Small Artery Occlusion Stroke Research Articles

The predictive value of serum F-actin on the severity and early neurological deterioration of acute ischemic stroke: Predictive value of F-actin in stroke

BackgroundF-actin is involved in the progression of ischemic stroke and is associated with the disruption of the blood-brain barrier. In this article, we evaluated serum F-actin as a biomarker in stroke severity and early neurological deterioration (END) in acute ischemic stroke. MethodsIn this study, serum F-actin was measured in consecutively collected 140 AIS patients and 144 healthy controls matched in gender and age by ELISA. Early neurological deterioration (END) was defined as the deterioration of neurological dysfunction within 72 hours of admission, with an increase of ≥ 4 points in the NIHSS score. Severe stroke was defined as a NIHSS score>8 at admission. ResultsThe serum F-actin level in AIS was significantly higher than healthy controls (p = 0.041). In large-artery atherosclerosis stroke and cardioembolic stroke, serum F-actin were significantly higher than that in small artery occlusion stroke (padjust = 0.019, padjust < 0.001, respectively).F-actin level above the critical value (>1.37 µg/L) was significantly associated with severe stroke (OR, 3.015; 95 %CI, 1.014–8.963; p = 0.047) . In addition, elevated level of F-actin was significantly associated with END (OR, 1.323; 95 % CI, 1.001-1.747, p = 0.049). When the level of F-actin was above the critical value (>2.17 µg/L), its association with END remained significant (OR, 6.303; 95 %CI, 2.160-18.394; p < 0.001) . ConclusionF-actin is an important blood biomarker in the early stage of AIS, and high levels of F-actin are valuable in determining the severity of stroke and predicting early neurological deterioration.

Clinical Differences between Radiographic and Physical Horizontal Gaze Deviation: Utility of Using the Two in Patients with Ischemic Stroke.

Radiographic horizontal gaze deviation (RHGD) has been identified as a useful finding on computed tomography (CT) that indicates the affected side in supratentorial ischemic stroke; however, it remains unclear whether RHGD is essentially the same phenomenon as physical horizontal gaze deviation (PHGD). To resolve the issue, this study was conducted. Retrospective analyses were performed for 671 patients with ischemic stroke and 142 controls who were hospitalized and underwent head CT. First, clinical findings were examined to find differences between RHGD-positive and RHGD-negative patients. Second, patients were classified by their stroke mechanisms and/or affected vascular territories. For each subgroup, RHGD was compared with PHGD in frequency. Third, the proportions for patients divided by positivity for PHGD and RHGD were calculated in the subgroups. Patients with RHGD had PHGD more often than those without. In all stroke subgroups, RHGD was more frequent than PHGD. The frequency difference was prominent in small-artery occlusion (SAO) and posterior inferior cerebellar artery (PICA) stroke. In SAO of the basilar artery pontine perforator, RHGD was positive in 25% and largely contralesionally-directed. In PICA stroke, lesions in the vestibulocerebellum were associated with contralesional RHGD. Moreover, lesions in the lateral medulla also caused RHGD, which was mainly directed to the ipsilesional side. PHGD-positive stroke without RHGD was infrequent, whereas RHGD-positive stroke without PHGD was commonly observed (PICA stroke, 45.9%; other subgroups, 21.1%-27.5%). RHGD had different characteristics from PHGD; therefore, assessments of both PHGD and RHGD may lead to more accurate diagnoses.

Association of Homocysteine with Acute Stroke and Its Subtypes in the Chinese Population.

Homocysteine (Hcy) is recognized as a risk factor for stroke. Our study examined the relationship between plasma Hcy levels and stroke, along with its subtypes, among Chinese patients who experienced an acute stroke episode. We retrospectively enrolled patients with acute stroke and age- and sex-matched healthy controls admitted to the First Affiliated Hospital of Xi'an Jiaotong University from October 2021 to September 2022. Ischemic stroke subtypes were classified using the modified TOAST criteria. Multivariate logistic regression models were employed to probe the associations of plasma Hcy levels with total stroke, ischemic stroke and its subtypes, and hypertensive intracerebral hemorrhage (HICH), and the correlation between plasma Hcy levels and the National Institute of Health Stroke Scale (NIHSS). The mean age of the total group was 63 years, with women representing 30.6% (246 individuals). Elevated Hcy levels were significantly associated with total stroke (OR 1.054, 95% CI: 1.038-1.070), HICH (OR 1.040, 95% CI: 1.020-1.060), ischemic stroke (OR 1.049, 95% CI: 1.034-1.065), and the TOAST subtypes of ischemic stroke in large-artery atherosclerosis (LAA) (OR 1.044, 95% CI: 1.028-1.062) and small-artery occlusion (SAO) (OR 1.035, 95% CI: 1.018-1.052), but not with cardioembolic (CE) stroke. Moreover, only in the case of SAO stroke were the Hcy levels positively correlated with the NIHSS score (B=0.030, 95% CI: 0.003-0.056, P=0.030). Plasma Hcy levels were found to be positively correlated with the risk of stroke, particularly in the context of LAA, SAO stroke, and HICH. Additionally, Hcy levels demonstrated a positive correlation with stroke severity in patients presenting with SAO stroke. These findings suggest potential clinical implications in stroke prevention, particularly for ischemic stroke (LAA, SAO subtypes) and HICH by employing homocysteine-lowering therapies. Future investigations are warranted to fully elucidate these associations.

