Serum neurofilament light chain: a predictive marker for outcomes following mild-to-moderate ischemic stroke.

Background: Biomarkers that reflect brain damage or predict functional outcomes may aid in guiding personalized stroke treatments. Serum neurofilament light chain (sNfL) emerges as a promising candidate for fulfilling this role. Methods: This prospective, observational cohort investigation included 319 acute ischemic stroke (IS) patients. The endpoints were the incidence of early neurological deterioration (END, an elevation of two or more points in the National Institute of Health stroke scale score within a week of hospitalization compared with the baseline) and functional outcome at 3 months (an mRS score of >2 at 3 months was categorized as an unfavorable/poor functional outcome). The association of sNfL, which was assessed within 24 h of admission, with END and unfavorable functional outcomes at follow-up was assessed via multivariate logistic regression, whereas the predictive value of sNfL for unfavorable functional outcomes and END was elucidated by the receiver operating characteristic curve (ROC). Results: Of 319 IS individuals, 89 (27.90%) suffered from END. sNfL not only reflects the severity of stroke measured by NIHSS score (p < 0.05) but also closely related to the severity of age-related white matter changes. Higher initial NIHSS score, severe white matter lesions, diabetes mellitus, and upregulated sNfL were significant predictors of END. Similarly, the multivariate logistic regression analysis results showed that elevated sNfL, a higher baseline NIHSS score, and severe white matter lesions were substantially linked with unfavorable outcomes for 3 months. Similarly, sNfL was valuable for the prediction of the 3 months of poor outcome (95%CI, 0.504-0.642, p = 0.044). Kaplan-Meier analysis shows that patients with elevated sNfL levels are more likely to reach combined cerebrovascular endpoints (log-rank test p < 0.05). Conclusion: This investigation suggests that sNfL can serve as a valuable biomarker for predicting END and 3-month poor functional outcomes after an IS and has the potential to forecast long-term cardiovascular outcomes.

The incidence of stroke and contribution of risk factors for stroke in high-risk stroke population in southwestern China.

OBJECTIVE: To estimate the incidence of stroke and determine the role that risk factors play in the high-risk stroke populace in southwest China. METHODS: This research employed a prospective cohort design that focused on the community. Eight communities in southwest China were selected randomly for this study. The residents aged 40 years and older who volunteered to participate were surveyed through face-to-face interviews. Those with a history of stroke or at least three of the eight stroke-related risk factors were categorized as the high-risk stroke population. A total of 2698 high-risk individuals were included in the study after a 4.7-year follow-up period. The incidence of stroke and the association between risk variables and stroke occurrence were estimated. RESULTS: During 4.7-year follow-up, the incidence of total stroke, ischemic stroke, and hemorrhagic stroke in high-risk stroke population were 5.0 %, 4.4 % and 0.9 % respectively. It should be noted that some participants experienced both cerebral infarction and cerebral hemorrhage during the follow-up period. The multivariate analytic model revealed that a personal history of stroke (OR=3.397, 95 % CI 2.365-4.878, p<.001) was substantially linked with an elevated risk of overall stroke. This correlation remained consistent for both ischemic and hemorrhagic stroke. CONCLUSIONS: This study revealed a high prevalence and incidence of stroke among a high-risk group in southwestern China. Furthermore, it demonstrated that individuals with a personal history of stroke are at an elevated risk of future stroke, suggesting the need for additional precautions in this population.

Inflammation and endothelial function relevant genetic polymorphisms, carotid atherosclerosis, and vascular events in high-risk stroke population.

Aim: To identify the associations of 19 single nucleotide polymorphisms (SNPs) in genes involved in inflammation and endothelial function and carotid atherosclerosis with subsequent ischemic stroke and other vascular events in the high-risk stroke population. Methods: This was a multicenter community-based sectional survey and prospective cohort study in Sichuan, southwestern China. Eight communities were randomly selected, and the residents in each community were surveyed using a structured face-to-face questionnaire. Carotid ultrasonography and DNA information were obtained from 2,377 out of 2,893 individuals belonging to a high-risk stroke population. Genotypes of the 19 SNPs in genes involved in inflammation and endothelial function were measured. All the 2,377 subjects were followed up for 4.7 years after the face-to-face survey. The primary outcome was ischemic stroke, and the secondary outcome was a composite of vascular events. Results: Among the 2,377 subjects, 2,205 (92.8%) completed a 4.7-year follow-up, 947 (42.9%) had carotid atherosclerosis [372 (16.9%) carotid vulnerable plaque, 405 (18.4%) mean IMT > 0.9 mm, 285 (12.0%) carotid stenosis ≥15%]. Outcomes occurred in 158 (7.2%) subjects [92 (4.2%) ischemic stroke, 17 (0.8%) hemorrhagic stroke, 48 (2.2%) myocardial infarction, and 26 (1.2%) death] during follow-up. There was a significant gene-gene interaction among ITGA2 rs1991013, IL1A rs1609682, and HABP2 rs7923349 in the 19 SNPs. The multivariate logistic regression model revealed that carotid atherosclerosis and the high-risk interactive genotypes among the three SNPs were independent with a higher risk for ischemic stroke (OR = 2.67, 95% CI: 1.52-6.78, p = 0.004; and OR = 3.11, 95% CI: 2.12-9.27, p < 0.001, respectively) and composite vascular events (OR = 3.04, 95% CI: 1.46-6.35, p < 0.001; and OR = 3.23, 95% CI: 1.97-8.52, p < 0.001, respectively). Conclusion: The prevalence of carotid atherosclerosis was shown to be very high in the high-risk stroke population. Specific SNPs, interactions among them, and carotid atherosclerosis were independently associated with a higher risk of ischemic stroke and other vascular events.

