjects [adjusted OR=2.06 (95% CI 9-3.04), 2.07 (95% CI 1.09-3.91), 2.05 (95% CI 1.24-3.38), and 2.76 (95% CI 1.55-4.91), respectively]. There was no difference between maternal and paternal heritable contribution.In conclusion, FHS was found in this study to be an independent risk factor for all strokes combined, for each stroke type, and for the large and small-artery disease stroke subtypes, but not for the cardioembolic and undetermined stroke subtypes.     

Abnormalities on ECG and telemetry predict stroke outcome at 3 months

BACKGROUND: ECG is a useful tool in monitoring vital functions in patients with acute stroke; however, fairly little evidence is available concerning the prevalence and the prognostic impact of ECG findings in patients with acute cerebral infarction and acute intracerebral haemorrhage (ICH). METHODS: This analysis was based on data from 692 patients with acute cerebral infarction, 155 patients with intracerebral haemorrhage (ICH), and 223 patients with transient ischaemic attack (TIA), who were admitted to hospital within 6 h of symptom onset. A 12 lead ECG was obtained on admission, and the patient was on telemetry for the first 12-24 h of hospitalisation. RESULTS: ECG abnormalities were observed in 60% of patients with cerebral infarction, 50% of patients with ICH, and 44% of patients with TIA. In multivariate analyses 3-month mortality in patients with ischaemic stroke was predicted by atrial fibrillation OR 2.0 (95% CI 1.3-3.1), atrio-ventricular block OR 1.9 (95% CI 1.2-3.9), ST-elevation OR (2.8, 95% CI 1.3-6.3), ST-depression OR 2.5 (95% CI 1.5-4.3), and inverted T-waves OR 2.7 (95% CI 1.6-4.6). This was independent of stroke severity, pre-stroke disability and age. In patients with ICH, sinus tachycardia OR 4.8 (95% CI 1.7-14.0), ST-depression OR 5.2 (95% CI 1.1-24.9), and inverted T-wave 5.2 (95% CI 1.2-22.5) predicted poor outcome. None of the changes reached significance in patients with TIA. In patients with severe cerebral infarction or ICH, heart rate did not decrease within the first 12 h after admission, which was the case in patients with mild to moderate stroke. Rapid heart rate predicted 3-month mortality in multivariate testing OR 1.7 (95% CI 1.02-2.7). CONCLUSIONS: ECG abnormalities are frequent in acute stroke and may predict 3-month mortality.     

Recurrent brain hemorrhage is more frequent than ischemic stroke after intracranial hemorrhage

OBJECTIVE: To characterize the rates of recurrent intracranial hemorrhage (ICH), ischemic stroke, and death in survivors of primary ICH. METHODS: Systematic review of studies reporting recurrent stroke in survivors of primary ICH, identified at index ICH and followed forward. Studies were identified by computerized search of the literature and review of reference lists. RESULTS: Ten studies published between 1982 and 2000 reporting 1,880 survivors of ICH, followed for a total of 6,326 patient-years (mean follow-up, 3.4 patient-years), were included. The aggregate rate of all stroke from five studies was 4.3% per patient-year (95% CI, 3.5% to 5.4%). The rate in the three population-based studies was higher than in the two hospital-based studies, 6.2% versus 4.0% per patient-year (p = 0.04). About three fourths of recurrent strokes were ICH. Considering all 10 studies, a total of 147 patients had a recurrent ICH, an aggregate rate of 2.3% per patient-year (95% CI, 1.9% to 2.7%). Based on data from four studies, patients with a primary lobar ICH had a higher rate of recurrent ICH than those with a deep, hemispheric ICH (4.4% versus 2.1% per patient-year; p = 0.002). The aggregate rates of subsequent ischemic stroke and mortality were 1.1% per patient-year (95% CI, 0.8% to 1.7%) and 8.8% per patient-year (95% CI, 5.2% to 11.0%). CONCLUSIONS: Recurrent stroke among survivors of primary ICH occurs at a rate of about 4% per patient-year, and most are recurrent ICH. Survivors of ICH have a higher risk of recurrent ICH than of ischemic stroke, and this has implications for the use of antithrombotic agents in these patients.     

Ischemic stroke subtypes : a population-based study of functional outcome, survival, and recurrence

BACKGROUND AND PURPOSE: There is scant population-based information on functional outcome, survival, and recurrence for ischemic stroke subtypes. METHODS: We identified all residents of Rochester, Minnesota, with a first ischemic stroke from 1985 through 1989 using the resources of the Rochester Epidemiology Project medical records linkage system. After reviewing medical records and imaging studies, we assigned patients to 4 major ischemic stroke categories based on National Institute of Neurological Diseases and Stroke Data Bank criteria: large-vessel cervical or intracranial atherosclerosis with stenosis (ATH, n=74), cardioembolic (CE, n=132), lacunar (LAC, n=72), and infarct of uncertain cause (IUC, n=164). We used the Rankin disability score to assess functional outcome and the Kaplan-Meier product-limit method and Cox proportional hazards regression analysis with bootstrap validation to estimate rates and identify predictors of survival and recurrent stroke among these patients. RESULTS: Rankin disabilities were different across stroke subtypes at the time of stroke and 3 months and 1 year later (P=0.001). LAC was associated with milder deficits compared with other subtypes. Mean follow-up among the 442 patients in the cohort was 3.2 years. Estimated rates of recurrent stroke at 30 days were significantly different (P<0.001): ATH, 18.5% (95% CI 9.4% to 27.5%); CE, 5.3% (95% CI 1.2% to 9.6%); LAC, 1.4% (95% CI 0.0% to 4.1%); and IUC, 3. 3% (95% CI 0.4% to 6.2%). After adjusting for age, sex, and stroke severity, infarct subtype was an independent determinant of recurrent stroke within 30 days (P=0.0006; eg, risk ratio for ATH compared with CE=3.3, 95% CI 1.2 to 9.3) but not long term (P=0.07). Four of 25 recurrent strokes within 30 days were procedure-related, each in patients with ATH. Five-year death rates were significantly different (P<0.001): ATH, 32.2% (95% CI 21.1% to 43.2%); CE, 80.4% (95% CI 73.1% to 87.6%); LAC, 35.1% (95% CI 23.6% to 46.0%); and IUC, 48.6% (95% CI 40.5% to 56.7%). With adjustment for age, sex, cardiac comorbidity, and stroke severity, the subtype of ischemic stroke was an independent determinant of long-term (P=0.018; eg, risk ratio for ATH compared with cardioembolic=0.47, 95% CI 0.29 to 0.77) but not 30-day survival (P=0.2). CONCLUSIONS: Early recurrence rates for ischemic stroke caused by ATH are higher than those for other subtypes and higher than previous non-population-based studies have reported. Some of the increased risk of early recurrence among patients with ATH may be iatrogenic. Patients with LAC have better poststroke functional status than those with other subtypes. Survival is poorest among those with ischemic stroke with a cardiac source of embolism.