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Background: Atherosclerosis is the main cause of cardiovascular diseases such as ischemic stroke and coronary heart disease. Gene-specific promoter methylation changes have been suggested as one of the causes underlying the development of atherosclerosis. We aimed to identify and validate specific genes that are differentially expressed through promoter methylation in atherosclerotic plaques. We performed the present study in four steps: (1) profiling and identification of gene-specific promoter methylation changes in atherosclerotic tissues; (2) validation of the promoter methylation changes of genes in plaques by comparison with non-plaque intima; (3) evaluation of promoter methylation status of the genes in vascular cellular components composing atherosclerotic plaques; and (4) evaluation of promoter methylation differences in genes among monocytes, T cells, and B cells isolated from the blood of ischemic stroke patients., Results: Upon profiling, AIRE1, ALOX12, FANK1, NETO1, and SERHL2 were found to have displayed changes in promoter methylation. Of these, AIRE1 and ALOX12 displayed higher methylation levels in plaques than in non-plaque intima, but lower than those in the buffy coat of blood. Between inflammatory cells, the three genes were significantly less methylated in monocytes than in T and B cells. In the vascular cells, AIRE1 methylation was lower in endothelial and smooth muscle cells. ALOX12 methylation was higher in endothelial, but lower in smooth muscle cells. Immunofluorescence staining showed that co-localization of ALOX12 and AIRE1 was more frequent in CD14(+)-monocytes than in CD4(+)-T cell in plaque than in non-plaque intima., Conclusions: Promoter methylation changes in AIRE1 and ALOX12 occur in atherosclerosis and can be considered as novel epigenetic markers.

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 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.)

Objective: We evaluated the relationship between hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and small-vessel disease (SVD) and atherosclerotic large-vessel disease (LVD) in stroke patients., Methods: A total of 825 noncardioembolic ischemic stroke patients whose plasma concentrations of total homocysteine were measured and whose MTHFR C677T polymorphism status was identified were included in this retrospective study. MRI of the brain and magnetic resonance angiography of the intracranial and extracranial cerebral arteries had been performed. SVD and LVD were assessed by the Scheltens scale (the SVD score) and by the number of atherosclerotic steno-occlusive arteries (the LVD score), respectively., Results: The TT genotype of the MTHFR C677T polymorphism was associated with hyperhomocysteinemia (p < 0.001), but not with SVD (p = 0.182) or LVD (p = 0.988) scores. Multiple logistic regression analysis showed that hyperhomocysteinemia was associated with SVD (odds ratio [OR] 1.04; 95% confidence interval [CI] 1.01-1.07; p = 0.005) and LVD (OR 1.02; 95% CI 1.00-1.05; p = 0.041) scores. Hyperhomocysteinemia was related to the LVD score of extracranial arteries (p = 0.008), but not to the LVD score of intracranial arteries (p = 0.730). In multiple logistic regression analysis, however, hyperhomocysteinemia was not related to the LVD score of extracranial arteries (p = 0.255)., Conclusions: Hyperhomocysteinemia was associated with SVD of the brain and LVD of cerebral arteries. The MTHFR C677T polymorphism was not related to SVD and LVD, although the TT genotype was an important determinant of hyperhomocysteinemia., (© 2014 American Academy of Neurology.)

