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BACKGROUND: The precise mechanisms leading to the development of heart failure with preserved ejection fraction (HFpEF) remain incompletely defined. In this study, an integrative approach utilizing untargeted proteomics and metabolomics was employed to delineate the altered proteomic and metabolomic profiles in patients with HFpEF compared to healthy controls. MATERIALS AND METHODS: Data were collected from a prospective cohort consisting of 30 HFpEF participants and 30 healthy controls, matched by gender and age. plasma samples were analyzed by multi-omics platforms. The quantification of plasma proteins and metabolites was performed using data-independent acquisition-based liquid chromatography-tandem mass spectrometry (LC-MS/MS) and ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), respectively. Additionally, Proteomic and metabolomic results were analyzed separately and integrated using correlation and pathway analysis. This was followed by the execution of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment studies to elucidate the biological relevance of the observed results. RESULTS: A total of 46 significantly differentially expressed proteins (DEPs) and 102 differentially expressed metabolites (DEMs) were identified. Then, GO and KEGG pathway enrichment analyses were performed by DEPs and DEMs. Integrated analysis of proteomics and metabolomics has revealed Tuberculosis and African trypanosomiasis pathways that are significantly enriched and the DEPs and DEMs enriched within them, are associated with inflammation and immune response. CONCLUSIONS: Integrated proteomic and metabolomic analyses revealed distinct inflammatory and immune response pathways in HFpEF, highlighting novel therapeutic avenues.
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Insuficiência Cardíaca , Inflamação , Metabolômica , Proteômica , Humanos , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/imunologia , Feminino , Masculino , Inflamação/metabolismo , Idoso , Pessoa de Meia-Idade , Espectrometria de Massas em Tandem , Metaboloma , Biomarcadores/sangue , Volume Sistólico , Estudos Prospectivos , Estudos de Casos e ControlesRESUMO
ABSTRACT: The current work was aimed at exploring the association between single nucleotide polymorphisms (SNPs) in the ICAM-1 gene, along with the identification of additional haplotypes and their potential role in the susceptibility to ischemic cardiomyopathy (ICM). The control group underwent a Hardy-Weinberg equilibrium test. The associations of genotypes and alleles with susceptibility to ICM were then analyzed using logistic regression analysis. Subsequently odds ratios (ORs) along with 95% confidence intervals (95% CI) were calculated. Interaction analysis was conducted between these SNPs. Furthermore, linkage disequilibrium analysis and haplotype analysis were performed on SNPs that showed interactions with each other. The incidence of ICM was significantly higher among individuals carrying the T allele of rs3093032 (OR = 2.032, 95% CI, 1.275-3.241, P = 0.003) relative to those with the C allele. In addition, CT genotype carriers had a higher susceptibility to ICM than CC genotype carriers (OR = 2.490, 95% CI, 1.445-4.29, P = 0.001). Furthermore, 3 SNPs (rs3093032, rs923366, rs3093030) exhibited a strong interaction with each other, whereas rs281437 showed no interaction with the other 3 SNPs. Individuals carrying the C rs3093032 -T rs923366 -C rs3093030 haplotype had an elevated risk of ICM compared with those carrying the C rs3093032 -C rs923366 -C rs3093030 haplotype (OR = 2.280, 95% CI, 1.568-3.315, P < 0.001). Moreover, individuals carrying the T rs3093032 -C rs923366 -C rs3093030 haplotype were more susceptible to ICM than those carrying the C rs3093032 -C rs923366 -C rs3093030 haplotype (OR = 2.388, 95% CI, 1.469-3.880, P < 0.001). Regarding rs3093032, the minor alleles and haplotypes are associated with an increased ICM risk: 3 SNPs (rs3093032, rs923366, rs3093030) in ICAM-1 have strong interaction with each other.