Hypertriglyceridemic waist phenotype: Association with initial neurological severity and etiologic subtypes in patients with acute ischemic stroke.

To explore the relationship of hypertriglyceridemic waist phenotype (HTWP) with initial neurological severity and etiologic subtypes in patients with acute ischemic stroke. The data for this study were collected from hospitalized patients within 72h of acute ischemic stroke onset at the Department of Neurology of the Affiliated Hospital of Beihua University from 1 July 2020 to 30 June 2022. The initial neurological severity was assessed by the National Institute of Health Stroke Scale (NIHSS) on the day of admission: NIHSS <6 was defined as mild stroke, and NIHSS ≥6 as moderate to severe stroke. HTWP was defined by fasting serum triglycerides ≥1.7 mmol/L and waist circumference ≥90 cm in men and ≥80 cm in women. Differentiation of etiologic subtypes was based on the method reported in the Trial of Org 10 172 in Acute Stroke Treatment. Multivariate logistic regression analysis was used to analyze the association of HTWP with initial neurological severity and etiologic subtypes. The study included 431 patients. Compared with the normal waist-normal blood triglyceride group, patients with HTWP had reduced risks of moderate to severe stroke [odds ratio (OR): 0.384, 95% confidence interval (CI): 0.170-0.869; P = 0.022]. In addition, the risk of small-artery occlusion stroke was 2.318 times higher in the HTWP group than in the normal triglyceride-normal waist (NWNT) group (OR: 2.318, 95% CI: 1.244-4.319; P = 0.008). Initial neurological severity was less severe in patients with HTWP, and HTWP was associated with an increased risk of small-artery occlusion stroke.

Circular RNA FUNDC1 for Prediction of Acute Phase Outcome and Long-Term Survival of Acute Ischemic Stroke.

Circular RNAs (CircRNAs) have shown promising potential in the diagnosis and the prediction of outcomes of stroke. This study aimed to explore the potential value of circRNAs for identifying acute neurological deterioration and estimating long-term survival for acute ischemic stroke (AIS). One hundred healthy controls and 200 patients with AIS within 72 h were recruited, 140 of whom were admitted within 24 h after onset. CircRNA levels in peripheral blood were measured by quantitative polymerase chain reaction (qPCR). Compared to the controls, the levels of three circRNAs were significantly increased in three subgroups of patients, including large artery atherosclerosis (LAA) stroke, small artery occlusion (SAO) stroke, and cardioembolism (CE) stroke (all P < 0.001). Among, LAA stroke patients had higher levels of circular RNA FUNDC1 (circFUNDC1) compared to SAO stroke patients (P = 0.015). CircFUNDC1 levels were positively correlated with National Institutes of Health Stroke Scale (NIHSS) scores on the 7th day only in LAA patients (P = 0.048, r = 0.226). It should be noted that the levels of circFUNDC1 in patients with early neurological deterioration (END), admitted within 24 h after onset, were significantly higher than those without END (P = 0.013). In addition, circFUNDC1 levels positively correlated with baseline NIHSS scores (P = 0.016, r = 0.203) or the 7th day NIHSS scores (P = 0.001, r = 0.289) in patients within 24 h after onset. Importantly, after 18 months of follow-up, a significant difference was observed on survival Kaplan-Meier curves (P = 0.042) between AIS patients with low (below cut-off) or high circFUNDC1 levels (above cut-off). Circulating circFUNDC1 could be a potential biomarker for predicting acute-phase outcome and long-term survival in AIS.

