Acute Noncardioembolic Ischemic Stroke Research Articles

Therapeutic-induced hypertension in patients with noncardioembolic acute stroke.

To evaluate the safety and efficacy of induced hypertension in patients with acute ischemic stroke. In this multicenter randomized clinical trial, patients with acute noncardioembolic ischemic stroke within 24 hours of onset who were ineligible for revascularization therapy and those with progressive stroke during hospitalization were randomly assigned (1:1) to the control and intervention groups. In the intervention group, phenylephrine was administered intravenously to increase systolic blood pressure (SBP) up to 200 mm Hg. The primary efficacy endpoint was early neurologic improvement (reduction in NIH Stroke Scale [NIHSS] score of ≥2 points during the first 7 days). The secondary efficacy endpoint was a modified Rankin Scale score of 0 to 2 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage/edema, myocardial infarction, and death. In the modified intention-to-treat analyses, 76 and 77 patients were included in the intervention and control groups, respectively. After adjustment for age and initial stroke severity, induced hypertension increased the occurrence of the primary (odds ratio 2.49, 95% confidence interval [CI] 1.25-4.96, p = 0.010) and secondary (odds ratio 2.97, 95% CI 1.32-6.68, p = 0.009) efficacy endpoints. Sixty-seven (88.2%) patients of the intervention group exhibited improvements in NIHSS scores of ≥2 points during induced hypertension (mean SBP 179·7 ± 19.1 mm Hg). Safety outcomes did not significantly differ between groups. Among patients with noncardioembolic stroke who were ineligible for revascularization therapy and those with progressive stroke, phenylephrine-induced hypertension was safe and resulted in early neurologic improvement and long-term functional independence. NCT01600235. This study provides Class III evidence that for patients with acute ischemic stroke, therapeutic-induced hypertension increases the probability of early neurologic improvement.

Retrospective Analysis of Argatroban in 353 Patients with Acute Noncardioembolic Stroke

Argatroban is a thrombin inhibitor agent for acute noncardioembolic ischemic stroke in Japan. We studied the prognosis in patients with acute stroke treated by argatroban in comparison with the control group with ozagrel in our hospital. A total of 513 patients with acute noncardioembolic ischemic stroke were enrolled retrospectively from our hospital database. Of all patients with stroke, 353 were administered with argatroban. The other 160 control patients were administered with ozagrel. The patients were examined as to their stroke types, the neurological severity according to the National Institutes of Health Stroke Scale (NIHSS), and clinical outcomes on discharge were determined according to the modified Rankin Scale (mRS). A total of 353 patients with acute noncardioembolic stroke, including 138 with lacunar infarction (LIs) and 215 with atherothrombotic infarction (ATI) showed functional recovery by argatroban, but the effectiveness of argatroban was not superior to ozagrel therapy defined by the control group. A total of 255 patients with ATI who were treated with both argatroban and ozagrel showed improvement by 1 point. We could not find any significant difference between argatroban and ozagrel in the 2 stroke subtypes, LI and ATI. We also found that combination therapy of argatroban and edaravone was not superior to argatroban monotherapy in clinical outcome. Argatroban therapy was not superior to control with ozagrel therapy in acute noncardioembolic ischemic stroke, including LI and ATI, regardless of the use of edaravone.

Could be considered serum anti-S-100 autoantibodies a biomarker in patients with acute non-cardioembolic ischemic stroke?

Could be considered serum anti-S-100 autoantibodies a biomarker in patients with acute non-cardioembolic ischemic stroke?

Baseline platelet parameters for predicting early platelet response and clinical outcomes in patients with non-cardioembolic ischemic stroke treated with clopidogrel.

