Atherosclerotic Stroke Patients Research Articles

Pathogenesis of cardiovascular diseases: effects of mitochondrial CF6 on endothelial cell function.

Cardiovascular disease (CVD) stands as a predominant global cause of morbidity and mortality, necessitating effective and cost-efficient therapies for cardiovascular risk reduction. Mitochondrial coupling factor 6 (CF6), identified as a novel proatherogenic peptide, emerges as a significant risk factor in endothelial dysfunction development, correlating with CVD severity. CF6 expression can be heightened by CVD risk factors like mechanical force, hypoxia, or high glucose stimuli through the NF-κB pathway. Many studies have explored the CF6-CVD relationship, revealing elevated plasma CF6 levels in essential hypertension, atherosclerotic cardiovascular disease (ASCVD), stroke, and preeclampsia patients. CF6 acts as a vasoactive and proatherogenic peptide in CVD, inducing intracellular acidosis in vascular endothelial cells, inhibiting nitric oxide (NO) and prostacyclin generation, increasing blood pressure, and producing proatherogenic molecules, significantly contributing to CVD development. CF6 induces an imbalance in endothelium-dependent factors, including NO, prostacyclin, and asymmetric dimethylarginine (ADMA), promoting vasoconstriction, vascular remodeling, thrombosis, and insulin resistance, possibly via C-src Ca2+ and PRMT-1/DDAH-2-ADMA-NO pathways. This review offers a comprehensive exploration of CF6 in the context of CVD, providing mechanistic insights into its role in processes impacting CVD, with a focus on CF6 functions, intracellular signaling, and regulatory mechanisms in vascular endothelial cells.

Role of Von Willebrand factor level as a biomarker in acute ischemic stroke

BackgroundVon Willebrand factor (VWF) is a large, multimeric glycoprotein that plays a role in thrombus formation; it is also an important mediator of inflammation. Our study aims to determine the association of VWF plasma level and acute ischemic stroke and determine plasma level of VWF in different subtypes of acute ischemic stroke. This case–control study was conducted on 90 subjects: 30 acute ischemic atherosclerotic stroke patients, 30 acute cardioembolic stroke patients and 30 healthy age and sex-matched control subjects. Stroke patients were recruited within the first week of stroke onset with an age range from 18 to 75 years. All subjects underwent complete neurological examination, duplex ultrasonography (U/S), CT brain, routine laboratory work-up and serum level of VWF.ResultsVWF serum levels were significantly elevated in patients of acute ischemic stroke, compared to control subjects. Higher plasma levels of VWF were observed in patients with acute ischemic atherosclerotic stroke.ConclusionSerum level of VWF can be used as a marker for acute ischemic stroke, especially the atherosclerotic subtype.

Blood pressure variability and outcome in atherosclerosis versus cardioembolism cerebral large vessel occlusion after successful thrombectomy.

Higher blood pressure variability (BPV) has been proven associated with worse functional outcome after endovascular treatment (EVT). However, this association is not established according to different stroke etiologies. In this study, we compared patients with the two highest proportions of stroke etiologies-cardioembolism (CE) and large-artery atherosclerosis (LAA), aiming to explore appropriate strategies of BP management for different etiologies. We enrolled patients with large vessel occlusion (LVO) in anterior circulation who underwent EVT and achieved successful recanalization retrospectively. 24-h blood pressure (BP) and BPV measured as blood pressure reduction (BPr), standard deviation (SD), coefficient of variation (CV), successive variation (SV), average real variability (ARV) after EVT were collected for systolic blood pressure (SBP) and diastolic blood pressure (DBP). The favorable outcome was defined as functional independence by 90-day modified Rankin Scale (mRS 0-2). In our cohort, higher BPV parameters significantly resulted in 90d functional dependence in CE-LVO patients (SBPSV OR: 1.083, 95%CI = 1.009-1.163; SBPARV OR: 1.121, 95%CI = 1.019-1.233; DBPSD OR: 1.124, 95%CI = 1.007-1.1256; DBPCV OR: 1.078, 95%CI = 1.002-1.161). However, for LAA-LVO patients, no positive results correlated 90d functional dependence with 24-hour BPV. Additionally, 90d functional dependence in CE patients with poor collaterals were significantly dependent on post-procedural BPV (DBPmax OR: 1.044, 95%CI = 1.002-1.087; DBPSD OR: 1.229, 95%CI = 1.022-1.1.479; DBPCV OR: 1.143, 95%CI = 1.009-1.295). Whereas to patients with good collaterals, there did not exist such a correlation. In summary, stroke etiologies should probably be taken into consideration to optimize individualized BP management strategies. In order to achieve better clinical outcomes for patients with acute ischemic stroke due to large vessel occlusion, stricter blood pressure management should be taken in cardioembolic stroke patients in contrast with large artery atherosclerotic stroke patients after successful endovascular therapy.

