scholarly journals Biomarkers Associated with Atrial Fibrillation in Patients with Ischemic Stroke: A Pilot Study from the NOR-FIB Study

2020 ◽  
Vol 10 (1) ◽  
pp. 11-20 ◽  
Author(s):  
Anna  Tancin Lambert ◽  
Xiang Y. Kong ◽  
Barbara Ratajczak-Tretel ◽  
Dan Atar ◽  
David Russell ◽  
...  

Background and Purpose: Cardioembolic stroke due to paroxysmal atrial fibrillation (AF) may account for 1 out of 4 cryptogenic strokes (CS) and transient ischemic attacks (TIAs). The purpose of this pilot study was to search for biomarkers potentially predicting incident AF in patients with ischemic stroke or TIA. Methods: Plasma samples were collected from patients aged 18 years and older with ischemic stroke or TIA due to AF (n = 9) and large artery atherosclerosis (LAA) with ipsilateral carotid stenosis (n = 8) and age- and sex-matched controls (n = 10). Analyses were performed with the Olink technology simultaneously measuring 184 biomarkers of cardiovascular disease. For bioinformatics, acquired data were analyzed using gene set enrichment analysis (GSEA). Selected proteins were validated using ELISA. Individual receiver operating characteristic (ROC) curves and odds ratios from logistic regression were calculated. A randomForest (RF) model with out-of-bag estimate was applied for predictive modeling. Results: GSEA indicated enrichment of proteins related to inflammatory response in the AF group. Interleukin (IL)-6, growth differentiation factor (GDF)-15, and pentraxin-related protein PTX3 were the top biomarkers on the ranked list for the AF group compared to the LAA group and the control group. ELISA validated increased expression of all tested proteins (GDF-15, PTX3, and urokinase plasminogen activator surface receptor [U-PAR]), except for IL-6. 19 proteins had the area under the ROC curve (AUC) over 0.85 including all of the proteins with significant evolution in the logistic regression. AUCs were very discriminant in distinguishing patients with and without AF (LAA and control group together). GDF-15 alone reached AUC of 0.95. Based on RF model, all selected participants in the tested group were classified correctly, and the most important protein in the model was GDF-15. Conclusions: Our results demonstrate an association between inflammation and AF and that multiple proteins alone and in combination may potentially be used as indicators of AF in CS and TIA patients. However, further studies including larger samples sizes are needed to support these findings. In the ongoing NOR-FIB study, we plan further biomarker assessments in patients with CS and TIA undergoing long-term cardiac rhythm monitoring with insertable cardiac monitors.

2020 ◽  
Vol 25 (45) ◽  
pp. 4827-4834 ◽  
Author(s):  
Limin Zhang ◽  
Xingang Li ◽  
Dongzhi Wang ◽  
Hong Lv ◽  
Xuezhong Si ◽  
...  

Background: A considerable proportion of acute noncardiogenic ischemic stroke patients continue to experience recurrent ischemic events after standard therapy. Aim: We aimed to identify risk factors for recurrent ischemic event prediction at an early stage. Methods : 286 non-cardioembolic ischemic stroke patients with the onset of symptoms within 24 hours were enrolled. Vascular risk factors, routine laboratory data on admission, thromboelastography test seven days after clopidogrel therapy and any recurrent events within one year were assessed. Patients were divided into case group (patients with clinical adverse events, including ischemic stokes, transient ischemic attack, myocardial infarction and vascular related mortality) and control group (events-free patients). The risk of the recurrent ischemic events was determined by the receiver operating characteristic curve and multivariable logistic regression analysis. Results: Clinical adverse events were observed in 43 patients (case group). The mean levels of Mean Platelet Volume (MPV), Platelet/Lymphocyte Ratio (PLR), Lymphocyte Count (LY) and Fibrinogen (Fib) on admission were significantly higher in the case group as compared to the control group (P<0.001). Seven days after clopidogrel therapy, the ADP-induced platelet inhibition rate (ADP%) level was lower in the case group, while the Maximum Amplitude (MA) level was higher in the case group as compared to the control group (P<0.01). The Area Under the Curve (AUC) of receiver operating characteristic(ROC) curve of LY, PLR, , Fib, MA, ADP% and MPV were 0.602, 0.614, 0.629, 0.770, 0.800 and 0.808, respectively. The logistic regression analysis showed that MPV, ADP% and MA were indeed predictive factors. Conclusion: MPV, ADP% and MA were risk factors of recurrent ischemic events after acute noncardiogenic ischemic stroke. Urgent assessment and individual drug therapy should be offered to these patients as soon as possible.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pusheng Quan ◽  
Kai Wang ◽  
Shi Yan ◽  
Shirong Wen ◽  
Chengqun Wei ◽  
...  

