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BACKGROUND: Ischemic cardiomyopathy (IC) is primarily due to long-term ischemia/hypoxia of the coronary arteries, leading to impaired cardiac contractile or diastolic function. A new form of cell death induced by copper, called "cuproptosis" is related to the development and progression of multiple diseases. The cuproptosis-related gene (CuGs) plays an important role in acute myocardial infarction, while the specific mechanisms of CuGs in ischemic cardiomyopathy remain unclear. METHODS: The expressions of CuGs and their immune characteristics were analyzed with the IC datasets obtained from the Gene Expression Omnibus, namely GSE5406 and GSE57338, identifying core genes associated with IC development. By comparing RF, SVM, GLM and XGB models, the optimal machine learning model was selected. The expression of marker genes was validated based on the GSE57345, GSE48166 and GSE42955 datasets. Construct a CeRNA network based on core genes. Therapeutic chemiacals targeting core genes were acquired using the CTD database, and molecular docking was performed using Autodock vina software. By ligating the left anterior descending (LAD) coronary artery, an IC mouse model is established, and core genes were experimentally validated using Western blot (WB) and immunohistochemistry (IHC) methods. RESULTS: We identified 14 CuGs closely associated with the onset of IC. The SVM model exhibited superior discriminative power (AUC = 0.914), with core genes being DLST, ATP7B, FDX1, SLC31A1 and DLAT. Core genes were validated on the GSE42955, GSE48166 and GSE57345 datasets, showing excellent performance (AUC = 0.943, AUC = 0.800, and AUC = 0.932). The CeRNA network consists of 218 nodes and 264 lines, including 5 core diagnostic genes, 52 miRNAs, and 161 lncRNAs. Chemicals predictions indicated 8 chemicals have therapeutic effects on the core diagnostic genes, with benzo(a)pyrene molecular docking showing the highest affinity (-11.3 kcal/mol). Compared to the normal group, the IC group,which was established by LAD ligation, showed a significant decrease in LVEF as indicated by cardiac ultrasound, and increased fibrosis as shown by MASSON staining, WB results suggest increased expression of DLST and ATP7B, and decreased expression of FDX1, SLC31A1 and DLAT in the myocardial ischemic area (p < 0.05), which was also confirmed by IHC in tissue sections. CONCLUSION: In summary, this study comprehensively revealed that DLST, ATP7B, FDX1, SLC31A1 and DLAT could be identified as potential immunological biomarkers in IC, and validated through an IC mouse model, providing valuable insights for future research into the mechanisms of CuGs and its diagnostic value to IC.
ABSTRACT
BACKGROUND: The influence of left atrial appendage volume (LAAV) on the recurrence of atrial fibrillation (AF) following radiofrequency catheter ablation remains unclear. OBJECTIVES: We performed a meta-analysis to assess whether LAAV is an independent predictor of AF recurrence following radiofrequency catheter ablation. METHODS: The PubMed and the Cochrane Library databases were searched until March 2022 to identify publications evaluating LAAV in association with AF recurrence after radiofrequency catheter ablation. Seven studies that fulfilled the specified criteria of our analysis were found. We used the Newcastle-Ottawa Scale to evaluate the quality of the studies. The pooled effects were evaluated depending on standardized mean differences (SMDs) or hazard ratios (HRs) with 95% confidence intervals (CIs). P values < 0.05 were considered statistically significant. RESULTS: A total of 1017 patients from 7 cohort studies with a mean follow-up 16.3 months were included in the meta-analysis. Data from 6 studies (943 subjects) comparing LAAV showed that the baseline LAAV was significantly higher in patients with AF recurrence compared to those without AF (SMD: -0.63; 95% CI: -0.89 to -0,37; all p values < 0.05; I2= 62.6%). Moreover, higher LAAV was independently associated with a significantly higher risk of AF recurrence after radiofrequency catheter ablation (HR: 1.10; 95% CI: 1.02 to 1.18). CONCLUSIONS: The meta-analysis showed that there is a significant correlation between LAAV and AF recurrence after radiofrequency catheter ablation, and the role of LAAV in AF patients should not be ignored in clinical practice.
FUNDAMENTO: A influência do volume do apêndice atrial esquerdo (VAAE) na recorrência de fibrilação atrial (FA) após ablação por cateter de radiofrequência permanece obscura. OBJETIVOS: Realizamos uma metanálise para avaliar se o VAAE é um preditor independente de recorrência de FA após ablação por cateter de radiofrequência. MÉTODOS: Os bancos de dados PubMed e Cochrane Library foram pesquisados até março de 2022 para identificar publicações avaliando o VAAE em associação com a recorrência de FA após ablação por cateter por radiofrequência. Foram encontrados 7 estudos que preencheram os critérios especificados de nossa análise. Usamos a Escala de Newcastle-Ottawa para avaliar a qualidade dos estudos. Os efeitos agrupados foram avaliados dependendo das diferenças médias padronizadas (DMPs) ou hazard ratios (HRs) com intervalos de confiança (ICs) de 95%. Valores de p < 0,05 foram considerados estatisticamente significativos. RESULTADOS: Um total de 1.017 pacientes de 7 estudos de coorte com um seguimento médio de 16,3 meses foram incluídos na metanálise. Dados de 6 estudos (943 indivíduos) comparando VAAE mostraram que o VAAE basal foi significativamente maior em pacientes com recorrência de FA em comparação com aqueles sem FA (DMP: −0,63; IC de 95%: −0,89 a −0,37; todos os valores de p < 0,05; I 2 = 62,6%). Além disso, maior VAAE foi independentemente associado a um risco significativamente maior de recorrência de FA após ablação por cateter de radiofrequência (HR: 1,10; IC de 95%: 1,02 a 1,18). CONCLUSÕES: A metanálise mostrou que existe uma correlação significativa entre o VAAE e a recorrência de FA após ablação por cateter de radiofrequência, e o papel do VAAE em pacientes com FA não deve ser ignorado na prática clínica.
