Influence of Metabolic Syndrome on the Long-Term Prognosis of Patients with Myocardial Infarction: A Meta-Analysis.

The influence of metabolic syndrome (MetS) on long-term prognosis of patients with myocardial infarction (MI), the most severe type of coronary artery disease, remains not fully determined. This systematic review and meta-analysis were conducted to investigate the association between MetS and long-term clinical outcomes of patients with MI. A systematic search of Medline, Web of Science, and Embase databases from inception to June 25, 2023, was conducted to obtain eligible studies. Only studies with follow-up duration for at least one year were considered. A random-effects model was utilized to pool the results, accounting for heterogeneity. Ten observational studies were included, which included 33 197 patients with MI. Among them, 17 244 (51.9%) were with MetS at baseline. During a follow-up duration of 12 to 48 months (mean: 22.5 months), patients with MetS were associated with higher incidence of major adverse cardiovascular events [risk ratio (RR): 1.35. 95% confidence interval (CI): 1.19 to 1.54, p<0.001; I2=64%] and all-cause deaths (RR: 1.34, 95% CI: 1.18 to 1.52, p<0.001; I2=23%), as compared to those without MetS at baseline. Subgroup analyses showed that the results were not significantly affected by study characteristics such as study country, design, type of MI, mean age of the patients, treatment with percutaneous coronary intervention, follow-up durations, or study quality scores (p for subgroup difference all>0.05). In patients with MI, MetS may be a risk factor of poor long-term prognosis.

The Role of MicroRNA-181a in Myocardial Fibrosis Following Myocardial Infarction in a Rat Model.

BACKGROUND The role of miR-181a in the development of cardiac disease and in particular, myocardial fibrosis following myocardial infarction (MI) remains unknown. The aim of this study was to explore the role of miR-181a in myocardial fibrosis in a rat model of MI and the expression of TGF-ß receptor III (TßRIII). MATERIAL AND METHODS Forty adult male Wistar rats were randomly divided into an MI model group (n=30) and a control group with (n=10). The rat MI model involved ligating the left anterior descending (LAD) coronary artery in the model group; the control group was treated with a sham operation. Cardiac function was assessed using cardiac ultrasound. Myocardial fibroblasts were extracted from the rat hearts and transfected with a miR-mimic or miR-inhibitor, and cell growth was measured using an MTT assay. The level of miR-181a expression was detected using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blots. RESULTS miR-181a expression was significantly increased during the progression of MI (P<0.05). Over-expression of miR-181a was associated with increased deposition of extracellular matrix (ECM) components, collagen I and fibronectin. This effect was reversed with the use of a miR-181a inhibitor (P<0.05). Upregulation of miR-181a suppressed the expression of TGF-ß receptor III (TßRIII) by binding with 3'-UTR. CONCLUSIONS In this rat model of MI, the findings were that miR-181a had a role in the progression of myocardial fibrosis. The findings require further studies to determine whether miR-181a might provide a novel therapeutic target to limit myocardial fibrosis following MI.

Copeptin and the prognosis of patients with coronary artery disease: a meta-analysis.

OBJECTIVES: Copeptin, the C-terminal portion of provasopressin, has been regarded as a marker of non-specific stress response and a potentially prognostic biomarker of cardiovascular diseases. This systematic review and meta-analysis was conducted to summarize the predictive role of baseline copeptin for the prognosis of patients with coronary artery disease (CAD). METHODS: Relevant observational studies with longitudinal follow-up were obtained by comprehensive search of PubMed, Embase, and Web of Science databases. A random-effects model was used to pool the results. RESULTS: Twenty-two studies with 19,821 patients with CAD were enrolled. Results of the meta-analyses revealed that a high copeptin at baseline was associated with a higher mortality risk (risk ratio [RR]: 1.76, 95% confidence interval [CI]: 1.49 to 2.09, p < 0.001; I2 = 70%) and an increased incidence of major adverse cardiovascular events (MACEs, RR: 1.49, 95% CI: 1.34 to 1.65, p < 0.001; I2 = 28%) in patients with CAD. Further results of sensitivity and subgroup analyses showed consistent associations between high copeptin with increased risks of mortality and MACEs in studies of patients with different ages, proportion of men, subtypes of CAD, study design, follow-up durations, and quality scores (p for subgroup effect all < 0.05). CONCLUSIONS: A high plasma level of copeptin is associated with higher risks of mortality and MACEs in patients with CAD. Measuring copeptin may be helpful for risk stratification in patients with CAD.

