Large Artery Atherosclerosis Patients Research Articles

Intravenous Thrombolysis Benefits Mild Stroke Patients With Large-Artery Atherosclerosis but No Tandem Steno-Occlusion.

At present, there is controversy regarding whether thrombolysis is beneficial for patients suffering from a mild stroke. In this study, we therefore sought to determine whether the therapeutic benefit of thrombolysis is dependent upon stroke subtype for those with mild stroke. We conducted a retrospective analysis of data from consecutive mild stroke patients (National Institutes of Health Stroke Scale ≤5) with and without recombinant tissue plasminogen activator (rt-PA) therapy. The TOAST (Trial of Org 10172 in acute stroke treatment) criteria was used to determine stroke subtypes. Patients suffering from large-artery atherosclerosis (LAA) were subdivided based upon whether or not they exhibited tandem steno-occlusion, as defined by the association of a proximal intracranial occlusion and a cervical internal carotid artery lesion (complete occlusion or severe stenosis ≥ 90%). For this study, favorable outcomes at 90 days of onset (modified Rankin Scale Score [mRS] of 0–1) were the primary measured outcome. Three hundred thirty-nine patients were included in the study. For patients with non-LAA, there were not statistically significant improvements in favorable outcomes for rt-PA treatment (p = 0.889, 0.929, 0.708; respectively). For patients with LAA, compared with non-treated group, rt-PA-treated patients had a significant in the rate of favorable outcomes at 90 days (82.8 vs. 64.9%; OR 2.59; 95%CI, 1.13–5.92; P = 0.024). Among LAA patients exhibiting tandem lesions, favorable outcomes were observed in 66.7% of rt-PA-treated patients, with no significant differences to those observed in untreated patients (OR 1.00; 95%CI, 0.23–4.28; p = 1.000). Among LAA patients without tandem lesions, compared with non-treated group, we found that rt-PA treatment was associated with a significant beneficial impact on favorable outcomes after 90 days (64.4 vs. 88.4%; OR 4.20; 95%CI, 1.43–12.30; p = 0.009). Our findings suggest that intravenous rt-PA is only beneficial in mild stroke patients with LAA-type strokes that do not exhibit tandem steno-occlusion.

A high neutrophil-to-lymphocyte ratio predicts hemorrhagic transformation of large atherosclerotic infarction in patients with acute ischemic stroke.

Increasing evidence suggests that inflammation is associated with the development of acute ischemic stroke (AIS). The neutrophil-to-lymphocyte ratio (N/L) is an important marker of inflammation and is highly correlated with mortality in stroke patients in recent studies. The N/L of patients who experience hemorrhagic transformation (HT) after AIS is know, but any relationship between N/L and large artery atherosclerosis (LAA) remains unclear, this is our present topic. We enrolled 185 patients with LAA-type HT in the development cohort from a prospective, consecutive, hospital-based stroke registry to this end. We matched these patients to 213 LAA patients who did not develop HT as controls. The incidence of HT after LAA was significantly greater (P<0.01) in patients with higher N/L. We developed a predictive nomogram (incorporating age, systolic blood pressure, the National Institutes of Health Stroke Scale, and the N/L) for LAA patients. The predictive power was good (area under the curve, AUC: 0.832, 95%CI: 0.791–0.872). Our findings were further validated in a validation cohort of 202 patients with AIS attributable to LAA (AUC:0.836, 95%CI:0.781–0.891). In summary, a high N/L is associated with an increased risk for HT after LAA.

Diagnostic Significance of Plasma Levels of Novel Adipokines in Patients With Symptomatic Intra- and Extracranial Atherosclerotic Stenosis.