PurposeThe present study investigated whether routine baseline platelet parameters(BPPs) detected before clopidogrel therapy in acute non-cardioembolic ischemic stroke(NCIS) could predict early platelet response and future clinical outcomes.ResultsThe CYP2C19 polymorphisms constituted independent risk factors for LCR. The number of female patients, the incidence of diabetes mellitus (DM), the level of low-density lipoprotein(LDL) cholesterol, and the neutrophil-to-lymphocyte ratio(NLR) were significantly high in the clinical clopidogrel resistance (CCR) group. However, none of the BPPs had a significant association with laboratory clopidogrel resistance (LCR) or discriminated with the cut-off values regarding LCR or CCR. The patients were divided into two groups according to the average mean platelet volume(MPV) or platelet count(PC). We found that the HbA1c level, the number of female patients, and the CCR were higher in the groups with elevated MPV (≥ 10.6fL) and PC (≥ 235 × 109/L); the LCR, the NIHSS score at discharge, and elevated MPV and PC were risk predictors for CCR.Materials and MethodsThis study included 196 patients with acute NCIS who underwent routine blood tests upon admission, were treated with clopidogrel, and were followed up for 6 months. Early platelet response was assessed and the CYP2C19 genetic variants were screened for. All participants were categorized into either laboratory clopidogrel resistance(LCR) or clinical clopidogrel resistance (CCR) groups.ConclusionsElevated baseline MPV and PC before clopidogrel therapy, as well as CYP2C19 gene variants, should be included in a risk algorithm for NCIS. Furthermore, other nongenetic clinical risk factors should be assessed for optimal prediction of the risk for thrombotic events because of individual variability in platelet response to clopidogrel.

Association of frequent genetic variants in platelet activation pathway genes with large-vessel ischemic stroke in Polish population

Platelets are critically involved in the development of cerebral ischemia. Our study aimed to establish an association between frequent (minor allele frequency (MAF) > 5%) genetic polymorphisms in 84 candidate genetic loci previously linked to platelet reactivity by the use of next-generation sequencing of exons from pooled DNA samples in Polish patients with a history of large-vessel ischemic stroke. Genetic analysis was performed on blood samples obtained from 500 patients (diagnosed with acute non-cardioembolic ischemic stroke with coexisting large-artery atherosclerosis) and age/sex/history of smoking matching 500 controls of Polish origin with high risk of cardiovascular disease. Sequencing of 10 pools (five for each ischemic and control groups) was performed on the Ilumina HiSeq2500 sequencer which generated an average of 36.1 (22.7–45.9 range) million pair-end 101 bp reads and 5.3 (3–7 range) Gbp per pooled sample consisting of 100 subjects. In total, we observed 789 frequent polymorphisms in the sequenced 84 genes (703 of single-nucleotide polymorphism (SNP) type and 86 indels). When the MAF between control and stroke groups was compared, only two intronic polymorphisms (1 SNP and 1 indel) in RGS7 (rs127445 36) and ANKS1B (rs398098426) genes, respectively, show statistically significant differences, which persisted after individual genotyping of the variants and adjustment for potential confounding factors. From the remaining variants, 35 polymorphisms displayed various degrees of nominal significance (from 0.6.3 × 10−5 to 5 × 10−2) and 754 polymorphisms did not show any statistical significance when comparison was evaluated for differences in MAF between the study groups. In conclusion, the results of the study demonstrate statistically significant differences in two frequent intronic genetic variants (in RGS7 and ANKS1B) that could be associated with the platelet function between ischemic stroke patients with coexisting large-vessel atherosclerosis and control patients having high vascular risk.

Treatment with Clopidogrel Prior to Acute Non-Cardioembolic Ischemic Stroke Attenuates Stroke Severity

Background: Clopidogrel reduces the risk of non-cardioembolic ischemic stroke, but it is unclear whether it affects the severity and outcome of stroke. We aimed at evaluating the effect of prior treatment with clopidogrel on acute non-cardioembolic ischemic stroke severity and in-hospital outcome. Methods: We prospectively studied 608 consecutive patients (39.5% males, age 79.1 ± 6.6 years) who were admitted with acute ischemic stroke. The severity of stroke was assessed at admission with the National Institutes of Health Stroke Scale (NIHSS). Severe stroke was defined as NIHSS ≥21. The outcome was assessed using the dependency rates that prevailed at the time of discharge (i.e. modified Rankin scale between 2 and 5) and with in-hospital mortality. Results: At admission, 397 patients did not have atrial fibrillation or heart valve disease. Among these 397 patients, 69 were receiving monotherapy with clopidogrel prior to stroke, 69 were receiving monotherapy with aspirin and 236 patients were not on any antiplatelet treatment. The prevalence of severe stroke was lower in patients who were receiving clopidogrel than in patients who were receiving aspirin and patients who were not on antiplatelets (1.4, 13.0 and 11.0%, respectively; p < 0.05). Independent predictors of severe stroke at admission were male gender (relative risk (RR) 0.31, 95% CI 0.12-0.78, p < 0.05) and treatment with clopidogrel prior to stroke compared with no antiplatelet treatment (RR 0.13, 95% CI 0.02-0.97, p < 0.05). Treatment with aspirin prior to stroke did not predict severe stroke compared with no antiplatelet treatment (RR 1.24, 95% CI 0.51-2.98, p = NS). The rate of dependency at discharge did not differ between patients who were receiving clopidogrel, patients who were receiving aspirin and those who were not on antiplatelets (57.9, 47.8 and 59.7%, respectively; p = NS). Independent predictors of dependency at discharge were age (RR 1.12, 95% CI 1.05-1.19, p < 0.001) and NIHSS at admission (RR 1.67, 95% CI 1.46-1.92, p < 0.001). In-hospital mortality rate also did not differ between patients who were receiving clopidogrel, patients who were receiving aspirin and those who were not on antiplatelets (4.3, 4.3 and 5.0%, respectively; p = NS). The only independent predictor of in-hospital mortality was NIHSS at admission (RR 1.22, 95% CI 1.14-1.30, p < 0.001). Conclusions: Treatment with clopidogrel prior to acute non-cardioembolic ischemic stroke attenuates the severity of stroke at admission but does not appear to affect the functional outcome at discharge or the in-hospital mortality of these patients.