Effect of admission serum glucose on the clinical prognosis of patients with acute ischemic stroke receiving alteplase intravenous thrombolysis.

Objective: To investigate the effect of admission serum glucose on the clinical prognosis of patients with acute ischemic stroke receiving intravenous alteplase thrombolysis. Methods: Patients with acute ischemic stroke who received intravenous alteplase thrombolysis between January 2016 and December 2017 were enrolled. The clinical prognosis was assessed using the modified Rankin Scale (mRs) at 90 days after onset. Univariate and multivariate logistic regression analyses were conducted to investigate whether admission serum glucose was an independent factor in the 90-day prognosis. The predictive value of admission serum glucose for a 90-day poor prognosis was evaluated using receiver operating characteristic (ROC) curves. All patients were divided into two groups based on admission serum glucose levels: high admission serum glucose (above the cut-off value) and low admission serum glucose (below the cut-off value). The 90-day prognosis of patients with different admission serum glucose was analyzed. Results: A total of 138 patients were enrolled, including 79 males (57.24%), with a mean age of (68 ± 12) years and a median baseline National Institutes of Health Stroke Scale (NIHSS) score of 9 (6 to 13.75). There were 74 cases (53.62%) in the good prognosis group and 64 cases (46.37%) in the poor prognosis group. The results of the univariate analysis indicated that admission serum glucose in the good prognosis group was significantly lower than that in the poor prognosis group [(7.45 ± 2.31) versus (8.80 ± 3.65), p < .05]. Logistic regression analysis revealed that the admission serum glucose level was an independent risk factor for clinical prognosis at 90 days after onset (OR = 1.24, 95% CI:1.01-1.52). ROC curve analysis showed that the cutoff value of admission serum glucose for predicting poor prognosis 90 days after intravenous thrombolytic therapy with alteplase was 6.77 mmol/l AUC (area under curve) 0.623, 95%CI: 0.53-0.72, sensitivity 68.80%, specificity 52.70%. When compared with the admission serum glucose ≥6.77 mmol/l group (83 cases), the 90-day mRS scores in the admission serum glucose <6.77 mmol/l group (55 cases) were lower [3 (1 to 5) scores versus 1 (0 to 3) scores, Z = 2.89, p < .05]. Conclusions: In patients with acute ischemic stroke receiving intravenous alteplase thrombolytic therapy, a higher admission serum glucose level is an independent predictor of adverse neurological outcomes at 90 days postoperatively.

Neutrophil-to-lymphocyte ratio is associated with stroke progression and functional outcome in patients with ischemic stroke.

OBJECTIVE: The objective of the present research was to examine the correlation between the neutrophil-to-lymphocyte ratio (NLR) and stroke progression (SP) as well as the functional outcome following an ischemic stroke (IS). METHODS: The current study was conducted as prospective observational research. A cohort of 341 participants diagnosed with IS was included in the study from March 2019 to August 2021. This study's primary measure of interest was the occurrence of SP within the initial week following hospital admission. The secondary outcome was functional status 3 months after IS as measured by a modified Rankin scale score. The association between NLR with SP, and poor functional outcomes was examined using multivariate logistic regression. The predictive value of NLR for SP and poor functional outcomes was evaluated using the receiver operating characteristic (ROC) curve. RESULTS: Among the 341 enrolled patients, 56 (16.4%) had SP, and 285 (83.6%) had no SP. The results of the multivariate logistic regression analysis demonstrated that the existence of diabetes mellitus and the NLR were independently associated with SP and poor functional outcomes. The area under the ROC curve of NLR in predicting poor functional outcome was 0.6117 (95% confidence interval, .5341-.6893, p = .0032), and the optimal cut-off point was 4.2139. The sensitivity and specificity of NLR in predicting poor functional outcomes were 52.7% and 72.0%, respectively. CONCLUSION: Patients with acute IS exhibited a very high incidence of SP. NLR may be a valuable prognostic indicator in clinical practice because it was independently associated with SP and a poor functional outcome.

Vulnerable Carotid Plaque is Associated with an Increased Risk of Intracerebral Hemorrhage in Individuals at High Risk of Stroke: A Chinese Population-based Cohort Study.