Predictive utility of stress tests in the detection of asymptomatic coronary artery disease in atherosclerotic stroke patients

IntroductionWhether and how atherosclerotic ischemic stroke patients should be investigated for asymptomatic coronary artery disease (CAD) is controversial. Our aim was to carry out a prospective observational study to determine the frequency and predictors of functionally significant coronary stenosis in these patients as well as the predictors of major adverse cardiovascular events (MACE) during post-stroke follow-up. Material and methodsFrom January 2014 to June 2018, patients with atherosclerotic ischemic stroke were referred from the stroke unit to our cardiovascular department 3+/- 1 months after the acute event where they benefited from evaluation of cardiovascular risk factors, vascular and myocardial disease. Main outcome was defined as the prevalence of myocardial ischemia defined by perfusion stress echography 3 months after stroke. Secondary outcome (MACE) was defined as the incidence of stroke, transient ischemic attack (TIA), acute coronary syndrome, cardiovascular (CV) death or coronary or peripheral revascularization during a 3 year follow-up. ResultsThree hundred and twenty five patients (92% of strokes and 8% TIA) were included and median follow-up was 1075 days. At 3 months post-stroke, myocardial ischemia was found in 17 patients (5.2%). During the 3 year follow-up, 11 MACE occurred (3.4%, all in the non-ischemic group) of which 6 were recurrent strokes. In multivariate analysis, myocardial ischemia was significantly associated with the number of atheromatous vascular beds (OR 4.3; 95% CI, 1.7 to 10.6) and ECG signs of necrosis (OR 6.5; 95% CI, 1.9 to 21.9). MACE were also associated with ECG signs of necrosis (OR 3.5; 95% CI, 1.3 to 9.1), and unrelated to myocardial ischemia. ConclusionMyocardial ischemia and CV events were infrequent and both strongly associated with ECG signs of necrosis, suggesting a low yield of stress tests and the potential for a more straightforward algorithm in the choice of patients eligible to coronary angiogram or other coronary imaging in post-stroke setting.

Assessment of risk factors and prescription analysis among embolic and atherosclerotic stroke patients in a charitable hospital-a retrospective study

Assessment of risk factors and prescription analysis among embolic and atherosclerotic stroke patients in a charitable hospital-a retrospective study

Screening of Phospholipids in Plasma of Large-Artery Atherosclerotic and Cardioembolic Stroke Patients With Hydrophilic Interaction Chromatography-Mass Spectrometry.

Ischemic stroke (IS) is a deadly and debilitating disease with a high incidence and recurrence rate in elderly people worldwide. Large-artery atherosclerotic (LAA) and cardioembolic (CE) stroke are two leading subtypes and require different management. As a complementary biochemistry method for current diagnostic techniques, a sensitive and accurate phospholipid (PL) targeted lipidomic method was developed in this study. Plasma PLs were selectively extracted with titanium dioxide/fibrous silica nanosphere material, then characterized and quantified with hydrophilic interaction chromatography-mass spectrometry. A total of 31 molecular species of PLs were determined and ten biomarkers including seven molecular species of sphingomyelins (SM d18:1/18:1, d18:1/18:0, d18:1/24:1, d18:1/16:1, d18:1/22:1, d18:1/24:2, and d18:1/16:0) and three molecular species of phosphatidylcholines (16:0/18:1, 16:0/18:2 and 16:0/22:6) showed significant differences in LAA, CE, and healthy control (HC) groups. The independent diagnostic capabilities of these PL biomarkers were successfully evaluated and validated with receiver operating characteristic curves. Additionally, the oleic acid-enriched SMs, which can result in atherogenic lipoprotein aggregation, were proved to be positively related to IS and may perform as the potential risk factors in the future. Meanwhile, valuable suggestions for dietary interventions as an essential source of endogenous PLs could be obtained from this study.