Heart Failure and Ischemic Stroke: A Bidirectional and Multivariable Mendelian Randomization Study.

Background: Heart failure (HF) is a potential cause of ischemic stroke (IS), and previous studies have reported an association between HF and IS. This study aimed to analyze the causal link between HF and IS using bidirectional and multivariable Mendelian randomization (MR) studies. Methods: Genetic variants significantly associated with HF and IS were selected in the MR analysis from two large genome-wide association studies. Bidirectional and multivariable MR analyses were performed to evaluate the effect of HF on IS or the effect of IS on HF. Results: Two-sample MR analysis showed causal effects of HF on IS of all causes [odds ratio (OR) = 1.555, 95% confidence interval (CI): 1.343–1.799, p = 3.35 × 10−9] and large artery atherosclerosis stroke (LAS) (OR = 1.678, 95% CI: 1.044–2.696, p = 3.03 × 10−5), while there was a suggestive effect of HF on cardioembolic stroke (CES) (OR = 3.355, 95% CI: 1.031–10.919, p = 0.044). Genetically predicted HF was not associated with small artery occlusion stroke. Bidirectional MR analysis showed causal effects of IS of all causes (OR = 1.211, 95% CI: 1.040–1.410, p = 0.014) and CES (OR = 1.277, 95% CI: 1.213–1.344, p = 6.73 × 10−21) on HF, while there were no causal effects of LAS on HF. Conclusion: This MR analysis provided evidence of the causal links between genetically predicted HF and IS. Subgroup analysis highlighted the causal or suggestive relationship between genetically predicted HF and LAS or CES. The potential causal links need further investigation with genetic information about other ancestries or etiologies of HF.

Platelet Endothelial Aggregation Receptor 1 Polymorphism Is Associated With Functional Outcome in Small-Artery Occlusion Stroke Patients Treated With Aspirin.

Background: The role of genetic polymorphisms is important in defining the patient's prognosis and outcomes in coronary artery disease. The present study aimed to explore the association between platelet endothelial aggregation receptor 1 (PEAR1) rs12041331 polymorphism and the outcomes in patients with acute ischemic stroke treated with aspirin or dual antiplatelet therapy (DAPT) with clopidogrel.Methods: A total of 868 ischemic stroke patients admitted to our hospital from January 1, 2016 to December 30, 2018 were retrospectively studied. The Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification defined stroke subtypes. These patients were treated with aspirin alone or DAPT. The genotype distribution of PEAR1 rs12041331 single-nucleotide polymorphism (AA, AC, and CC) between different TOAST subtypes and treatment groups was assessed, and the clinical impact of genetic variants on functional outcomes defined by the National Institutes of Health Stroke Scale, modified Rankin Scale, and Barthel Index was analyzed using univariate and multivariate logistic regression models.Results: Among the 868 stroke patients, the PEAR1 AA genotype was 16%, GA was 47%, and GG was 36%. Forty-four percent had aspirin alone, and 56% had DAPT. Overall, the distribution of PEAR single-nucleotide polymorphism was not significant among the two treatment groups or subtypes of TOAST. In contrast, in patients treated with aspirin alone, PEAR1 AA tended to be higher in the small-artery occlusion (SAO) subtype when compared with the no-lacunar subtype, including cardioembolism and large-artery atherosclerosis. PEAR1 AA genotype was significantly associated with favorable functional outcomes at day 7 and discharge only in SAO patients treated with aspirin alone compared with the GG genotype. Multivariate regression models further suggested that AA genotype was independently associated with favorable outcomes in this group after being adjusted for three common stroke risk factors such as age, hypertension history, and C-reactive protein level [odds ratio (OR) 0.23, 95% confidence interval (CI), 0.07–0.64, P = 0.02 for 7-day National Institutes of Health Stroke Scale; OR 0.2, 95% CI, 0.06–0.66, P = 0.03 for 7-day modified Rankin Scale, and OR 0.25, 95% CI, 0.08–0.72, P = 0.03 for 7-day Barthel Index, respectively].Conclusion: The impact of PEAR1 rs12041331 polymorphism on aspirin depends on the TOAST subtype. PEAR1 AA carrier with SAO stroke is most sensitive to aspirin therapy. PEAR1 AA is an independent factor for the short-term functional outcomes in SAO patients treated with aspirin alone.Clinical Registration Number: 1800019911.

