Objective To evaluate the associations of 16 variants in clopidogrel-relevant genes with early neurological deterioration (END) in acute ischemic stroke (AIS) patients receiving clopidogrel treatment. Methods AIS patients admitted to the Department of Neurology of three hospitals between June 2014 and January 2015 were included. The 16 variants in clopidogrel-relevant genes were examined using mass spectrometry. Gene-gene interactions were analyzed by generalized multifactor dimensionality reduction (GMDR) methods. The primary outcome was END within the 10 days of admission. Results A total of 375 patients with AIS were included. Among the 375 patients, 95 (25.33%) patients developed END within the first 10 days of admission. Among the 16 variants, only CYP2C19*2 rs4244285 AG+AA was associated with END using single-locus analytical approach (P<0.001). GMDR analysis revealed that there was a synergistic effect of gene-gene interactions among CYP2C19*2 rs4244285, P2Y12 rs16863323, and GPⅢa rs2317676 on risk for END (P=0.019). Cox regression analysis showed that the high-risk interactive genotype was independent predictor for END [hazard ratio=2.184, 95% confidence interval (1.472, 3.238), P=0.004]. Conclusions END is very common in patients with AIS. Interactions among CYP2C19*2 rs4244285, P2Y12 rs16863323, and GPⅢa rs2317676 may confer a higher risk for END. It may be very important to modify clopidogrel therapy for the patients carrying the high-risk interactive genotype.
ObjectiveTo explore the association of elongase of very long chain fatty acids family member 6 (ELOVL6) gene with increased risk of large-artery atherosclerosis stroke (LAA) in Han Chinese population in Chengdu.MethodsHan Chinese populations in Chengdu, Sichuan were chosen for this study using the case-control design between January 2015 and December 2017. The genotypes and haplotypes of six single nucleotides polymorphisms (SNPs) of ELOVL6 gene (rs3813825, rs17041272, rs4141123, rs9997926, rs6824447, and rs12504538) were analyzed in different genetic models in entire samples, and gene-enviromental interaction analyses were also carried out to get an insight of the risk factors for LAA. At the same time, we also analyzed the gene expression profile in peripheral blood mononuclear cells between groups.ResultsA total of 240 LAA cases and 211 healthy controls were enrolled in this study. All the enrolled subjects presented CC genotype of rs9997926, while the other five SNPs (rs3813825, rs17041272, rs4141123, rs6824447, and rs12504538) were genotyped successfully in all the enrolled subjects. rs17041272 polymorphism and TGTTG haplotype were significantly associated with LAA risk in studied population [CC/(CG+GG): odds ratio (OR)=0.640, 95% confidence interval (CI) (0.423, 0.968), P=0.034; TGTTG: OR=1.776, 95%CI (1.069, 2.951), P=0.024], and the interaction among rs17041272, rs6824447 SNPs and dyslipidemia increased susceptibility to LAA [OR=2.737, 95%CI (1.715, 4.368), P<0.001]. The ELOVL6 gene expression level was higher in LAA subjects (t=−3.167, P=0.003).ConclusionsELOVL6 gene is associated with LAA risk in Han nationality of Chinese population in Chengdu, and the interaction of gene-environmental risk factors could be of great importance in pathophysiology of LAA.
ObjectiveTo systematically evaluate the association between MTHFR gene C677T polymorphism and susceptibility to young and middle-aged adult ischemic stroke among Chinese population. MethodsSuch databases as PubMed, EMbase, The Cochrane Library (Issue 11, 2013), CBM, CNKI, VIP and WanFang Data were systemically searched to collect case-control studies published from Jan 1990 to Dec 2013. RevMan 5.2 was used to quantitatively analyzed the qualified and included studies, the pooled odds ratio (ORs) with 95% confidence interval (CI) were calculated; Stata 12.0 software were used for sensitivity and publication bias analysis. ResultsA total of 10 studies were included, which involved 787 cases and 766 controls. The results of meta-analysis showed that, in overall young and middle-aged adult group (aged less than 60), individuals that carried T allele risked more with ischemic stroke than those carried C allele (OR=1.42, 95%CI 1.07 to 1.89, P=0.02); more susceptibility to ischemic stroke was found among people of TT genotype compared with those of CC genotype (OR=2.11, 95%CI 1.58 to 2.81, P=0.00), as well as those of TT+TC genotype compared with CC genotype (OR=1.97, 95%CI 1.55 to 2.51, P=0.00), and those of TT genotype compared with TC+CC genotype (OR=1.42, 95%CI 1.13 to 1.77, P=0.00). Increased risk was also observed in TT+TC genotype compared with CC genotype in young adult subgroup (aged less than 45) (OR=1.66, 95%CI 1.19 to 2.32, P=0.00). ConclusionMTHFR gene C677T polymorphism is significantly associated with susceptibility to young and middle-aged adult ischemic stroke among Chinese population, and more risk may exist in middle-aged adult population.