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Cardiomiopatias , Predisposição Genética para Doença , Humanos , Molécula 1 de Adesão Intercelular/genética , Frequência do Gene , Estudos de Casos e Controles , Genótipo , Haplótipos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
The current study investigated the association between polymorphisms of the ICAM-1 gene and prognosis of Ischemic cardiomyopathy (ICM), and developed a prognostic nomogram for ICM on the basis of ICAM-1 gene variants. The current study included totally 252 patients with ICM. In addition, PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) was used to genotype SNPs in the ICAM-1 gene in the patients. Later, the nomogram model was built by combining clinical data and ICAM-1 gene variants. This study used the least absolute shrinkage and selection operator (LASSO) regression model to optimize feature selection into an ICM prognostic model. Furthermore, multivariate Cox-regression was applied to build the prognostic model, which included clinical and gene features chosen by the LASSO regression model. Following that, the receiver operating characteristic (ROC) curve, C-index, calibration plot analyses and decision curve analysis (DCA) were carried out to evaluate the discrimination ability, consistency, and clinical utility of the prognostic model, and the bootstrap method was adopted for internal validation. predicting factors rs112872667, treating by PCI or CABG, ventricular arrhythmia, left ventricular end-diastolic diameter (LVDD), use of ß-blockers, systolic blood pressure (SBP), heart rate (HR), and serum sodium were incorporated into the prognostic nomogram. The constructed nomogram performed well in discrimination ability, as observed by the time-dependent C-index. Furthermore, as shown by calibration curves, our nomogram's predicted probabilities were highly consistent with measured values. With threshold probabilities, DCA suggested that our nomogram could be useful in the clinic. mutation of rs112872667 have critical predictive value on the prognosis of ICM, ICM patients with the mutant genotype (CT or TT) have higher survival probability than those with the wild genotype (CC). Mutation of rs112872667 in ICAM-1 gene have critical predictive value on the prognosis of ICM, ICM patients with the mutant genotype (CT or TT) have higher survival probability than those with the wild genotype (CC).
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Cardiomiopatias , Intervenção Coronária Percutânea , Humanos , Nomogramas , Molécula 1 de Adesão Intercelular/genética , Prognóstico , Polimorfismo de Nucleotídeo Único/genética , Fator Intrínseco , Cardiomiopatias/genéticaRESUMO
BACKGROUND: The role of inflammation in venous thromboembolism (VTE) has been the focus of recent research. The NLRP3/IL-1/NF-κB signaling pathway and cytokines such as IL-1, regulated by macrophage polarization, may be the key indicators of a prethrombotic state; however, the mechanisms by which they affect the occurrence of VTE remain unclear. METHODS: We used neurobiological clamps to stimulate the vein wall to induce vascular endothelial damage to generate a rat model of VTE, applied enzyme-linked immunosorbent assay and real time-polymerase chain reaction technology to identify key proteins (IL1ß, Caspase-1, NLRP3, and NF-κB P65), gene mRNA levels and protein expression levels of the NLRP3/IL-1/NF-κB signaling pathway in each group of Sprague Dawley rats, and observed the polarization state of M1 (CD86) and M2 (CD206) macrophages using immunohistochemistry. RESULTS: A dark red, small thrombus developed in the inferior vena cava immediately after modeling in the model and inhibitor groups. The plasma levels of IL-1 and TNF-α, mRNA expression of key proteins (IL1ß, Caspase-1, NLRP3, and NF-κB P65), and expression of key proteins (IL1ß, Caspase-1, NLRP3, and NF-κB P65) in VTE model rats were significantly higher than inhibitor, sham operation, and normal control groups (P < 0.05). Six hours after VTE modeling, M1 type macrophages were more significantly increased than M2 type macrophages in thrombus tissue (P < 0.05). CONCLUSIONS: Our analyses demonstrated that the nod-like receptor protein3/Interleukin-1/nuclear factor-κB signaling pathway and macrophage polarization are important in the occurrence and development of VTE and that their target regulation may become a new strategy for VTE prevention and treatment.
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NF-kappa B , Tromboembolia Venosa , Ratos , Animais , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos Sprague-Dawley , Resultado do Tratamento , Transdução de Sinais , Macrófagos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Caspases/metabolismoRESUMO
Myocardial contrast echocardiography (MCE) and two-dimensional speckle tracking echocardiography (2D-STE) were used to detect left ventricular myocardial microcirculation perfusion and myocardial systolic function in dilated cardiomyopathy (DCM) and to explore the relationship between the two.Conventional ultrasound, MCE, and 2D-STE examinations were performed on 30 patients and 30 controls. Left ventricular microcirculation perfusion, left ventricular longitudinal strain (GLS), and circumferential strain (GCS) were analyzed to further compare the correlation between left ventricular perfusion and myocardial strain parameters.Regional myocardial perfusion was reduced in patients with DCM, manifesting as a decrease in the rising slope (A) of the mid-segment of the posterior septum, the peak intensity (PI) of the mid-segment of the anterior septum and the posterior septum, the apical segment of the lateral wall, the area under the curve (AUC) of the posterior septum, the basal segment of the posterior wall, the anterior septum, posterior septum, posterior wall, mid-segment of the lateral wall, and apical segment of the lateral wall and the overall average PI and AUC of the mid-segment, compared with that in the controls (P < 0.05). The left ventricular systolic function and the strain parameters GLS and GCS of DCM patients were lower than those of the controls (P < 0.001). Correlation analysis revealed a positive correlation between the A of the mitral valve and GCS (r = 0.372, P = 0.043), and MV-E/e' had a positive correlation with the AUC of the basal and intermediate segments (r = 0.379, P = 0.039; r = 0.404, P = 0.027).In patients with DCM, regional myocardial microcirculation perfusion is reduced, and myocardial strain is impaired. Myocardial perfusion has a good positive correlation with myocardial mechanics.