OBJECTIVES: To assess the association between carotid artery plaques and the risk of incident intracerebral hemorrhage (ICH) event in high-risk individuals for stroke. METHODS: We conducted a population-based cohort study using the longitudinal participant-level data of a multicenter, cross-sectional survey in southwestern China. 2644 high-risk participants for stroke were enrolled in the year 2015. The primary outcome was new-onset ICH events during a five-year follow-up period. Multivariate logistic regression was performed to identify the association between carotid plaque and new-onset ICH. Stratified analyses and interaction tests were conducted to identify variables that might modify the association between vulnerable carotid plaque and ICH. RESULTS: Among 2644 high-risk individuals enrolled, carotid plaques were found in 904 (34.2%) subjects, including 479 (18.1%) with stable plaques and 425 (16.1%) with vulnerable plaques. During a five-year follow-up period, 22 (0.83%) participants developed ICH. Vulnerable carotid plaque was associated with an increased risk of new-onset ICH in multivariable analyses (adjusted RR 3.72, 95 % CI 1.32 to 10.46, p=0.013). Stratified analyses and interaction analyses demonstrated the association between vulnerable carotid plaque and ICH was not changed by age, family history of stroke, hemorrhagic stroke and chronic disease, smoking, drinking, physical activity, BMI, antihypertensives, and antithrombotic drugs (all p for interaction>0.05). However, among the female cohort, participants with vulnerable plaques had a significantly higher risk of ICH compared with participants without vulnerable plaques (crude RR=9.8; 95%CI: 3.1-31.3, p<0.001; adjusted RR=26.3, 95%CI: 5.5-124.5, p<0.001), but not in man (p>0.05). CONCLUSION: In Chinese individuals at high risk of stroke, vulnerable carotid artery plaques are associated with an increased risk of intracerebral hemorrhage independent of classical vascular risk factors, especially in female individuals.

Variants in genes related to inflammation and endothelial function can increase the risk for carotid atherosclerosis in southwestern China.

Aim: To investigate the potential association between polymorphisms in genes involved in endothelial function, inflammation and carotid atherosclerosis. Methods: This was a three-center, population-based sectional survey conducted in Sichuan province of southwestern China. We randomly selected 8 different communities in Sichuan, and the residents in each community volunteered to participate in the survey by face-to-face questionnaire. A total of 2,377 residents with high stroke risk population in the 8 communities were included. Carotid atherosclerosis was evaluated by carotid ultrasound, and the 19 single nucleotide polymorphisms (SNPs) in 10 endothelial function as well as inflammation relevant genes were measured in the high stroke risk population. Carotid atherosclerosis was defined by the presence of carotid plaque or any carotid stenosis ≥15% or mean intima-media thickness (IMT) > 0.9 mm. Generalized multifactor dimensionality reduction (GMDR) approach was used to analyze gene-gene interactions among the 19 SNPs. Results: Among the 2,377 subjects with high stroke risk, 1,028 subjects had carotid atherosclerosis (43.2%), of which 852 (35.8%) cases had carotid plaque, 295 (12.4%) cases had ≥15% carotid stenosis, whereas 445 (18.7%) had mean IMT > 0.9 mm. Multivariate logistic regression revealed that IL1A rs1609682 TT and HABP2 rs7923349 TT served as independent risk factors for carotid atherosclerosis (OR, 1.45, 95% CI: 1.034-2.032, p = 0.031, and OR, 1.829, 95% CI: 1.228-2.723, p = 0.003). GMDR analysis indicated that there was a significant gene-gene interaction found among IL1A rs1609682, ITGA2 rs1991013, and HABP2 rs7923349. After adjusting the covariates, the high-risk interactive genotypes in the 3 variants were significantly associated with a significantly higher risk for carotid atherosclerosis (OR, 2.08, 95% CI: 1.257-5.98, p < 0.001). Conclusion: The prevalence of carotid atherosclerosis was observed to be extremely high in the high-risk stroke population in southwestern China. There were associations observed between the specific variants in inflammation and endothelial function relevant genes and carotid atherosclerosis. The high-risk interactive genotypes among IL1A rs1609682, ITGA2 rs1991013, and HABP2 rs7923349 significantly increased the risk of carotid atherosclerosis. These results are expected to provide novel strategies for the prevention of carotid atherosclerosis. The gene-gene interactive analysis used in this study may be very helpful to elucidate complex genetic risk factors for carotid atherosclerosis.

Major intracranial arterial stenosis influence association between baseline blood pressure and clinical outcomes after thrombolysis in ischemic stroke patients.