Background: Adipokines have been proven to be associated with atherosclerotic diseases such as ischemic stroke and coronary heart disease. The role of novel adipokines in the development of symptomatic intracranial atherosclerotic stenosis (sICAS) and extracranial atherosclerotic stenosis (sECAS) has not yet been investigated. This study aimed to evaluate the plasma levels of novel adipokines in patients with sICAS and sECAS and their associations with the prognosis of sICAS groups.Methods: A total of 134 patients with acute ischemic stroke attribute to large-artery atherosclerosis (LAA) and 66 age- and sex-matched controls without atherosclerotic stenosis (NCAS) were included in this study. The LAA group was further sub-classified as sICAS (n = 102) and sECAS (n = 32) according to the location of atherosclerosis. Demographics, clinical parameters, angiographical features and plasma levels of novel adipokines (apelin, visfatin, omentin, RBP-4) were assayed and compared among groups.Results: LAA patients had significantly lower levels of omentin [39.92 (30.74–52.61) ng/ml vs. 54.42 (34.73–79.91) ng/ml, P < 0.001] and visfatin [11.32 (7.62–16.44) ng/ml vs. 13.01 (9.46–27.54) ng/ml, P < 0.001] than those in the NCAS group. Multiple logistic regression analysis identified that the lowest tertile of omentin was independently associated with LAA (OR, 3.423; 95% CI, 1.267–9.244, when referenced to the third tertile). Levels of omentin, visfatin and RBP-4 showed no significant difference between sICAS and sECAS groups. However, median concentrations of apelin were lower in sECAS [84.94 (46.88–130.41) ng/mL) than in sICAS [118.64 (93.22–145.08) ng/mL, P = 0.002] and NCAS [114.38 (80.56–162.93) ng/mL, P = 0.004]. Logistic regression analysis showed that the lowermost tertile of apelin was independently associated with sECAS (OR, 5.121; 95% CI, 1.597–16.426) when adjusted for risk factors. As for sICAS patients, spearman coefficient analysis showed no significant correlation between these four adipokines and the severity of sICAS or the number of vessels with intracranial stenoses. Patients with severe stroke had lower levels of apelin (P = 0.005), while the other three adipokines showed no such difference. During follow up, no difference was found between these four novel adipokines and short- and long-term outcome of sICAS.Conclusions: Lower levels of omentin are independent biomarkers of LAA while low apelin plasma levels seem to be risk factors of sECAS.

Safety and Efficacy of Tirofiban Combined With Mechanical Thrombectomy Depend on Ischemic Stroke Etiology.

Background and Purpose: The clinical use of tirofiban for patients with acute ischemic stroke (AIS) who underwent mechanical thrombectomy (MT) remains controversial. We aimed to evaluate the safety and efficacy of tirofiban combined with MT in AIS patients.Methods: Patients with AIS who underwent MT from January 2014 to December 2018 were enrolled in three stroke units in China. Subgroup analyses were performed based on stroke etiology which was classified according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria. Safety outcomes were in-hospital intracerebral hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH) and mortality at 3-month. Efficacy outcomes were favorable functional outcome and functional independence at 3-month and neurological improvement at 24 h, 3 d and discharge.Results: In patients with large artery atherosclerosis (LAA) stroke, multivariate analyses revealed that tirofiban significantly decreased the odds of in-hospital ICH (adjusted OR = 0.382, 95% CI 0.180–0.809) and tended to increase the odds of favorable functional outcome at 3-month (adjusted OR = 3.050, 95% CI 0.969–9.598). By contrast, in patients with cardioembolism (CE) stroke, tirofiban was not associated with higher odds of favorable functional outcome at 3-month (adjusted OR = 0.719, 95% CI 0.107–4.807), but significantly decreased the odds of neurological improvement at 24 h and 3d (adjusted OR = 0.185, 95% CI 0.047–0.726; adjusted OR = 0.268, 95% CI 0.087–0.825).Conclusions: Tirofiban combined with MT appears to be safe and effective in LAA patients, but has no beneficial effect on CE patients.