Background: To investigate whether ischemic lesion burden including lesion pattern, number, and volume would vary depending on risk stratification of aortic atheroma (AA)., Methods: Acute stroke patients were enrolled if they had (1) acute ischemic lesions on diffusion-weighted imaging within 5 days of symptom onset, (2) cardioembolic stroke established through extensive workup, and (3) only ascending or arch AA detected by transesophageal echocardiography as an embolic source. AA was classified as complex (protruding ≥4 mm into the aortic lumen or any mobile or ulcerative component) or simple (<4 mm)., Results: Eighty-one patients (male: 65.4% and age: 66.7 ± 11.0 years) were included in the study. Thirty-four patients (41.9%) had complex atheroma. These patients had a greater number of ischemic lesions (median: 2 lesions [range: 1-42] versus one lesion [range: 1-27], P = .017) and a larger infarct size (9.01 cc [range: 3.58-49.14] versus 4.6 cc [range: 2.3-13.28), P = .056) than the simple atheroma group. Multivariable logistic regression analysis showed that ischemic lesion volume was independently associated with complex atheroma (odds ratio: 1.03, 95% confidence interval: 1.002-2.148, P = .035), while multiple lesions were related (odds ratio: 3.03, 95% confidence interval: .88-10.42, P = .079)., Conclusions: Ischemic lesion burden in patients with AA differed according to AA characteristics, suggesting that the morphological features of AA could reflect an embolic potential of AA., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Single small subcortical infarctions (SSSIs), so-called lacunae, are typically caused by lipohyalinosis of a perforator artery. However, SSSIs can be caused by underlying large parent arterial disease or microatheroma of the proximal portion of a perforator artery. We sought to investigate whether indicators for small vessel disease (SVD) and atherosclerosis in patients with SSSI differ according to lesion location and the presence of parent artery disease., Methods: We assessed 449 patients who had an SSSI (lesion diameter ≤ 20 mm) in the perforator territory of middle cerebral artery (n = 244), basilar artery (n= 141), and vertebral artery (n = 64) on diffusion-weighted imaging performed within 48 hours of stroke onset. We divided SSSI into 3 groups according to lesion location and the presence of parent artery disease: (1) SSSI with parent artery disease (SSSI+PAD); (2) proximal SSSI without PAD (pSSSI-PAD); and (3) distal SSSI without PAD (dSSSI-PAD). The prevalence of SVD indicators (leukoaraiosis and microbleeds) and atherosclerosis indicators (cerebral atherosclerosis and coronary heart disease) were compared among the groups., Results: SSSI+PAD had the highest prevalence of atherosclerosis indicators and the lowest prevalence of SVD indicators, whereas dSSSI-PAD had the lowest prevalence of atherosclerosis indicators and the highest prevalence of SVD indicators. pSSSI-PAD showed intermediate features. Atherosclerosis indicators significantly increased and SVD indicators significantly decreased as the vascular territory became lower (from middle cerebral artery, basilar artery to vertebral artery)., Conclusions: Differences in SVD and atherosclerosis indicators suggest that SSSI has a heterogeneous pathogenesis according to lesion location and the presence of PAD.

Background: An acute perfusion-diffusion mismatch is known to be the strongest predictor of infarct growth. However, the differential patterns of clinical and radiological evolution according to stroke mechanism are unknown., Methods: The study retrospectively reviewed consecutive patients who had 1) acute middle cerebral artery (MCA) territory infarction, 2) diffusion- and perfusion-weighted imaging (DWI and PWI) and MR angiography within 24 h of onset, and follow-up DWI 5 days later, 3) stenosis (> or =50%) or occlusion of MCA on baseline imaging, 4) a baseline PWI-DWI mismatch >20%, and 5) either atherosclerotic MCA disease (MCAD) or cardioembolism (CE). National Institutes of Health Stroke Scale (NIHSS) scores and infarct volume at baseline and 5 days were obtained., Results: Of 90 patients, 52 had MCAD and 38 had CE. At baseline, CE group had more severe stroke (median NIHSS, 9 vs. 5; p=0.001) and larger infarct volume (median 8.32 cc vs. 3.0 cc; p=0.034) than MCAD group. During the 1-week period, CE group had larger infarct volume growth (median 12.85 cc vs. 3.02 cc; p=0.004) than MCAD group, although clinical improvement based on NIHSS (baseline minus 5-day) tended to be higher for CE than MCAD group (median 3 vs. 1; p=0.08). The correlation between infarct volume and NIHSS score was stronger in CE (r=0.841) compared to MCAD (r=0.582) group at 5-day., Conclusions: Substantial differences in the clinico-radiological evolution of acute ischemic stroke exist according to stroke mechanism. These data emphasize the importance of the stroke mechanism in the design of MRI-based acute stroke trials.