Objectives To investigate the relationship between SG13S114 and SG13S32 polymorphisms in ALOX5AP gene and risk of ischemic stroke in Chinese population. Methods We searched Web of Science, EMbase, PubMed, CNKI, CBM and WanFang Data databases to collect case-control studies on SG13S114 and SG13S32 polymorphisms of ALOX5AP gene and risk of ischemic stroke in Chinese from inception to February 2017. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. Meta-analysis was then performed by Stata 12.0 software. Results A total of 20 studies were included. The results of meta-analysis showed that SG13S114 polymorphism in ALOX5AP gene was associated with risk of ischemic stroke in Chinese (A vs. T: OR=1.12, 95%CI 1.00 to 1.27, P=0.05; TA+AA vs. TT: OR=1.14, 95%CI 1.01 to 1.28, P=0.04; AA vs. TT: OR=1.33, 95%CI 1.07 to 1.65, P=0.012). However, no significant association between SG13S32 polymorphism and ischemic stroke in Chinese was found. Conclusions SG13S114 polymorphisms in ALOX5AP gene is associated with risk of ischemic stroke in Chinese, in which the A allele of ALOX5AP may be a risk factor.
ObjectiveTo conduct an objective record of stroke patient’s retinal diseases by retinal photography, and analyze the incidence of various retinal diseases between different subtypes of stroke.MethodsFrom June to October 2007, the consecutive cases of stroke admitted to the Department of Neurology, West China Hospital of Sichuan University were prospectively registered. Ischemic stroke patients were classified into different subtypes by the Oxfordshire Community Stroke Project criteria, and intracerebral hemorrhage (ICH) patients were classified based on the clinical manifestation and neuroimaging. We collected other clinical data associated with the incidence of stroke. The retinal abnormalities including retinopathy, arteriovenous nicking and arteriolar narrowing were recorded. Multivariate logistic regression was performed to investigate the relationship between retinal abnormalities and stroke.ResultsThis study included 199 patients with ischemic stroke and 95 patients with ICH. Among the patients with ischemic stroke, 43 (21.6%) had retinopathy, 52 (26.1%) presented with arteriovenous nicking, and 43 (21.6%) developed arteriolar narrowing. Among the patients with ICH, retinopathy occurred in 23 (24.2%), arteriovenous nicking occurred in 14 (14.7%), and arteriolar narrowing occurred in 25 (26.3%). In multivariate analysis, retinopathy was independently associated with partial anterior circulation infarct (PACI) (P=0.029) and anterior ICH (P=0.041).ConclusionsRetinopathy is independently associated with PACI and anterior ICH. Further community-based study with large sample should be conducted to confirm the predictive value of retinal diseases on the incidence of anterior stroke.