AbstractThis study aimed to identify potential novel drug candidates and targets for Parkinson’s disease. First, 970 genes that have been reported to be related to PD were collected from five databases, and functional enrichment analysis of these genes was conducted to investigate their potential mechanisms. Then, we collected drugs and related targets from DrugBank, narrowed the list by proximity scores and Inverted Gene Set Enrichment analysis of drug targets, and identified potential drug candidates for PD treatment. Finally, we compared the expression distribution of the candidate drug-target genes between the PD group and the control group in the public dataset with the largest sample size (GSE99039) in Gene Expression Omnibus. Ten drugs with an FDR < 0.1 and their corresponding targets were identified. Some target genes of the ten drugs significantly overlapped with PD-related genes or already known therapeutic targets for PD. Nine differentially expressed drug-target genes with p < 0.05 were screened. This work will facilitate further research into the possible efficacy of new drugs for PD and will provide valuable clues for drug design.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Joon-tae Kim ◽  
Hee-Joon Bae ◽  

Introduction: Atrial fibrillation (AF) and large artery diseases (LAD) share several risk factors and often coexist in the same patient. Optimal treatments for acute ischemic stroke (AIS) patients with concomitant AF and LAD have not been extensively studied so far. Objective: This study aimed to compare the effectiveness of the addition of antiplatelet (AP) to oral anticoagulant (OAC) with that of OAC alone in AIS with AF according to the LAD. Methods: Using a multicenter stroke registry, acute (within 48h of onset) and mild-to-moderate (NIHSS score ≤15) stroke patients with AF were identified. Propensity scores using IPTW were used to adjust baseline imbalances between the OAC+AP group and the OAC alone group in all patients and in each subgroup by LAD. The primary outcome was major vascular events, defined as the composite of recurrent stroke, MI, and all-cause mortality at up to 3 months after index stroke. Results: Among the 5469 patients (age, 72±10yrs; male, 54.9%; initial NIHSS score, 4 [2-9]), 79.0% (n=4323) received OAC alone, and 21.0% (n=1146) received OAC+AP. By weighted Cox proportional hazards analysis, a tendency of increasing the risk of 3-months primary composite events in the OAC+AP group vs the OAC alone (HR 1.36 [0.99-1.87], p=0.06), with significant interaction with treatments and LAD (Pint=0.048). Briefly, among patients with moderate-to-severe large artery stenosis, tendency of decrease in 3-months primary composite events of the OAC+AP group, compared with OAC alone group, was observed (HR 0.54 [0.17-1.70]), whereas among patients with complete occlusion, the OAC+AP group markedly increased the risk of 3-months composite events (HR 2.00 [1.27-3.15]), compared with the OAC alone group. No interaction between direct oral anticoagulant and warfarin on outcome was observed (Pint=0.35). Conclusion: In conclusion, treatment with addition of AP to OAC had a tendency to increase the risk of 3-months vascular events, compared with OAC alone in AIS with AF. However, the effects of antithrombotic treatment could be modified according to the LAD, with substantial benefits of OAC alone in subgroup of large artery occlusion. Our results address the need for the further study to tailor the optimal treatment in AIS with concomitant AF and LAD.