BACKGROUND: This study aimed to investigate the relationship between baseline blood pressure (BP) and clinical outcomes after thrombolysis for acute ischemic stroke (AIS) in different intracranial arterial stenosis subgroups. METHODS: AIS patients from multicenter with intravenous thrombolysis were retrospectively enrolled from January 2013 to December 2021. We categorized participants into severe (≥ 70%) and nonsevere (< 70%) stenosis of major intracranial arteries subgroups. The primary outcome was unfavorable functional outcome defined as 3-month modified Rankin Scale (mRS) ≥2. The association coefficients between baseline BP and functional outcomes were estimated in general linear regression model. The interactive effect was tested to determine the influence of intracranial arterial stenosis on the association between BP and clinical outcomes. RESULTS: A total of 329 patients were included. Severe subgroup was detected in 151 patients with average age of 70.5. Association between baseline diastolic BP (DBP) and unfavorable functional outcome in intracranial artery stenosis subgroups was significantly different (p for interaction < .05). In nonsevere subgroup, higher baseline DBP was associated with higher risk of unfavorable outcome (OR 1.11, 95% CI 1.03 to 1.20, p = .009) compared with severe subgroup (OR 1.02, 95% CI 0.97 to 1.08, p = .341). Besides, intracranial artery stenosis also modified association between baseline systolic BP (SBP) and 3-month death (p for interaction < .05). In severe subgroup, higher baseline SBP was associated with decreased 3-month death risk (OR 0.88, 95% CI 0.78 to 1, p = .044) compared with nonsevere subgroup (OR 1, 95% CI 0.93 to 1.07, p = .908). CONCLUSIONS: The major intracranial artery state modulates association between baseline BP and 3-month clinical outcomes after intravenous thrombolysis.

CYP metabolic pathway related gene polymorphism increases the risk of embolic and atherothrombotic stroke and vulnerable carotid plaque in southeast China.

OBJECTIVE: To investigate the association of CYP metabolic pathway-related genetic polymorphisms with the susceptibility to ischemic stroke and stability of carotid plaque in southeast China. METHODS: We consecutively enrolled 294 acute ischemic stroke patients with carotid plaque and 282 controls from Wenling First People's Hospital. The patients were divided into the carotid vulnerable plaque group and stable plaque group according to the results of carotid B-mode ultrasonography. Polymorphisms of CYP3A5 (G6986A, rs776746), CYP2C9*2 (C430T, rs1799853), CYP2C9*3 (A1075C, rs1057910), and EPHX2 (G860A, rs751141) were determined using polymerase chain reaction and mass spectrometry analysis. RESULTS: EPHX2 GG may reduce the susceptibility to ischemic stroke (OR = 0.520, 95% CI: 0.288 ∼ 0.940, P = 0.030) and AA+AG may increase the risk for ischemic stroke (OR = 1.748, 95% CI: 1.001 ∼ 3.052, P = 0.050). The distribution of CYP3A5 genotypes showed significant differences between the vulnerable plaque and stable plaque groups (P = 0.026). Multivariate logistic regression analysis found that CYP3A5 GG could reduce the risk of vulnerable plaques (OR = 0.405, 95% CI: 0.178 ∼ 0.920, P = 0.031). CONCLUSION: EPHX2 G860A polymorphism may reduce the stroke susceptibility, while other SNPs of CYP genes are not associated with ischemic stroke in southeast China. Furthermore CYP3A5 polymorphism was related with carotid plaque instability.

Inflammation and endothelial function-related gene polymorphisms are associated with carotid atherosclerosis-A study of community population in Southwest China.

OBJECTIVES: To investigate the relationships between 18 single nucleotide polymorphisms with carotid atherosclerosis and whether interactions among these genes were associated with an increased risk of carotid atherosclerosis. METHODS: Face-to-face surveys were conducted with individuals aged 40 or older in eight communities. A total of 2377 individuals were included in the study. Ultrasound was used to detect carotid atherosclerosis in the included population. 18 loci of 10 genes associated with inflammation and endothelial function were detected. Gene-gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR). RESULTS: Among the 2377 subjects, 445 (18.7%) subjects had increased intima-media thickness in the common carotid artery (CCA-IMT), and 398 (16.7%) subjects were detected with vulnerable plaque. In addition, NOS2A rs2297518 polymorphism was associated with increased CCA-IMT, IL1A rs1609682, and HABP2 rs7923349 polymorphisms were associated with vulnerable plaque. Besides, GMDR analysis showed significant gene-gene interactions among TNFSF4 rs1234313, IL1A rs1609682, TLR4 rs1927911, ITGA2 rs1991013, NOS2A rs2297518, IL6R rs4845625, ITGA2 rs4865756, HABP2 rs7923349, NOS2A rs8081248, HABP2 rs932650. CONCLUSION: The prevalences of increased CCA-IMT and vulnerable plaque were high in Southwestern China's high-risk stroke population. Furthermore, inflammation and endothelial function-related gene polymorphisms were associated with carotid atherosclerosis.

Serum neurofilament light chain levels are associated with early neurological deterioration in minor ischemic stroke.