Missense Variants in Hypoxia-Induced VEGFA/VEGFR2 Signaling Predict the Outcome of Large Artery Atherosclerotic Stroke.

Collateral density variations are a major determinant of stroke outcome. Here, we explored the association of missense variants in hypoxia-induced VEGFA/VEGFR2 signaling and stroke outcome. We recruited 683 large artery atherosclerotic (LAA) stroke patients as the training set from Nanjing Stroke Registry Program between August 2013 and January 2016. To validate the findings from the training set, we recruited an additional 333 LAA stroke patients between February 2016 and January 2017 as the validation set. Genotyping of target SNPs (rs11549465 [HIF-1α], rs11549467 [HIF-1α], rs1870377 [VEGFR2], and rs2305948 [VEGFR2]) was conducted using a SNPscan method. Unfavorable outcome was defined as a modified Rankin Scale (mRS) score > 2 at three months after index event. In the training set, the AA genotype of rs1870377 led to a decreased risk of unfavorable outcomes in the recessive model (AA vs. TA + TT, OR 0.60, 95% CI 0.38-0.95, P = 0.031). This was confirmed in the validation set (OR 0.43, 95% CI 0.21-0.86, P = 0.017) and the combined set (OR 0.54, 95% CI 0.36-0.79, P = 0.002). We also found that A allele was a protective factor for stroke outcome in both validation set and combined set (OR 0.70, 95% CI 0.49-0.99, P = 0.044 and OR 0.77, 95% CI 0.63-0.94, P = 0.012, respectively). In silico analysis indicated that the rs1870377 variant led to structural alterations in VEGFR2 that may influence its activity. Our findings demonstrate that the rs1870377 in the hypoxia-induced VEGFA/VEGFR2 axis predicts the 3-month outcome of patients with LAA stroke.

Association of statin pretreatment with collateral circulation and final infarct volume in acute ischemic stroke patients: A meta-analysis

Background and aimsStatin pretreatment (SP) is associated with improved outcomes in acute ischemic stroke (AIS) patients. Collateral circulation status and final infarct volume (FIV) are independent predictors of functional outcome in AIS. MethodsWe sought to evaluate the association of SP with collateral circulation and FIV in AIS patients. We used a random-effects model for all the analyses, and pooled standardized mean differences (SMDs) and odds ratios (OR) on the FIV and collateral status according to SP history, respectively. ResultsWe identified 9 eligible studies (1186 AIS patients). History of SP was associated with lower FIV (SMD = 0.25, 95%CI: 0.07–0.42, p = 0.005) compared to negative history of SP. A trend towards good collateral scores was observed in the SP group (OR = 1.45; 95% CI, 0.92–2.29, p = 0.11). Subgroup analysis demonstrated reduced FIV among atherosclerotic stroke patients with history of SP (SMD = 0.49; 95% CI, 0.19–0.80, p = 0.001). ConclusionsSP appears to be associated with decreased FIV, especially in atherosclerotic AIS.

Beneficial effects of pre-stroke statins use in cardioembolic stroke patients with atrial fibrillation: a hospital-based retrospective analysis.