2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Rui He ◽  
Guoyou Wang ◽  
Ting Li ◽  
Huarui Shen ◽  
LijuanZhang

Abstract Background Postoperative ischemic stroke is a devastating complication following total hip arthroplasty (THA). The purpose of the current study was to investigate the incidence of postoperative acute ischemic stroke (AIS) in patients ≥70 years old with THA for hip fracture after 90 days and independent risk factors associated with 90-day AIS. Methods A multicenter retrospective study was conducted, patients ≥70 years old with THA for hip fracture under general anesthesia were included from February 2017 to March 2020. Patients with AIS within 90 days after THA were identified as AIS group; patients with no AIS were identified as no AIS group. The baseline characteristics and risk factors were collected, multivariable logistic regression was used to identify independent risk factors of 90-dayAIS. Results: 2517 patients (mean age 76.18 ± 6.01) were eligible for inclusion in the study. 2.50% (63/2517) of patients had 90-day AIS. Compared with no AIS, older age, diabetes, hyperlipidemia, atrial fibrillation (AF) and higher D-dimer value were more likely in patients with AIS (P < 0.05), and anticoagulant use was fewer in patients with AIS. ROC curve analysis showed that the optimal cut point of D-dimer for AIS was D-dimer≥4.12 μg/ml. Multivariate logistic regression analysis showed that D-dimer≥4.12 μg/ml [adjusted odds ratio (aOR), 4.44; confidence interval (CI), 2.50–7.72; P < 0.001], older age (aOR, 1.08; 95%CI, 1.03–1.12; P < 0.001), hyperlipidemia (aOR, 2.28; 95%CI, 1.25–4.16; P = 0.007), atrial fibrillation (aOR, 5.84; 95% CI, 1.08–15.68; P = 0.001), and diabetes (aOR, 2.60; 95% CI, 1.56–4.39; P < 0.001) were associated with increased risk of 90-day AIS after THA. Conclusions In conclusion, we found that the incidence of 90-day AIS in patients≥70 years old with THA for hip fracture was 2.5%. Older age, diabetes, hyperlipidemia, AF and higher D-dimer value were independent risk factors for 90-day AIS in patients≥70 years old with THA for hip fracture.


2021 ◽  
Vol 41 (4) ◽  
Author(s):  
Dengliang Lei ◽  
Yue Chen ◽  
Yang Zhou ◽  
Gangli Hu ◽  
Fang Luo

Abstract Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers worldwide. Neovascularization is closely related to the malignancy of tumors. We constructed a signature of angiogenesis-related long noncoding RNA (lncRNA) to predict the prognosis of patients with HCC. The lncRNA expression matrix of 424 HCC patients was downloaded from The Cancer Genome Atlas (TCGA). First, gene set enrichment analysis (GSEA) was used to distinguish the differentially expressed genes of the angiogenesis genes in liver cancer and adjacent tissues. Next, a signature of angiogenesis-related lncRNAs was constructed using univariate and multivariate analyses, and receiver operating characteristic (ROC) curves were used to assess the accuracy. The signature and relevant clinical information were used to construct the nomogram. A 5-lncRNA signature was highly correlated with overall survival (OS) in HCC patients and performed well in evaluations using the C-index, areas under the curve, and calibration curves. In summary, the 5-lncRNA model can serve as an accurate signature to predict the prognosis of patients with liver cancer, but its mechanism of action must be further elucidated by experiments.


2021 ◽  
Vol 21 (2) ◽  
pp. 42-53
Author(s):  
A Petrovicova ◽  
E Kurca ◽  
A Andrasova ◽  
J Bernatova ◽  
P Blasko ◽  
...  

Abstract Introduction: Cardioembolic etiology is assumed to be the most frequent cause of cryptogenic strokes. The detection of subclinical paroxysmal atrial fibrillation (AF) is important in the correct choice of preventive treatment. The aim of this prospective study was to detect the incidence of AF in patients with a cryptogenic stroke or transient ischemic attack (TIA) and to evaluate the association between the presence of AF and selected single-nucleotide polymorphisms (SNP). Methods: Patients with a cryptogenic stroke/ TIA (n=100) and a control group (n=15) of volunteers without significant cardiovascular disease were included in the study during the period of 2014 to 2019. To detect AF they underwent 12 months of ECG monitoring using an implanted loop recorder (ILR). Genotyping for SNPs rs10033464, rs2200733, rs225132, and rs2106261 was performed by a high resolution melting analysis. Results: We found AF to be present in 24 (24%) patients with a cryptogenic stroke/TIA, versus no subjects in the control group. The SNPs rs2106261, rs2200733, rs225132, and rs10033464 were not found to be associated with AF in our study (p=0.240; 1.000; 0.887; 0.589). However, a weak trend for a higher frequency of rs2106261 risk allele A homozygotes was observed in the patients with AF compared to the patients without AF (0.416 vs. 0.263, p=0.073). Homozygotes for allele A of rs2106261 were also present in a significantly higher frequency in AF patients compared to the controls (0.416 vs. 0.133, p = 0.012). Conclusion: In our study paroxysmal AF was a probable etiological factor in 24% of patients with cryptogenic ischemic stroke / TIA during the 12 months of monitoring. The homozygous allele A of rs2106261 was identified to be the possible genetic risk factor of AF, but this should be verified in larger cohorts. The study has been registered at www.clinicaltrials.gov, identifier NCT02216370.