Higher Levels of Cystatin C Are Associated with Extracranial Carotid Artery Steno-Occlusive Disease in Patients with Noncardioembolic Ischemic Stroke

Background: Large artery atherosclerosis is a major cause of ischemic stroke worldwide. Differential biomarker profiles associated with extra- and intracranial atherosclerosis are a topic of considerable interest. Cystatin C (CysC), a marker of renal function, is a risk factor for cardiovascular disease. Aim: We sought to determine whether CysC levels were associated with extra- and intracranial large artery stenosis (LAS) in patients with acute ischemic stroke. Methods: We retrospectively analyzed data of acute noncardioembolic ischemic stroke patients who were admitted to our stroke center within 5 days from symptom onset. Serum CysC levels were measured using latex agglutination turbidimetric immunoassay. Extra- and intracranial LAS were defined as ≥50% diameter stenosis or occlusion of the relevant internal carotid artery (ICA) and/or middle cerebral artery (MCA) using carotid echography and volume rendering on magnetic resonance angiography. Multivariate logistic analyses were used to assess the association between CysC levels and LAS after adjustment for potential confounders. Results: Of 205 patients (mean age 70.2 years), 76 (37.1%) had LAS. The distribution of LAS was 29 extracranial ICA, 34 intracranial ICA/MCA (8 ICA only, 25 MCA only, 1 ICA+MCA) and 13 tandem stenosis (both extracranial ICA and intracranial ICA/MCA). Levels of CysC were higher in patients with extracranial ICA stenosis than in those with intracranial ICA/MCA stenosis (1.23 ± 0.33 vs. 0.97 ± 0.21 mg/l, p < 0.001). In multivariate analysis, the highest CysC tertile (>1.04 mg/l) was significantly associated with extracranial ICA stenosis (adjusted odds ratio [OR] 5.01, 95% confidence interval [CI] 1.51-16.63, p = 0.009) after adjustment for age, sex, diabetes, chronic kidney disease, current smoking, systolic blood pressure, HDL cholesterol, high-sensitivity C-reactive protein (hs-CRP) and premorbid lipid-lowering drugs use. When CysC was considered as a continuous variable, 1 SD increase in CysC was significantly associated with extracranial ICA stenosis (adjusted OR 3.01, 95% CI 1.58-5.72, p = 0.001). However, there were no significant associations between CysC levels and intracranial ICA/MCA stenosis. In addition, CysC levels showed a weak but statistically significant correlation with hs-CRP levels (r = 0.195, p = 0.021). Using receiver operating characteristic curve analysis, CysC value displayed good performance in discriminating extracranial ICA stenosis (c-statistic 0.79, 95% CI 0.69-0.89, p < 0.001). Conclusions: This preliminary study suggests that higher levels of CysC were independently associated with symptomatic extracranial ICA stenosis, but not with intracranial ICA/MCA stenosis in patients with noncardioembolic stroke. Our findings provide new insights into the link between serum CysC and carotid atherosclerosis.