Association of Left Ventricular Hypertrophy and Atrial Fibrillation with Hemorrhagic Evolution of Small Vessel Disease

ObjectivesCerebral small vessel disease (SVD) is often associated with hypertension and may evolve towards intracerebral hemorrhage (ICH) or lacunar ischemic stroke. However, the factors favoring the evolution towards ICH or lacunar stroke are not well understood. Materials and MethodsThis retrospective study included 326 consecutive patients (71.1±13.2 years, 38% women): 143 with deep ICH and 183 with lacunar lesions (LL) <2 cm, which were visible in a deep location on brain CT scan. Among LL patients, 143 had a small-artery occlusion (SAO) stroke according to the TOAST classification. Clinical characteristics plus laboratory and neuroradiological variables of these patients had been prospectively collected and a subgroup underwent echocardiography. ResultsIn multivariate analysis, ICH patients (97% hypertensive), compared to SAO patients (89% hypertensive), had greater left ventricular wall thickness (LVWT; OR 4.15, 95%CI 1.64-10.53, for those with LVWT ≥ 1.4 cm, 70% of whom were hemorrhagic) and lower prevalence of white matter lesions (OR 0.30, 95%CI 0.13-0.70), ever smokers (OR 0.39, 95%CI 0.18–0.82) and diabetics (OR 0.29, 95% CI 0.10-0.84). Moreover, ICH patients had a greater prevalence of atrial fibrillation than LL patients (OR 3.14, 95%CI 1.11-8.93), and so they were more often anticoagulated. ConclusionsMost SVD patients were hypertensive, but those evolving towards ICH were characterized by organ damage at the cardiac level (increase in LVWT and atrial fibrillation), while those evolving towards lacunar stroke were characterized by a higher prevalence of smokers and diabetics, and by organ damage at the cerebral level (white matter lesions).

Association between polymorphisms in ABO gene and stroke patients with small artery occlusion in southern Chinese Han population.

The purpose of this study was to investigate associations between two single nucleotide polymorphisms (SNPs) rs505922 and rs532436 in ABO gene and the risk of small artery occlusion stroke (SAO) in southern Chinese Han population. Our case-control study comprising 121 patients with SAO and 136 controls. All participants were Han population of southern China. IS sub-type was defined on the basis of the TOAST criteria. SAO was strictly diagnosed after a systematic physical examination and neuroimaging via MRI. Genotype analysis was conducted by the snapshot technique. The distribution of rs532436 genotype between these two groups showed a statistically significant difference (P=0.048) while that of rs505922 genotype showed no significant difference (P=0.572). SNP rs532436 was significantly associated with SAO in overdominant model (GA vs. GG+AA) after adjusting for age, hypertension history, diabetes history and cigarette smoking (adjusted OR=2.03, 95% CI: 1.14-3.62, P=0.016). However, under all genetic models, the rs505922 polymorphism failed to show association with SAO. The resultsindicate that rs532436 polymorphism in ABO gene may have association with SAO in southern Chinese Han population.

Association between Low-Density Lipoprotein Cholesterol Levels and Proximal Single Subcortical Infarction in Comparison with Distal Single Subcortical Infarction

PurposeSingle subcortical infarction (SSI) in the middle cerebral artery (MCA) territory can be classified into proximal SSI (pSSI) and distal SSI (dSSI) based on the heterogeneous pathogenesis. It is hypothesized that pSSI is more relevant with atherosclerosis, as low-density lipoprotein cholesterol (LDL-C) is the major atherogenic lipoprotein, we conducted the present study to investigate the association between LDL-C levels and pSSI in comparison with dSSI. Patients and methodsThis study is a subset of the Chinese Intracranial Atherosclerosis study. A total of 380 with SSI in the MCA territory classified as small artery occlusion stroke were enrolled in this study. 3.0-T magnetic resonance imaging (MRI) was performed to categorize the participants into two groups, pSSI (extending to the basal surface of MCA) and dSSI (not extending to the basal surface of MCA). ResultsOut of the 380 enrolled participants (273 men and 107 women), the proportion of pSSI and dSSI were 53.2% (202/380) versus 46.8% (178/380) based on MRI. The results of univariate and multivariate logistic regression were both at the borderline level of statistical significance. Further stratified analyses revealed that age is an interaction factor (P = 0.03), the association between LDL-C levels and the pSSI in participants aged over 65 had a significant positive relation (OR: 1.56; 95%CI: 1.14-2.12). ConclusionLDL-C level is an independent risk factor for pSSI in patients aged over 65. Our result is in accordance with the hypothesis that pSSI is more relevant with atherosclerosis, thus appropriate treatment should be applied differently to pSSI and dSSI.

