Project description:Exosomal circRNA sequencing was used to identify differentially expressed circRNAs between LAA stroke and normal controls. From a further validation stage, the results were validated using RT-qPCR.
Project description:Purpose: This study aimed to explore the differential expression profiles of exosomal lncRNAs and evaluated their potential utility in the accurate diagnosis of LAA stroke. Methods: LncRNA profiles of exosomes in large artery atherosclerosis stroke and controls were generated by high-throughput sequencing. The sequence reads that passed quality filters were analyzed at the transcript isoform level with Hisat2, Trapnell, STAR. qRT–PCR validation was performed using TaqMan and SYBR Green assays. Results: A total of 1020 differentially expressed lncRNAs were identified in LAA stroke patients. GO and KEGG pathway analyses indicated that their target genes are involved in atherosclerosis-related pathways, including inflammation, cell adhesion, and cell migration. 8 exosomal lncRNAs were confirmed with qRT–PCR.The result showed that the expression trend of differential expressed lncRNAs in validation was consistent with RNA-seq.Conclusion: Our study showed the differential expression of lncRNAs in plasma exosomes and presented related diagnostic potential for LAA stroke for the first time. The results suggested that exosomal lncRNA could be potential diagnostic tools in LAA stroke. Circular RNAs (circRNAs), novel endogenous noncoding RNAs, play diverse roles in ischemic stroke. Recently, the abundance and stability of circRNAs in exosomes have been identified. However, a comprehensive analysis of exosomal circRNAs in large artery atherosclerotic (LAA) stroke has not yet been reported. We performed RNA sequencing (RNA-Seq) to comprehensively identify differentially expressed exosomal circRNAs in five paired LAA and normal controls. RNA-Seq identified a total of 462 circRNAs in peripheral exosomes; there were 25 differentially expressed circRNAs among them. Additionally, circRNA competing endogenous RNA (ceRNA) network and translatable analysis revealed the potential functions of the exosomal circRNAs in LAA progression. Two ceRNA pathways involving 5 circRNAs, 2 miRNAs, and 3 mRNAs were confirmed by qRT-PCR. In the validation cohort, receiver operating characteristic (ROC) curve analysis identified two circRNAs as possible novel biomarkers, and a logistic model combining two and four circRNAs increased the area under the curve compared with the individual circRNAs.
Project description:BackgroundCoronary artery disease (CAD) occurs at younger age in India but only a limited number of studies have evaluated risk factors and management status. This is a multisite observational registry to assess risk factors and treatment patterns in young patients presenting with acute coronary syndrome (ACS) and stable ischemic heart disease (IHD).MethodsWe recruited 997 young patients (men <55, women <65y) presenting with ACS or stable IHD successively at 22 centers across India. Details of baseline risk factors and management status were obtained. Descriptive statistics are reported.ResultsMean age of participants was 49.1±8y, 72% were men and 68% had ACS. Family history of CAD was in 50%, diabetes 44%, hypertension 49%, history of dyslipidemia 11%, smoking/tobacco use 39%, and sedentary habits in 20%. 1.3% had "possible familial hypercholesterolemia". Metabolic risk factors (high BMI, diabetes and hypertension) were significantly greater in women (p<0.01). Women were older at diagnosis of CAD and presented more often with non-ST elevation ACS. In the study cohort antiplatelet use was in 85%, beta-blockers 38%, statins 63% and ACE inhibitors/ARBs in 41% while in ACS patients it was 80.5%, 54.6%, 80.8% and 40.8%, respectively. 35.9% patients underwent percutaneous coronary intervention while coronary bypass surgery was performed in 10.4%.ConclusionsConventional risk factors including family history continue to play a pivotal role in premature CAD in Indians. Women have more of metabolic risk factors, present at a later age and have non-ST elevation ACS more often. There is a need to focus on improving use of evidence-based drug therapies and interventions.
Project description:Objectives: The combination of systemic thrombolysis and mechanical thrombectomy is indicated in patients with ischemic stroke due to a large vessel occlusion (LVO) and these treatments are time-dependent. Rapid identification of patients with suspected LVO also in a prehospital setting could influence the choice of the destination hospital. Aim of this pilot study was to evaluate the predictive role of a new stroke scale for LVO, comparing it to other scores. Patients and Methods: All consecutive patients admitted to our comprehensive stroke center with suspected ischemic stroke were studied with a CT angiography and 5 different stroke scales were applied. The Large ARtery Occlusion (LARIO) stroke scale consists of 5 items including the assessment of facial palsy, language alteration, grip and arm weakness, and the presence of neglect. A Receiving Operating Characteristic curve was evaluated for each stroke scale to explore the level of accuracy in LVO prediction. Results: A total of 145 patients were included in the analysis. LVO was detected in 37.2% of patients. The Area Under Curve of the LARIO score was 0.951 (95%CI: 0.902-0.980), similar to NIHSS and higher than other scales. The cut-off score for best performance of the LARIO stroke scale was higher than 3 (positive predictive value: 77% and negative predictive value: 100%). Conclusion: The LARIO stroke scale is a simple tool, showing high accuracy in detecting LVO, even if with some limitations due to some false positive cases. Its efficacy has to be confirmed in a pre-hospital setting and other centers.