急性期非心原性脳梗塞患者における離床時の自律神経系活動評価の意義

〔目的〕急性期非心原性脳梗塞患者における病型による自律神経系活動の差異について明らかにする．〔対象〕対象は，急性期非心原性脳梗塞患者33名（年齢71.5歳，男性23名，女性10名）である．〔方法〕心電図は，安静，離床，回復の3条件で測定した．自律神経系活動指標（副交感神経系活動：lnHF，交感神経系活動：LF/HF）は，心拍変動解析により算出した．ラクナ梗塞患者とアテローム血栓性脳梗塞患者での自律神経系活動の比較を行った．〔結果〕ラクナ梗塞患者はアテローム血栓性脳梗塞患者に比べ，安静時のlnHFは低下（5.1 vs. 6.1），離床時のLF/HFは亢進していた（3.0 vs. 1.4）．〔結語〕急性期では，ラクナ梗塞患者は，アテローム血栓性脳梗塞患者に比し，自律神経系活動が低下する可能性がある．

Admission leukocytosis, C-reactive protein and erythrocyte sedimentation rate in acute noncardioembolic cerebral ischemia: influence on early outcome

Background There is growing evidence regarding the role of inflammation in the pathogenesis of ischemic stroke, especially nonembolic types of ischemic stroke. Despite this, there is a need to investigate the direct impact of inflammatory markers on the early outcome in nonembolic ischemic stroke. Objective The aim of the present study was to determine whether positive inflammatory markers such as raised erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and leukocytosis could be used as biochemical predictors for poor early outcome in patients with acute noncardioembolic ischemic stroke. Patients and methods A total of 60 patients(40 men and 20 women; median age: 64.5 years) with first attack of noncardioembolic ischemic stroke were included in the study. Full clinical assessment and routine laboratory investigation were conducted for all patients. MRI of brain, ECG, and cardiac echo were carried out to confirm the diagnosis and exclude cases with embolic stroke. Blood samples for all patients within the first 24 h of onset of symptoms were taken for assessment of ESR, qualitative CRP, and leukocyte count on admission. National Institute of Health Stroke Scale was used for all patients after 7 days. On the basis of their scores patients were divided into two groups: 40 patients with favorable outcome were included in the first group and 20 patients with bad outcome in the second group. Results There was significant difference between the two groups regarding ESR value, and the leukocyte count was higher in the group with bad prognosis. In addition, positive CRP was associated more with the same group in statistically significant way. Conclusion Inflammatory markers play an important role in detecting the early outcome of noncardioembolic stroke.

VASP phosphorylation and genetic polymorphism for clopidogrel resistance in Chinese patients with non-cardioembolic ischemic stroke

BackgroundClopidogrel resistance(CR)is found in non-cardioembolic ischemic stroke (NCIS) patients. However, it is still largely unknown how to identify CR in NCIS patients by laboratory and genetic characteristics. MethodsA total of 95 patients with acute NCIS were recruited. Phosphorylation of the vasodilator stimulated phosphoprotein (VASP) was detected using flow cytometry, and genes(CYP2C19,CYP3A4) were detected using the Sanger method. The baseline of platelet reactivity index (BPRI) before clopidogrel treatment and the platelet reactivity index with clopidogrel treatment (CPRI) for 7days were measured. Laboratory clopidogrel resistance (LCR) was defined as CPRI of ≥50%.Clinical clopidogrel resistance (CCR) was defined as the presence of progressive stroke during hospitalization, stroke recurrence or occurrence of other ischemic vascular events within 6months. ResultsThe incidence of LCR was 41.05% and 18.95% developed CCR. The incidence of LCR was significantly higher in GA/AA patients with CYP2C19 (681G>A) (χ2=11.16, P=0.001) and CYP2C19 (636G>A) (χ2=4.829, P=0.028) than in wildtype GG patients. CYP2C19 (681G>A) (OR 6.272, 95%CI 2.162,18.199,P=0.001) and CYP2C19 (636G>A) (OR: 5.625,95%CI 1.439, 21.583,P=0.013) were risk factors for LCR. patients with LCR were more likely to develop CCR (χ2=6.021, P=0.014). The probability of CCR was markedly increased in GA/AA patients with CYP2C19 (681G>A) (χ2=10.341, P=0.001). We identified CYP2C19 (681G>A) (OR 7.814, 95%CI 1.816, 33.618 P=0.006), Essen score (OR 8.351, 95%CI 1.848, 37.745 P=0.006), and LCR (OR 5.881, 95%CI 1.373, 25.192, P=0.017) as risk factors for CCR. ConclusionIn clinical practice,LCR and CYP2C19 gene polymorphism should be assessed in NCIS patients receiving clopidogrel treatment.The Chinese Clinical Trial Registry number: ChiCTR-ONC-13003406