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Cardiomiopatia Dilatada/fisiopatologia , Ecocardiografia/métodos , Coração/fisiopatologia , Imagem de Perfusão do Miocárdio/métodos , Adulto , Cardiomiopatia Dilatada/diagnóstico por imagem , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Coronary artery spasm is an important pathophysiological mechanism in some forms of myocardial ischemic disease. The relationship between inflammatory markers, mean platelet volume (MPV), and coronary artery spasm is unclear. METHODS AND RESULTS: During coronary angiography, methylergometrin was injected intravenously to 345 patients with chest pain but without significant coronary disease on angiogram to provoke coronary artery spasm. Based on provocation test results, patients were divided into 2 groups: spasm group (60 patients) and nonspasm group (285 patients). Inflammatory markers (C-reactive protein, CRP; white blood cells; polymorphonuclear neutrophils, PMN; monocytes, MO; lymphocytes, LY), hemostasis markers (MPV; platelet count; fibrinogen [FIB]; D-dimers), and traditional risk factors (body mass index; hyperlipidemia; triglycerides [TGs]; total, low-density, and high-density lipoprotein cholesterol [TC, LDL-C, and HDL-C]) were measured and compared between groups. More male patients experienced spasm (23.56% vs. 11.11%, P = 0.002). CRP, PMN, and MO were significantly higher in the spasm group (P < 0.05). There was no significant difference in serum levels of LDL-C, HDL-C, TG, TC, LY, MPV, and FIB between groups. Smoking and hyperlipidemia were more common among patients with spasm; males more frequently were smokers (58.04% vs. 46.78%, P = 0.041). By multivariate analysis, smoking, PMN, and MO were significantly associated with coronary artery spasm with odds ratios of 3.52 (95% CI 1.79-6.90, P = 0.0001), 1.21 (95% CI 1.07-1.46, P = 0.04), and 5.35 (95% CI 1.37-21.07, P = 0.01), respectively. CONCLUSIONS: Inflammation may partake in the pathogenesis of coronary artery spasm. Smoking, PMN count, and MO count appear to be clinical risk factors for coronary artery spasm. Conversely, coronary artery spasm does not seem to be associated with abnormalities in thrombogenesis.
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Biomarcadores/sangue , Angiografia Coronária , Vasoespasmo Coronário/diagnóstico , Hemostasia , Inflamação , Volume Plaquetário Médio , Vasoespasmo Coronário/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Previous findings have indicated the potential benefits of the Chinese traditional medicine Qiliqiangxin (QLQX) in heart failure. Here we performed a double-blind, randomized controlled trial to evaluate the efficacy and safety of QLQX in patients with heart failure and reduced ejection fraction (HFrEF). This multicenter trial, conducted in 133 hospitals in China, enrolled 3,110 patients with HFrEF with NT-proBNP levels of ≥450 pg ml-1 and left ventricular ejection fraction of ≤40%. Participants were randomized to receive either QLQX capsules or placebo (four capsules three times daily) alongside standard heart failure therapy. The trial met its primary outcome, which was a composite of hospitalization for heart failure and cardiovascular death: over a median follow-up of 18.3 months, the primary outcome occurred in 389 patients (25.02%) in the QLQX group and 467 patients (30.03%) in the placebo group (hazard ratio (HR), 0.78; 95% confidence interval (CI), 0.68-0.90; P < 0.001). In an analysis of secondary outcomes, the QLQX group showed reductions in both hospitalization for heart failure (15.63% versus 19.16%; HR, 0.76; 95% CI, 0.64-0.90; P = 0.002) and cardiovascular death (13.31% versus 15.95%; HR, 0.83; 95% CI, 0.68-0.996; P = 0.045) compared to the placebo group. All-cause mortality did not differ significantly between the two groups (HR, 0.84; 95% CI, 0.70-1.01; P = 0.058) and adverse events were also comparable between the groups. The results of this trial indicate that QLQX may improve clinical outcomes in patients with HFrEF when added to conventional therapy. ChiCTR registration: ChiCTR1900021929 .