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 High blood pressure variability (BPV) is associated with recurrent stroke. We investigated the association between BPV, new ischemic lesions (NILs), and white matter lesion (WML) growth in patients with ischemic stroke due to intracranial atherosclerosis (ICAS). METHODS This study was performed as a post-hoc analysis of the STABLE-ICAS trial, which enrolled subacute ischemic stroke patients with symptomatic ICAS (>50% stenosis) and hypertension. BPV was measured at the office (visit by visit) and at home (day by day). Patients were divided into 3 groups (tertiles) according to their home BPV. WML growth and the occurrence of NILs were compared among the 3 groups. Multivariable analyses were performed to identify the independent risk factors of WML growth and NILs. RESULTS Of the 111 enrolled patients, 69 patients (67.6%) demonstrated WML growth and 15 patients (13.7%) had NILs. Patients with higher BPV demonstrated a more WML growth (50% vs. 61.8% vs. 83.8; P = 0.02, by tertiles) and more NILs (5.4% vs. 5.4% vs. 29.7%; P = 0.002, by tertiles). In multivariable analyses, old age [odds ratio (OR) = 1.052 (95% confidence interval (CI) = 1.005–1.101); P = 0.03] and home BPV [OR = 1.149 (95% CI = 1.013–1.304); P = 0.02] were independently associated with WML growth. Low mean diastolic blood pressure [OR = 0.913 (95% CI = 0.874–0.984); P = 0.02] and high home BPV [OR = 1.287 (95% CI = 1.086–1.526); P = 0.004] were independently associated with NILs at follow-up. CONCLUSIONS High BPV is associated with WML growth and NIL in ischemic stroke patients with symptomatic ICAS. BPV monitoring at home may be helpful. [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: Atherosclerosis is one of the main mechanisms of stroke and cardiovascular diseases and is associated with increased risk of recurrent stroke and cardiovascular events. Intima-medial thickness (IMT) is a well-known surrogate marker of atherosclerosis and has been used to predict stroke and cardiovascular events. However, the clinical significance of IMT and IMT change in stroke has not been investigated in well-designed studies. The PreventIon of CArdiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage-Intima-Media Thickness (PICASSO-IMT) sub-study is designed to investigate the effects of cilostazol, probucol, or both on IMT in patients with stroke.Methods: PICASSO-IMT is a prospective sub-study of the PICASSO study designed to measure IMT and plaque score at 1, 13, 25, 37, and 49 months after randomization.Results: The primary outcome is the change in mean carotid IMT, which is defined as the mean of the far-wall IMTs of the right and left common carotid arteries, between baseline and 13 months after randomization.Conclusion: PICASSO-IMT will provide the largest IMT data set in a stroke population and will provide valuable information about the clinical significance of IMT in patients with ischemic stroke. [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]

Cilostazol is an antiplatelet drug often used in Asian countries like Korea, Japan, and China. However, it is rarely used in the west. Cilostazol inhibits phosphodiesterase, increases cyclic AMP concentrations, and consequently inhibits platelet aggregation. Interestingly, it also has vasodilatory activity, inhibits vascular smooth muscle proliferation, and protects the endothelium. Studies in Asia have shown that cilostazol is effective in the secondary prevention of stroke. Moreover, it is significantly less likely to cause bleeding complications than aspirin. Additional trials have shown that cilostazol is effective in the prevention of intracranial atherosclerosis progression. Unfortunately, cilostazol has rarely been studied in non-Asian stroke patients and, accordingly, the benefits of cilostazol are less well appreciated in Europe and America than in Asia. Although further studies are required, we suggest that at least some stroke patients (e.g., patients prone to bleeding, patients with intracranial atherosclerosis, etc.) may readily benefit from cilostazol regardless of ethnicity. [ABSTRACT FROM AUTHOR]