Abstract TP229: High Neutrophil-to-Lymphocyte Ratio Predicts Early Neurological Deterioration in Ischemic Stroke Patients

Introduction: Ischemic stroke patients experienced frequent early neurological deterioration (END) events. Since ischemic stroke has also been shown as inflammatory disease, the neutrophil-to-lymphocyte ratio (NLR) may associated with END events. However, the direct study regarding this association has not been addressed. Hypothesis: We evaluated the association between NLR and END in ischemic stroke patients. Methods: We included consecutive ischemic stroke patients between 2010 and 2015. END was defined as an increase ≥ 2 on the total National Institutes of Health Stroke Scale (NIHSS) score or ≥ 1 on the motor NIHSS score within 72 hours of admission. The NLR was calculated as the ratio of the absolute neutrophil count to the absolute lymphocyte count. Results: A total of 1,152 patients were included. END occurred in 154 (13%) patients and the median NLR value was 2.47 [1.59-3.97]. In multivariate analysis, NLR remained an independent predictor of END [adjusted odds ratio (aOR) = 1.071, 95% confidence interval (CI) = 1.025 to 1.119, P = 0.002]. Age, initial thrombolysis treatment, fasting blood sugar, and total cholesterol levels were also significant, being independent of NLR values. These results were more prominent in large artery atherosclerosis group (aOR = 1.107, 95% CI = 1.031 to 1.188, P = 0.005), while stroke patients with small vessel occlusion (aOR = 1.114, 95% CI = 0.895 to 1.387, P = 0.335) or cardioembolic (aOR = 1.028, 95% CI = 0.912 to 1.159, P = 0.649) mechanisms did not show statistical significance. Conclusions: A high NLR level was associated with END in ischemic stroke patients, especially in large artery atherosclerosis patients. The NLR may hep to identify high-risk patients in time and provide clues for further studies about inflammatory pathophysiology of ischemic stroke.

Intravenous Thrombolysis Is Safe and Effective for the Cryptogenic Stroke in China: Data From the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS-China)

BackgroundThe intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) therapy is safe and efficient during the treatment of acute ischemic stroke. Nonetheless, the different outcomes among various stroke subgroups have limited data with regard to the safety and efficacy of cryptogenic stroke (CS). The present study compared the safety and efficacy when IVT with rt-PA was used for the treatment of CS and the other stroke subtypes. MethodsThis study classified the IVT with rt-PA patients within 4.5 hours after stroke onset, based on the trial of ORG 10172 in acute stroke treatment criteria in terms of diagnostic evaluation. The data were obtained from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China database, a large multicenter prospective registry. A multivariable logistic regression model was employed to compare the differences between the subtypes in symptomatic intracerebral hemorrhage (sICH) within 7 days and studied the mortality and the outcome during 90 days. ResultsIn total, 1118 patients were recruited; of these, 131 (11.7%) suffered from CS and 987 (88.3%) with the other etiology. In the CS group, patients were younger than those in the other etiology groups (P < .001). Moreover, it had a lower prevalence of previous stroke (P = .0117), receiving antiplatelet drug in 24 hours prior to thrombolysis (P = .0017), and functional independence (mRS > 1 before stroke, P = .003). The CS group had lower blood pressure (systolic blood pressure P = .0001; diastolic blood pressure; P = .0212) before thrombolysis, atrial fibrillation (P < .001), and diabetes mellitus (P = .0005). Transient ischemic attack, hypertension, hyperlipidemia, blood glucose, receiving anticoagulants in 24 hours prior to thrombolysis, and standard dosage of rt-PA were equally distributed in both groups. After the adjustment of confounders between the CS and the other subgroups, no obvious differences were observed in sICH rate and mortality (P > .05) The CS patients exhibited excellent recovery (mRS, 0-1; 63.78%) and functional independence (mRS, 0-2; 74.8%) than the large artery atherosclerosis patients. ConclusionsIVT with rt-PA is a safe and effective method for the treatment of CS patients.