Shear wave elastography measured liver stiffness-spleen size-to-platelet ratio for the prediction of high-risk oesophageal varices: a meta-analysis.

OBJECTIVES: The potential predictive role of shear wave elastography (SWE) measured liver stiffness-spleen size-to-platelet ratio score (LSPS) for high-risk oesophageal varices (HREV) in patients with cirrhosis remains controversial. A systematic review and meta-analysis was performed to investigate the diagnostic efficacy of SWE-measured LSPS for HREV. METHODS: Relevant studies were retrieved by searching PubMed, Embase, Web of Science, Wanfang, and CNKI databases. Only studies comparing the diagnostic efficacy of SWE-measured LSPS with oesophagogastroduodenoscopy for HREV in patients with cirrhosis were included. Pooled sensitivity and specificity were calculated with a random-effect model. RESULTS: Overall, eight cohorts were included. Four of them used point SWE (pSWE) and the other four used 2D-SWE. Pooled results showed that a high LSPS measured by pSWE and 2D-SWE were both associated with satisfying diagnostic efficacy for endoscopic-evidenced HREV, with pooled sensitivity, specificity, diagnostic odds ratio, and pooled area under receiver operating characteristic curve of 0.86, 0.86, 39.36, and 0.92 for pSWE-derived LSPS, and 0.77, 0.86, 20.64, and 0.89 for 2D-SWE-derived LSPS. No significant difference was observed in the diagnostic efficacy between pSWE- and 2D-SWE-derived LSPS ( P all > 0.05). Significant heterogeneity was observed. However, further subgroup and meta-regression analysis failed to show that differences in study design, sex, diagnosis (compensated or overall cirrhosis), or LPSP cutoffs may lead to heterogeneity ( P for subgroup difference > 0.05). CONCLUSION: A high LSPS with liver stiffness measured by pSWE or 2D-SWE shows satisfying predictive accuracy for HREV in patients with cirrhosis.

Association between low-density lipoprotein cholesterol level and mortality in patients with cardiogenic shock: a retrospective cohort study.

AIMS: Inflammation plays a key role in the pathophysiology of cardiogenic shock (CS). Low-density lipoprotein cholesterol (LDL-C) is a biomarker of inflammation and is used to predict prognostic outcomes of several diseases. The primary purpose of this study was to evaluate if LDL-C can be used as a biomarker to predict the mortality of CS. METHODS AND RESULTS: Records of critically ill patients with CS were identified from the Medical Information Mart for Intensive Care III database. A multivariate Cox regression model was employed to adjust for imbalances by incorporating parameters and potential confounders.A total of 551 critically ill patients with CS were enrolled for this analysis, including 207 with LDL-C <1.8 mmol/L and 344 with LDL-C ≥1.8 mmol/L. Results of multivariate Cox regression models found that higher concentration of LDL-C (LDL-C ≥1.8mmol/L) was associated with a reduced risk of in-hospital mortality (HR 0.66, 95% CI 0.50 to 0.87; p=0.003) and 28-day mortality (HR 0.61, 95% CI 0.46 to 0.80; p=0.002) LDL-C in patients with CS. Patients with LDL-C ≥1.8 mmol/L were independently associated with improved in-hospital survival (HR 0.32, 95% CI 0.20 to 0.52, p<0.001) and 28-day survival (HR 0.51, 95% CI 0.33 to 0.73, p=0.002) compared with patients with LDL-C <1.8 mmol/L. The impact of LDL-C on in-hospital mortality and 28-day mortality persisted in patients with acute coronary syndrome (ACS) and was not statistically significant in the non-ACS subgroup. CONCLUSIONS: Our study observed that increased LDL-C level was related with improved survival in patients with CS, but not with improved outcomes in patients with uncomplicated ACS. The results need to be verified in randomised controlled trials.

Higher Plasma Pentraxin-3 Level Predicts Adverse Clinical Outcomes in Patients With Coronary Artery Disease: A Meta-Analysis of Cohort Studies.