Subject(s)
Atrial Appendage , Atrial Fibrillation , Catheter Ablation , Humans , Atrial Fibrillation/diagnostic imaging , Atrial Fibrillation/surgery , Atrial Appendage/diagnostic imaging , Atrial Appendage/surgery , Cohort Studies , Catheter Ablation/adverse effects , Recurrence , Treatment OutcomeABSTRACT
Resumo Fundamento A influência do volume do apêndice atrial esquerdo (VAAE) na recorrência de fibrilação atrial (FA) após ablação por cateter de radiofrequência permanece obscura. Objetivos Realizamos uma metanálise para avaliar se o VAAE é um preditor independente de recorrência de FA após ablação por cateter de radiofrequência. Métodos Os bancos de dados PubMed e Cochrane Library foram pesquisados até março de 2022 para identificar publicações avaliando o VAAE em associação com a recorrência de FA após ablação por cateter por radiofrequência. Foram encontrados 7 estudos que preencheram os critérios especificados de nossa análise. Usamos a Escala de Newcastle-Ottawa para avaliar a qualidade dos estudos. Os efeitos agrupados foram avaliados dependendo das diferenças médias padronizadas (DMPs) ou hazard ratios (HRs) com intervalos de confiança (ICs) de 95%. Valores de p < 0,05 foram considerados estatisticamente significativos. Resultados Um total de 1.017 pacientes de 7 estudos de coorte com um seguimento médio de 16,3 meses foram incluídos na metanálise. Dados de 6 estudos (943 indivíduos) comparando VAAE mostraram que o VAAE basal foi significativamente maior em pacientes com recorrência de FA em comparação com aqueles sem FA (DMP: −0,63; IC de 95%: −0,89 a −0,37; todos os valores de p < 0,05; I 2 = 62,6%). Além disso, maior VAAE foi independentemente associado a um risco significativamente maior de recorrência de FA após ablação por cateter de radiofrequência (HR: 1,10; IC de 95%: 1,02 a 1,18). Conclusões A metanálise mostrou que existe uma correlação significativa entre o VAAE e a recorrência de FA após ablação por cateter de radiofrequência, e o papel do VAAE em pacientes com FA não deve ser ignorado na prática clínica.
Abstract Background The influence of left atrial appendage volume (LAAV) on the recurrence of atrial fibrillation (AF) following radiofrequency catheter ablation remains unclear. Objectives We performed a meta-analysis to assess whether LAAV is an independent predictor of AF recurrence following radiofrequency catheter ablation. Methods The PubMed and the Cochrane Library databases were searched until March 2022 to identify publications evaluating LAAV in association with AF recurrence after radiofrequency catheter ablation. Seven studies that fulfilled the specified criteria of our analysis were found. We used the Newcastle-Ottawa Scale to evaluate the quality of the studies. The pooled effects were evaluated depending on standardized mean differences (SMDs) or hazard ratios (HRs) with 95% confidence intervals (CIs). P values < 0.05 were considered statistically significant. Results A total of 1017 patients from 7 cohort studies with a mean follow-up 16.3 months were included in the meta-analysis. Data from 6 studies (943 subjects) comparing LAAV showed that the baseline LAAV was significantly higher in patients with AF recurrence compared to those without AF (SMD: −0.63; 95% CI: −0.89 to −0,37; all p values < 0.05; I2= 62.6%). Moreover, higher LAAV was independently associated with a significantly higher risk of AF recurrence after radiofrequency catheter ablation (HR: 1.10; 95% CI: 1.02 to 1.18). Conclusions The meta-analysis showed that there is a significant correlation between LAAV and AF recurrence after radiofrequency catheter ablation, and the role of LAAV in AF patients should not be ignored in clinical practice.