Using Extracellular Circulating microRNAs to Classify the Etiological Subtypes of Ischemic Stroke

There is no effective biological method to classify ischemic stroke subtypes. In this study, we first performed a systematical gene array study on serum microRNAs with different ischemic stroke subtypes including 13 normal control subjects (NCs) and 87 ischemic stroke (IS) patients including 23 cardioembolism (CARD), 26 large artery atherosclerosis (LAA), 27 lacunar infarct (LAC), and 11 stroke of undetermined etiology (SUE). Validation was performed by using an independent cohort of 20 NCs and 85 IS patients including 28 CARD, 23 LAA, 18 LAC, and 16 SUE. In the pilot discovery gene array study, we found specific serum microRNA signatures between different ischemic stroke subtypes (CARD, LAA, LAC, and SUE). We further validated 6 microRNAs [miR-125b, miR-125a, let-7b, let-7e, miR-7-2-3p, miR-1908] in a different group of ischemic stroke subtypes by using an independent cohort of 20 NCs, 28 CARD, 23 LAA, 18 LAC, and 16 SUE. Moreover, these circulating miRNAs were further detected to be differentially expressed between pre- vs. post-stroke in different ischemic stroke subtypes. The ROC analysis showed that miR-125b, miR-125a, let-7b, and let-7e could discriminate CARD patients from normal controls and other subtypes. Furthermore, ROC curves shown that miR-7-2-3p and miR-1908 showed significant area-under-the-curve values in both LAA and LAC patients. In conclusion, these results demonstrated that circulating miRNAs in sera could be potentially novel risk factors that involve in the pathogenesis of ischemic stroke subtypes.

Procedural and clinical outcomes of endovascular recanalization therapy in patients with cancer-related stroke

Objective Embolism due to coagulopathy might be the main pathomechanism underlying cancer-related stroke (CRS). CRS patients with a large artery occlusion could be candidates for endovascular recanalization therapy (ERT), although its procedural and clinical outcomes are not well known. This study aimed to investigate the procedural and clinical outcomes of ERT in CRS patients and the characteristics associated with outcomes compared with those of conventional stroke patients. Methods A registry of consecutive acute ischemic stroke patients who underwent ERT between January 2011 and October 2015 was retrospectively reviewed. CRS patients are described as those who had (a) cryptogenic stroke with advanced or metastatic cancer; (b) no other possible causes of stroke such as cardioembolism (CE) and large artery atherosclerosis (LAA); and (c) elevated D-dimer levels or diffusion-restricted lesions in multiple vascular territories. We compared procedural and clinical outcomes at discharge among CRS, CE, and LAA patients. Results A total of 329 patients were finally enrolled in this study; of these, 19 were CRS patients. The rate of successful recanalization, defined as modified treatment in cerebral infarction grade 2b or 3, was lower in the CRS group than in the LAA and CE groups (63% versus 84% versus 84%, p = .06). CRS subtype was an independent predictor for successful recanalization after ERT in the multivariate analysis (odds ratio, 0.317; 95% confidence interval, 0.116-0.867; p < .001). No significant difference in the rate of good clinical outcomes at discharge was observed among groups. Conclusions Although clinical outcomes at discharge were similar for CE and LAA patients, complete recanalization seemed more difficult to achieve in CRS patients than in conventional stroke patients.

Differential impact of white matter hyperintensities on long-term outcomes in ischemic stroke patients with large artery atherosclerosis

BackgroundThe presence of white matter hyperintensity (WMH) is related to poor long-term outcomes in stroke patients. However, the long-term outcome is unknown in patients with both large artery atherosclerosis (LAA) and WMH.MethodsWe investigated the impact of WMH on long-term outcome in patients with LAA. Consecutive patients in a prospective stroke registry were included. Patients were followed for a median of 7.7 years (interquartile range, 5.6–9.7). The degree of WMH was assessed by Fazekas grade on fluid-attenuated inversion recovery images. Total WMH burden was calculated by summation of Fazekas scores in periventricular and deep white matter. Severe WMH was defined as total burden score ≥ 3.ResultsAmong 2529 patients, 639 patients (25.3%) were classified with the LAA subtype. After applying exclusion criteria, the data from 538 patients were analyzed. The mean patient age was 65.7 ± 10.3 years. Severe WMHs were found in 243 patients (45.2%). During follow-up, 200 patients (37.2%) died. Cox regression analysis showed that LAA patients with severe WMH had a 1.50-fold (95% CI, 1.12–2.00, p = 0.007) higher death rate compared to those without. In the older age group (≥65 years), Cox regression revealed that patients with severe WMH had a 1.75-fold (95% CI, 1.15–2.65, p = 0.008) higher 5-year death rate, whereas the younger age group did not have this association.ConclusionThe degree of WMH might be a surrogate marker for long-term outcome in patients with LAA. Atherosclerotic burdens in both small and large arteries might impact long-term prognosis in ischemic stroke patients.