Objectives: Patients with minor ischemic stroke (MIS) frequently suffer from early neurological deterioration (END) and become disabled. Our study aimed to explore the association between serum neurofilament light chain (sNfL) levels and END in patients with MIS. Methods: We conducted a prospective observational study in patients with MIS [defined as a National Institutes of Health Stroke Scale (NIHSS) score 0-3] admitted within 24 h from the onset of symptoms. sNfL levels were measured at admission. The primary outcome was END, defined as an increase in the NIHSS score by ≥2 points within 5 days after admission. Univariate and multivariate analyses were performed to explore the risk factors associated with END. Stratified analyses and interaction tests were conducted to identify variables that might modify the association between sNfL levels and END. Results: A total of 152 patients with MIS were enrolled, of which 24 (15.8%) developed END. The median sNfL level was 63.1 [interquartile range (IQR), 51.2-83.4] pg/ml on admission, which was significantly higher than that of 40 age- and sex-matched healthy controls (median 47.6, IQR 40.8-56.1 pg/ml; p < 0.001). Patients with MIS with END had a higher level of sNfL (with ND: median 74.1, IQR 59.5-89.8 pg/ml; without END: median 61.2, IQR 50.5-82.2 pg/ml; p = 0.026). After adjusting for age, baseline NIHSS score, and potential confounding factors in multivariate analyses, an elevated sNfL level (per 10 pg/mL) was associated with an increased risk of END [odds ratio (OR) 1.35, 95% confidence interval (CI) 1.04-1.77; p = 0.027). Stratified analyses and interaction tests demonstrated that the association between sNfL and END did not change by age group, sex, baseline NIHSS score, Fazekas' rating scale, hypertension, diabetes mellitus, intravenous thrombolysis, and dual antiplatelet therapy in patients with MIS (all p for interaction > 0.05). END was associated with an increased risk of unfavorable outcomes (modified Rankin scale score ranging from 3 to 6) at 3 months. Conclusion: Early neurological deterioration is common in minor ischemic stroke and is associated with poor prognosis. The elevated sNfL level was associated with an increased risk of early neurological deterioration in patients with minor ischemic stroke. sNfL might be a promising biomarker candidate that can help to identify patients with minor ischemic stroke at high risk of neurological deterioration, for reaching individual therapeutic decisions in clinical practice.

Folate receptor-mediated targeted therapy for rheumatoid arthritis by methotrexate-phospholipid complex nano-emulsions.

Rheumatoid arthritis (RA) is a common autoimmune and inflammatory disease. Activated macrophages in arthritic joints play a prominent role in the initiation and persistence of RA. Despite great progress in the clinical treatment of RA, poor response and high discontinuation due to systemic toxicity remain unsolved issues, especially the well-known methotrexate (MTX). Therefore, active targeted delivery of therapeutic drugs to pathogenic cells in arthritic joints is essential to increase in situ activity and decrease systemic toxicity. Here, we developed an MTX-loaded macrophage-targeted nano-emulsion (NE) based on the overexpression of folate receptor (FR) on activated macrophages, the inherent high affinity of FR for folate (FA), as well as the property of MTX and phospholipids to form complexes (MTX@PC). Intravenous injection of DID-labelled MTX@PC-FA NEs into adjuvant-induced arthritis (AIA) mice, in vivo images and flow cytometry results revealed that the NEs were highly targeted to inflamed joints and macrophages, respectively. Therapeutic studies suggested that this strategy was conducive to achieve high efficacy and low toxicity of MTX in the treatment of RA. Our research highlights MTX@PC-FA NEs as a potential treatment option for RA targeting the FR-expressed activated macrophages.

Sex-specific association between inflammation and endothelial function relevant gene and vulnerable carotid plaque.

Objectives: We aimed to explore sex-specific association between genes involved in inflammation and endothelial function and vulnerable carotid plaque, a subclinical precursor of ischemic stroke. Methods: Carotid plaque and plaque phenotype were assessed by carotid ultrasound in high-risk participants for stroke drawn from a multicenter, cross-sectional survey in southwestern China. We examined 18 single nucleotide polymorphisms (SNPs) in 10 genes related to inflammation and endothelial function. Sex differences in the genotype of the candidate SNPs and risk of vulnerable carotid plaques were assessed. Interaction tests were performed to identify the SNPs that might modify the association between the sex and vulnerable plaques. For SNPs with suggestive evidence for interaction with sex (p for interaction<0.05), stratification analysis by sex was performed to evaluate the sex-specific association between the SNP and vulnerable plaques. Results: 2,644 high-risk individuals were enrolled, comprising 1,202 (45.5%) men and 1,442 (54.5%) women. Vulnerable carotid plaques were detected in 425 (16.1%) participants. Among candidate SNPs, the genotype frequencies of 5 SNPs (TNFSF4 rs11811788, TNFSF4 rs1234313, IL6R rs4845625, VCAM1 rs2392221, and ITGA2 rs1991013) were significantly different between sex (all p < 0.05). Univariable and multivariable analyses suggested that male individuals had a significantly higher prevalence of vulnerable carotid plaques (20.0% vs. 12.8%, adjusted OR 1.72, 95% CI 1.12-2.66, p = 0.014), while none of the candidate SNPs was significantly associated with vulnerable plaques (all p > 0.05). Interaction tests found the association between sex and vulnerable plaques is affected by the genotype of IL6R rs4845625 (p for interaction = 0.031). Stratification analysis revealed a strong association between IL6R rs4845625 and vulnerable carotid plaque in man (dominant model TT vs. CT + CC: adjusted OR 1.52, 95% CI 1.12-2.07, p = 0.007; codominant model TT vs. CC: adjusted OR 1.50, 95% CI 1.00-2.25, p = 0.048) but not in women (p > 0.05 in all genetic models). Conclusion: The rs4845625 polymorphism in IL6R has sex-specific effects on vulnerable carotid plaque in Chinese Han high-risk individuals for stroke. Our findings provide a plausible genetic basis underlying the sex difference in carotid plaque vulnerability.