IntroductionStatins are widely used in stroke patients. The AHA/ASA guidelines recommend aggressive statin therapy in atherosclerotic stroke patients. Their beneficial effects are due to both their hypolipemic and pleiotropic properties. The aim of this study was to establish potential benefits from statin use in ischemic stroke patients with the diagnosis of atrial fibrillation (AF).Material and methodsIschemic stroke patients with AF were enrolled in the study. Group I, the statin group (n = 181), consisted of patients who had been treated with statins before stroke. Group II, the non-statin group (n = 153), consisted of patients who had not received such treatment in the last year. In-hospital mortality and neurological deficit on admission and at discharge were analyzed using the National Institutes of Health Stroke Scale (NIHSS) score.ResultsPatients from the non-statin group had greater initial and discharge NIHSS scores (10 vs. 11.9, probability value p < 0.05; 7.6 vs. 9.5, p < 0.05 respectively). The improvement in NIHSS score was greater in the statin group (73.5% vs. 59.5%, p < 0.01). In-hospital mortality was more frequent in the non-statin group (9.9% vs. 18.3%, p < 0.05).ConclusionsDespite the predominant use of statins in atherothrombotic stroke patients, we demonstrated the beneficial effects of statins in cardioembolic stroke patients. Detailed cardiovascular screening for statin therapy should be carried out in all AF patients with regard to primary and secondary stroke prevention.

Impact of Tag Single Nucleotide Polymorphisms (SNPs) in CCL11 Gene on Risk of Subtypes of Ischemic Stroke in Xinjiang Han Populations.

BackgroundCCL11 is an important inflammatory cytokine associated with inflammation-related diseases such as atherosclerosis and stroke. The aim of this study was to investigate the relationship between CCL11 gene polymorphism with subtypes of ischemic stroke in Xinjiang Han populations.Material/MethodsThe improved multiple ligase detection reaction (iMLDR) method was used to analyze the genotypes of 6 tag SNPs in the CCL11 gene (rs1129844, rs17809012, rs1860183, rs1860184, rs4795898, and rs4795895) in a case-control study of 406 lacunar stroke patients, 214 large-artery atherosclerotic (LAA) stroke patients, and 425 controls.ResultsWe found the GG genotype of rs4795895 was significantly associated with increased risk of lacunar stroke (adjusted OR=1.676, 95%CI=1.117–2.515), and the GA genotype of rs17809012 was associated with a significant increase in risk of LAA stroke (adjusted OR=1.337, 95%CI=1.127–1.585). Hypertension stratification analyses showed that the GA genotype of rs17809012 was significantly associated with LAA stroke in the hypertensive group (adjusted OR=1.274, 95%CI=1.015–1.601). In the non-hypertensive group, the GA genotype of rs17809012 was significantly associated with LAA stroke (adjusted OR=1.361, 95%CI=1.041–1.780). The GG genotype of rs4795895 (adjusted OR=1.147, 95%CI=1.115–4.134) and the TT genotype of rs1860184 were significantly associated with lacunar stroke (adjusted OR=2.440, 95%CI=1.550–3.840).ConclusionsThis study demonstrates that the CCL11 gene could play an important role in the pathogenesis of lacunar stroke and LAA stroke in the Han population of China.

Association of cytochrome P4502E1 and NAD(P)H:quinone oxidoreductase 1 genetic polymorphisms with susceptibility to large artery atherosclerotic ischemic stroke: a case-control study in the Turkish population.

Stroke, a major cause of death and disability, is described as interruption or severe reduction of blood flow in cerebral arteries. Oxidative stress plays an important role in the pathogenesis of atherosclerosis and carotid atherosclerosis is a risk factor for stroke. Combination of multiple environmental and genetic risk factors is thought to increase stroke. Therefore, investigation of the polymorphisms of enzymes is of crucial importance to determine the molecular etiology of the disease. To test this hypothesis, we performed a case-control study in which we compared the distribution of CYP2E1 and NQO1 genotypes between 245 large artery atherosclerotic ischemic stroke patients and 145 controls, using PCR-RFLP. A significant difference was observed between stroke patients and controls with respect to the CYP2E1*5B genotype (odds ratio; OR 8.069, P=0.011) and allele (OR 7.876, P=0.011) distribution. However, this polymorphism was not a significant predictor of disease status in logistic regression analysis. NQO1*2 polymorphism genotype distribution was significantly different between patients and controls (P=0.027) and heterozygote *1*2 genotype was found to be a protective factor against large artery atherosclerotic ischemic stroke in logistic regression analysis (OR 0.562, P=0.018). This is the first study conducted regarding the association of CYP2E1 and NQO1 genetic polymorphisms and large artery atherosclerotic ischemic stroke risk in Turkish population.