Enteric-Coated Aspirin Versus Other Antiplatelet Drugs in Acute Non-Cardioembolic Ischemic Stroke: Post-marketing Study in Japan

Japanese guidelines recommend aspirin 160-300mg/day, starting within 48h, for patients with acute cerebral infarction. However, there are few reports evaluated in Japanese patients. Our objective was to examine the safety and efficacy of enteric-coated aspirin, compared with other oral antiplatelet drugs, in Japanese patients with acute ischemic stroke. We performed a prospective, non-randomized, observational and multicenter study between June 2005 and December 2007. Patients with symptomatic acute ischemic stroke, including transient ischemic attack (TIA), who started enteric-coated aspirin or other antiplatelet drugs within 7days of hospitalization were registered. Outcome measures evaluated within 3months were incidence of cerebral and non-cerebral hemorrhagic events, recurrence of ischemic stroke or TIA, non-cerebral ischemic events and death from any cause. Overall, 2,548 and 830 patients treated with enteric-coated aspirin (100-300mg/day) or other antiplatelet drugs, respectively, were registered; approximately 60% were male, mean age was 70years, 85% had pre-existing cardiovascular disease or other complications. Enteric-coated aspirin of 100mg was mainly prescribed, and only approximately half of the patients were started on it within 48h after onset of ischemic stroke. Safety and efficacy population excluded patients without follow-up data were 2,521 in enteric-coated aspirin and 807 in other antiplatelets. Hemorrhagic events occurred in 46 (1.8%) in the enteric-coated aspirin group and in 13 (1.6%) in the other antiplatelet drugs group, there was not significant. Recurrent ischemic stroke or TIA occurred in 39 (1.5%) of the enteric-coated aspirin and in 18 (2.2%) of other antiplatelet drugs, and there were any-cause death in 16 (0.6%) and 8 (1.0%). Incidences were slightly lower in the enteric-coated aspirin group compared with the other antiplatelet drugs group, but not statistically significant. It seems that these results showed the safety and efficacy of the enteric-coated aspirin in acute stroke care in Japanese patients. Incidence of hemorrhagic events was comparable between the enteric-coated aspirin group and the other antiplatelet drugs group.

Early Dual Versus Mono Antiplatelet Therapy for Acute Non-Cardioembolic Ischemic Stroke or Transient Ischemic Attack

Background— Emerging studies suggest that early administration of dual antiplatelet therapy may be better than monotherapy for prevention of early recurrent stroke and cardiovascular outcomes in acute ischemic stroke and transient ischemic attack (TIA). We performed a meta-analysis of randomized, controlled trials evaluating dual versus mono antiplatelet therapy for acute noncardioembolic ischemic stroke or TIA. Methods and Results— We assessed randomized, controlled trials investigating dual versus mono antiplatelet therapy published up to November 2012 and the CHANCE trial (Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events), for efficacy and safety outcomes in adult patients with acute noncardioembolic ischemic stroke or TIA with treatment initiated within 3 days of ictus. In total, 14 studies of 9012 patients were included in the systematic review and meta-analysis. Dual antiplatelet therapy significantly reduced risk of stroke recurrence (risk ratio, 0.69; 95% confidence interval, 0.60–0.80; P &lt;0.001) and the composite outcome of stroke, TIA, acute coronary syndrome, and all death (risk ratio, 0.71; 95% confidence interval, 0.63–0.81; P &lt;0.001) when compared with monotherapy, and nonsignificantly increased risk of major bleeding (risk ratio, 1.35; 95% confidence interval, 0.70–2.59, P =0.37). Analyses restricted to the CHANCE Trial or the 7 double-blind randomized, controlled trials showed similar results. Conclusions— For patients with acute noncardioembolic ischemic stroke or TIA, dual therapy was more effective than monotherapy in reducing risks of early recurrent stroke. The results of the CHANCE study are consistent with previous studies done in other parts of the world.