Persistence of drug therapy is associated with ischemic stroke and other vascular events in high-risk stroke population.

The high-risk stroke populations are significantly associated with an increased risk of stroke or other vascular events. Although proven primary and secondary stroke prevention medications are available, persistent use is required to be effective. However, the persistence of drug therapy and its association with outcomes in the high-risk stroke population have received limited study in China. Hence, according to the China National Stroke Screening Survey (CNSSS) program in 2015, we performed this multicenter population-based cross-sectional survey and prospective cohort study in Sichuan of southwestern China. The residents aged ≥ 40 years volunteered to participate in a face-to-face survey in 8 communities. Subjects with at least three of eight stroke-related risk factors or a history of stroke were defined as high-risk stroke population. The interviewers recorded individuals' medications at a face-to-face survey, and all the high-risk stroke population was followed up for 4.7 years. The persistence of antihypertensives, hypoglycemics, lipid-lowering medications, and antithrombotics for stroke was evaluated. The primary outcome was new stroke. Secondary outcomes included new composite vascular events of stroke, myocardial infarction, and death during follow-up periods. Among 16,892 participants, 2,893 (17.1%) participants were high-risk stroke population and 2,698 (93.3%) participants completed to follow-up. The 4.7-year persistence of therapy rate of antihypertensives, hypoglycemics, lipid-lowering medications, and antithrombotics was 38.0%, 39.9%, 43.9%, and 59.8%, respectively. The total persistence of therapy rate for antihypertensives, hypoglycemics, lipid-lowering medications, and antithrombotics was 47.6% (136/286) in patients with hypertension, diabetes, dyslipidemia, and stroke at the same time. During the 4.7-year follow-up, there were 118 (4.4%) new ischemic stroke, 24 (0.9%) hemorrhagic stroke, 53 (2.0%) myocardial infarctions, and 33 (1.2%) deaths. After adjusting for the covariates, 4.7-year persistence of antihypertensives, hypoglycemics, lipid-lowering therapy, antithrombotics, and total persistence was independently associated with less new ischemic stroke and less new composite vascular events. Thus, more effective public education and efforts to understand and enhance the persistence of drug therapy are crucial to improve population health and decrease stroke and other vascular events for the high-risk stroke population.

Prevalence and Risk Factors of High-Risk Population for Stroke: A Population-Based Cross-Sectional Survey in Southwestern China.

With the aging of the population and the change of lifestyle in China, the prevalence and risk factors of the high-risk population for stroke may change. However, few studies performed community-based high-risk stroke population surveys in China. Hence, we performed this multicenter, cross-sectional, and community-based survey in Sichuan of southwestern China, according to the China National Stroke Screening Survey (CNSSS) program in 2015. The residents aged ≥ 40 years volunteered to participate in the face-to-face survey in 8 communities in Sichuan. The 8 communities were selected using the cluster randomization method. Subjects with at least three of the eight stroke-related risk factors were classified as a high-risk population for stroke. Otherwise were classified as a low-risk population for stroke. Furthermore, 1,011 individuals were randomly selected among the low-risk population for stroke as controls. Among 16,892 participants, 2,369 (14.0%) were high-risk population for stroke. After full adjustments, all eight risk factors for stroke were significantly associated with the high-risk population for stroke (P < 0.001). The largest contributor was hypertension [population-attributable risk (PAR) 28.4%], followed by physical inactivity (PAR 14.2%), dyslipidemia (PAR 11.2%), overweight/obesity (PAR 9.4%), diabetes (PAR 7.2%), family history (PAR 6.8%), smoking (PAR 5.9%), and atrial fibrillation (PAR 3.5%). Carotid atherosclerosis was more serious in the high-risk population for stroke than in controls (P < 0.05). The prevalence of the high-risk population for stroke was high in southwestern China. Hypertension, physical inactivity, and dyslipidemia were stronger contributors for the high-risk population for stroke. Individual-level and population-level interventions for these leading risk factors are very important for the primary prevention of stroke.

Acute improvement in the attention network with repetitive transcranial magnetic stimulation in Parkinson's disease.

