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Background and Purposes: Until now, limited data are available about the potential effect of coexisting small vessel disease (SVD) on the long-term outcome of stroke patients with intracranial large artery atherosclerosis (ILAA). Methods: A prospective study was performed on 293 patients with symptomatic ILAA, who were divided into 4 groups (group I, single intracranial large artery atherosclerosis (SILAA) without SVD; group II, multiple intracranial large arteries atherosclerosis (MILAA) without SVD; group III, SILAA with SVD; group IV, MILAA with SVD) and followed up for recurrent stroke or death. Results: The 3-year cumulative risks of recurrent stroke were 18% for SILAA without SVD, 38% for MILAA without SVD, 21% for SILAA with SVD and 34% for MILAA with SVD. The 3-year cumulative risks of death were 6, 7, 20 and 22%, respectively. Compared with SILAA without SVD, more recurrent stroke occurred in MILAA without SVD (log-rank 3.83; p = 0.050) and MILAA with SVD (log-rank 7.79; p = 0.014), and the higher risk of death (log-rank 9.472; p = 0.002) was found in group MILAA with SVD. A Cox proportional-hazards regression model showed that MILAA with SVD may be a predictor of recurrent stroke (hazard ratio 2.001; 95% CI 1.108-3.934; p = 0.044), and a borderline predictor for death (hazard ratio 3.180; 95% CI 0.895-10.987; p = 0.073). Conclusion: Coexisting SVD is very common and may predict poor outcome in stroke patients with symptomatic ILAA. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and Purpose: The purpose of this study was to evaluate the effect of metabolic syndrome on ischemic stroke in Chinese subjects with type 2 diabetes. Methods: Anthropometric parameters (waist circumference and body mass index), blood pressure, and plasma biochemical (lipid and glycemic profiles) were collected. Subjects with type 2 diabetes were categorized by the criteria of the updated Adult Treatment Panel III (ATP III) with the modified definitions of obesity in Asians. Transcranial Doppler was performed to define middle cerebral artery stenosis. Results: Of 2,197 patients (age 55.4 ± 11.3 years; male 40.8%; median follow-up period 8.7 years, interquartile range 7.8–9.5 years) without symptoms of cerebrovascular disease, evidence of middle cerebral artery stenosis was identified in 272 subjects (12.4%). According to NCEP ATP III criteria, 1,324 (60.3%) patients had MetS at baseline. Ischemic stroke occurred in 184 (8.4%, 184/2197) patients during follow-up. Patients with incident stroke had a higher prevalence of MetS compared with those without stroke (p = 0.004), and the number of components of MetS was also significantly increased in patients with stroke (p = 0.001). Cox regression demonstrated that MetS was not associated with incident stroke. Conclusions: In Chinese type 2 diabetic patients, metabolic syndrome does affect stroke occurrence with a higher stroke incidence among those with metabolic syndrome, but stroke occurrence seems to be better explained by other vascular risk factors than by metabolic syndrome. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Subclinical brain infarct (SBI) is associated with subsequent stroke and cognitive decline. A longitudinal epidemiological study suggests that statins may prevent development of SBI. We investigated the effects of statins upon development of brain infarct by performing a post-hoc analysis of the Regression of Cerebral Artery Stenosis (ROCAS) study. Methods: The ROCAS study is a randomized, double-blind, placebo-controlled study evaluating the effects of simvastatin 20 mg daily upon progression of asymptomatic middle cerebral artery stenosis among stroke-free individuals over 2 years. A total of 227 subjects were randomized to either placebo (n = 114) or simvastatin 20 mg daily (n = 113). The number of brain infarcts as detected by MRI was recorded at baseline and at the end of the study. The primary outcome measure was the number of new brain infarcts at the end of the study. Results: Among the 227 randomized subjects, 33 (14.5%) had SBI at baseline. At the end of the study, significantly fewer subjects in the active group (n = 1) had new brain infarcts compared with the placebo group (n = 8; p = 0.018). The new brain infarcts of subjects in the active group were subclinical. Among the placebo group, the new brain infarcts of 3 subjects were symptomatic while those of the remaining 5 subjects were subclinical. Among putative variables, multivariate regression analysis showed that only the baseline number of SBIs (OR = 6.27, 95% CI 2.4–16.5) and simvastatin treatment (OR = 0.09, 95% CI 0.01–0.82) independently predicted the development of new brain infarcts. Conclusions: Consistent with findings of the epidemiological study, our study suggests that statins may prevent the development of a new brain infarct. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The progression of cerebral atherosclerosis increases the risk of stroke and vascular events. Given the known benefits of statins in retarding coronary and carotid atherosclerosis progression, we studied the effects of statins on asymptomatic middle cerebral artery (MCA) stenosis progression. Methods: We conducted a randomized, double-blind, placebo-controlled study to evaluate the effects of simvastatin on the progression of MCA stenosis among stroke-free individuals who had mild to moderately elevated LDL cholesterol (3.0–5.0 mmol/l). Two hundred and twenty-seven subjects were randomized to either placebo (n = 114) or simvastatin 20 mg daily (n = 113). The severity of MCA stenosis at baseline and at the end of the study was graded by MRA into normal, minimal (<10%), mild (10–49%), moderate (50–90%) and severe (>90%). The primary outcome was the change in grading of MCA stenosis over 2 years. Results: At the end of the study, the LDL cholesterol level decreased by 1.43 and 0.12 mmol/l for the active and placebo groups, respectively (p < 0.001). There was no significant difference in the proportion of patients having stable, progressive and regressive MCA stenosis between the placebo (72, 22 and 6%) and active groups (78.6, 15.5 and 5.8%). The all-cause mortality was significantly lower in the active group (n = 0) relative to the placebo group (n = 7, p = 0.014). Any clinical events were also lower in the active group (n = 5) than in the placebo group (n = 13, p = 0.052). Conclusions: Simvastatin 20 mg daily had no apparent effect upon the evolution of asymptomatic MCA stenosis over 2 years. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Despite the rapid progress in stroke prevention, effective acute stroke treatment except for thrombolysis is still lacking. Hypoperfusion is related to unfavorable functional outcome, further strokes and long-term mortality. Therefore, the need for a safe and effective way of increasing the cerebral blood flow seems obvious. Currently, there is a growing body of evidence to suggest that external counterpulsation (ECP) may enhance the blood supply to the brain and thus may be beneficial to patients with ischemic stroke. Methods: A MEDLINE search in combination with a search for papers in Chinese literature in the Wan Fang and China Academic Journal databases was carried out. Results: Preliminary investigations suggested that ECP may improve the clinical outcome of stroke patients. However, well-designed clinical studies exploring the therapeutic effects of ECP in ischemic stroke are very limited. Conclusions: Randomized-controlled trials with a large sample size are needed to further define the efficacy and safety of ECP in acute stroke management. Future studies should provide insight into the value of ECP in ischemic stroke as well as its possible mechanisms. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: In Chinese populations, middle cerebral artery (MCA) stenosis is the most commonly identified intracranial vascular lesion, and has been shown to be associated with an increased risk of secondary stroke mortality, but has yet to be reported for primary events. We assess whether asymptomatic MCA stenosis is associated with mortality in Chinese type 2 diabetic patients. Methods: The presence of MCA stenosis was determined by transcranial Doppler and mortality data were collated in the Hong Kong Death Registry. Cox proportional hazards regression was used to determine if the MCA stenosis (n = 272, 53.7% 2-vessel disease) in 2,197 diabetics was associated with all-cause or vascular disease mortality, including after adjustment for conventional vascular risk factors. Anthropometric and fasting biochemical parameters were compared between diabetic patients with MCA stenosis and without evidence of stenosis. Results: A total of 191 deaths were identified (30.9% of vascular disease origin) during a follow-up of 18,279 patient years over 8.32 years. After adjustment for age, gender and diabetes duration, the hazard ratios for vascular mortality for 1- and 2-vessel disease were 2.47 (95% CI = 1.13–5.38) and 4.47 (95% CI = 2.24–8.82), p < 0.001 for trend, for increasing vascular mortality with increasing severity of cerebrovascular involvement, but 0.81 (95% CI = 0.45–1.47) and 2.23 (95% CI = 1.45–1.47), p = 0.001 for trend, for all-cause mortality. For vascular mortality, further adjustments for anthropometric and fasting biochemical parameters, or existing disease and treatment history increased the hazard ratios for 1-vessel disease slightly but attenuated the risk for 2-vessel disease evidently, 2.81 (95% CI = 1.10–7.16) and 2.85 (95% = CI 1.11–7.33), p = 0.026. Conclusion: The presence of MCA stenoses was an independent predictor of vascular mortality in these diabetics. More aggressive treatment of risk factors in these subjects merits further evaluation. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Atherosclerotic stenosis of large intracranial arteries, especially the middle cerebral artery (MCA), is a common cause of stroke in Chinese patients. We aimed to describe the morphological features of atherosclerotic stenosis in the MCA and to investigate their relationship with cerebral infarcts from a postmortem series. Methods: We studied the morphological features of the MCAs in consecutive postmortem adults aged 45 years or above. The following parameters were evaluated by a single observer blinded to the clinical history: (1) thickness of fibrous cap; (2) extent of lipid area; (3) degree of luminal stenosis; (4) presence of intraplaque hemorrhage, neovasculature, thrombus and calcification. A semiquantitative assessment of macrophage and T lymphocyte infiltration was made by immunohistochemical staining for CD68 and CD45RO. Results: Seventy-six cases were recruited. Atherosclerotic plaques of more than 40% cross-sectional area luminal narrowing stenosis were found in 69 MCAs (45.4%, 69/152). The results demonstrated that the degree of luminal stenosis, the percentage of the plaques containing more than 40% lipid area and the prevalence of intraplaque hemorrhage, neovasculature and thrombus were higher in those plaques associated with infarct, and the mean index of both CD45RO and CD68 was higher among those associated with infarct (p < 0.01). Binary logistic regression showed that stenosis (p = 0.003; odds ratio, OR = 1.050), lipid area (p = 0.048, OR = 1.698) and presence of neovasculature (p = 0.040, OR = 3.471) were independent risk factors of MCA infarcts. Conclusions: Luminal stenosis caused by atherosclerotic plaque, percentage of lipid area and presence of intraplaque neovasculature may play a key role in leading to ischemic stroke. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Backgrounds: Intracranial atherosclerosis is the commonest vascular lesion for ischemic stroke in Asians. Most research on risk factors for middle cerebral artery (MCA) stenosis has been conducted in symptomatic patients with ischemic stroke or transient ischemic attack. The present study aimed to investigate risk factors for MCA stenosis in an asymptomatic population in Rongqi County in Southern China. Methods: We assessed 1,068 asymptomatic subjects over 50 years of age by transcranial Doppler. Medical history documentation and investigation of biochemical markers were performed for each subject. Multivariant, unconditioned, logistic regression analyses were employed to assess the risk factors associated with MCA stenosis. Results: MCA stenosis was found in 63 subjects (5.9%). Male gender, advancing age, hypertension, diabetes and systolic blood pressure were significant risk factors for MCA stenosis (p < 0.001). Based on logistic regression analyses, 4 factors emerged as independent risk factors (p < 0.001) of MCA stenosis: male gender [95% confidence interval (CI) = 1.49–4.66, OR = 2.63], age (95% CI = 1.01–1.06, OR = 1.04), hypertension (95% CI = 4.57–18.35, OR = 9.16) and diabetes mellitus (95% CI = 3.09–11.29, OR = 5.9). Conclusion: MCA stenosis is relatively common among asymptomatic Chinese subjects. Male gender, advanced age, hypertension and diabetes mellitus are risk factors for MCA stenosis. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The presence of microembolic signals (MES) may indicate an increased risk of recurrent ischemic events in patients with stroke. The optimal management of such patients is uncertain. We report the effect of clopidogrel in addition to aspirin on the number of MES in a series of patients with ischemic stroke and transient ischemic attack (TIA) due to large-vessel disease. Methods: 8 patients with either extracranial or intracranial artery stenosis were identified in 30-min MES studies by transcranial Doppler sonography as having MES. All patients were on antiplatelet therapy prior to baseline transcranial Doppler monitoring. The patients were subsequently treated with clopidogrel in addition to aspirin. Repeat MES studies were performed between day 3 and 7 with aspirin and clopidogrel. Results: All patients were Chinese. The median interval time from symptom onset to initial MES study was 7 days (range of 2–30). MES donor sites included 4 severely stenosed or occluded internal carotid arteries and 4 stenosed middle cerebral arteries. The median MES number at baseline was 8 (range 3–51). Repeat MES studies showed a significant decrease in MES (p = 0.012, Wilcoxon signed ranks test). 4 patients had complete cessation of MES and all patients showed a decline in MES. No patient had recurrent strokes or bleeding complications. Conclusion: The rapid and significant decline of MES in our stroke and TIA patients suggests the possible efficacy of dual antiplatelet therapy with aspirin and clopidogrel in patients with MES and symptomatic large-artery occlusive disease. Randomized controlled trials should be conducted to confirm this preliminary observation. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Traditionally hypoperfusion and embolism are considered separate important causes of stroke in patients with arterial occlusive disease. However, although hypoperfusion and embolism differ in mechanisms and location, they generally coincide in severe obstructive lesions and cause washout disturbances of embolism in low perfusion territories distal to stenosis. Unless the collateral blood supply is sufficient to prevent ischemia, multiple remote spot-like infarctions occur within the hypoperfused brain territory. In border-zone distributed infarction – long suspected to result from hemodynamic compromise alone – complementary interaction of embolisation and hypoperfusion territories has to be considered. Thus hypoperfusion with embolism or embolism alone are the most common explanations for stroke, the former often associated with less severe clinical deficits than the latter. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Intracranial artery calcification is common but the prevalence and determinants are not well established. We aim to describe the prevalence and location of calcification in intracranial arteries according to brain multi-detector-row computed tomography (MDCT) images, and to investigate its correlation with potential risk factors. Methods: We studied consecutive men and women referred for brain CT in December 2004. All patients received a questionnaire regarding their medical history related to atherosclerosis, including traditional risk factors of atherosclerosis, serum chemistry values and inflammatory markers. All CT examinations were done with a 16-slice MDCT and the severity of intracranial artery calcification was categorized. Results: Four hundred and ninety patients aged 1.4–101 years (62.92 ± 19.04; mean ± SD) were included in our study. There were 340 patients (69.4%) who had intracranial artery calcification. The highest prevalence of intracranial artery calcification was seen in the internal carotid artery (60%), followed by vertebral artery (20%), middle cerebral artery (5%) and basilar artery (5%). Patients with calcification were significantly older than those without calcification (p < 0.001). A significantly higher prevalence of calcification was present among patients with hypertension (p < 0.001), diabetes (p < 0.001), renal failure (p < 0.05), atrial fibrillation (p < 0.05), smoking (p < 0.05), hyperlipidemia (p < 0.001), ischemic heart disease (p < 0.05) and ischemic stroke (p < 0.001). Mean values of serum phosphate, serum urea and CRP level were also significantly higher in patients with intracranial artery calcification (p < 0.05, respectively), and there was a trend that patients with intracranial calcification had a higher white blood cell count (p = 0.070). Stepwise multiple logistic regression showed age (RR = 2.795 per 10 years), a history of ischemic stroke (RR = 3.915), and white blood cell count (RR = 1.107) to be independently associated with intracranial artery calcification. Conclusions: Calcification of the intracranial arteries is associated with age, history of ischemic stroke and white blood cell count. Further prospective studies to investigate the clinical significance of intracranial artery calcification are needed. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Conventional and genetic risk factors have been reported to play a role in the pathogenesis of ischaemic stroke, and differences may explain the heterogeneity of disease presentation in different populations. In Chinese, middle cerebral artery (MCA) stenosis is the most commonly identified intracranial vascular lesion. The involvement of renin-angiotensin system (RAS) gene polymorphisms in this condition has not been determined. Objectives: To determine whether conventional and RAS genetic vascular risk factors are associated with MCA stenosis, asymptomatic Chinese type II diabetic patients with and without MCA stenosis matched for age, gender and diabetes duration were compared. Methods: Biochemical parameters and the genotype and allele frequencies of three RAS gene polymorphisms, the angiotensin-converting enzyme (ACE) insertion/deletion, angiotensinogen (AGT) M235T and angiotensin II type 1 receptor (AT1R) A1166C polymorphisms were then compared between 217 diabetics with and 490 matched diabetic controls without MCA stenosis selected from 2,202 diabetics. Results: MCA stenosis was associated with significantly increased systolic blood pressure, LDL-cholesterol and albuminuria, yet diastolic blood pressure and glucose levels were lower. There was an increased prevalence of hypertension and use of blood pressure-lowering agents in the MCA stenosis patients. Albuminuria was also more commonly found in these patients. Hypertensive status, systolic blood pressure and albuminuria were strong, independent predictors of the presence of MCA stenosis. No differences in the RAS polymorphism distributions were observed between patients with and without MCA stenosis. Conclusions: In these asymptomatic type II diabetics, blood pressure indices and albuminuria, but not RAS gene polymorphism, were closely associated with MCA stenosis. [ABSTRACT FROM AUTHOR]