Association of DIAPH1 gene polymorphisms with ischemic stroke.

DIAPH1 is a formin protein involved in actin polymerization with important roles in vascular remodeling and thrombosis. To investigate potential associations of DIAPH1 single-nucleotide polymorphisms (SNPs) with hypertension and stroke, 2,012 patients with hypertension and 2,210 controls, 2,966 stroke cases [2,212 ischemic stroke (IS), 754 hemorrhagic stroke (HS)] and 2,590 controls were enrolled respectively in the case-control study. A total of 4,098 individual were included in the cohort study. DIAPH1 mRNA expression was compared between 66 IS [43 small artery occlusion (SAO) and 23 large-artery atherosclerosis (LAA)] and 58 controls. Odds ratio (OR), hazard ratio (HR) and 95% confidence interval (CI) were calculated by logistic and cox regression analysis. Rs7703688 T>C variation was significantly associated with an increased risk of IS [OR (95% CI) was 1.721 (1.486-1.993), P=4.139×10-12]. Association of rs7703688 with stroke risk was further validated in the cohort study [adjusted HRs (95% CIs) for additive and recessive models were 1.385 (1.001-1.918), P=0.049, and 2.882 (1.038-8.004), P=0.042, respectively)]. DIAPH1 mRNA expression was significantly downregulated in IS. In SAO stroke subtype, DIAPH1 expression has an increased trend among rs251019 genotypes (Ptrend=0.048). These novel findings suggest that DIAPH1 variation contributes to genetic susceptibility to stroke risk, especially the SAO subtype of IS.

Risk Profile of Ischemic Stroke Caused by Small-Artery Occlusion vs. Deep Intracerebral Hemorrhage.

Background: Small-artery occlusion (SAO) subtype accounts for a quarter of the cases of ischemic stroke and is mainly caused by pathological changes in cerebral small vessels, which also involve in deep intracerebral hemorrhage (dICH). However, the factors that drive some cases to SAO and others to dICH remained incompletely defined.Material and Methods: This study is a cross-sectional study from the China National Stroke Registry that included consecutive patients with ischemic stroke or intracerebral hemorrhage between August 2007 and September 2008. We compared the risk profile between the two subgroups using multivariable logistic regression.Results: A total of 1,135 patients with SAO stroke and 1,125 dICH patients were included for analyses. Generally, patients with SAO stroke were more likely to be male (odds ratio = 0.74, confidence interval = 0.58–0.94) and have diabetes (0.30, 0.22–0.40), higher atherogenic lipid profiles, higher body mass index (0.96, 0.94–0.99), higher waist/height ratio (0.12, 0.03–0.48), higher platelet count (0.84, 0.77–0.91), and higher proportion of abnormal estimated glomerular filtration rate (<90, ml/min/1.73 m2) (0.77, 0.62–0.95). Conversely, patients with dICH were more likely to have higher blood pressure parameters, inflammation levels (white blood cell count: 1.61, 1.48–1.76; high sensitivity C-reactive protein: 2.07, 1.36–3.16), and high-density lipoprotein-c (1.57, 1.25–1.98).Conclusions: The risk profile between SAO stroke and dICH were different. Furthermore, despite of traditional indexes, waist/height ratio, platelet count, inflammation levels, lipid profile, and estimated glomerular filtration rate also play important roles in driving arteriolosclerosis into opposite ends.

Big Data Approaches to Phenotyping Acute Ischemic Stroke Using Automated Lesion Segmentation of Multi-Center Magnetic Resonance Imaging Data.

Background and Purpose- We evaluated deep learning algorithms' segmentation of acute ischemic lesions on heterogeneous multi-center clinical diffusion-weighted magnetic resonance imaging (MRI) data sets and explored the potential role of this tool for phenotyping acute ischemic stroke. Methods- Ischemic stroke data sets from the MRI-GENIE (MRI-Genetics Interface Exploration) repository consisting of 12 international genetic research centers were retrospectively analyzed using an automated deep learning segmentation algorithm consisting of an ensemble of 3-dimensional convolutional neural networks. Three ensembles were trained using data from the following: (1) 267 patients from an independent single-center cohort, (2) 267 patients from MRI-GENIE, and (3) mixture of (1) and (2). The algorithms' performances were compared against manual outlines from a separate 383 patient subset from MRI-GENIE. Univariable and multivariable logistic regression with respect to demographics, stroke subtypes, and vascular risk factors were performed to identify phenotypes associated with large acute diffusion-weighted MRI volumes and greater stroke severity in 2770 MRI-GENIE patients. Stroke topography was investigated. Results- The ensemble consisting of a mixture of MRI-GENIE and single-center convolutional neural networks performed best. Subset analysis comparing automated and manual lesion volumes in 383 patients found excellent correlation (ρ=0.92; P<0.0001). Median (interquartile range) diffusion-weighted MRI lesion volumes from 2770 patients were 3.7 cm3 (0.9-16.6 cm3). Patients with small artery occlusion stroke subtype had smaller lesion volumes ( P<0.0001) and different topography compared with other stroke subtypes. Conclusions- Automated accurate clinical diffusion-weighted MRI lesion segmentation using deep learning algorithms trained with multi-center and diverse data is feasible. Both lesion volume and topography can provide insight into stroke subtypes with sufficient sample size from big heterogeneous multi-center clinical imaging phenotype data sets.