PURPOSE: To investigate the effect of two weeks of repetitive transcranial magnetic stimulation (rTMS) on the attention network in Parkinson's disease (PD) patients. MATERIALS AND METHODS: Sixty PD patients were randomly divided into equal-sized active- and sham-rTMS groups. Executive function was assessed by neuropsychological tests including the Trail-Making Test (TMT), word fluency test, digit span, Wisconsin Card Sorting Test (WCST) and Stroop test. The attention network was evaluated by the attention network test (ANT). rTMS (5 Hz) was applied over the left dorsolateral prefrontal cortex (DLPFC) in the active-rTMS group, and the sham-rTMS group underwent sham stimulation, both for two weeks. All tests were performed before and after rTMS. RESULTS: After active rTMS, nonparametric analysis revealed significant improvements in categories completed (CC) (p < 0.001) in the WCST and reaction times (RTs) in part 3 (p = 0.002) and the Stroop interference effect (SIE) (p < 0.001) in the Stroop test. Regarding the ANT, the RTs of the executive control network were significantly reduced (p < 0.001). There was no significant change after sham rTMS. CONCLUSIONS: In the short term, in PD patients, rTMS improved the executive control network involved in resolving conflicting information. However, it showed milder effects on neuropsychological test outcomes assessing executive function, which may involve different neuromechanisms.Implications for rehabilitationCognitive impairment is common in patients with Parkinson's disease (PD), and it is related to functional disability and reduced quality of life.Attention is a main component of the cognitive system, and attention deficits are responsible for disability.This study demonstrates that rTMS is beneficial for cognitive rehabilitation in PD, as patients showed improved performance on the attention network test and neuropsychological tests.

Inflammation and endothelial function relevant genetic polymorphisms in carotid stenosis in southwestern China.

Aim: To evaluate the relationship between carotid stenosis with variants in genes referred to inflammation and endothelial function. Methods: There was a multi-center, cross sectional survey in southwestern China. The eight communities were selected at random in southwestern China. The residents aged ≥40 years volunteered to participate in face-to-face survey. Subjects with at least three of the aforementioned eight stroke related risk factors or a history of stroke were classified as high-risk population for stroke. A total of 2,377 subjects were the high-risk population for stroke in the eight communities, and degree of carotid stenosis was assessed by carotid ultrasound. Genotypes of 6 variants in 3 genes related to inflammation and endothelial function were examined. Gene-gene interaction was analyzed by generalized multifactor dimensionality reduction (GMDR). Results: Carotid stenosis were found in 295 (12.41%) subjects, of whom 51 (17.29%) had moderate or severe stenosis. According to multivariate logistic regression analysis, we found that HABP2rs7923349TT was independent risk factor for carotid stenosis (OR, 1.96, 95% CI: 1.22-3.13, P = 0.005) and ITGA2rs1991013AG and HABP2rs7923349TT were independent risk factors for moderate to severe carotid stenosis (OR, 2.28, 95% CI: 1.28-4.07, P = 0.005; OR, 2.90, 95% CI: 1.19-7.08, P = 0.019). GMDR analysis showed that there was a significant gene-gene interaction between ITGA2 rs4865756 and HABP2 rs7923349, and the high-risk interactive genotype in the two variants was independently associated with a higher risk for carotid stenosis after adjusting the covariates (OR,1. 42, 95% CI 1.10-1.84, P = 0.008). Conclusions: Prevalence of carotid stenosis was very high in the high-risk stroke population in southwestern China. Variants in genes referred in endothelial function were associated with the carotid stenosis. The high-risk interactive genotype in ITGA2 rs4865756 and HABP2 rs7923349 was independently associated with a higher risk for carotid stenosis.

Stroke Lateralization in Large Hemisphere Infarctions: Characteristics, Stroke-Related Complications, and Outcomes.

Objectives: To assess the hemispheric differences in characteristics, stroke-related complications, and outcomes of patients with large hemisphere infarctions (LHI). Methods: We enrolled consecutive patients admitted within 24 h after the diagnosis of LHI (defined as an ischemic stroke involving more than 50% of the territory of the middle cerebral artery in computed tomography and/or magnetic resonance imaging). Univariate and multivariate analysis were performed to explore the association between lateralization and stroke-related complications and clinical outcomes. Results: A total of 314 patients with LHI were enrolled, with 171 (54.5%) having right hemispheric involvement. Right-sided patients with LHI had lower baseline National Institutes of Health Stroke Scale (NIHSS) score (18 vs. 22, p < 0.001), higher frequency of atrial fibrillation (69.0 vs. 52.4%, p = 0.003), and higher proportion of cardio-embolism (73.1 vs. 56.6%, p = 0.013) than the left. Right-sided LHI had higher incidence rates of malignant brain edema (MBE) (48.5 vs. 30.8%, p = 0.001) and a composite of cardiovascular events (29.8 vs. 17.5%, p = 0.011) during hospitalization. The incidence rate of 1-month mortality (34.5 vs. 23.8%, p = 0.036) was higher in right-sided patients with LHI, but there were no hemispheric differences in the incidence rates of 3-month mortality and unfavorable outcome (both p > 0.05). Multivariate analyses suggested right hemisphere involvement was independently associated with increased risk of MBE (adjusted OR 2.37, 95% CI 1.26-4.43, p = 0.007) and composite of cardiovascular events (adjusted OR 2.04, 95% CI 1.12-3.72, p = 0.020). However, it was not independently associated with 1-month death, 3-month mortality, and 3-month unfavorable outcome (all p > 0.05). Conclusions: Right-sided patients with LHI had higher frequency of atrial fibrillation and cardio-embolism than the left-sided patients. Right hemisphere involvement was independently associated with increased risk of MBE and composite of cardiovascular events during hospitalization, whereas stroke lateralization was not an independent predictor of mortality and unfavorable outcome in patients with LHI.