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Object: This study investigated the correlation between polymorphisms of the ICAM-1 gene and prognosis of Ischemic cardiomyopathy (ICM), and developed a prognostic model for predicting the prognosis ICM on the basis of ICAM-1 gene variants. Methods: The current study included totally 576 patients with ICM. All patients are randomly divided into training group with 399 patients and validation group with 177 patients. The prognostic model was constructed by using the data of training group. Univariable Cox-regression analysis was performed, including clinical and gene variants, then used the least absolute shrinkage and selection operator (LASSO) regression model to optimize feature selection. Furthermore, multivariate Cox-regression was applied to build the prognostic nomogram model, which included clinical and gene features chosen by the LASSO regression model. Following that, the receiver operating characteristic (ROC) curve, C-index, calibration plot analyses and decision curve analysis (DCA) were carried out to evaluate the discrimination ability, consistency, and clinical utility of the prognostic model. Results: Predicting factors rs281430, ventricular arrhythmia, treating by PCI or CABG, use of ß-blockers, heart rate (HR), serum sodium level, left ventricular end-diastolic diameter (LVDD) were the risk factors of the prognosis of ICM, incorporated these factors into the prognostic nomogram model. The constructed nomogram performed well in discrimination ability, as observed by the ROC and C-index. Furthermore, as shown by calibration curves, our nomogram's predicted probabilities were highly consistent with measured values. With threshold probabilities, DCA suggested that our nomogram could be useful in the clinic. Conclusion: rs281430 mutation (from AA genotype to AG or GG genotype) is a risk factor for ICM patients to have a higher survival probability; the survival probability of ICM patients with the mutant genotype (AG or GG) is lower than those with the wild genotype (AA).
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AIMS: Chronic heart failure (CHF) remains a major health issue worldwide. In the present study, we aimed to identify novel circulating biomarkers for CHF using serum proteomics technology and to validate the biomarker in three independent cohorts. METHODS AND RESULTS: The isobaric tags for relative and absolute quantitation technology was utilized to identify the potential biomarkers of CHF. The validation was conducted in three independent cohort. Cohort A included 223 patients with ischaemic heart disease (IHD) and 321 patients with ischaemic heart failure (IHF) from the CORFCHD-PCI study. Cohort B recruited 817 patients with IHD and 1139 patients with IHF from the PRACTICE study. Cohort C enrolled 559 non-ischaemic heart disease patients with CHF (n = 316) or without CHF (n = 243). We found the expression of a-1 antitrypsin (AAT) was elevated significantly in patients with CHF compared with that in the patients with stable IHD using statistical and bioinformatics analyses. In a validation study, there was a significant difference between patients with stable IHD and patients with IHF in AAT concentration either in cohort A (1.35 ± 0.40 vs. 1.64 ± 0.56, P < 0.001) or in cohort B (1.37 ± 0.42 vs. 1.70 ± 0.48, P < 0.001). The area under the receiver operating characteristic curve was 0.70 [95% confidence interval (CI): 0.66 to 0.74, P < 0.001] in cohort A and 0.74 (95% CI: 0.72 to 0.76, P < 0.001) in cohort B. Furthermore, AAT was negative correlated with left ventricular ejection fraction (r = -0.261, P < 0.001). After adjusting for confounders using a multivariate logistic regression analysis, AAT remained an independent association with CHF in both cohort A (OR = 3.14, 95% CI: 1.667 to 5.90, P < 0.001) and cohort B (OR = 4.10, 95% CI: 2.97 to 5.65, P < 0.001). This association was also validated in cohort C (OR = 1.86, 95% CI: 1.02 to 3.38, P = 0.043). CONCLUSIONS: The present study suggests that serum AAT is a reliable biomarker for CHF in a Chinese population.
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OBJECTIVE: To investigate methylenetetrahydrofolate reductase (MTHFR) gene C677T mutation and plasma homocysteine (Hcy) levels in Uygur patients with venous thromboembolism (VTE) in Xinjiang. METHODS: A total of 222 VTE patients including 74 Uygur and 148 Han ethnic patients were examined, and 86 Uygur ethnic and Han 134 ethnic healthy people were included as controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was applied to detect MTHFR gene C677T polymorphism and plasma Hcy levels were measured by fluorescence polarization immunoassay. RESULTS: The MTHFR gene C677T genotypes distribution in Uygur VTE patients and control groups were: TT [28.38% (35/86) vs. 12.79% (11/86), P < 0.05], CT [41.89% (31/74) vs. 52.33% (45/86), P > 0.05]and CC [29.73% (22/74) vs. 34.88% (30/86), P > 0.05], respectively; and in Han VTE patients and control groups were: TT[27.03% (40/148) vs. 14.92% (20/134), P < 0.05], CT [44.59% (66/148) vs. 52.99% (71/134), P > 0.05] and CC [28.38% (42/148) vs. 32.09% (43/134), P > 0.05], respectively. SNP genotyping distribution frequency in Uygur and Han ethnic population was similar between controls and between VTE patients (P > 0.05). Plasma levels of Hcy in MTHFR gene TT genotype were statistically higher than CT and CC genotype (P < 0.05). After adjusting for age, gender, smoking history, hyperlipidemia, hypertension, diabetes, and MTHFR genotype, multifactor logistic regression analysis showed that plasma Hcy level (OR = 1.025, 95%CI 1.003 - 1.046, P = 0.024) and obesity (OR = 4.660, 95%CI 1.417 - 15.324, P = 0.011) were independent risk factors for Uygur ethnic patients with VTE while plasma Hcy level (OR = 1.020, 95%CI 1.006 - 1.034, P = 0.004) and smoking (OR = 2.867, 95%CI 1.062 - 6.586, P = 0.024) were independent risk factors for Han ethnic patients with VTE. CONCLUSION: MTHFR C677T polymorphism (TT genotype carrier) and increased plasma levels of Hcy are risk factors for Uygur and Han ethnic patients with VTE in Xinjiang.
