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Background and Purpose: In patients with acute ischemic stroke caused by large artery atherosclerosis, clopidogrel plus aspirin versus aspirin alone might be more effective to prevent recurrent cerebral ischemia. However, there is no clear evidence., Methods: In this multicenter, double-blind, placebo-controlled trial, we randomized 358 patients with acute ischemic stroke of presumed large artery atherosclerosis origin within 48 hours of onset to clopidogrel (75 mg/d without loading dose) plus aspirin (300-mg loading followed by 100 mg/d) or to aspirin alone (300-mg loading followed by 100 mg/d) for 30 days. The primary outcome was new symptomatic or asymptomatic ischemic lesion on magnetic resonance imaging within 30 days. Secondary outcomes were 30-day functional disability, clinical stroke recurrence, and composite of major vascular events. Safety outcome was any bleeding., Results: Of 358 patients enrolled, 334 (167 in each group) completed follow-up magnetic resonance imaging. The 30-day new ischemic lesion recurrence rate was comparable between the clopidogrel plus aspirin and the aspirin monotherapy groups (36.5% versus 35.9%; relative risk, 1.02; 95% confidence interval, 0.77-1.35; P=0.91). Of the recurrent ischemic lesions, 94.2% were clinically asymptomatic. There were no differences in secondary outcomes between the 2 groups. Any bleeding were more frequent in the combination group than in the aspirin monotherapy group, but the difference was not significant (16.7% versus 10.7%; P=0.11). One hemorrhagic stroke occurred in the clopidogrel plus aspirin group., Conclusions: Clopidogrel plus aspirin might not be superior to aspirin alone for preventing new ischemic lesion and clinical vascular events in patients with acute ischemic stroke caused by large artery atherosclerosis., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00814268., (© 2016 American Heart Association, Inc.)

Background and Purpose: Middle cerebral artery steno-occlusive disease (MCAD) is not an uncommon cause of ischemic stroke in young Asians. Aside from atherosclerosis, the pathogenesis of MCAD include various nonatherosclerotic vasculopathies, most of which are yet to be defined. This study investigated the pathogenesis of symptomatic isolated MCAD in young Asian patients using high-resolution magnetic resonance imaging (HR-MRI) and mutation analysis of RNF213., Methods: Patients aged <60 years with stroke or transient ischemic attack caused by MCAD were prospectively enrolled. Patients with a confirmed diagnosis of moyamoya disease, dissection, and vasculitis; with significant steno-occlusion in cerebral arteries other than the MCA; or with high-risk cardioembolic source were excluded. Using high-resolution MRI, patients were classified into an atherosclerosis group and a nonatherosclerosis group., Results: Eighty-one patients were enrolled, 45 (56.6%) in the atherosclerosis and 36 (44.4%) in the nonatherosclerosis group. The nonatherosclerosis group was significantly younger (P=0.013), had a smaller number of vascular risk factors (P=0.001), showed a lower homocysteine level (P<0.001), thinner intima-media thickness (P=0.006), and had more frequent heterozygotes at RNF213 (P=0.045) than the atherosclerosis group. Diffusion-weighted image lesion pattern showed no significant differences in assumed stroke mechanisms between the 2 groups., Conclusions: Nonatherosclerotic pathogenesis are common in young Asians with symptomatic isolated MCAD. Clinical findings, high-resolution MRI features, and results of RNF213 mutation analysis suggest that moyamoya disease is responsible etiologically for a significant portion of nonatherosclerotic lesions. Symptomatic isolated MCAD may be an early manifestation of moyamoya disease in young Asian adults., (© 2016 American Heart Association, Inc.)