ObjectiveTo systematically review the correlation between atrial fibrillation and prognosis of patients with ischemic stroke after intravenous thrombolysis. MethodsLiterature search was carried out in PubMed, EMbase, Web of Science, The Cochrane Library (Issue 4, 2014), CBM and WanFang Data up to April 2014 for the domestic and foreign cohort studies on atrial fibrillation and prognosis of patients with ischemic stroke after intravenous thrombolysis. Two reviewers independently screened literature according to inclusion and exclusion criteria, extracted data, and assessed methodological quality of included studies. Then meta-analysis was performed using RevMan 5.2. ResultsA total of 7 cohort studies were finally included involving 69 017 cases. The results of meta-analysis showed that, compared with patients without atrial fibrillation, atrial fibrillation reduced 3-month favourable nerve function of patients with atrial fibrillation (OR=0.85, 95%CI 0.73 to 0.98, P=0.03) but did not influence the risk of death after intravenous thrombolysis (OR=1.47, 95%CI 0.75 to 2.86, P=0.26); and increased the risks of intracranial haemorrhagic transformation (OR=1.36, 95%CI 1.26 to 1.47, P < 0.001) and symptomatic intracranial hemorrhage after intravenous thrombolysis (OR=1.43, 95%CI 1.02 to 1.99, P=0.04). ConclusionFor patients with ischemic stroke, atrial fibrillation does not influence the risk of death, but it increases the risks of intracranial hemorrhage, and worsens 3-month favourable nerve function of after intravenous thrombolysis. For those patients, more assessment before intravenous thrombolysis and more monitoring after intravenous thrombolysis are necessary. Due to limited quality and quantity of the included studies, the abovementioned conclusion still needs to be verified by conducting more high quality studies.
ObjectivesTo systematically review the efficacy and safety of mechanical thrombectomy for patients with acute ischemic stroke in different ages.MethodsPubMed, EMbase, The Cochrane Library, Web of Science, CNKI, and WanFang Data databases were electronically searched to collect randomized controlled trials (RCTs) and non-randomized controlled trials (non-RCTs) on the efficacy and safety of mechanical thrombectomy for patients with acute ischemic stroke in different ages from inception to August, 2019. Two reviewers independently screened literature, extracted data and assessed risk of bias of included studies, then, meta-analysis was performed by using Stata 12.0 software.ResultsA total of 13 studies involving 2 995 patients were included. The results of meta-analysis showed that compared with the control group, patients aged 80 and above had no statistically significant difference in reperfusion success rates (OR=0.90, 95%CI 0.71 to 1.14, P=0.378), and incidence of symptomatic intracranial hemorrhage (OR=1.30, 95%CI 0.86 to 1.94, P=0.212), however, with higher incidence of arbitrary intracranial bleeding events (OR=1.61, 95%CI 1.28 to 2.04, P<0.001), 3-month mortality (OR=2.14, 95%CI 1.73 to 2.64, P<0.001) and lower good functional prognosis rate at 3 months (OR=0.46, 95%CI 0.30 to 0.71, P<0.001).ConclusionsCurrent evidence suggests that people aged 80 and above can obtain effective perfusion through mechanical thrombectomy, however, the incidence of postoperative adverse outcome events is higher and the prognosis is relatively poor. Due to limited quality and quantity of the included studies, more high-quality studies are required to verify above conclusions.
Objective To investigate the predictive factors of clinical progression and short-term prognosis of cerebral infarction caused by large artery atherosclerosis (LAA). MethodsPatients with acute LAA cerebral infarction who were hospitalized in the Department of Neurology, Lianyungang Hospital of Traditional Chinese Medicine between January 2016 and May 2019 were included. On admission, the patients’ medical history was collected. The degree of neurological deficit was assessed, blood pressure, blood glucose, blood lipids, plasma homocysteine, lipoprotein-associated phospholipase A2 (Lp-PLA2) were measured, and intracranial and extracranial blood vessels related test results were collected. Within 72 hours of onset, the Scandinavian Stroke Scale (SSS) was used to determine whether the patients’ condition progressed. The modified Rankin scale was used to evaluate the short-term prognosis at 30 days of onset. The related factors of clinical progression and short-term prognosis of LAA cerebral infarction were analyzed. Results Finally, 100 patients were included. According to the SSS assessment results within 72 hours of onset, 27 cases were divided into the progression group and 73 cases in the non-progression group. There was no significant difference in gender and age between the two groups (P>0.05). According to the evaluation results of the modified Rankin scale at 30 days of onset, they were divided into 31 cases in the poor prognosis group and 69 cases in the good prognosis group. There was no significant difference in gender and age between the two groups (P>0.05). Logistic regression analysis showed that plasma Lp-PLA2 [odds ratio (OR)=1.013, 95% confidence interval (CI) (1.007, 1.018), P<0.001], SSS score [OR=0.910, 95%CI (0.842, 0.985), P=0.019], and history of hypertension [OR=5.527, 95%CI (1.241, 24.613), P=0.025] were the predictors of disease progression within 72 hours. SSS score [OR=0.849, 95%CI (0.744, 0.930), P<0.001], carotid artery stenosis [OR=9.536, 95%CI (1.395, 65.169), P=0.021] and progressive stroke [OR=8.873, 95%CI (1.937, 40.640), P=0.005] were the predictors of short-term prognosis of LAA cerebral infarction. Conclusions History of hypertension and high levels of plasma Lp-PLA2 are predictors of early progression of cerebral infarction. Carotid artery stenosis and progressive stroke are predictors of adverse outcomes in the acute phase of cerebral infarction. Neurological scores on admission was a predictor for short-term adverse outcomes in the early and acute phases.
