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This study aimed to investigate the association between non-traditional lipid profiles and the risk of 1-year vascular events in patients who were already using statins before stroke and had admission LDL-C < 100 mg/dL. This study was an analysis of a prospective, multicenter, nationwide registry of consecutive patients with acute ischemic stroke patients who treated with statin before index stroke and LDL-C < 100 mg/dL on admission. Non-traditional lipid profiles including non-HDL, TC/HDL ratio, LDL/HDL ratio, and TG/HDL ratio were analyzed as a continuous or categorical variable. The primary vascular outcome within one year was a composite of recurrent stroke (either hemorrhagic or ischemic), myocardial infarction (MI) and all-cause mortality. Hazard ratios (95% Cis) for 1-year vascular outcomes were analyzed using the Cox PH model for each non-traditional lipid profiles groups. A total of 7028 patients (age 70.3 ± 10.8years, male 59.8%) were finally analyzed for the study. In unadjusted analysis, no significant associations were observed in the quartiles of LDL/HDL ratio and 1-year primary outcome. However, after adjustment of relevant variables, compared with Q1 of the LDL/HDL ratio, Q4 was significantly associated with increasing the risk of 1-year primary outcome (HR 1.48 [1.19-1.83]). For the LDL/HDL ratio, a linear relationship was observed (P for linearity < 0.001). Higher quartiles of the LDL/HDL ratio were significantly and linearly associated with increasing the risk of 1-year primary vascular outcomes. These findings suggest that even during statin therapy with LDL-C < 100 mg/dl on admission, there should be consideration for residual risk based on the LDL/HDL ratio, following stroke., (© 2024. The Author(s).)

It is uncertain whether the prognostic power of white matter hyperintensity (WMH) on post-stroke outcomes is modulated as a function of initial neurological severity, a critical determinant of outcome after stroke. This multi-center MRI study tested if higher WMH quintiles were associated with 3-month poor functional outcome (modified Rankin Scale ≥ 3) for mild versus moderate-to-severe ischemic stroke. Mild and moderate-to-severe stroke were defined as admission National Institute of Health Stroke Scale scores of 1-4 and ≥ 5, respectively. Mean age of the enrolled patients (n = 8918) was 67.2 ± 12.6 years and 60.1% male. The association between WMH quintiles and poor functional outcome was modified by stroke severity (p-for-interaction = 0.008). In mild stroke (n = 4994), WMH quintiles associated with the 3-month outcome in a dose-dependent manner for the 2nd to 5th quintile versus the 1st quintile, with adjusted-odds-ratios (aOR [95% confidence interval]) being 1.29 [0.96-1.73], 1.37 [1.02-1.82], 1.60 [1.19-2.13], and 1.89 [1.41-2.53], respectively. In moderate-to-severe stroke (n = 3924), however, there seemed to be a threshold effect: only the highest versus the lowest WMH quintile was significantly associated with poor functional outcome (aOR 1.69 [1.29-2.21]). WMH burden aggravates 3-month functional outcome after mild stroke, but has a lesser modulatory effect for moderate-to-severe stroke, likely due to saturation effects., (© 2024. The Author(s).)

There is no blood biomarker diagnostic of arterial thrombosis. We investigated if arterial thrombosis per se was associated with alterations in complete blood count (CBC) and white blood cell (WBC) differential count in mice. Twelve-week-old C57Bl/6 mice were used for FeCl 3 -mediated carotid thrombosis (n = 72), sham-operation (n = 79), or non-operation (n = 26). Monocyte count (/µL) at 30-min after thrombosis (median 160 [interquartile range 140-280]) was ~ 1.3-fold higher than at 30-min after sham-operation (120 [77.5-170]), and twofold higher than in non-operated mice (80 [47.5-92.5]). At day-1 and -4 post-thrombosis, compared with 30-min, monocyte count decreased by about 6% and 28% to 150 [100-200] and 115 [100-127.5], which however were about 2.1-fold and 1.9-fold higher than in sham-operated mice (70 [50-100] and 60 [30-75], respectively). Lymphocyte counts (/µL) at 1- and 4-days after thrombosis (mean ± SD; 3513 ± 912 and 2590 ± 860) were ~ 38% and ~ 54% lower than those in the sham-operated mice (5630 ± 1602 and 5596 ± 1437, respectively), and ~ 39% and ~ 55% lower than those in non-operated mice (5791 ± 1344). Post-thrombosis monocyte-lymphocyte-ratio (MLR) was substantially higher at all three time-points (0.050 ± 0.02, 0.046 ± 0.025, and 0.050 ± 0.02) vs. sham (0.003 ± 0.021, 0.013 ± 0.004, and 0.010 ± 0.004). MLR was 0.013 ± 0.005 in non-operated mice. This is the first report on acute arterial thrombosis-related alterations in CBC and WBC differential parameters., (© 2023. The Author(s).)