Background: Genetic variants may play a role in determining the location of cerebral atherosclerosis. We aimed to investigate the association between RNF213, MMP2, and genetic polymorphisms linked to vascular tortuosity with the location of cerebral arterial atherosclerosis. Methods: A prospective case-control study was conducted on patients with ischemic stroke and age- and sex-matched stroke-free controls. The stroke patients were categorized into those with intracranial artery atherosclerosis (ICAS), extracranial artery atherosclerosis (ECAS), and small vessel occlusion (SVO). Six single nucleotide polymorphisms (SNPs) including rs2118181 (FBN1), rs2179357 (SLC2A10), rs1036095 (TGFBR2), rs243865 (MMP2), rs1800470 (TGFB1), and rs112735431 (RNF213) were analyzed with the TaqMan Genotyping Assay, and the distribution of genotypes across groups was compared. Results: None of the 6 SNPs were associated with stroke on comparing the 449 stroke patients (71 with ECAS, 169 with ICAS, and 209 with SVO) to the 447 controls. In the subgroup analysis, the adjusted odds ratios (aORs) for age and sex indicated a significant association between rs112735431 and ICAS in the allele comparison analysis and in the additive and dominant model analyses. rs112735431 was associated with anterior circulation involvement and increased burden of cerebral atherosclerosis. rs2179357 was significantly associated with ICAS in the recessive model analysis, and rs1800470 was significantly associated with ECAS in the recessive model analysis when compared to controls. Conclusion: rs112735431 was associated with ICAS and increased atherosclerosis burden in Korean stroke patients. Further studies are needed to elucidate the role of rs112735431 and to confirm the association of rs2179357 and rs1800470 with cerebral atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: In the previous prospective observational study, we found that cerebral atherosclerosis is an independent predictor of acute stroke after coronary artery bypass grafting (CABG). However, it is unknown whether intracranial cerebral atherosclerosis (ICAS) is important as much as extracranial cerebral atherosclerosis (ECAS) in estimating the risk of post-CABG adverse events. Extending the previous study, we aimed to investigate the immediate and long-term prognostic value of the location of cerebral atherosclerosis in CABG patients. Methods: This follow-up study of previously reported prospective cohort included 1,367 consecutive patients who received CABG between 2004 and 2007. All patients underwent preoperative magnetic resonance angiography (MRA) to assess intracranial and ECAS, both defined by significant steno-occlusion (≥50%). Participants were classified into 4 groups according to the location of cerebral atherosclerosis: no cerebral atherosclerosis, ECAS only, ICAS only, and ECAS + ICAS. Post-CABG stroke within 14 days (immediate outcome) and mortality (long-term outcome) following CABG were compared between the groups. Survival data for all participants through June 2016 were obtained from the Korean National Registry of Vital Statistics. The Cox proportional hazards model was used to estimate the hazard ratio (HR) of post-CABG stroke and mortality; patients lacking cerebral atherosclerosis were defined as the reference group. Results: The median follow-up duration after CABG was 9.2 years (interquartile range 8.4–10.2 years). Of the participants, 278 (20.3%) patients had ICAS only, while 269 (19.7%) and 347 (25.4%) showed ECAS only and ECAS + ICAS, respectively, in their preoperative MRA. Having ICAS only (HR 5.07; 95% CI 1.37–18.75; p = 0.015) and having ECAS + ICAS (HR 8.43; 95% CI, 2.48–28.61; p = 0.001) independently predicted the immediate stroke, whereas being with ECAS only did not (HR 1.71; 95% CI 0.35–8.50; p = 0.509). Conversely, ICAS-only status was not independently associated with long-term mortality (HR 1.22; 95% CI 0.90–1.65; p = 0.207), whereas ECAS-only status (HR 1.42; 95% CI 1.05–1.90; p = 0.021) and ECAS + ICAS status (HR 1.58; 95% CI 1.20–2.07; p = 0.001) showed independent associations. Conclusions: Over 10 years of follow-up, cerebral atherosclerosis significantly associated with the development of adverse outcomes after CABG. The prognostic value of ICAS might be different from that of ECAS; immediate post-CABG stroke was more closely associated with ICAS, whereas there was a closer association between long-term post-CABG mortality and ECAS. [ABSTRACT FROM AUTHOR]