ABSTRACT
Background: The treatment of atrial fibrillation (AF) has made significant progress, but the prevention of AF has not received the attention it deserves. A few recent large-sized studies have conducted dose response analysis and reported different conclusions from previous studies on alcohol consumption and AF risk. Objectives: The aim of this study is to examine the potential non-linear association between alcohol consumption and risk of AF and explore the potential differences of gender. Methods: In this updated dose-response meta-analysis, PubMed, Embase and Cochrane databases were searched until June 2022. Risk estimates were reported as relative risk (RR) with 95% confidence intervals (CIs). The random-effects restricted cubic spline models are used to evaluate the potential non-linear association between alcohol consumption and AF risk. Results: A total of 10,151,366 participants with 214,365 cases of AF enrolled in 13 prospective studies. The overall meta-analysis showed that a 1 drink/day increase in alcohol consumption increased the risk of AF by 6% (RR: 1.06; 95% CI: 1.03-1.08). In gender subgroup analysis, pooled results were different between men (RR: 1.08; 95% CI: 1.05-1.11) and women (RR: 1.05; 95% CI: 0.96-1.14). A linear relationship between alcohol consumption and risk of AF was found in men (p = 0.87) while a J-shaped curve was observed in women (p = 0.00). Regional subgroup analysis yielded broadly comparable results in Americas (RR: 1.07; 95% CI: 1.03-1.12), Europe (RR: 1.04; 95% CI: 0.99-1.1) and Asia (RR: 1.07; 95% CI: 0.99-1.14). Conclusion: The relationship between AF risk and alcohol consumption is linear in men, while a potential non-linear J-shaped relationship is shown in women. Condensed abstract: We conducted a dose-response meta-analysis on the relationship between alcohol consumption and risk of atrial fibrillation. We merged the data of over 10 million participants and found gender differences in the pattern of association with AF and alcohol consumption. The relationship between AF risk and alcohol consumption is linear in men, while a potential non-linear J-shaped relationship is shown in women. In summary, this research is vital in furthering our understanding of the role of alcohol consumption in new-onset AF, especially among different genders.
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BACKGROUND: Angiotensin-converting enzyme (ACE) gene polymorphisms have recently been shown to be associated with risk of developing left ventricular hypertrophy (LVH). However, the results were controversial. We aimed to conduct this meta-analysis to further confirm the association between ACE rs4646994 polymorphism and hypertrophic cardiomyopathy (HCM)/dilated cardiomyopathy (DCM). METHODS: PubMed, Embase, the Chinese National Knowledge Information, and Wanfang databases were searched for eligible studies. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of included studies. Then we evaluated the association between ACE gene mutation and HCM/DCM by calculating odds ratios (ORs) and 95% confidence intervals (95% CIs). Subgroup analysis was further performed to explore situations in specialized subjects. Sensitivity analysis and publication bias was assessed to confirm the study reliability. RESULTS: There were 13 studies on DCM (2004 cases and 1376 controls) and 16 studies on HCM (2161 controls and 1192 patients). ACE rs4646994 polymorphism was significantly associated with DCM in all genetic models. However, in HCM, four genetic models (allele model, homozygous model, heterozygous model, and dominant model) showed significant association between ACE rs4646994 polymorphism and DCM. In subgroup analysis, we found that ACE rs4646994 polymorphism was significantly associated with DCM/HCM in Asian population. Finally, we also conducted a cumulative meta-analysis, which indicates that the results of our meta-analysis are highly reliable. CONCLUSION: ACE rs4646994 polymorphism increases the risk of DCM/HCM in Asians, but not in Caucasians. More case-control studies are needed to strengthen our conclusions and to assess the gene-gene and gene-environment interactions between ACE rs4646994 polymorphism and DCM/HCM.
Subject(s)
Cardiomyopathy, Dilated/genetics , Cardiomyopathy, Hypertrophic/genetics , Peptidyl-Dipeptidase A/genetics , Polymorphism, Single Nucleotide , Asian People/genetics , Cardiomyopathy, Dilated/enzymology , Cardiomyopathy, Dilated/ethnology , Cardiomyopathy, Hypertrophic/enzymology , Cardiomyopathy, Hypertrophic/ethnology , Case-Control Studies , Gene-Environment Interaction , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Risk Assessment , Risk Factors , White People/geneticsABSTRACT
Objective: Epidemiological studies have reported inconsistent findings for the association between sleep duration and metabolic syndrome. We aimed to clarify the effects of short and long sleep durations on metabolic syndrome in adults by performing a meta-analysis. Methods: Adopting random-effects models, this study analyzed the effects of short and long sleep durations based on data from prospective cohort studies and cross-sectional studies retrieved from four electronic databases from inception to May 2020. Results: We collected data from 235,895 participants included in nine prospective cohort studies and 340,492 participants included in 27 cross-sectional studies. In cohort studies, short sleep duration was associated with an increased risk of metabolic syndrome (RR, 1.15; 95% CI, 1.05-1.25, I 2 = 63.1%, P < 0.001) compared with normal sleep duration. While long sleep duration was not associated with new-onset metabolic syndrome (RR, 1.02, 0.85-1.18, I 2 = 38.0%, P = 0.491). In cross-sectional studies, both short (OR, 1.06, 95% CI, 1.01-1.11, I 2 = 66.5%, P < 0.001) and long (OR, 1.11, 95% CI, 1.04-1.17, I 2 = 73.8%, P < 0.001) sleep durations were associated with a high prevalence of metabolic syndrome. Conclusions: Only a short sleep duration was associated with an increased risk of metabolic syndrome. Future studies should address whether the association is casual and modifiable.