This study aimed to elucidate whether low-density lipoprotein cholesterol (LDL-C) levels differentially affect functional outcomes after intravenous thrombolysis (IVT) depending on prestroke statin use. Patients with acute ischemic stroke treated with IVT were categorized into low, intermediate, and high LDL-C groups based on LDL-C levels at admission (< 100/100-130/ > 130 mg/dl, respectively). Multivariable logistic regression analyses were performed to explore the relationships between LDL-C and clinical outcomes (good outcomes at 3 months, modified Rankin Scale scores 0-2). The interaction between LDL-C levels and prestroke statin use regarding functional outcomes was investigated. Among the 4711 patients (age, 67 ± 12 years; males, 62.1%) who met the eligibility criteria, compared with the high LDL-C group, the low and intermediate LDL-C groups were not associated with good outcomes at 3 months according to the multivariable analysis. A potential interaction between the LDL-C group and prestroke statin use on good outcomes at 3 months was observed (P interaction  = 0.07). Among patients with prestroke statin use, low (aOR 1.84 [1.04-3.26]) and intermediate (aOR 2.31 [1.20-4.47]) LDL-C groups were independently associated with a greater likelihood of having a 3-month good outcome. Our study showed that LDL-C was not associated with a 3-month good outcome, but prestroke statin use could modify the influence of LDL-C levels on functional outcomes after IVT., (© 2022. The Author(s).)

We investigated a multicenter registry to identify estimated event rates according to CHA2DS2-VASc scores in patients with acute ischemic stroke (AIS) and atrial fibrillation (AF). The additional effectiveness of antiplatelets (APs) plus oral anticoagulants (OACs) compared with OACs alone considering the CHA2DS2-VASc scores was also explored. This study retrospectively analyzed a multicenter stroke registry between Jan 2011 and Nov 2017, identifying patients with acute ischemic stroke with AF. The primary outcome event was a composite of recurrent stroke, myocardial infarction, and all-cause mortality within 1 year. A total of 7395 patients (age, 73 ± 10 years; men, 54.2%) were analyzed. The primary outcome events at one year ranged from 5.99% (95% CI 3.21-8.77) for a CHA2DS2-VASc score of 0 points to 30.45% (95% CI 24.93-35.97) for 7 or more points. After adjustments for covariates, 1-point increases in the CHA2DS2-VASc score consistently increased the risk of primary outcome events (aHR 1.10 [1.06-1.15]) at 1-year. Among OAC-treated patients at discharge (n = 5500), those treated with OAC + AP (vs. OAC alone) were more likely to experience vascular events, though among patients with a CHA2DS2-VASc score of 5 or higher, the risk of primary outcome in the OAC + AP group was comparable to that in the OAC alone group (P int  = 0.01). Our study found that there were significant associations of increasing CHA2DS2-VASc scores with the increasing risk of vascular events at 1-year in AIS with AF. Further study would be warranted.

Uncertainty regarding an optimal antiplatelet regimen still exists in patients with breakthrough acute ischemic stroke (AIS) while on aspirin. This study provides an analysis of a prospective multicenter registry between April 2008 and April 2014. Eligible patients were on aspirin at the time of AIS and treated with antiplatelet regimens (aspirin, clopidogrel, or clopidogrel-aspirin). Potential factors associated with the choice of each antiplatelet regimen were explored and included a predictive risk score for future vascular events, the Essen Stroke Risk Score (ESRS). A total of 2348 patients (age, 69 ± 11 years; male, 57.7%) were analyzed, and 55.3%, 25.3% and 19.4% were treated with clopidogrel-aspirin, aspirin and clopidogrel, respectively. While the likelihood of choosing clopidogrel-aspirin increased as the ESRS increased, the likelihood of choosing aspirin decreased as the ESRS increased (P trend  < 0.001). The ESRS category (0-1/2-3/ ≥ 4) modified the effect of antiplatelet regimens for 1-year vascular events (P interaction  < 0.01). Among patients with ESRS ≥ 4, clopidogrel-aspirin (HR 0.47 [0.30-0.74]) and clopidogrel (HR 0.30 [0.15-0.60]) significantly reduced the risk of outcome events. Our study showed that more than half of the patients with aspirin failure were treated with clopidogrel-aspirin. In particular, a higher ESRS, which indicates an increased risk of recurrent stroke, was associated with the choice of clopidogrel-aspirin rather than aspirin.

We recently generated a high-resolution supratentorial vascular topographic atlas using diffusion-weighed MRI in a population of large artery infarcts. These MRI-based topographic maps are not easily applicable to CT scans, because the standard-reference-lines for axial image orientation (i.e., anterior-posterior commissure line versus orbito-meatal line, respectively) are 'not parallel' to each other. Moreover, current, widely-used CT-based vascular topographic diagrams omit demarcation of the inter-territorial border-zones. Thus, we aimed to generate a CT-specific high-resolution atlas, showing the supratentorial cerebrovascular territories and the inter-territorial border-zones in a statistically rigorous way. The diffusion-weighted MRI lesion atlas is based on 1160 patients (67.0 ± 13.3 years old, 53.7% men) with acute (<1-week) cerebral infarction due to significant (>50%) stenosis or occlusion of a single large cerebral artery: anterior, middle, or posterior cerebral artery. We developed a software package enabling the transformation of our MR-based atlas into a re-oriented CT space corresponding to the axial slice orientations used in clinical practice. Infarct volumes are individually mapped to the three vascular territories on the CT template-set, generating brain maps showing the voxelwise frequency of infarct by the affected parent vessel. We then mapped the three vascular territories collectively, generating a dataset of Certainty-Index (CI) maps to reflect the likelihood of a voxel being a member of a specific vascular territory. Border-zones could be defined by using either relative infarct frequencies or CI differences. The topographic vascular territory atlas, revised for CT, will allow for easier and more accurate delineation of arterial territories and borders on CT images.