Statin Pretreatment and Microembolic Signals in Large Artery Atherosclerosis.

Although statin pretreatment (SP) is associated with better outcomes in patients with acute cerebral ischemia after an ischemic stroke/transient ischemic attack, data on the underlying mechanism of this beneficial effect are limited. We sought to evaluate the potential association between SP and microembolic signal (MES) burden in acute cerebral ischemia because of large artery atherosclerosis (LAA). We prospectively evaluated consecutive patients with first-ever acute cerebral ischemia because of LAA in 3 tertiary stroke centers over a 2-year period. All patients underwent continuous 1-hour transcranial Doppler monitoring of the relevant vessel at baseline (≤24 hours). SP was recorded and dichotomized as high dose or low-to-moderate dose. SP was documented in 43 (41%) of 106 LAA patients (mean age, 65.4±10.3 years; 72% men; low-to-moderate dose, 32%; high dose, 8%). There was a significant (P=0.022) dose-dependent effect between SP and MES prevalence: no SP (37%), SP with low-to-moderate dose (18%), and SP with high dose (0%). Similarly, a significant (P=0.045) dose-dependent effect was documented between SP and MES burden: no SP (1.1±1.8), SP with low-to-moderate dose (0.7±1.6), and SP with high dose (0±0). In multivariable logistic regression analysis adjusting for demographics, vascular risk factors, location of LAA, stroke severity, and other prevention therapies, SP was associated with lower likelihood of MES presence (odds ratio, 0.29; 95% confidence interval, 0.09-0.92; P=0.036). In addition, SP was found also to be independently related to higher odds of functional improvement (common odds ratio, 3.33; 95% confidence interval, 1.07-10.0; P=0.037). We found that SP in patients with acute LAA is related with reduced MES presence and lower MES burden with an apparently dose-dependent association.

Mean platelet volume/platelet count ratio as a predictor of 90-day outcome in large artery atherosclerosis stroke patients

ABSTRACTObjective: Previous studies reported a lower platelet count (PC) level and a higher mean platelet volume (MPV) level in severe ischemic stroke. We define MPV/PC as the platelet ratio (PR). This study investigates the relationship between PR and 90-day outcome of large artery atherosclerosis (LAA) stroke.Materials and Methods: A retrospective analysis was conducted on 338 LAA patients in two hospitals by looking up the electronic medical record (EMR). The 90-day functional outcome was divided into good and poor according to the modified Rankin Scale (mRS) score.Results: Multivariate logistic regression analysis of the First Affiliated Hospital of Wenzhou Medical University (Hospital 1) revealed that PR (OR1.083, 95%CI [1.044, 1.123], P < 0.001) and National Institutes of Health Stroke Scale (NIHSS) score were independent predictors of the poor outcome. Analysis from the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University (Hospital 2) showed that PR (OR1.071, 95%CI [1.039, 1.104], P < 0.001), NIHSS score and age were independent adverse prognostic predictors. Furthermore, higher quartiles of PR presented an incremental OR value compared to the first quartile PR in multivariate regression. In Hospital 1, the cut-off value of PR to predict 90-day outcome was 39.23 (sensitivity: 74.24%, specificity: 55.17%, area under the curve (AUC): 0.694, P < 0.001). In Hospital 2, the optimal cut-off value of PR was 46.08 (sensitivity: 61.40%, specificity: 73.74%, AUC: 0.695, P < 0.001).Conclusions: Platelet ratio on admission is an independent predictor for 90-day outcome in LAA stroke patients and it has a good predictive effect.