20-hydroxyeiscosatetraenoic acid may be as a predictor of malignant middle cerebral artery infarction in patients with massive middle cerebral artery infarction.

BACKGROUND: Early identification of massive middle cerebral artery infarction (MCAI) at risk for malignant MCAI (m-MCAI) may be useful in selecting patients for aggressive therapies. The aim of this study was to determine whether CYP metabolites may help to predict impending m-MCAI. METHODS: This is a prospective, two-center observational study in 256 patients with acute massive MCAI. Plasma levels of 20-hydroxyeicosatetraenoic acid (20-HETE), epoxyeicosatrienoic acids, and dihydroxyeicosatrienoic acids were measured at admission. Brain computed tomography (CT) was performed at admission and repeated between day 3 and 7, or earlier if there was neurological deterioration. The primary outcome was m-MCAI. The m-MCAI was diagnosed when follow-up brain CT detected a more than two-thirds space-occupying MCAI with midline shift, compression of the basal cisterns, and neurological worsening. RESULTS: In total of 256 enrolled patients, 77 (30.1%) patients developed m-MCAI. Among the 77 patients with m-MCAI, 60 (77.9%) patients died during 3 months of stroke onset. 20-HETE level on admission was significantly higher in patients with m-MCAI than those without m-MCAI. There was an increase in the risk of m-MCAI with increase of 20-HETE levels. The third and fourth quartiles of 20-HETE levels were independent predictors of m-MCAI (OR: 2.86; 95% CI: 1.16 - 6.68; P = 0.025, and OR: 4.23; 95% CI: 1.35 - 8.26; P = 0.002, respectively). CONCLUSIONS: Incidence of m-MCAI was high in patients with massive MCAI and the prognosis of m-MCAI is very poor. Elevated plasma 20-HETE may be as a predictor for m-MCAI in acute massive MCAI, and it might useful in clinical practice in therapeutic decision making.

Cerebral Microbleed Burden in Ischemic Stroke Patients on Aspirin: Prospective Cohort of Intracranial Hemorrhage.

Objective: This investigation aimed at studying the prevalence of cerebral microbleeds (CMBs), including risk factors and the correlation of CMBs to ischemic stroke (IS) patient end results. Methods: Four hundred and fifty-nine acute IS cases were recruited between April 2014 and December 2016. Cerebral microbleeds were analyzed using susceptibility-weighted imaging (SWI) brain MRI scan. The enrolled patients with acute IS were followed up for 12-24 months, with a median follow-up time of 19 months. The follow-up endpoint events including recurrent ischemic stroke (RIS), intracranial hemorrhage (ICH), transient ischemic attack (TIA), mortality, and cardiovascular events. The associations between vascular risk factors and CMBs in IS patients were analyzed using univariate and multivariate logistic regression analysis. Cox regression model was employed for evaluating CMB impact on clinical outcome. Results: Among 459 enrolled patients, 187 (40.7%) had CMBs and 272 (59.2%) had no CMB. In comparison with patients with no CMBs, age was higher and hypertension was more frequent in patients with CMBs. Multivariate logistic regression analyses revealed age and hypertension were independently associated with the presence of CMBs. Among the patient cohort, 450 cases completed the follow-up. During the follow-up period, 22 (4.9%) of patients developed ICH, 12 (2.7%) developed TIA, 68 (15.1%) developed RIS, cardiovascular events occurred in 20 (4.44%), and 13 (2.89%) cases were mortalities. Compared with patients without CMBs, IS patients with CMBs have an increased prevalence of ICH (p < 0.05). However, no statistically valid variations regarding other outcome incidences between both groups was identified (p > 0.05). The incidence of ICH was elevated in tandem with elevations in number of CMBs. Following adjusting for age, multivariate Cox proportional-hazards regression analysis revealed that CMBs ≥10 were independent predictors of ICH in acute IS patients. Conclusion: Age and hypertension are independently associated with the presence of CMBs. Intracranial hemorrhage incidence rate was increased with the number of CMBs, and the number of CMBs ≥10 were independent predictors of ICH in acute stroke patients.