Abstract WMP70: Enhancement of Atherosclerosis Prediction by Interaction of Circulating mir-212 with Hemoglobin A1c, Lipoprotein(a), and High-density Lipoprotein Cholesterol

Background and Objectives: The present study aimed to identify atherosclerosis-related circulating miRNAs and to evaluate their interaction with other cardiovascular risk markers to improve the prediction of atherosclerosis presence. Methods: We used miRNA profiling to identify atherosclerosis-related miRNAs using serum of 8 non-atherosclerotic and 7 severe atherosclerotic ischemic stroke patients. Expression of the target miRNAs identified was validated in 38 non-atherosclerotic and 37 atherosclerotic patients. Associations of the target miRNAs with other cardiovascular risk markers to predict atherosclerosis presence were analyzed using forward logistic regression analysis. Interactions of miRNAs with risk markers in the prediction of atherosclerosis presence were analyzed using accuracy and discrimination analysis. Results: miR-212, -30c, -372, -454, and, -744 were identified as atherosclerosis-related miRNAs. Only miR-212 showed a significant increase in expression in atherosclerotic patients of the validation population. Of various established markers tested, hemoglobin A1c, high-density lipoprotein cholesterol, and lipoprotein(a) were independently related with atherosclerosis presence in the validation population. miR-212 significantly increased the accuracy (three markers, 78.55%; three markers+miR-212, 84.6%) and area under the receiver operating characteristic curve (three markers, 0.8258; three markers+miR-212, 0.8646) of atherosclerosis prediction by the three existing markers. Conclusion: We identified circulating miR-212 as a novel marker of atherosclerosis. miR-212 synergistically enhanced the prediction of atherosclerosis-presence in combination with hemoglobin A1c, high-density lipoprotein cholesterol, and lipoprotein(a). Thus, miR-212 is expected to improve the prediction of atherosclerosis using peripheral blood of patients.

Abstract TP127: Mortality and Recurrence in Atherosclerotic Ischemic Stroke: Long-term Follow-up

Background and purpose: Atherosclerotic ischemic stroke is the second most frequent etiology of stroke in the adult population. Functional outcome, mortality and recurrence of stroke rates on the long-term follow-up are poorly studied. This study investigates long-term outcome among patients with ischemic stroke secondary to atherosclerotic causality, and identifies the main factors associated with poor outcome, recurrence, and death. Methods: We analyzed data from our consecutive acute ischemic stroke database, over a period of 25 years (1990-2015). The endpoints were: bad outcome (Modified Rankin Score ≥3), recurrence and mortality at discharge, and final follow-up. Multivariate Cox and Kaplan-Meier analysis were used to estimate the probability of death and recurrence. Results: A total of 946 consecutive atherosclerotic stroke patients were included (571 [60.4%] males, median age 65 years [interquartile range 57-73 years] for the entire population); dyslipidemia (64.2%), hypertension (63.3%), diabetes (35.0%), and active smoking history (31.8%) were the most prevalent risk factors.After a median follow-up of 38 months (IQR 12-75 months), 59.3% patients had a bad outcome at discharge. A result of 26.1% had stroke recurrence (median time until recurrence: 9 months [IQR 12-84 months], with 12.9% cases presenting ≥2 recurrences), and 24.1% were dead (median time to death: 18.5 months [IQR 11-74 months]) at the final follow-up period. After multivariate adjustment, hypertension (HR 4.2, CI 95% 2.8-6.1; p&lt;0.001) was the strongest predictor of recurrence. Additionally, diabetes (HR 2.6, CI 95% 2.0-3.5; p&lt;0.001), bad functional outcome after recurrence (HR 2.3, CI 95% 1.9-2.9; p&lt;0.001), age ≥65 years (HR 2.2, CI 95% 1.7-2.9; p&lt;0.001), and active smoking (HR 1.8, CI 95% 1.3-2.3; p&lt;0.001) were the strongest predictors of mortality. Conclusions: Atherosclerotic ischemic stroke has a high rate of recurrence, associated mainly with hypertension. Mortality is predicted by diabetes, bad functional outcome at recurrence, and older age.