Sex differences in outcomes and associated factors among stroke patients with small artery occlusion in China

BackgroundSex differences in outcomes after small artery occlusion (SAO) stroke have not been well described, particularly in a Chinese population. We aimed to assess sex differences in outcomes and related risk factors among patients with SAO.MethodsAll consecutive patients with SAO were recruited between May 2005 and September 2014. Clinical features and risk factors were recorded. The mortality, recurrence, and dependency rates at 3 months after stroke were assessed.ResultsA total of 2524 patients with SAO were included in this study. There was a higher frequency of mild stroke, current smoking, and alcohol consumption in men than in women. Women were more likely than men to be older, to have diabetes and obesity, and to have higher total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels. There were worse outcomes in men than in women at 3 months after stroke (P < 0.05). There were more independent risk factors of poor outcome in men than in women. Older age was a common predictive factor of outcome both in men and in women. In men, low triglyceride levels and high fasting plasma glucose levels were independent risk factors for mortality; in addition, a high low-density lipoprotein cholesterol level was associated with recurrence. Moreover, in men, moderate and severe stroke, and high total cholesterol and fasting plasma glucose levels were risk factors for dependency. A negative association was found between low-density lipoprotein cholesterol level and risk of mortality and between total cholesterol level and risk of recurrence in women.ConclusionsThese findings suggest that it is crucial to control conventional risk factors and fasting plasma glucose and lipid levels among patients with SAO, especially male patients, to reduce the burden of stroke in China.

Role of Blood Lipids in the Development of Ischemic Stroke and its Subtypes: A Mendelian Randomization Study.

Statin therapy is associated with a lower risk of ischemic stroke supporting a causal role of low-density lipoprotein (LDL) cholesterol. However, more evidence is needed to answer the question whether LDL cholesterol plays a causal role in ischemic stroke subtypes. In addition, it is unknown whether high-density lipoprotein cholesterol and triglycerides have a causal relationship to ischemic stroke and its subtypes. Our aim was to investigate the causal role of LDL cholesterol, high-density lipoprotein cholesterol, and triglycerides in ischemic stroke and its subtypes through Mendelian randomization (MR). Summary data on 185 genome-wide lipids-associated single nucleotide polymorphisms were obtained from the Global Lipids Genetics Consortium and the Stroke Genetics Network for their association with ischemic stroke (n=16 851 cases and 32 473 controls) and its subtypes, including large artery atherosclerosis (n=2410), small artery occlusion (n=3186), and cardioembolic (n=3427) stroke. Inverse-variance-weighted MR was used to obtain the causal estimates. Inverse-variance-weighted multivariable MR, MR-Egger, and sensitivity exclusion of pleiotropic single nucleotide polymorphisms after Steiger filtering and MR-Pleiotropy Residual Sum and Outlier test were used to adjust for pleiotropic bias. A 1-SD genetically elevated LDL cholesterol was associated with an increased risk of ischemic stroke (odds ratio: 1.12; 95% confidence interval: 1.04-1.20) and large artery atherosclerosis stroke (odds ratio: 1.28; 95% confidence interval: 1.10-1.49) but not with small artery occlusion or cardioembolic stroke in multivariable MR. A 1-SD genetically elevated high-density lipoprotein cholesterol was associated with a decreased risk of small artery occlusion stroke (odds ratio: 0.79; 95% confidence interval: 0.67-0.90) in multivariable MR. MR-Egger indicated no pleiotropic bias, and results did not markedly change after sensitivity exclusion of pleiotropic single nucleotide polymorphisms. Genetically elevated triglycerides did not associate with ischemic stroke or its subtypes. LDL cholesterol lowering is likely to prevent large artery atherosclerosis but may not prevent small artery occlusion nor cardioembolic strokes. High-density lipoprotein cholesterol elevation may lead to benefits in small artery disease prevention. Finally, triglyceride lowering may not yield benefits in ischemic stroke and its subtypes.