Objective The core indicator pool of ischemic stroke (IS) was constructed to provide a basis for the establishment of the core outcome set (COS), so as to improve the consistency of clinical research and evaluation results of traditional Chinese medicine (TCM) treatment for IS. Methods In this study, the mixed methods research (MMR) convergent parallel design was used to carry out qualitative research and quantitative research at the same time, and the two research results were integrated to reach a conclusion. Quantitative research comprehensively collected the multi-source efficacy evaluation indicators of TCM treatment of IS, and carried out descriptive statistical analysis based on frequency theory. Semi-structured interviews were used in the qualitative research, relevant interest groups were selected to understand the evaluation indicators of the IS efficacy of TCM treatment that they were concerned about, and NVivo software was used for in-depth analysis, coding, classification, and extraction of the efficacy indicators. Based on the principle of pillar integration, quantitative and qualitative research results were integrated to construct an element pool of evaluation indicators for the treatment of IS with traditional Chinese medicine. Results A total of 437 standard papers, 71 registered trial protocols, 100 real-world medical data cases and several guideline consensus policy documents were included in the quantitative study, and a total of 314 indicators in the acute phase of IS, 154 indicators in the recovery phase, and 104 indicators in the sequelae phase were extracted. In the qualitative research part, a total of 32 indicators in the acute stage of IS, 34 indicators in the recovery stage and 35 indicators in the sequelae stage were extracted through interviews. Through group discussion and the principle of pillar integration, an element pool of IS indicators was formed, including 279 IS indicators in the acute stage, 142 indicators in the recovery stage and 91 indicators in the sequelae stage. Conclusion Based on the MMR convergent parallel design, the element pool of the characteristic indicators of the therapeutic effect of IS in TCM is constructed to meet the needs, which provides the preliminary work basis for the construction of the core outcome set of IS in the next stage.
Objective To investigate the risk factors and the prevention and cure methods of ischemic stroke during low intensity anticoagulation therapy after mechanical heart valve replacement. Methods From March 2004 to July 2008，twentythree patients with ischemic stroke after mechanical heart valve replacement had been researched(ischemic stroke group). One hundred and twenty patients who had undergone mechanical heart valve replacement were randomly chosen in the same period as control group. Gender, age, the dose of warfarin , anticoagulation intensity(INR), INR review interval, left atrial diameter and heart rhythm were compared between the two groups, and the risk factors of ischemic stroke were analyzed by logistic regression analysis. Results (1) Patients in ischemic stroke group all discharged from hospital after treatment, and they were followed up for 1 month-3 years after discharged. All the patients’ neurological complications improved obviously, and no recurrent embolism and severe hemorrhage was found. (2) There was no statistical significance between two groups in gender, age and the dose of warfarin（Pgt;0.05）. (3) Nonconditional logistic regression analysis on influence factors showed that atrial fibrillation（P=0.000）, left atrial enlargement（P=0.002）, low anticoagulation intensity（P=0.012） and longtime INR review interval（P=0.047）were the risk factors of ischemic stroke during low intensity anticoagulation therapy after mechanical heart valve replacement. Conclusions (1)The prognosis of ischemic stroke during low intensity anticoagulation therapy after mechanical heart valve replacement is better than that of intracranial hemorrhage, and the occurrence of ischemic stroke is related to many risk factors. (2)The influences of risk factors should be minimized in order to avoid ischemic stroke. (3) Early low intensity anticoagulation therapy is safe and effective for patients with ischemic stroke after heart valve replacement.