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Homocisteína/sangue , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Tromboembolia Venosa/sangue , Tromboembolia Venosa/genética , Adulto , Idoso , Povo Asiático/genética , Etnicidade/genética , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
Metabolic syndrome (MetS) is a recognised risk factor for arterial thromboembolism. However, whether MetS is also a risk factor for venous thromboembolism (VTE) is uncertain. PubMed, Embase, Web of science, and Cochrane databases were searched for case-control and cohort studies as well as conference proceedings of the International society on Thrombosis and Haemostasis (ISTH), and the Women's Health International Symposium Thrombosis and Hemostasis Branch (WHITH) published on or before March 1, 2021, to identify eligible studies. All included articles were assessed by two investigators using the Newcastle-Ottawa scale (NOS). We calculated odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the association between VTE and MetS by using random or fixed-effects models. There were 31 case-control and 5 cohort studies with a total of 78,529 participants that fulfilled the inclusion criteria, MetS (OR 1.49; 95% CI 1.29-1.73) and its critical component obesity (OR 2.03; 95% CI 1.74-2.37), hypertension (OR 1.40; 95% CI 1.19-1.64) and diabetes mellitus (OR 1.22; 95% CI 1.01-1.48) were significant risk factors for VTE. MetS and its critical component obesity may contribute to the multifactorial pathogenesis of VTE. Key Words: Venous thromboembolism, Metabolic syndrome, Obesity.
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Diabetes Mellitus , Síndrome Metabólica , Tromboembolia Venosa , Feminino , Humanos , Síndrome Metabólica/epidemiologia , Obesidade/complicações , Obesidade/epidemiologia , Fatores de Risco , Tromboembolia Venosa/epidemiologiaRESUMO
Objective: Previous research has linked single nucleotide polymorphisms (SNPs) in the ICAM-1 gene to an increased risk of developing ischemic cardiomyopathy (ICM); however, a diagnostic model of ICM according to the ICAM-1 variant has not yet been developed. Therefore, this study aimed to explore the correlation between SNPs in ICAM-1 and the presence of ICM, along with developing a diagnostic model for ICM based on the variants of the ICAM-1 gene. Method: This study recruited a total of 252 patients with ICM and 280 healthy controls. In addition, all the participants were genotyped for SNPs in the ICAM-1 gene by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Using the training dataset of 371 people, we constructed a nomogram model based on ICAM-1 gene variants and clinical variables. To optimize the feature choice for the ICM risk model, a least absolute shrinkage and selection operator (LASSO) regression model was adopted. We also employed multivariable logistic regression analysis to build a prediction model by integrating the clinical characteristics chosen in the LASSO regression model. Following the receiver operating characteristic (ROC), a calibration plot and decision curve analysis (DCA) were used to evaluate the discrimination, calibration, and clinical usefulness of the predictive model. Result: The predictors involved in the prediction nomogram included age, smoking, diabetes, low-density lipoprotein-cholesterol, hemoglobin, N-terminal pro-B-type natriuretic peptide, ejection fraction, and the rs5491 SNP. The nomogram model exhibited good discrimination ability, with the AUC value of ROC of 0.978 (95%CI: 0.967-0.989, P < 0.001) in the training group and 0.983 (95% CI: 0.969-0.998, P < 0.001) in the validation group. The Hosmer-Lemeshow test demonstrated good model calibration with consistency (P training group = 0.937; P validation group = 0.910). The DCA showed that the ICM nomogram was clinically beneficial, with the threshold probabilities ranging from 0.0 to 1.0. Conclusion: The AT genotype in rs5491 of the ICAM-1 gene was associated with having a higher frequency of ICM. Individuals carrying the mutant AT genotype showed a 5.816-fold higher frequency of ICM compared with those with the AA genotype. ICM patients with the AT genotype also had a higher rate of cardiogenic death. We, therefore, developed a nomogram model that could offer an individualized prediction of ICM risk factors.