Abstract 4: Statin Pretreatment and Microembolic Signal Burden in Patients With Acute Large-artery Atherosclerotic Stroke: A Dose-dependent Effect

Background &amp; Purpose: Although statin pretreatment (SP) is associated with better early outcomes in acute ischemic stroke (AIS) patients, there are limited data regarding the underlying mechanism of this beneficial effect. We sought to evaluate the potential association between SP and microembolic signal (MES) burden in patients with acute cerebral ischemia (ACI) due to large-artery atherosclerosis (LAA). Methods: We prospectively evaluated consecutive patients admitted with first-ever ACI due to LAA in three tertiary stroke centers over a two-year period. LAA was diagnosed according to TOAST criteria. LAA location (extracranial vs. intracranial, posterior vs. anterior) was confirmed using CT or MR angiography. All patients underwent continuous 1-hour TCD monitoring of affected vessel at baseline (≤24 hrs from symptom onset) to identify both the presence and number of MES (MES burden). SP was recorded and dichotomized as high (rosuvastatin 40mg or atorvastatin 80mg) or low-to-moderate dose (HD &amp;LMD). Functional outcome (FO) at 1 month was evaluated using the modified Rankin Scale (mRS). Results: SP was documented in 43 (41%) out of 106 LAA patients (mean age 65±10 years; 72% men; median NIHSS-score: 2, interquartile range: 0-4; LMD 32%, HD 8%). There was a significant (p=0.022) dose-dependent effect between SP and prevalence of MES on TCD: no SP (37%), SP with LMD (18%) and SP with HD (0%). Similarly, a significant (p=0.045) dose-dependent effect was documented between SP and MES burden: no SP (1.1±1.8), SP with LMD (0.7±1.6) and SP with HD (0±0). Patients with SP had better FO (median mRS-score: 1, interquartile range: 0-2) than patients without SP (median mRS-score:0, interquartile range: 0-2, p=0.004 by Cochran-Mantel-Haenszel test). In multivariable logistic regression analysis adjusting for demographics, vascular risk factors, LAA location, stroke severity, and other prevention therapies (antiplatelets, antihypertensives, antidiabetics) only SP (OR=0.29, 95%CI: 0.09-0.92, p=0.036) and current smoking (OR=3.09, 95%CI: 1.05-9.07, p=0.040) were associated with MES presence. Conclusion: SP in patients with acute LAA is associated with reduced MES presence and lower MES burden. This effect appears to be dose-dependent.

Adiponectin Gene Polymorphism and Ischemic Stroke Subtypes in a Chinese Population

As an adipose tissue-specific protein, adiponectin has been suggested as a protective factor for stroke, acting through anti-inflammatory and antiatherogenic effects. Therefore, we aimed to investigate whether 3 polymorphisms (rs1501299, rs2241767, and rs3774261) in the adiponectin (ADIPOQ) gene and their haplotypes were associated with ischemic stroke (IS) and its subtypes in a Chinese population. ADIPOQ gene rs1501299, rs2241767, and rs3774261 polymorphisms were analyzed in 385 IS patients, including 182 patients with large-artery atherosclerosis (LAA), 203 patients with small-vessel occlusion (SVO), and 418 matched controls. The subjects were genotyped by using polymerase chain reaction-restriction fragment length polymorphism analysis. In univariate logistic analysis, the A allele frequency of rs2241767 was moderately higher in IS and LAA patients than that in controls (P = .028 and P = .017, respectively). Compared with the wide-type AA homozygote, both the genotype GG and the dominant model (GG+AG) of rs2241767 moderately increased the risk of LAA (P = .040 and P = .034, respectively). In multivariate logistic regression analysis, the genotype GG of rs2241767 was independently related to IS and LAA patients (adjusted, odds ratio [OR] = 1.822, 95% confidence interval [CI]: 1.037-3.202, P = .037 and OR = 2.051, 95% CI: 1.041-4.041, P = .038, respectively) rather than SVO. In contrast, no relationship was observed between the polymorphism of rs1501299 and rs3774261 and either subtype of IS using both univariate and multivariate logistic regression analyses. In addition, the Trs1501299-Grs2241767-Ars3774261 haplotype showed a moderately increased risk of IS and LAA (OR = 1.595, 95% CI: 1.058-2.406, P = .025 and OR = 1.709, 95% CI: 1.047-2.789, P = .031, respectively) but not of SVO. In conclusion, this study tentatively demonstrated that the polymorphism of rs2241767 and the Trs1501299-Grs2241767-Ars3774261 haplotype were associated with susceptibility to IS and LAA in a Chinese population.