Thrombin generation in acute cardioembolic and non-cardioembolic ischemic stroke

Objective. Increased thrombin generation, as measured by the Calibrated Automated Thrombogram (CAT), has recently been reported to predict ischemic stroke, especially stroke with a cardioembolic source. However, there are few studies on thrombin generation using CAT in patients with manifest ischemic stroke, particularly in patients with cardioembolic stroke not yet on anticoagulation. Materials and methods. Therefore, a prospective cohort study of 205 stroke patients > 45 years of age was performed. They were recruited during their hospital stay or shortly thereafter. Inclusion criteria were ischemic stroke or TIA within two weeks and no atrial fibrillation (AF) in the history or at inclusion. Patients received a thumb ECG device in order to detect silent AF. Blood samples were collected at inclusion and after 1 month. Thrombin generation in plasma after addition of tissue factor was assessed in patients and in healthy controls. Results. Mean age of patients was 72 ± 7 years and 43% were females. Peak thrombin concentrations were variable among stroke patients but overall significantly higher at both time points (p < 0.0001) compared to controls, and tended to be highest in patients in whom paroxysmal atrial fibrillation was subsequently documented. Conclusion. Thrombin generation in patients with acute cardioembolic and non-cardioembolic schemic stroke/TIA is variable but overall higher compared to healthy subjects. The long-term prognostic value of thrombin generation in patients with a recent ischemic stroke deserves further investigation.

Secondary Prevention of New Vascular Events with Lifestyle Intervention in Patients with Noncardioembolic Mild Ischemic Stroke: A Single-Center Randomized Controlled Trial

Background: Lifestyle modification is associated with a substantially decreased risk of cardiovascular events. However, the role of lifestyle intervention for secondary prevention in patients with noncardioembolic ischemic stroke is inadequately defined. We assessed the hypothesis that lifestyle intervention can reduce the onset of new vascular events in patients with noncardioembolic mild ischemic stroke. Methods: We conducted an observer-blind randomized controlled trial that enrolled 70 patients (48 men, mean age 63.5 years) with acute noncardioembolic mild ischemic stroke. The patients were allocated in equal numbers to a lifestyle intervention group or a control group. We performed lifestyle interventions, which comprised exercise training, salt restriction and nutrition advice for 24 weeks. Then all patients were prospectively followed up for occurrence of the primary endpoints, including hospitalization due to stroke recurrence and the onset of other vascular events. We also evaluated systolic blood pressure (SBP) at the clinic and at home, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), hemoglobin A1c (HbA1c) and high-sensitivity C-reactive protein (hs-CRP) to compare the efficacy of the lifestyle interventions. Results: This trial was terminated earlier than expected because of the prespecified early stopping rule for efficacy. After the 24-week intervention period, the intervention group showed a significant increase in daily physical activity and a significant decrease in salt intake (physical activity, p = 0.012; salt intake, p < 0.001), with a significant difference between the randomized groups (physical activity, p < 0.001; salt intake, p = 0.018). Similarly, blood pressure was decreased and the HDL-C levels were increased in the intervention group (SBP, p < 0.001; HDL-C, p = 0.018), with significant differences between the randomized groups (SBP, p < 0.001; HDL-C, p = 0.022). In contrast, LDL-C, HbA1c and hs-CRP tended to decrease in the intervention group, but this decrease did not achieve significance. After a median follow-up period of 2.9 years, 12 patients allocated to the control group and 1 patient in the lifestyle intervention group experienced at least 1 vascular event. A sequential plans analysis indicated the superiority of the lifestyle intervention in interim analysis. Kaplan-Meier survival curves after the log-rank test showed a significant prognostic difference between the randomized groups (p = 0.005). Conclusions: Lifestyle intervention with appropriate medication is beneficial for reducing the incidence of new vascular events and improving vascular risk factors in patients with noncardioembolic mild ischemic stroke.

Prognostic Value of Inflammatory Mediators in 1-Year Outcome of Acute Ischemic Stroke with Middle Cerebral Artery Stenosis

Background and Purpose. Inflammation exists in inception, progression, and reperfusion of acute ischemic stroke. Insightful understanding of correlation in inflammatory mediators and stroke severity with intracranial artery stenosis may improve rational stroke therapy. Methods. We prospectively recruited 977 patients with acute noncardioembolic ischemic stroke with MCA stenosis by MRA as none to mild (<50%), moderate (50–69%), severe (70–99%), or occlusive (100%). The peripheral levels of WBC, homocysteine (HCY), and high sensitivity C-reactive protein (hs-CRP) were recorded. All patients were assessed of 1-year outcome by mRS as favorable (0–2) or poor (3–6). Results. The levels of WBC, HCY, and hs-CRP had no significant differences in patients with categorized MCA stenosis (all P > 0.05). Higher levels of WBC, HCY, and hs-CRP were found in patients with 1-year poor outcome (all P < 0.05), but only hs-CRP is an independent predictor (OR 1.06, 95% CI 1.027–1.093, P = 0.0003). The combination of any two of increased hs-CRP (>3 mg/L), WBC (>6.91 × 109/L), and HCY (>15 μmol/L) had higher power in predicting 1-year poor outcome than the single elevated mediator. Conclusions. Elevated hs-CRP independently predicts 1-year poor outcome in acute stroke. The combination of increased hs-CRP, WBC, or HCY had a stronger predictive value in poor outcome than individual elevated mediator.