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BACKGROUND: Venous thromboembolism (VTE) is the third most common cause of cardiovascular death worldwide, following coronary heart disease and stroke, and many risk factors for VTE are not yet clear. Our study investigated the association between multiple inflammatory gene polymorphisms and VTE prognosis, aiming to find a new predictor of VTE prognosis. METHODS: Based on our previous studies, we detected the plasma levels of serum amyloid A protein (SAA), interleukin-1 (IL-1) and tumor necrosis factor-a (TNF-a) and their 8 gene polymorphisms by ELISA and a multiplex ligation detection reaction (iMLDR) method in 284 patients with VTE. All subjects were followed up for 5 years. RESULTS: The 5-year follow-up results of this study showed that 62 of the 284 patients (21.83%) had reached the endpoint (all-cause death). Kaplan-Meier survival analyses revealed that the mortality rate of VTE patients with a high Simplified Pulmonary Embolism Severity Index (SPESI) score and carrying IL-1 rs1800587 mutation genotypes was significantly increased (log-rank p=0.000 and 0.034 respectively). The multifactor Cox regression results confirmed that the mortality rate of patients who carrying IL-1 rs1800587 mutation genotypes was significantly increased (HR=2.982; 95% CI: 1.681-5.100). The mortality rate of those carrying IL-1 rs1143634 mutation genotypes was significantly decreased (HR=0.294; 95% CI: 0.132-0.652). There were no significant differences in mortality rates between wild-type and mutant genotypes of IL-1 rs1143634, IL-1 rs2234650, SAA rs11603089, and TNF-α rs1800629 (P>0.05). CONCLUSION: A high SPESI score and the presence of the IL-1 rs1800587 mutant genotype predict shorter survival in patients with VTE, whereas the IL-1 rs1143634 genotype is associated with a lower mortality rate. Screening for mutations in inflammation-related genes has prognostic value in the clinical management of VTE.
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BACKGROUND: Early change in local intracoronary hemostasis following drug-eluting (DES) and bare metal stent (BMS) implantation has never been assessed in stable angina patients. METHODS: Markers of local platelet activation (soluble glycoprotein V [sGPV] and P-Selectin [CD62P]), coagulation activation (tissue factor [TF], prothrombin fragments 1 + 2 [F1 + 2] and activated factor VII [FVIIa]) and fibrinolysis markers (D-dimers [DD], fibrinogen [FIB], tissue plasminogen activator [t-PA], and plasminogen activator inhibitor type-1 complexes [PAI-1]) were determined in 20 patients with stable angina who underwent percutaneous coronary intervention (PCI). All patients were pretreated with clopidogrel, aspirin, and enoxaparin. Systematic balloon predilation was performed before DES (9 patients) and BMS (11 patients) implantation. All blood samples were drawn 10-20 mm distal to the lesion site. RESULTS: No significant changes in levels of platelet activation markers occurred during PCI. There was a transient significant increase in TF (14%; P = 0.004), in F1 + 2 (40%; P = 0.001), and FVIIa (31%; P = 0.007) following angioplasty. Similarly, a significant 43% increase was observed in DD levels following balloon predilation, associated with an increase of 46%, 60%, and 70% in FIB, t-PA and PAI-1 levels, respectively (all P < 0.0001). All these markers returned to baseline values after stent implantation. No difference was observed between DES and BMS. CONCLUSIONS: Early changes in local hemostasis activation following PCI, were related to balloon predilation. Neither DES nor BMS increased markers of platelet activation, coagulation, or fibrinolysis, under dual antiplatelet and anticoagulant pretreatment.