Cerebral vasomotor reactivity predicts the development of acute stroke in patients with internal carotid artery stenosis

ObjectiveTo investigate the relationship between cerebral vasomotor reactivity (VMR) and acute stroke in patients with internal carotid artery stenosis. Methods54 patients with internal carotid artery stenosis were enrolled. VMR was calculated by transcranial Doppler monitoring of the velocity of blood flow. 3-Dimensional dynamic contrast enhanced magnetic resonance angiography was used to detect stenosis, and diffusion weighted imaging was used to detect infarction. ResultsVMR value was significantly lower in patients with carotid artery stenosis than in control group (T=3.112, P=0.002), and significantly lower in patients with aortic atherosclerotic stroke than in non-infarct group (T=10.930, P=0.000). However, VMR value was significantly higher in patients with new-onset small-artery occlusion stroke than in non-infarction group (T=−2.538, P=0.013). Scatter plots showed that aortic atherosclerotic stroke occurred mainly in patients with severe internal carotid artery stenosis, and VMR value in cerebral artery significantly decreased. ConclusionDecreased VMR value is an important prognostic factor for the occurrence of aortic atherosclerotic stroke, and can be used as a reference for preoperative hemodynamic evaluation in patients with internal carotid artery stenosis.

Elevated blood viscosity is associated with cerebral small vessel disease in patients with acute ischemic stroke

BackgroundIncreased level of blood viscosity, which is one of the major factors that determine blood rheology, has been reported as a risk factor or predictor for cerebrovascular events. We investigated how blood viscosity is associated with acute stroke and chronic radiological manifestations of cerebral small vessel disease, and how blood viscosity changes after stroke.MethodsWe prospectively enrolled consecutive patients with acute ischemic stroke. Whole blood viscosities at a low or high shear rate were measured using a scanning capillary tube viscometer, and were referred to as diastolic blood viscosity (DBV) and systolic blood viscosity (SBV), respectively. Correlations between blood viscosity and acute stroke etiology or chronic radiological manifestations of cerebral small vessel disease were investigated. The temporal profiles of blood viscosity at the onset of stroke and follow-up at 1 and 5 weeks were investigated.ResultsOf the 127 patients admitted with acute ischemic stroke, 63 patients were included in the final analyses. DBV at the onset of stroke was significantly higher in small artery occlusion (SAO) stroke than in other stroke subtypes (p = 0.037). DBV showed a significant positive correlation with the number of chronic lacunes (r = 0.274, p = 0.030). The temporal profiles of DBV in SAO stroke showed a transient decrease due to the hydration therapy after 1 week and recurrent elevation at 5 week follow-up (p = 0.009).ConclusionsOur study suggests that elevated DBV may play a role in the development of acute and chronic manifestations of cerebral small vessel disease. The recurring elevation of DBV in SAO stroke indicates that sufficient hydration and additional therapeutic interventions targeting blood viscosity may be needed in patients with SAO stroke.

Association of Oxidized Low-Density Lipoprotein With Prognosis of Stroke and Stroke Subtypes

The association between oxidized low-density lipoprotein (oxLDL) and the long-term prognosis of stroke is unclear. The aim of this study is to investigate whether oxLDL levels contribute to the prognosis of stroke and stroke subtypes. All patients with ischemic stroke were recruited from the SOS-Stroke (Study of Oxidative Stress in Patients With Acute Ischemic Stroke) and classified into 5 different subtypes, according to the TOAST criteria (Trial of Org 10172 in Acute Stroke Treatment). We measured oxLDL levels and followed up with patients at 1 year after stroke onset. We analyzed the association between oxLDL and the clinical outcomes of death and poor functional outcome (modified Rankin Scale score of 3-6) of stroke and different stroke subtypes. Among the 3688 patients included in this study, 293 (7.94%) were deceased at the 1-year follow-up and 1020 (27.66%) had a poor functional outcome. Patients in the highest oxLDL quartile had a higher risk of 1-year stroke mortality (hazard ratio, 1.61; 95% confidence interval, 1.10-2.33; P<0.001) and a poor functional outcome (odds ratio, 1.48; 95% confidence interval, 1.15-1.89; P<0.001) compared with the lowest oxLDL quartile. In the subgroup analyses, oxLDL was only significantly associated with death and poor functional outcome in the large-artery atherosclerosis subgroup (P<0.05) and small-artery occlusion subgroup (P<0.05). High levels of oxLDL were associated with the high risk of death and poor functional outcome within 1 year after stroke onset, especially in large-artery atherosclerosis and small-artery occlusion stroke subtypes.