Background: The progression of carotid intima–media thickness (CIMT) is closely associated with ischemic stroke recurrence. However, the efficacy of cilostazol on preventing CIMT progression in stroke patients has never been investigated properly by a prospective trial. Methods: This study is a part of “Trial of Cilostazol in Symptomatic Intracranial Arterial Stenosis-2.” Six centers that are available to measure CIMT according to the protocol participated in this substudy. After 7 months of randomization, the changes of CIMT were compared between cilostazol group and clopidogrel group. CIMT was measured by a semiautomated software (Intimascope) and was presented as the mean of maximum (CIMT-max) and average (CIMT-ave) of both common carotid arteries. Linear logistic regression analysis and analysis of covariance were performed to verify the independent factors associated with CIMT progression. Results: Among the 85 patients, 39 subjects were assigned to cilostazol group and 46 subjects to clopidogrel group. Follow-up CIMT significantly decreased in cilostazol group (CIMT-max: −.03 ± .11 and CIMT-ave: −.02 ± .08) compared with the increase in clopidogrel group (CIMT-max: .04 ± .20 and CIMT-ave: .04 ± .11; P = .05 and P = .04, respectively). Female, diabetes, and smoking were independently associated with the progression of CIMT, whereas the use of cilostazol was against CIMT progression from the results of linear regression analysis (P = .03 for both CIMT-max and CIMT-ave). The use of cilostazol also well predicted less progression of CIMT at follow-up after adjusting for baseline CIMT values and conventional risk factors (CIMT-max: P = .04 and CIMT-ave: P = .03). Conclusion: Cilostazol has a beneficial effect in preventing the progression of CIMT in ischemic stroke patients. [Copyright &y& Elsevier]

Background and Purpose: Although cardiac embolism has been shown to be the leading stroke mechanism of posterior cerebral artery (PCA) territory infarction, intrinsic PCA atherosclerotic disease may play a more important role in regions where intracranial diseases are prevalent. We aimed to assess the etiologies and stroke pattern of PCA territory infarction in a Korean population. Method: We reviewed consecutive patients with acute PCA territory infarction who underwent diffusion-weighted MRI (DWI) and magnetic resonance angiography (MRA) within 7 days after onset. Results: A total of 205 patients (male 56%, mean age 65.4 ± 12.4 years) were recruited. ‘Superficial’, ‘deep’ and ‘superficial plus deep’ infarcts accounted for 26.3, 47.8 and 25.9% of infarcts, respectively. There were 126 patients who had infarcts limited to the PCA territory, whereas 79 patients had concomitant infarcts in other territories. Large artery atherosclerosis (LAA, 42.4%) was the most frequent etiology, followed by cardiogenic embolism (20%), small-vessel occlusion (20%), undetermined (18%) and other determined (3%) etiology. Among the 87 patients with LAA, 38 had intrinsic PCA disease without atherosclerosis in the proximal vessels. In these patients, stroke mechanisms included atheromatous branch occlusion (n = 19), in situ thrombotic occlusion (n = 11) and artery-to-artery embolism (n = 8). While the occipital area was the most frequently involved in general, the ventrolateral thalamic area was more frequently involved than the occipital area in patients with intrinsic PCA atherosclerotic disease. Conclusion: The patterns of PCA territory infarction are different according to underlying etiologies. In our population, intrinsic atherosclerotic disease is a relatively important cause of PCA territory infarction that produces strokes through a variety of mechanisms. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Intracranial atherosclerosis is a common cause of stroke, accounting for about 50% of ischaemic stroke in Asia and 8% in North America. Many prospective studies have confirmed that intracranial stenosis is an independent predictor for poor outcomes such as recurrent vascular event and death, despite the use of antiplatelet agents. The annual event rate is about 15% per year. The dismal outcome prompts the study of more aggressive treatment strategies, including warfarin and endovascular intervention. We have reviewed the published literature for the treatment of symptomatic intracranial stenosis. The Warfarin–Aspirin Symptomatic Intracranial Disease (WASID) trial and Warfarin–Aspirin Recurrent Stroke Study (WARSS) studies failed to show that oral anticoagulation was better than aspirin in IAS. Initial encouraging results were found in the use of dual antiplatelet therapy in arresting the progression of stenosis. The results of the endovascular studies are mixed: there are more encouraging results with recent advances of technology in stent design, but a randomized controlled study is still lacking. Although there is still no established therapy for IAS, the results of ongoing randomized clinical trials to study dual antiplatelet agents and the use of endovascular intervention may soon provide clinicians with more evidence to better manage patients with this condition. [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.