Serum YKL-40, a prognostic marker in patients with large-artery atherosclerotic stroke.

Inflammation comprises important aspects of large-artery atherosclerosis (LAA) stroke pathophysiology. YKL-40 is a new and emerging biomarker that is associated with both acute and chronic inflammations. Elevated serum concentrations of YKL-40 have been reported in patients with atherosclerosis and other cardiovascular diseases. This study investigates whether serum YKL-40 concentrations on admission can predict 3-month clinical outcomes after LAA stroke. We recruited control patients (n=85) and those with LAA stroke (n=141) according to the TOAST classification system. The modified Rankin scale at 3months after stroke was used to evaluate the prognosis. The prognostic accuracy was assessed by the receiver operating characteristic curve. Serum YKL-40 level was significantly higher for LAA patients than for controls (P<.001). Patients with poor outcomes (n=36) had significantly increased serum YKL-40 concentrations on admission (P=.01). High YKL-40 levels predicted poor functional outcome (OR=6.47, P=.02). Moreover, the combination of YKL-40 level and the NIHSS score could improve the prognostic accuracy of the NIHSS in predicting functional outcome (combined areas under the curve, 0.87; 95% CI, 0.80-0.94; P<.001). The level of serum YKL-40 is a significant and independent biomarker to predict the clinical outcome of LAA stroke.

Abstract TMP17: Statin Pretreatment is Associated With Better Early Outcomes in Acute Large-Artery Atherosclerotic Stroke

Background &amp; Purpose: Statin pretreatment is associated with better functional outcomes and lower risk of mortality in acute ischemic stroke (AIS). We hypothesized that this association may be accentuated in AIS due to large-artery atherosclerosis (LAA) that carries the highest risk of early stroke recurrence. Methods: Consecutive patients with acute LAA were prospectively evaluated from seven tertiary-care stroke centers during a three-year period. Statin pretreatment, demographics, vascular risk factors, admission and discharge NIHSS-scores were recorded. The outcome events of interest were neurological improvement during hospitalization (quantified as the relative decrease in NIHSS-score at discharge in comparison to hospital admission), favorable functional outcome (FFO, defined as mRS-score of 0-1), recurrent stroke and death at 1-month. Statistical analyses were performed using univariate and multivariate Cox regression models adjusting for potential confounders. All analyses were repeated following propensity score matching. Results: Statin pretreatment was documented in 192 (37.2%) out of 516 consecutive LAA patients (mean age: 65±13 years; 60.8% men; median NIHSS-score: 9 points, interquartile range: 5-18). Neurological improvement during hospitalization was greater in patients with than without statin pretreatment in unmatched and matched analyses (66.7% vs. 34.8%; p&lt;0.001). Statin pretreatement was associated higher rates of 30-day FFO in unmatched and matched (OR for FFO: 0.48; 95%CI: 0.31-0.75) analyses. Statin pretreatment was related to lower risk of 1-month mortality and stroke recurrence in unmatched and matched analyses (HR for recurrent stroke: 0.11; 95%CI: 0.02-0.46, HR for death: 0.24, 95%CI: 0.08-0.75). Conclusions: Statin pretreatment in patients with acute LAA appears to be associated with better early outcomes in terms of neurological improvement, disability, survival and stroke recurrence.