Background: Association between plasma pentraxin-3 (PTX-3) and clinical outcomes in patients with coronary artery disease (CAD) remains not fully determined. An updated meta-analysis of cohort studies was performed to systematically evaluate the association. Methods: Cohort studies evaluating the association between plasma PTX-3 and adverse outcomes [mortality and major adverse cardiovascular events (MACEs)] in adults with CAD were identified by systematic search of PubMed, Embase, and Web of Science databases. Only studies with multivariate analysis were included. A random-effects model incorporating the potential intrastudy heterogeneity was used for the meta-analysis. Results: A total of 16 studies including 11,007 patients were included. Pooled results showed that patients with highest level of PTX-3 were independently associated with higher risk of mortality [adjusted risk ratio (RR): 2.09, 95% CI: 1.60 to 2.74, p < 0.001; I 2 = 50%] and MACEs (adjusted RR: 1.80, 95% CI: 1.43 to 2.28, p < 0.001; I 2 = 49%). Subgroup analyses showed that the associations between PTX-3 and poor prognosis in CAD were consistent in patients with ST-segment elevation myocardial infraction, non-ST-segment elevation acute coronary syndrome, and stable CAD (p < 0.05 for each subgroup). Besides, the association between PTX-3 and increased incidence of mortality and MACEs were consistent in short-term (within 1 year) and long-term (over 1 year) studies and in studies with or without adjustment of C-reactive protein (CRP) (p < 0.05 for each subgroup). Conclusion: Higher plasma PTX-3 is associated with poor prognosis in patients with CAD, which may be independent of the CAD subtype, follow-up durations, and adjustment of CRP.

Identification of key miRNA-gene pairs in gastric cancer through integrated analysis of mRNA and miRNA microarray.

Nowadays, the current bioinformatic methods have been increasingly applied in the field of oncological research. In this study, we expect a better understanding of the molecular mechanism of gastric cancer from the bioinformatic methods. By systematically addressing the differential expression of microRNAs (miRNAs) and mRNAs between gastric cancer specimens and normal gastric specimens with the application of bioinformatics tools, A total of 206 DEGs and 38 DEMs were identified. The Gene Ontology (GO) analysis of Annotation, Visualization and Integrated Discovery (DAVID) database revealed that the differentially expressed genes (DEGs) were significantly enriched in biological process, molecular function and cellular component, while Kyoto Encyclopedia of Genes and Genomes (KEGG) database showed DEGs were significantly enriched in 8 signal pathways. The miRNA-gene regulatory network was constructed based on 385 miRNA-gene (DEM-DEG) pairs, consisting of 35 miRNAs and 107 target genes. In the regulatory network, the top 5 up-regulated genes were Transmembrane Protease, Serine 11B (TMPRSS11B), regulator of G protein signaling 1 (RGS1), cysteine rich angiogenic inducer 61 (CYR61), inhibin subunit beta A (INHBA), syntrophin gamma 1 (SNTG1), and the top 5 down-regulated genes were tumor necrosis factor receptor superfamily, member 19 (TNFRSF19), pleckstrin homology domain containing B2 (PLEKHB2), Tax1 binding protein 3 (TAX1BP3), presenilin enhancer, gamma-secretase subunit (PSENEN), NME/NM23 nucleoside diphosphate kinase 3 (NME3). Based on the gastric cancer patient database from Kaplan-Meier Plotter tools, we found that 8 of 10 genes with most significant changes in the miRNA-gene regulatory network possessed a prognostic value for survival time of gastric cancer patients. Patients with higher level of RGS1, PLEKHB2, TAX1BP3 and PSENEN in gastric cancer had a longer survival time compared with the patients with lower level of these genes. On the contrary, patients with higher level of INHBA, SNTG1, TNFRSF19 and NME3 were found associated with a shorter survival time. In conclusion, our findings provided several potential targets regarding gastric cancer, which may result in a new strategy to treat gastric cancer from a system rather than a single-gene perspective.

Activation of the Cholinergic Anti-inflammatory Pathway Attenuated Angiotension II-Dependent Hypertension and Renal Injury.