Background: The geometric properties of the parental artery affect the development of local atherosclerosis and perforator infarction. In this study, we aimed at investigating the association between vascular geometry of the posterior cerebral artery (PCA) and the development of isolated lateral thalamic infarction (LTI), the most frequent type of thalamic infarction. Methods: The geometric properties of the corresponding PCA in LTI patients were assessed and they include the diameters of the distal basilar artery (BA) and proximal PCA, distal BA - PCA angle, first PCA angle (angle between P1 and P2), and the presence of the posterior communicating artery (Pcom). These parameters obtained from the ipsilesional PCA were compared with the contralesional PCA and the corresponding PCA in age- and sex-matched controls. Results: Forty-five LTI patients were enrolled. The ipsilesional PCA in LTI patients demonstrated a greater ipsilesional P1 - P2 angle (81.4 ± 22.6 vs. 71.3 ± 23.2°, respectively; p = 0.04) and a higher prevalence of Pcom (42.2 vs. 13.3%; p = 0.002) when compared to control subjects. In comparison with the contralesional PCA, ipsilesional PCA demonstrated a smaller diameter, larger angle between P1 and P2 segment, and a higher prevalence of Pcom. The presence of hyperlipidemia (OR 3.548 (1.283-9.811); p = 0.02) and Pcom (OR 3.507 (1.104-11.135); p = 0.03) was a factor that was independently associated with LTI. Conclusions: Local hemodynamics in the PCA may be influenced by the P1 - P2 angle and the presence of Pcom, which are associated with the development of LTI. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background Conventional risk factors cannot explain the individual or ethnic difference in the location of cerebral atherosclerosis. Vascular geometry may play a role on this. Aim To investigate the association between the geometrical properties of the middle cerebral artery and intracranial atherosclerosis. Methods Stroke patients with either symptomatic middle cerebral artery or proximal internal carotid artery diseases were enrolled. The diameter, length, and tortuosity (arc-chord ratio, by percent) of the middle cerebral artery was compared between stroke patients and the age- and gender-matched healthy subjects. The geometrical property was also compared between the symptomatic middle cerebral artery and the normal-looking contralateral middle cerebral artery, and between the contralateral middle cerebral arteries in patients with symptomatic middle cerebral artery and proximal internal carotid artery diseases. Results One hundred seventy-seven patients (101 with middle cerebral artery disease and 76 with proximal internal carotid artery disease) were studied. Symptomatic middle cerebral artery was more tortuous (119·31 ± 16·95 vs. 112·98 ± 14·16; P = 0·009) than the contralateral middle cerebral artery. The contralateral middle cerebral artery of patients with symptomatic middle cerebral artery disease demonstrated a smaller proximal diameter ( P = 0·007) and a greater vascular tortuosity than the contralateral middle cerebral artery of patients with proximal internal carotid artery disease (112·01 ± 12·25 vs. 107·46 ± 9·35; P = 0·008) and corresponding middle cerebral artery of healthy control subjects (112·01 ± 12·25 vs. 108·73 ± 9·79; P = 0·04). Young age, female, small diameter, the absence of diabetes, and high tortuosity of the contralateral middle cerebral artery were independently associated with middle cerebral artery atherosclerotic disease. Conclusions High tortuosity and small diameter are related to middle cerebral artery atherosclerosis, probably by altering hemodynamics. Different degree of tortuosity may be one of the reasons for individual differences in location of cerebral atherosclerosis. [ABSTRACT FROM AUTHOR]

Background The location of plaque may be associated with the vascular geometry. Aim We aimed to examine the relationship between the geometry of middle cerebral artery and the plaque location detected by high-resolution magnetic resonance imaging. Methods Among patients with a single subcortical infarction without a significant middle cerebral artery stenosis on magnetic resonance angiography, those with a plaque detected from high-resolution magnetic resonance imaging were prospectively enrolled. The shape of middle cerebral artery was measured from the coronal view, and was classified as straight, U-shaped, inverted U-shaped, and S-shaped. The location of the plaque was divided into superior and inferior, and analyzed according to the shape of middle cerebral artery. Results Among the 40 patients, the shape of middle cerebral artery was straight in 7 (17·5%), U-shaped in 10 (15·0%), inverted U-shaped in 11 (27·5%), and S-shaped in 12 patients (30·0%). The superior plaque was more closely associated with straight (85·7%) or U-shaped middle cerebral arteries (90·0%), whereas inverted U-shaped (81·8%) and S-shaped middle cerebral arteries (75·0%) were more often associated with inferior plaque. The prevalence of symptomatic plaque was higher in superior than inferior plaques (70·0% vs. 25·0%, P = 0·004). Multivariate analysis showed that straight and U-shaped middle cerebral artery was the only significant factor associated with the superior plaque. Conclusion The shape of middle cerebral artery may be a factor determining the location of early atherosclerotic plaque. [ABSTRACT FROM AUTHOR]

The article provides comparison of novel-oral anticoagulants with warfarin for treating ischemic stroke patients with nonvalvular atrial fibrillation (NVAF). It reveals the comparison of the lesion pattern, number of atherosclerotic vessels, and the stroke mechanism between strokes. It also mentions the use of novel oral anticoagulant (NOAC) for preventing cardioembolism.