High serum levels of sclerostin and Dickkopf-1 are associated with acute ischaemic stroke

Background and aimsSclerostin and Dickkopf-1 (Dkk-1) are potent antagonists of Wnt signalling and might therefore play important roles in cardiovascular disease. We investigated whether serum sclerostin and Dkk-1 levels are associated with acute ischaemic stroke and specific stroke subtypes. MethodsSerum levels of sclerostin and Dkk-1 were measured by ELISA on day 1 and on day 6 after stroke in 62 patients with large artery atherosclerotic (LAA) stroke, on day 1 after stroke in 62 age- and gender-matched patients with small-artery occlusion (SAO) stroke and on admission in 62 healthy controls. Stroke severity was determined based on the National Institutes of Health Stroke Scale (NIHSS) and by measuring stroke volume on diffusion-weighted imaging. Outcome was measured by the modified Rankin Scale (mRS) on day 90. ResultsCompared with controls, serum sclerostin and Dkk-1 levels were significantly higher in both patients with LAA stroke and with SAO stroke, and no difference was detected between the stroke subtypes. Sclerostin and Dkk-1 levels remained stable between the first and sixth day after stroke in the patients with LAA stroke. Receiver operating characteristic curve analysis was used to evaluate sclerostin and Dkk-1 as markers of a high risk of stroke and produced area under curve values of 0.773 and 0.776. Adjusted logistic regression showed that serum sclerostin and Dkk-1 levels remained as independent markers of stroke. No correlations were found between sclerostin or Dkk-1 levels and stroke severity or stroke outcome. ConclusionsHigh serum levels of sclerostin and Dkk-1 are associated with acute ischaemic stroke.

Correlations of platelet-leukocyte aggregates with P-selectin S290N and P-selectin glycoprotein ligand-1 M62I genetic polymorphisms in patients with acute ischemic stroke

BackgroundPlatelet-leukocyte aggregations (PLA) play key roles in acute ischemic stroke (AIS) process and they are formed by the combination of P-selectin (SELP) expressed on the surface of the platelet membranes with P-selectin glycoprotein ligand-1(PSGL-1) expressed on the surface of the leukocytes. There are genetic polymorphisms in SELP and PSGL-1. We tested the differences in all kinds of PLA among subtypes of AIS and the association of SELP S290N and PSGL-1 M62I polymorphism with AIS to assess the correlations of PLA with SELP S290N and PSGL-1 M62I genetic polymorphisms. MethodsOne hundred and forty-eight patients with acute ischemic stroke, including thirty patients with large artery atherosclerosis stroke (LAA), twenty-four patients with cardioembolism (CE) and ninety-four patients with small artery occlusion stroke (SAO), and eighty-eight control subjects were evaluated. The lab parameters and levels of PLA were measured within 3h after the ischemic event in the case subjects and within empty stomach in the control subjects. In all subjects, SELP S290N and PSGL-1 M62I polymorphisms were also measured. ResultsPlatelet-monocyte aggregates (PMA), platelet-lymphocyte aggregates (PLyA) and platelet-neutrophil aggregates (PNA) in LAA group, CE group and SAO group were all higher than that in control group (P=0.000 for all comparisons). Compared with LAA group, PMA and PLyA in CE group were significantly higher (P=0.018 and P=0.003, respectively). Compared with SAO group, PMA and PLyA in CE group were also significantly higher (P=0.041 and P=0.019, respectively). Compared with control group, there were significantly differences of I allele frequencies of PSGL-1 M62I in LAA group and SAO group (OR=2.249, 95%CI: 1.175–4.304, P=0.021 and OR=2.055, 95%CI: 1.269–3.328, P=0.004, respectively). In SAO group, there were significantly differences of PNA among MM, MI and II genotype of PSGL-1 M62I (P=0.008). ConclusionsPLA increased in AIS patients rapidly within 3h. The I allele of PSGL-1 M62I was associated with risk of developing AIS, especially LAA and SAO. SAO patients with the II genotype of PSGL-1 M62I have the higher level of PNA.