Angiopoietin-like protein 4 serum levels and gene polymorphisms are associated with large artery atherosclerotic stroke

BackgroundAngiopoietin-like protein 4 (ANGPTL4) is a central player in lipid metabolism and atherosclerosis and may thus be involved in ischaemic stroke. However, no study in humans has investigated the association of ANGPTL4 gene polymorphisms or serum levels with ischaemic stroke. MethodsWe investigated the influence of the tagged single nucleotide polymorphisms (tSNPs) rs4076317 (c.207C>G) and rs1044250 (c.797C>T; T266M) of the ANGPTL4 gene on ischaemic stroke risk in a large group of 712 large artery atherosclerotic (LAA) stroke patients and 828 controls. In addition, we examined the association of the serum ANGPTL4 levels with lipid metabolism, LAA stroke severity and ischaemic volume in a sample of 302 LAA stroke patients and 307 controls. ResultsThe findings reveal that rs4076317 exerts a co-dominant effect on lower serum TG levels compared with common homozygotes. Fewer stroke cases were homozygous for variants of rs4076317 compared with the controls (7.0% vs. 10.9%). The serum ANGPTL4 levels in patients were significantly higher than those in the controls in a univariate manner (P=0.001) and after adjustment for other risk factors (1.463 [1.215–1.835]; P<0.001). Consistently, the ANGPTL4 levels were statistically correlated with higher NIHSS scores (r=0.172, P=0.003) and larger lesion volumes (r=0.124, P=0.031). ConclusionWe concluded that the tagged SNPs and high serum levels of ANGPTL4 are associated with LAA stroke and the lipid characteristics.

Lower levels of plasma adiponectin and endothelial progenitor cells are associated with large artery atherosclerotic stroke

Background: Both adiponectin and endothelial progenitor cells (EPCs) have been proposed recently with anti-atherosclerosis effects. However, their impacts on vascular outcomes in patients with large artery atherosclerosis (LAA) are unclear. This study aimed to investigate the relationship between adiponectin, EPCs and stroke with a case-control design. Methods: The study cohort included 127 patients (61.3 ± 11.0 years; 73.2% men) with LAA stroke and 58 control subjects (60.9 ± 9.2 years; 70.7% men) referred for adiponectin and EPCs levels testing. We collected demographic, clinical, angiographical features, and laboratory data. Influence of adiponectin and EPCs levels on cerebral atherosclerosis and LAA stroke was analyzed with regression models. Results: The levels of adiponectin and EPCs in atherosclerotic stroke patients were significantly lower compared with matched controls (p < 0.05). Logistic regression analysis identified that reduced levels of adiponectin and EPCs were closely correlated with cerebral atherosclerosis and LAA stroke. The associations remained significant after adjustment for age, sex and other confounders. Additionally, partial correlation analysis revealed a significant positive association between adiponectin and three subpopulations of EPCs levels (CD34+CD133+CD309+cells: r = 0.510, p = 0.001; CD34+ CD133−CD309+cells: r = 0.262, p = 0.004; CD34−CD133+CD309+cells: r = 0.348, p < 0.001). Conclusions: Adiponectin is positively correlated with EPCs levels, and both of them are independently associated with LAA stroke.

Factors Associated with Severity of Leukoaraiosis in First-ever Lacunar Stroke and Atherosclerotic Ischemic Stroke Patients