Abstract: Background: Various biomarkers are linked with the pathophysiology of atherosclerosis. We hypothesized that these factors may be associated with the location and burden of cerebral atherosclerosis. Methods: We evaluated 177 consecutive patients with chronic (>6 months) ischemic stroke: 68 with small vessel occlusion (SVO) and 109 with large-artery atherosclerosis (LAA), with the latter further sub-classified into 80 patients with intracranial atherosclerosis (ICAS) and 29 with extracranial atherosclerosis (ECAS). The number of ≥50% steno-occlusions on magnetic resonance angiography was used to assess the burden of atherosclerosis. Serum concentrations of the biomarkers (matrix metalloproteinases (MMP)-2 and -9, homocysteine, interleukin (IL)-6, tumor necrosis factor-α, C-reactive protein, adiponectin, leptin, resistin, free fatty acid, and lipoprotein(a)) and the metabolic syndrome were measured in each study subject. Results: Decreased plasma concentrations of MMP-2 (p = 0.020) and homocysteine (p = 0.038) were more closely associated with ICAS than with ECAS, whereas increased IL-6 concentrations were related to severe (≥4 steno-occlusions) atherosclerosis (p = 0.031). Multiple logistic regression analysis showed that the lowest tertile of MMP-2 was independently associated with ICAS (OR 4.84, 95% CI 1.29–18.19, p = 0.022). Conclusion: Low MMP-2 plasma levels are associated with intracranial location of cerebral atherosclerosis, suggesting that MMP-2 may play a role in the development of ICAS. [Copyright &y& Elsevier]

Objectives: We aimed to define the relationship between cerebral atherosclerosis and stroke after coronary artery bypass grafting (CABG). Background: Although cerebral atherosclerosis may play a crucial role in the advent of post-CABG stroke, only extracranial carotid artery disease has been extensively studied, and the effects of atherosclerosis on the mechanisms underlying post-CABG stroke remain unclear. Methods: Pre-operative magnetic resonance angiography was performed on 1,367 consecutive CABG patients to assess intracranial and extracranial cerebral atherosclerosis. Disease severity was evaluated by atherosclerosis score, as determined by the number of steno-occlusions of cerebral arteries and the degree thereof. Post-CABG strokes (within 14 days) were classified as atherosclerotic (strokes attributable to pre-defined atherosclerosis) or other (strokes caused by other mechanisms). Associations between post-CABG stroke and each type of atherosclerotic disease (extracranial carotid artery disease, intracranial, extracranial, or extracranial and/or intracranial cerebral atherosclerosis), differentiated according to the involved arteries, were analyzed. Results: Stroke occurred in 33 patients, and the atherosclerosis score was independently associated with stroke development (odds ratio: 1.35; 95% confidence interval: 1.16 to 1.56). Atherosclerotic stroke was defined in 15 (45%), and constituted >40% of both immediate (within 24 h) and delayed strokes. Intracranial, extracranial, and extracranial and/or intracranial cerebral atherosclerosis were significantly associated with stroke. Conclusions: Cerebral atherosclerosis was closely related to the occurrence of post-CABG stroke, being both an independent risk factor for and the cause of a significant proportion of strokes. Pre-operative evaluation of intracranial and extracranial cerebral arteries, apart from the extracranial carotid artery, may be useful to predict the likelihood of post-CABG stroke. [ABSTRACT FROM AUTHOR]