The association of statin therapy and high-sensitivity C‐reactive protein level for predicting clinical outcome in acute non-cardioembolic ischemic stroke

BackgroundStatins reportedly have anti-inflammatory effects aside from their cholesterol-lowering effect. We investigated the effects of statins on serum hs-CRP level and clinical outcome of acute ischemic stroke (IS) patients. MethodsThis prospective cohort study consequently evaluated patients with acute IS in a single medical center. Serum hs-CRP levels were measured at different time points (within 48h and 30days post-stroke). The patients' clinical and laboratory data on admission were analyzed. ResultsTotal 100 patients with acute IS were divided in the statin group (n=50) and the non-statin group (n=50). Serum hs-CRP level was similar in the 2 groups within 48h after acute IS, but was significantly lower in the statin group on Day 30 compared to the non-statin group (p<0.05). The statin group also had favorable 3-month outcome compared to the non-statin group (p<0.05). After adjustments for covariance using stepwise logistic regression, only NIHSS on admission (OR=1.38, 95% CI=1.06–1.80; p=0.02) and hs-CRP in the acute phase (OR=1.74, 95% CI=1.30–2.33; p=0.001) were significantly and independently predictive of 3-month outcome. ConclusionStatin therapy reduces serum hs-CRP level and may be associated with favorable 3-month outcome in patients after acute IS.

Cost-effectiveness Analysis of the Neuroprotective Agent Edaravone for Noncardioembolic Cerebral Infarction

The free radical scavenger edaravone has been reported useful for improvement in activities of daily living and for prevention of recurrent stroke in the edaravone versus sodium ozagrel in acute noncardioembolic ischemic stroke (EDO) trial. The aim of this report was to evaluate the cost-effectiveness of edaravone compared to the intravenous antiplatelet drug ozagrel sodium (ozagrel) for noncardioembolic stroke (non-CES) based on the EDO trial data. A cost-effectiveness analysis was performed using the Markov model, which also incorporated the long-term course after the acute stage of non-CES. From the perspective of a health care payer, direct medical costs and nursing care costs were taken into account in the cost analysis. The quality-adjusted life year (QALY) served as an indicator of effectiveness. Simulation at 5 and 10 years after the onset of non-CES was carried out. The study involved 68-year-old patients with non-CES, selected against the EDO trial subject selection criteria. A 14-day treatment with edaravone 60 mg/day or ozagrel 160 mg/day was assumed as acute treatment for non-CES. The use of edaravone was associated with a reduction in total costs (0.51 million yen [$6,374] at 5 years and 0.64 million yen [$8,039]) at 10 years after the onset of non-CES) and improvement in QALYs (0.23 at 5 years and 0.38 at 10 years). Compared to ozagrel therapy, edaravone therapy was a cost-saving strategy for treating non-CES. Compared to ozagrel therapy, edaravone therapy for non-CES is not only useful from a clinical viewpoint, but also valuable from a socioeconomic perspective.

Associations of cigarette smoking with intracranial atherosclerosis in the patients with acute ischemic stroke