Leukoaraiosis (LA) is an indicator of small vessel disease, but little is known about the relationship between the severity of LA and etiologic subtype of ischemic stroke. Our study aimed to investigate the factors associated with the severity of LA and the relationship between the severity of LA and etiologic subtype of ischemic stroke. A total of 791 patients with first-ever ischemic stroke within 7 days were enrolled in our study. We evaluated cranial magnetic resonance imagings including severity of LA in periventricular and deep white matter, severity of silent lacunar infarcts (SLIs), etiologic subtype of ischemic stroke, and topographic patterns of acute cerebral infarcts. Severity of LA was graded as grade 0 when Fazekas scores = 0, grade 1 when Fazekas scores ranged from 1 to 2, and grade 2 when Fazekas scores were greater than or equal to 3. Multivariable ordinal logistic regression was used to analyze the factors associated with the severity of LA. A total of 748 patients (94.6%) had LA, the numbers and proportions of grade 0, grade 1, and grade 2 LA were 43 patients (5.4%), 413 patients (52.2%), and 335 patients (42.4%), respectively. In multivariable ordinal logistic regression analysis, increasing age, higher diastolic blood pressure, admission National Institutes of Health Stroke Scale scores less than or equal to 3, presence of SLIs, and small artery occlusion (SAO) subtype of ischemic stroke were found to be independently associated with higher grade of LA. LA is prevalent in first-ever ischemic stroke patients. Severe LA is more frequently associated with higher grades of SLIs and ischemic stroke due to SAO.

Abstract T P86: Lipid Profiling Reveals Galatosylceramide Increasing in Plasma of Atherosclerotic Stroke

The development and innovation of new technique in metabonomics research and its application in medicine provides important resolution in screening biomarkers and targets for further investigation. The metabonomics research has unique advantages of facility, objection and reliability compared with other -omics studies. Lipidomics research was development based on metabonomics and has supreme merits in study of lipids related disease. Method: The carotid arthrosclerosis patients with stroke suffered before were recruited in this research. The items of lipid related laboratory examinations of these patients are normal because of well controlling under drug-taken. The peripheral blood of these patients was drawn and the plasma was isolated after centrifugation. The lipids from plasma were extracted by the standard Folch method. Then the lipids samples were injected for lipid profile analysis by 2D QoF LC/MS. The qualitative differentiations of these lipids were based on their m/z value, characteristic of the compounds fragmentation, direct and relative retention time of each lipid class. On the establishment of the lipids identification, we validated this newly 2D QoF LC/MS method following these measurements including its calibration equations, low of the detection and relative standard deviation. Result: Compared with native subjects, 518 different types of lipids molecular from 17 classes were identified from plasma of atherosclerosis patients by the method of 2D QoF LC/MS; The galactosylceramide and glucoceramide were identified separately although they were same of molecular weight; We proved that the levels of galactosylceramide, rather than glucoceramide were increasing in atherosclerotic stroke patients. Conclusion: the increasing levels of galactosylceramide in plasma of atherosclerosis patients hint that the immune effects induced by lipids play an important role in atherosclerosis.

Antioxidant effects of statins in patients with atherosclerotic cerebrovascular disease.

Background and PurposeOxidative stress is involved in the pathophysiological mechanisms of stroke (e.g., atherosclerosis) and brain injury after ischemic stroke. Statins, which inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, have both pleiotropic and low-density lipoprotein (LDL)-lowering properties. Recent trials have shown that high-dose statins reduce the risk of cerebrovascular events. However, there is a paucity of data regarding the changes in the oxidative stress markers in patients with atherosclerotic stroke after statin use. This study evaluated changes in oxidative stress markers after short-term use of a high-dose statin in patients with atherosclerotic stroke.MethodsRosuvastatin was administered at a dose of 20 mg/day to 99 patients who had suffered an atherosclerotic stroke and no prior statin use. Blood samples were collected before and 1 month after dosing, and the serum levels of four oxidative stress markers-malondialdehyde (MDA), oxidized LDL (oxLDL), protein carbonyl content (PCO), and 8-hydroxy-2'-deoxyguanosine (8-OHdG)-were evaluated to determine the oxidation of MDA and lipids, proteins, and DNA, respectively, at both of those time points.ResultsThe baseline levels and the degrees of reduction after statin use differed among the oxidative stress markers measured. MDA and PCO levels were associated with infarct volumes on diffusion-weighted imaging (r=0.551, p<0.05, and r=0.444, p=0.05, respectively). Statin use decreased MDA and oxLDL levels (both p<0.05) but not the PCO or 8-OHdG level. While the reduction in MDA levels after statin use was not associated with changes in cholesterol, that in oxLDL levels was proportional to the reductions in cholesterol (r=0.479, p<0.01), LDL (r=0.459, p<0.01), and apolipoprotein B (r=0.444, p<0.05).ConclusionsThe impact of individual oxidative stress markers differs with time after ischemic stroke, suggesting that different oxidative markers reflect different aspects of oxidative stress. In addition, short-term use of a statin exerts antioxidant effects against lipid peroxidation via lipid-lowering-dependent and -independent mechanisms, but not against protein or DNA oxidation in atherosclerotic stroke patients.