Project description:Intracranial atherosclerosis burden is an arising key index for the risk and prognosis for Intracranial Atherosclerosis Stenosis (ICAS). The present study estimated one-year prognosis for patients of symptomatic ICAS with different degrees of intracranial atherosclerosis burden (ICASB) and identified whether the category of multiple and single acute infarction was associated with atherosclerosis burden. A total of 2864 consecutive patients, from 22 hospitals across China, who experienced an acute cerebral ischemia <7 days after onset of symptoms were evaluated. All patients underwent magnetic resonance angiography, and the degree of intracranial stenosis with the ICASB was calculated. The patients were categorized into three groups according to ICASB grading: <4, 4-5 and >5scores. Multivariate Cox proportional hazards regression models were used to estimate the impact of the hazard ratios(HR) of the putative determinants of recurrent stroke in one year. In the groups with ICASB 4-5 and ICASB >5scores recurrent stroke were significantly higher than the other (P<0.0001). On multivariate logistic analysis, ICASB (4-5) indicated more stroke recurrence at 12 months (adjusted hazard ratio, 1.96; 95% confidence interval, 1.08-3.56; P=0.027), compared to the ICASB<4scores and >5 groups (P<0.001). Moreover, proportion of single and multiple infarction lesions differs with different ICASB. Multiple lesions were related with higher of ICASB(P<0.001). Intracranial atherosclerosis burden was associated with recurrent stroke at 12 months. Multiple infarction lesions were associated with higher ICASB score which indicate higher risk of recurrent.
Project description:BackgroundSouth-Asian's are predisposed to early onset type 2 diabetes (T2DM). The prevalence of cardio-metabolic risk-factors in young Sri-Lankans is unknown.Methodology/principal findingsTo determine by questionnaire and anthropometry the prevalence of first degree family history (FH) of T2DM, physical inactivity, raised waist circumference (WC) and raised body mass index (BMI) in a representative healthy urban population selected by cluster sampling. Those with ? 2 risk-factors were evaluated for metabolic syndrome (MS) and recruited for an intervention trial. Of 23,296 participants screened, 22,507 (53% Female) were eligible [8,497 aged 10-14 yrs, 4,763 aged 15-19 yrs and 9,247 aged 20-40 yrs]. 51% had none of the 4 risk-factors, 26% 1 risk-factor and 23% (5,163) ? 2 risk-factors of whom 4,532 were assessed for MS. Raised BMI was noted in 19.7% aged 10-14 yrs, 15.3% between 15-19 yrs, and between 20-40 yrs, 27.4% of males vs. 21.8% of females p<0.001. Prevalence of raised WC was greater in females for each age group: 42.7% vs. 32.1%; 28.1% vs. 16.1%; 34.5% vs. 25.7% (p<0.05 for all) as was physical inactivity: 39.9% vs. 14.5%; 51.7% vs. 20.0%; 62.7% vs. 41.3% which rose in both sexes with age (p<0.05 for all). FH of T2DM was present in 26.2%. In 4532 (50%<16 yrs) with ? 2 risk-factors, impaired fasting glycaemia/impaired glucose tolerance (pre-diabetes) prevalence was 16%. MS was more prevalent in males [10-16 yrs (13.0% vs. 8.8%), 16-40 yrs (29.5% vs. 20.0%) p<0.001 for both].Conclusions/significanceThere is a high prevalence of modifiable cardio-metabolic risk-factors in young urban Sri-Lankans with significant gender differences. A primary prevention intervention trial is ongoing in this cohort. Clinical Trial Registration Number SLCTR/2008/World Health Organization (WHO) international clinical trial registry platform.