Background: Angiotensin II (AngII) induces renal fibrosis, characterized by fibroblast proliferation, inflammatory cell infiltration and excessive extracellular matrix deposition, all of which was relevant closely to hypertension. The vagus nerve-related cholinergic anti-inflammatory pathway (CAP) modulates local and systemic inflammatory responses. The aim of present study was to determine the effect of CAP on renal inflammation and fibrosis. Methods and Results: AngII-induced hypertension was induced in vivo by 14-days low-dose AngII infusion from osmotic minipumps. We used GTS-21 dihydrochloride, a selective nicotinic acetylcholine receptor agonist. Daily intraperitoneal GTS-21 injection and/or vagotomy started after hypertension was confirmed and continued for 4 weeks. The elevated blood pressure caused by AngII was significantly attenuated by GTS-21. Improved baroreflex sensitivity was observed after GTS-21 administration. Masson stain and immunoblotting revealed that deposition of excessive fibrosis and overexpression of inflammatory cytokines induced by AngII was reduced by GTS-21. To determine the role of autonomic control in CAP, unilateral vagotomy was performed. Vagotomy weakened the effect of CAP on AngII-induced hypertension. In vitro, GTS-21 suppressed NF-κB activation, attenuated AngII-induced epithelial-mesenchymal transition and reduced inflammation and fibrosis in NRK-52E cells; α-bungarotoxin (α-Bgt, an α7-nAChR selective antagonist) partly inhibited these effects. Conclusion: CAP protected against AngII-induced hypertension via improvement in autonomic control, suppression of NF-κB activation, and reduction of renal fibrosis and inflammatory response.

Role of pyroptosis in cardiovascular diseases.

Pyroptosis is a form of programmed necrosis, and is morphologically and mechanistically unique form of programmed cell death compared to others, such as apoptosis and autophagic cell death. More specifically, pyroptosis features gasdermin family-mediated membrane pore formation and subsequent cell lysis, as well as release of pro-inflammatory intracellular contents including IL-1ß, IL-18 and HMGB1. Mechanistically, pyroptosis is driven by two main signaling pathways - one mediated by caspase-1 and the other by caspase-4/5/11. Recent studies show that pyroptosis is implicated in several cardiovascular diseases. In this review, we summarize recent scientific discoveries of pyroptosis's involvement in atherosclerosis, myocardial infarction, diabetic cardiomyopathy, reperfusion injury and myocarditis. We also organized new and emerging evidence suggesting that pyroptosis signaling pathways may be potential therapeutic targets in cardiovascular diseases.

Alteration of Cholinergic Anti-Inflammatory Pathway in Rat With Ischemic Cardiomyopathy-Modified Electrophysiological Function of Heart.

BACKGROUND: With chronic ischemia after myocardial infarction, the resulting scar tissue result in electrical and structural remodeling vulnerable to an arrhythmogenic substrate. The cholinergic anti-inflammatory pathway elicited by vagal nerve via α7 nicotinic acetylcholine receptors (α7-nAChR) can modulate local and systemic inflammatory responses. Here, we aimed to clarify a novel mechanism for the antiarrhythmogenic properties of vagal nerve during the ischemic cardiomyopathy (ICM). METHODS AND RESULTS: Left anterior descending artery of adult male Sprague-Dawley rats was ligated for 4 weeks to develop ICM. Western blot revealed that eliciting the cholinergic anti-inflammatory pathway by nicotine treatment showed a significant reduction in the amounts of collagens, cytokines, and other inflammatory mediators in the left ventricular infarcted border zone via inhibited NF-κB activation, whereas it increased the phosphorylated connexin 43. Vagotomy inhibited the anti-inflammatory, anti-fibrosis, and anti-arrhythmogenic effect of nicotine administration. And immunohistochemistry confirmed that the nicotine administration-induced increase of connexin 43 was located in intercellular junctions. Furthermore nicotine treatment suppressed NF-κB activation in lipopolysaccharide-stimulated RAW264.7 cells, and α-bungarotoxin (an α7-nAChR selective antagonist) partly inhibited the nicotine-treatment effect. In addition, 4-week nicotine administration slightly improved the cardiac function, increased cardiac parasympathetic tone, decreased the prolonged QTc, and decreased the arrhythmia score of programmed electric stimulation-induced ventricular arrhythmia. CONCLUSIONS: Eliciting the cholinergic anti-inflammatory pathway exerts anti-arrhythmogenic effects against ICM-induced ventricular arrhythmia accompanied by downregulation of cytokines, downgenerating of collagens, decrease in sympathetic/parasympathetic ratio, and prevention of the loss of phosphorylated connexin 43 during ICM. Our findings may suggest a promising therapy for the generation of ICM-induced ventricular arrhythmia by eliciting the cholinergic anti-inflammatory pathway.