Author(s):  
Bo Xiao ◽  
Liyan Liu ◽  
Zhuoyuan Chen ◽  
Aoyu Li ◽  
Pingxiao Wang ◽  
...  

Melanoma is the most common cancer of the skin, associated with a worse prognosis and distant metastasis. Epithelial–mesenchymal transition (EMT) is a reversible cellular biological process that plays significant roles in diverse tumor functions, and it is modulated by specific genes and transcription factors. The relevance of EMT-related lncRNAs in melanoma has not been determined. Therefore, RNA expression data and clinical features were collected from the TCGA database (N = 447). Melanoma samples were randomly assigned into the training (315) and testing sets (132). An EMT-related lncRNA signature was constructed via comprehensive analyses of lncRNA expression level and corresponding clinical data. The Kaplan-Meier analysis showed significant differences in overall survival in patients with melanoma in the low and high-risk groups in two sets. Receiver operating characteristic (ROC) curves were used to measure the performance of the model. Cox regression analysis indicated that the risk score was an independent prognostic factor in two sets. Besides, a nomogram was constructed based on the independent variables. Gene Set Enrichment Analysis (GSEA) was applied to evaluate the potential biological functions in the two risk groups. Furthermore, the melanoma microenvironment was evaluated using ESTIMATE and CIBERSORT algorithms in the risk groups. This study indicates that EMT-related lncRNAs can function as potential independent prognostic biomarkers for melanoma survival.


2019 ◽  
Vol 10 (3) ◽  
pp. 1932-1935
Author(s):  
Raad Hassan Najim ◽  
Bilal Jamal kamal

Background: Stroke is a common cause of morbidity and mortality worldwide, and it is the third leading cause of medical death in developed countries. Stroke can be classified into ischemic disease (80%) and hemorrhagic disease (20). Subject and methods: A case-control study done in the period extending from November 2013 to April 2014 in neuro medicine department in Azadi teaching hospital in Kirkuk city in Iraq. This study involving 2 study groups, each one of them, including 50 patients. The first group (cases) included 50 patients diagnosed as having an ischemic stroke by neurologist their ages were less than 45 years .in  another group (control), 50 patients involved admitted to the same hospital with no history of prior ischemic stroke. Results: Fifty patients with stroke of ischemic orgin and 50 controls included in the study. Table 1 summarize demographic and clinical characteristics of patients and control groups, control was older than ischemic stroke patient with no significant correlation (P-value=0.33). Gender distribution showing a significant correlation in regarding female sex in both groups (P-value=0.001). Ischemic stroke according to our findings is more prevalent in those patients with Hypertension with 66% of patients in comparison to 42% of control patients with P-value of 0.0001, diabetic patients with double percentage (72%) to those in control group (36%) with P-value of 0.0001,coronary arterial disease ,valvular heart disease and rhythm disease such as atrial fibrillation seen to be more popular  in those patients with ischemic stroke with no significant value in regarding to patients having coronary and valvular heart disease (P-value=0.11,0.21) and strongly associated with those patient presented with atrial fibrillation (P-value=0.0001). Conclusion: Elevated anticardiolipin antibodies are seen to be as an independent risk factor for ischemic stroke.