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Angina Pectoris/cirurgia , Angioplastia Coronária com Balão , Stents Farmacológicos/efeitos adversos , Hemostasia , Stents/efeitos adversos , Idoso , Anticoagulantes/uso terapêutico , Biomarcadores/sangue , Coagulação Sanguínea , Feminino , Fibrinólise , Fibrinolíticos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Ativação Plaquetária , Implantação de Prótese/efeitos adversos , Implantação de Prótese/métodos , Resultado do TratamentoRESUMO
No data are available on the efficacy and safety of a combination of fondaparinux and thrombolysis in the setting of high to intermediate risk pulmonary embolism (PE). Patients submitted to thrombolysis and fondaparinux, presenting with > or =1 of the following criteria were included: (1) cardiogenic shock, (2) syncope, (3) > or =1 proximal thrombo-embolus at CT scan, (4) positive troponin test, (5) echocardiographic findings indicating right ventricular (RV) dysfunction. In-hospital results included death, recurrent PE, persistent RV dysfunction at 48 h echocardiography, bleeding complications. Twenty seven patients were included; 22 received a 2 h infusion of rt-PA and 5 received a 2 h infusion of streptokinase. Ten patients presented with cardiogenic shock (37%), 8 with syncope (30%), all had RV dysfunction. 82% of patients had an uneventful in-hospital course. One patient died during hospital stay from refractory shock. Thrombolysis failed in 2 patients (7%), requiring successful rescue surgical embolectomy. Bleeding events occurred in 2 patients (7%), of whom 1 required blood transfusion. Despite the small sample size, our data suggest that fondaparinux procures adequate tolerability compared to standard current therapy in combination with thrombolysis in high to intermediate risk PE.
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Polissacarídeos/administração & dosagem , Embolia Pulmonar/tratamento farmacológico , Terapia Trombolítica/métodos , Idoso , Quimioterapia Adjuvante , Terapia Combinada , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Fondaparinux , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Fenindiona/administração & dosagem , Fenindiona/análogos & derivados , Polissacarídeos/efeitos adversos , Embolia Pulmonar/complicações , Embolia Pulmonar/mortalidade , Embolia Pulmonar/terapia , Risco , Estreptoquinase/administração & dosagem , Terapia Trombolítica/efeitos adversos , Ativador de Plasminogênio Tecidual/administração & dosagem , Resultado do TratamentoRESUMO
BACKGROUND: The relationship between inflammation and venous thromboembolism (VTE) has not been fully elucidated. METHODS: Based on our previous studies, we detected the plasma levels of serum amyloid A protein (SAA), interleukin-1 (IL-1), and tumor necrosis factor-a (TNF-a) and their 8 gene polymorphisms by ELISA and a multiplex ligation detection reaction (iMLDR) method in 284 patients with VTE and 268 healthy controls. RESULTS: Levels of SAA (P=0.032), IL-1 (P=0.045), and TNF-a (P=0.040) were significantly higher in the VTE group than in the control group. Recessive model analysis of the IL-1 rs1800587 variant showed that the risk of VTE in patients with the GG + GA genotype was significantly higher than that in patients with the AA genotype [odds ratio (OR): 4.444; 95% CI: 1.466-13.470]. Recessive model analysis of the IL-1 rs2234650 polymorphism showed that the risk of VTE in patients with the CC + CT genotype was significantly lower than that in patients with the TT genotype (OR: 0.500; 95% CI: 0.268-0.934). Multivariate logistic regression analysis showed that the TT genotype at IL-1 rs2234650 (OR: 2.086; 95% CI: 1.091-3.985) was an independent risk factor for VTE. The AA genotype of IL-1 rs1800587 (OR: 0.226; 95% CI: 0.074-0.890) was an independent protective factor against VTE. CONCLUSIONS: In summary, an intrinsic relationship may exist between inflammatory activation and the occurrence of VTE.
RESUMO
BACKGROUND: Early local platelet activation after coronary intervention identifies patients at increased risk of acute stent thrombosis (AST). However, early changes in platelet activation in coronary circulation following drug-eluting stent (DES) implantation have never been reported. METHODS: In a prospective study of 26 consecutive elective stable angina patients, platelet activation was analyzed by measuring soluble glycoprotein V (sGPV) and P-selectin (CD62P) before and after implantation of either DES or bare metal stent (BMS). All patients were pretreated with clopidogrel (300 mg loading dose) and aspirin (75 mg orally) the day before the procedure. Blood samples were drawn from the coronary ostium and 10 - 20 mm distal to the lesion site. RESULTS: Consistent with the lower baseline clinical risk, the levels of CD62P and sGPV were within normal reference range, both in the coronary ostium and distal to the lesion before percutaneous coronary intervention (PCI) procedure. The levels of CD62P and sGPV did not change significantly (CD62P: (31.1 +/- 9.86) ng/ml vs (29.5 +/- 9.02) ng/ml, P = 0.319 and sGPV: (52.4 +/- 13.5) ng/ml vs (51.8 +/- 11.7) ng/ml, P = 0.674, respectively) after stent implantation when compared with baseline. Changes in these platelet activation markers did not differ between stent types. CONCLUSIONS: Intracoronary local platelet activation does not occur in stable angina patients before and immediately following DES implantation when dual anti-platelet is administered.