BackgroundAlthough cigarette smoking has been established as an important risk factor for stroke, the effect on the atherosclerotic stenosis, which are based on observational studies, have been controversial. We set out to examine the differences in the risk factors between smokers and nonsmokers and to investigate the association of cigarette smoking with cerebral arterial stenosis. MethodsA total of 989 consecutive patients with acute noncardioembolic ischemic stroke were prospectively enrolled from June 2004 to January 2010. The risk factor profiles were compared between smokers and nonsmokers. We analyzed the degree of stenosis in all MRA, and evaluated influencing factors in the patients with intracranial atherosclerosis (ICAS) and extracranial atherosclerosis (ECAS) who were randomly matched by age and sex. ResultsThere were differences in the distribution of risk factors between the 467 (70.0%) nonsmokers and the 215 (30.0%) smokers. Nonsmokers were older (71.7±11.0 versus 61.7±12.0, p<0.001) and had a higher frequency of hypertension than smokers had (75.4% versus 64.0%, p=0.002). When smokers and nonsmokers were age- and sex-matched, smoking was more prevalent in patients with ICAS than with ECAS (32.9% versus 28.2%). Conditional regression analysis revealed that smoking and hypertension increased the odds of ICAS [smoking, odds ratio (OR): 1.83, p=0.026; hypertension, OR: 1.84, p=0.01], whereas hyperlipidemia increased the odds of ECAS (OR: 1.87, p=0.034). ConclusionThe distributions of the major risk factors for ischemic stroke were different between smokers and nonsmokers. Cigarette smoking may be more associated with ICAS than with ECAS after adjusting for potential risk factors.

Utility of the Assessment of Echogenicity in the Identification of Symptomatic Carotid Artery Atheroma Plaques in Ischemic Stroke Patients

Background and Purpose: Echogenicity of atheroma carotid plaques is related to a higher risk of stroke. Clinical and subjective ultrasound criteria are used to identify symptomatic plaques, but the standardized grayscale median (GSM) value may be an objective tool for this diagnosis. Our aim was to analyze the utility of assessing the echogenicity of atheroma carotid plaques in the identification of symptomatic plaques. Methods: Observational prospective study with inclusion of acute noncardioembolic anterior cerebral circulation ischemic stroke patients. Only patients with bilateral atheroma plaques were included. Echogenicity of plaques was measured by a digital and standardized grayscale system in carotid ultrasound B-mode (longitudinal projection) conducted within the first week after admission. Results: Sixty-six patients were included and 132 plaques were examined. Symptomatic atheroma plaques were less echogenic than asymptomatic ones (GSM 20.0 vs. 29.0; p = 0.002). A ROC curve analysis showed the predictive value of GSM with an AUC of 0.707 (95% CI 0.592–0.823; p = 0.002) and pointed to a value of 24.4 as the optimal cut-off level to identify a plaque as symptomatic (74% sensitivity; 67% specificity). This GSM cut-off point remained significantly associated with a high probability of symptomatic plaque even after the inclusion of the degree of carotid stenosis (either >70% or >50%) in the multivariate logistic regression models. Conclusions: The assessment of echogenicity of atheroma carotid plaques by the GSM value combined with clinical characteristics and stenosis degree may be useful in the identification of symptomatic plaques.

Clopidogrel vs. Aspirin Treatment on Admission Improves 5-Year Survival After a First-ever Acute Ischemic Stroke. Data from the Athens Stroke Outcome Project

Background and Aims We undertook this study to compare the impact of aspirin vs. clopidogrel treatment on 5-year survival of patients experiencing a first-ever acute ischemic noncardioembolic stroke. Methods This was a retrospective study involving patients with an acute ischemic stroke who had an indication for antiplatelet therapy (atherothrombotic, lacunar and cryptogenic stroke subtype). A total of 1228 (383 women) hospitalized due to an acute first-ever stroke and receiving aspirin ( n = 880) or clopidogrel ( n = 348) were finally involved. To determine the factors that independently predict 5-year survival statistical analysis including the Kaplan-Meier survival curve and multifactorial analysis (Cox regression) was performed. Results Subjects treated with clopidogrel had improved 5-year survival compared with those receiving aspirin (log rank test: 16.4, p <0.0001). The difference in survival was evident as early as 6 months from index stroke: cumulative survival 93.8% for aspirin vs. 97% for clopidogrel (log rank test: 4.01, p = 0.045). The composite cardiovascular event (including stroke recurrence, myocardial infarction, unstable angina, coronary revascularization, aortic aneurysm rupture, peripheral atherosclerotic artery diseases, and sudden death) rates were lower in the clopidogrel group ( n = 60, 17.2%) compared with the aspirin ( n = 249, 28.3%) group (log rank test: 12.4, p <0.0001). This preferential effect of clopidogrel over aspirin was independent of age, gender, presence of cardiovascular disease other than stroke or cardiovascular risk factors as well as irrespective of the severity of stroke and days of hospitalization. Conclusions This study supports that clopidogrel is superior to aspirin in preventing death and cardiovascular events after an acute noncardioembolic ischemic stroke.