Changes in platelet GPIbα and ADAM17 during the acute stage of atherosclerotic ischemic stroke among Chinese

Glycoprotein (GP) Ibα ectodomain shedding has important implications for thrombosis and hemostasis. A disintegrin and metalloproteinase 17 (ADAM17) was identified to play an essential role in agonist induced GPIbα shedding. The relationship of GPIbα shedding and ADAM17 in the acute stage of atherosclerotic ischemic stroke (AIS) patients has not been thoroughly studied. A total of 306 patients and 230 controls matched for age, sex, race, history of hypertension and diabetes mellitus were enrolled in the study. GPIbα, ADAM17, glycocalicin were detected by flow cytometry, Western blotting, and enzyme-linked immunosorbent assay (ELISA) respectively. Compared with the control group, the expression of GPIbα in patients with acute ischemic stroke was significantly lower (P=0.000, P<0.01). Plasma glycocalicin and ADAM17 in AIS group were higher than those in control group (P=0.699, P=0.000). Pearson's analysis showed glycocalicin bore no correlation with GPIbα in AIS patients (r=0.095, P>0.05). GPIbα and National Institute of Health Stroke Scale (NIHSS) had negative correlation (r=-0.514, P<0.01). Our findings indicate that ADAM17 may be a risk factor for ischemic stroke in Chinese and the expression of GPIbα can serve as a measure for stroke severity.

Abstract WP231: Detection of Intramural Hematoma by Susceptibility Weighted Image in Vertebral Artery Dissection

Objectives The radiologic diagnosis of vertebral artery dissection (VAD) depends on the characteristic intraluminal findings on angiographic study although the pathology of VAD is intramural hematoma. We aimed to know whether ‘intramural hematoma sign (IHS)’ on susceptibility weighted image (SWI) in vertebral artery is specific for VAD. Methods We retrospectively analyzed SWI and phase map images of the consecutive patients with ischemic stroke in the vertebral artery territory from August 2009 to July 2012. We divided the patients into 2 groups; VAD related stroke and atherosclerotic stroke. Diagnostic criteria of VAD related stroke were (a) presence of posterior neck pain or occipital headache and (b) features of VAD at computed tomography angiography or contrast enhanced magnetic resonance angiography or digital subtraction angiography. Angiographic evidence of VAD which is subdivided into three groups: aneurysmal dilatation without stenosis, pearl-and string, and steno-occlusive without aneurysmal dilatation. IHS was considered positive if the patient had (a) eccentric hypointense signal lesion in vertebro-basilar artery on SWI and (b) this signal should be hyperintense on phase map suggesting blood products other than calcification. An experienced neuroradiologist blinded to clinical information was asked to judge the presence of IHS. For statistical analysis, two by two contingency tables by Fisher’s exact test were performed. Results Among the 137 patients with ischemic stroke in the vertebral artery territory, SWI and phase map images were available in 47 patients who were included for our analysis. Among them, 14 patients were diagnosed as an ischemic stroke due to VAD and 33 patients had no VAD (atherosclerotic stroke). Compared to atherosclerotic stroke patients, patients with VAD-related stroke had more headache (64% vs 15%, P=0.016). Among the 14 patients with VAD-related stroke, IHS was detected in 9 cases while only 2 of 33 patients with atherosclerotic stroke showed IHS (sensitivity 64% and specificity 94%). In Fisher’s exact test analysis, the IHS was significantly associated with VAD (p &lt; 0.001). Conclusion The intramural hematoma sign on SWI was significantly associated with vertebral artery dissection.