2020 ◽  
Author(s):  
Changjiang Xue ◽  
Na Wu ◽  
Yali Fan ◽  
Jing Ma ◽  
Qiao Ye

Abstract Background Silicosis is a progressive pneumoconiosis characterized by interstitial fibrosis following exposure to silica dust. This study aimed to identify potential noninvasive metabolic biomarkers for the diagnosis and monitoring of this condition by pilot and validation analyses of patients with silicosis in metabolomics studies.Methods Patients with silicosis, dust-exposed workers (DEWs) without silicosis and age-matched healthy controls were recruited in a case-control study. Plasma samples were collected, and metabolomics analyses by ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) were conducted. Distinct metabolic features (DMFs) among the groups were identified in the pilot study and were validated in the validation study. The enriched signalling pathways of these DMFs were determined. The ability of DMFs to discriminate among the groups in the validation study was analysed through receiver operating characteristic (ROC) curves. The correlations between DMFs and clinical features were also explored.Results Twenty-nine DMFs and 9 DMFs were detected in the plasma of the DEW and silicosis groups, respectively, compared with the control group; these features showed the same trend in the pilot study and the validation study. Sphingolipid metabolism was the major metabolic pathway in the DEWs, and arginine and proline metabolism was associated with silicosis. Twenty DMFs in the DEWs and 3 DMFs in the patients with silicosis showed a discriminatory ability with ROC curve analysis. The abundance of kynurenine was higher in Stage III silicosis than in Stage I or Stage II silicosis. L-arginine and kynurenine were both negatively correlated with the percentage of forced vital capacity predicted in silicosis.Conclusions Distinct metabolic features of plasma samples related to sphingolipid metabolism and arginine and proline metabolism were identified in the DEW and silicosis groups, respectively. L-arginine and kynurenine may have a predictive role in the diagnosis and severity of silicosis.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Bodin ◽  
A Bisson ◽  
N Clementy ◽  
B Pierre ◽  
J Herbert ◽  
...  

Abstract Atrial fibrillation (AF) may be associated with sinus node disease (SND) presenting as a brady-tachy syndrome (BTS), known to be at risk for embolic ischemic stroke (IS). It remains unclear whether the risk of IS is increased in patients with isolated SND. Methods This French longitudinal cohort study was based on the national database covering hospital care from for the entire population (PMSI) from 2010 to 2015. We compared incidences of IS in patients with a diagnosis of AF or SND to that in a control group of patients with a main diagnosis of cardiac condition (excluding those with AF or SND, history of stroke and mechanical valve or mitral stenosis). Results Of 1,732,412 patients included in the cohort, 1,601,435 (92.44%) had isolated AF, 102,849 (5.94%) had isolated SND and 28,128 (1.62%) had BTS. The control group with cardiac condition included 479,108 patients. Incidence of IS progressively increased when considering patients from the control population, patients with isolated SND, with BTS or with isolated AF (0.67%/yr, 1.95%/yr, 3.03%/yr and 5.48%/yr respectively). These differences were seen in all strata of CHA2DS2VASc score (table). SND patients with a CHA2DS2-VASc score ≥3 had a yearly incidence of IS >2%, comparable to AF population with a CHA2DS2-VASc score ≥1. Incidence (%/year) of ischemic stroke CHA2DS2-VASc AF population SND population “Control” population Women Men Women Men Women Men All scores 6.72% 4.37% 1.93% 1.96% 0.67% 0.68% Score = 0 – 1.960% – 1.211% – 0.217% Score = 1 2.337% 3.046% 0.538% 1.486% 0.166% 0.345% Score = 2 3.917% 4.499% 0.879% 1.541% 0.298% 0.580% Score = 3 7.572% 4.733% 2.207% 2.084% 0.541% 0.907% Score = 4 7.016% 4.820% 2.363% 2.305% 0.930% 1.278% Score = 5 6.725% 5.345% 2.845% 2.849% 1.249% 1.553% Score = 6 7.637% 7.543% 3.319% 4.109% 1.737% 2.031% Score = 7 10.196% 13.927% 4.663% 7.708% 2.346% 4.089% Score = 8 17.654% 12.607% 8.519% 11.904% 2.446% 2.355% Conclusion Patients with isolated SND had a lower risk of IS than patients with AF or BTS. However, SND patients had a non-neglectable risk of IS during follow-up which was higher than in a “control” population. Whether oral anticoagulation may bring a significant clinical benefit might be studied in patients with SND at highest risk of IS.


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