Association of TRAIL and Its Receptors with Large-Artery Atherosclerotic Stroke.

ObjectiveTo investigate the association of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors, osteoprotegerin (OPG) and death receptor 5 (DR5) with large-artery atherosclerosis (LAA) stroke and its prognosis.MethodsWe included patients with LAA stroke (n = 132) according to the TOAST classification system and controls (n = 60). To evaluate the extent and severity of cerebral atherosclerosis, the LAA stroke group was subdivided into 3 subgroups by number of cerebral arteries with atherosclerotic stenosis (≥50%): single, double and multiple (≥3). Plasma levels of TRAIL, OPG and DR5 were measured by ELISA. Ordinal logistic regression was used to analyze the association between the plasma levels of TRAIL, OPG, DR5 and the severity of cerebral atherosclerosis. Prognosis was determined by the Modified Rankin Scale at 3 months after stroke. Receiver operating characteristic (ROC) curve was used to evaluated TRAIL as a predictor of prognosis.ResultsPlasma TRAIL level was significantly lower for LAA patients than controls (P<0.001), while plasma OPG and DR5 levels were higher (both P<0.001). Logistic regression analysis revealed that risk of severe cerebral atherosclerosis was reduced significantly with increased plasma level of TRAIL (OR 0.438; 95% CI 0.282–0.681; P<0.001), whereas increased with high plasma levels of OPG and DR5 (OR 2.707; 95% CI 1.702–4.302, P <0.001; OR 3.593; 95% CI 1.878–6.869, P <0.001). Plasma TRAIL level was negatively correlated with the prognosis (r = - 0.372, P <0.001). The optimal cut-off value of TRAIL for prognosis was 848.63 pg/mL. The sensitivity and specificity at this cut-off value were 63.1% and 86.2%, respectively. After adding the plasma TRAIL level into the multivariate model of ROC, the area under the ROC curve was increased from 0.639 to 0.785, but the change was not statistical significant (P = 0.146).ConclusionsTRAIL and its receptors OPG and DR5 may be involved in LAA stroke and the plasma level of TRAIL may be a biomarker predicting the severity of cerebral atherosclerosis and the prognosis of LAA stroke.

Non-cardioembolic Mechanisms in Cryptogenic Stroke: Clinical and Diffusion-weighted Imaging Features

BackgroundThe role of several cardiogenic risk factors, including patent foramen ovale, in patients with cryptogenic stroke has been extensively studied. However, little attention has been paid to the role of non-cardioembolic causes of cryptogenic stroke. We therefore sought to identify the characteristics of cryptogenic stroke.MethodsWe studied 832 patients with acute infarction in the middle cerebral arterial territory. We divided the patients into four subtypes: 402 with large artery atherosclerosis (LAA), 133 with cardioembolism, 182 with small arterial occlusion (SAO), and 115 with cryptogenic stroke. We compared risk factors and lesion patterns observed by diffusion-weighted imaging (DWI) between patients with cryptogenic stroke and those with stroke of other subtypes.ResultsBoth risk factors and DWI lesion patterns differed between the cryptogenic and cardioembolic groups (P<0.05). Risk factors for cryptogenic stroke were similar to those for the LAA and SAO groups. Similarly, DWI lesion patterns for cryptogenic stroke were similar to LAA patients. Large cortical infarcts on DWI were more common in the cardioembolic group than in the LAA or cryptogenic groups (P<0.001). In contrast, deep, non-lacunar (OR 5.02; 95% CI 2.68~9.40; P<0.001) and superficial perforator infarcts (OR 2.23; 95% CI 1.08~4.59; P=0.029) were independently associated with the cryptogenic group.ConclusionsOur results indicate that non-cardioembolic causes, such as macro- and microangiopathy, are important mechanisms in the pathogenesis of cryptogenic stroke.