Project description:BACKGROUND AND PURPOSE:Epidemiological studies show strong associations between kidney dysfunction and risk of ischemic stroke (IS), the mechanisms of which are incompletely understood. We investigated whether these associations may reflect shared heritability because of a common polygenic basis and whether this differed for IS subtypes. METHODS:Polygenic models were derived using genome-wide association studies meta-analysis results for 3 kidney traits: estimated glomerular filtration rate using serum creatinine (eGFRcrea: n=73?998), eGFR using cystatin C (eGFRcys: n=22?937), and urinary albumin to creatinine ratio (n=31?580). For each, single nucleotide polymorphisms passing 10 P value thresholds were used to form profile scores in 4561 IS cases and 7094 controls from the United Kingdom, Germany, and Australia. Scores were tested for association with IS and its 3 aetiological subtypes: large artery atherosclerosis, cardioembolism, and small vessel disease. RESULTS:Polygenic scores correlating with higher eGFRcrea were associated with reduced risk of large artery atherosclerosis, with 5 scores reaching P<0.05 (peak P=0.004) and all showing the epidemiologically expected direction of effect. A similar pattern was observed for polygenic scores reflecting higher urinary albumin to creatinine ratio, of which 3 associated with large artery atherosclerosis (peak P=0.01) and all showed the expected directional association. One urinary albumin to creatinine ratio-based score also associated with small vessel disease (P=0.03). The global pattern of results was unlikely to have occurred by chance (P=0.02). CONCLUSIONS:This study suggests possible polygenic correlation between renal dysfunction and IS. The shared genetic components may be specific to stroke subtypes, particularly large artery atherosclerotic stroke. Further study of the genetic relationships between these disorders seems merited.
Project description:ObjectivesThe cause of ischemic stroke remains unknown, cryptogenic, in 25% of young and middle-aged patients. We hypothesized that if atherosclerosis is prominent in cryptogenic stroke, it would have a similar proinflammatory protein signature as large artery atherosclerosis (LAA) stroke.Materials & methodsBlood was collected in the acute phase and after 3 months from cryptogenic (n = 162) and LAA (n = 73) stroke patients aged 18-69 years and once from age-matched controls (n = 235). Cryptogenic stroke was divided into Framingham Risk Score (FRS) quartiles to compare low and high risk of atherosclerosis. Plasma concentrations of 25 proteins were analyzed using a Luminex multiplex assay. The discriminating properties were assessed with discriminant analysis and C-statistics.ResultsWe identified proteins that separated cryptogenic and LAA stroke from controls (area under the curves, AUCs ≥ 0.85). For both subtypes, RANTES, IL-4, and IFN-γ contributed the most at both time points. These associations were independent of risk factors of atherosclerosis. We also identified proteins that separated cryptogenic strokes in the lowest quartile of FRS from those in the highest, and from LAA stroke (AUCs ≥ 0.76), and here eotaxin and MCP-1 contributed the most.ConclusionsThe protein signature separating cases from controls was different from the signature separating cryptogenic stroke with low risk of atherosclerosis from those with high risk and from LAA stroke. This suggests that increased RANTES, IL-4, and IFN-γ in stroke may not be primarily related to atherosclerosis, whereas increased eotaxin and MCP-1 in cryptogenic stroke may be markers of occult atherosclerosis as the underlying cause.
Project description:In major ischemic stroke caused by a large artery occlusion, neuronal loss varies considerably across individuals without revascularization. This study aims to identify which patient characteristics are most highly associated with this variability. Demographic and clinical information were retrospectively collected on a registry of 878 patients. Imaging biomarkers including Alberta Stroke Program Early CT score, noncontrast head computed tomography infarct volume, perfusion computed tomography infarct core and penumbra, occlusion site, collateral score, and recanalization status were evaluated on the baseline and early follow-up computed tomography images. Infarct growth rates were calculated by dividing infarct volumes by the time elapsed between the computed tomography scan and the symptom onset. Collateral score was graded into four levels (0, 1, 2, and 3) in comparison with the normal side. Correlation of perfusion computed tomography and noncontrast head computed tomography infarct volumes and infarct growth rates were estimated with the nonparametric Spearman's rank correlation. Conditional inference trees were used to identify the clinical and imaging biomarkers that were most highly associated with the infarct growth rate and modified Rankin Scale at 90 days. Two hundred and thirty-two patients met the inclusion criteria for this study. The median infarct growth rates for perfusion computed tomography and noncontrast head computed tomography were 11.2 and 6.2 ml/log(min) in logarithmic model, and 18.9 and 10.4 ml/h in linear model, respectively. Noncontrast head computed tomography and perfusion computed tomography infarct volumes and infarct growth rates were significantly correlated (rho=0.53; P < 0.001). Collateral status was the strongest predictor for infarct growth rates. For collateral=0, the perfusion computed tomography and noncontrast head computed tomography infarct growth rate were 31.56 and 16.86 ml/log(min), respectively. Patients who had collateral >0 and penumbra volumes>92 ml had the lowest predicted perfusion computed tomography infarct growth rates (6.61 ml/log(min)). Collateral status was closely related to the diversity of infarct growth rates, poor collaterals were associated with a faster infarct growth rates and vice versa.