Assuntos
Angina Pectoris/cirurgia , Stents Farmacológicos , Ativação Plaquetária , Adulto , Idoso , Angina Pectoris/sangue , Biomarcadores , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Selectina-P/sangue , Glicoproteínas da Membrana de Plaquetas/análise , Estudos ProspectivosRESUMO
BACKGROUND: The aim of this study was to reveal the association between Methylene tetrahydrofolate reductase (MTHFR) gene mutations (C677T, A1298C and C1317T) and risk of venous thromboembolism (VTE) in Han and Uyghur population in Xinjiang. MATERIAL AND METHOD: We conducted a case control study composed of 246 cases, including 86 Uyghur and 160 Han ethnic diagnosed VTE were admitted in the First Affiliated Hospital of Xinjiang Medical University between January 2008 to December 2012, and 292 population including 122 Uyghur ethnic and 170 Han ethnic were studied as controls. To detect the polymorphism of MTHFR gene C677T, A1298T, and C1317T, Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was applied. Fluorescence polarization immunoassay was adopted to determine the plasma levels Homocysteine (Hcy), folic acid and vitaminB12 (VitB12). The association of the polymorphism of MTHFR and levels Hcy, folic acid and VitB12 with VTE was analyzed. RESULTS: The MTHFR gene C677T genotypes distribution in Uyghur VTE patients and control groups were: TT (27.91% vs. 12.29%), CT (41.86% vs. 52.46%) and CC (30.23% vs. 35.25%), respectively; and in Han VTE patients and control groups were: TT (27.49% vs. 14.71%), CT (44.38% vs. 53.53%) and CC (28.13% vs. 31.76%), respectively, and there were significant differences in TT genotype of MTHFRC677T between VTE patients and controls in both Uyghur and Han ethnic (Uyghur: x(2)=8.070, P=0.005; Han: x(2)=8.159, P=0.004). However, there were no significant differences in the MTHFR gene A1298T and C1317T genotyping distribution frequency in Uygur and Han ethnic between VTE patients and controls (P>0.05). Plasma levels of Hcy in MTHFR gene TT genotype were statistically higher than CT and CC genotype (P<0.05). After adjusting for age, gender, smoking, hypertension, hyperlipidemia, diabetes and MTHFR genotype for plasma Hcy levels, multifactor logistic regression analysis showed (OR=1.025, 95% CI 1.003-1.046, P=0.024) and obesity (OR=4.660, 95% CI 1.417-15.324, P=0.011) were independent risk factors for Uygur ethnic with VTE while plasma Hcy levels (OR=1.020, 95% CI 1.006-1.034, P=0.004) and smoking (OR=2.867, 95% CI 1.062-6.586, P=0.024) were independent risk factors for Han ethnic with VTE. CONCLUSIONS: Our finding supports significant role of MTHFR gene in VTE and evidence of genetically determined HHcy contribute a risk for VTE, and a smoker with tHcy has positive association with a risk of VTE.
RESUMO
The aim of the present study was to reveal the contribution of single nucleotide polymorphisms of the interleukin6 (IL6) gene and the progression of venous thromboembolism (VTE). A casecontrol study composed of 246 VTE patients, including 160 from the Han population (76 males and 84 females, mean age 57.41±13.25 years), 86 from the Uyghur population (41 males and 45 females, mean age 51.61±13.73 years) and 292 gender and ethnicitymatched control participants, including 170 from the Han population (91 males and 79 females, mean age 55.82±11.83 years) and 122 from the Uyghur population (64 males and 58 females, mean age 53.52±13.64 years) were enrolled in the present study. The results demonstrated that the serum levels of IL6, Creactive protein (CRP), Ddimer, fibrinogen, plasminogen activator inhibitor1 and leptin were significantly higher in the VTE group compared with the control group (P<0.05). The frequencies of the 572C/G promoter polymorphisms of the IL6 genotypes CC, CG and GG were identified to be 34, 48 and 18% in the Han population and 33, 47 and 20% in the Uyghur population, respectively. The allele frequency distributions of the C and G alleles were 58 and 42% in the Han population and 56 and 43% in the Uyghur population, respectively. Significant differences were identified in the 572C/G promoter polymorphisms between the VTE group and the control group (P<0.05). For the 597G/A polymorphism, all individuals carried the GG and GA genotype; AA genotypes were not detected. Logistic regression analysis was used to identify the risk factors for VTE, adjusting by confounding factors, the results of which demonstrated that the CC homozygote of the IL6 572G/C, CRP, IL6 and highdensity lipoproteincholesterol were independent risk factors of VTE (P<0.05). In conclusion, the 572G/C genotype of IL6 may be a genetic marker of VTE in the Han and Uyghur populations.