Circular RNA PARG adjusts miR-140-3p to influence progression in sepsis.

Sepsis has been characterized as a frequent medical problem with high mortality and severe complication medical problem in the intensive care unit (ICU). Here, qRT-PCR was used to examine circRNA PARG expression levels in patients with sepsis and in human pulmonary microvascular endothelial cells (HPMEC). Lipopolysaccharide (LPS)-simulated HPMEC were hybridized using RNA-Fluorescence in situ hybridization to confirm the location of circRNA PARG and miR-140-3p. The biological role of downregulated circRNA PARGin cellular proliferation, apoptosis, and inflammatory and apoptosis responses was evaluated. performed A dual-luciferase reporter assay was performed to determine the relationship between the circRNA PARG with miR-140-3p. In this study,circRNA PARG aberrant expression was found, and the effects of circRNA PARG on lipopolysaccharide (LPS)-stimulated apoptosis of HPMEC cells were further investigated. Down-regulated circRNA PARG led to significant alleviation of LPS-simulated cell apoptosis via inhibition of inflammatory and apoptosis-related genes, while upregulated circRNA PARG exhibited the opposite effects. Further findings indicated that circRNA PARG positively modulated the relative level of miR-140-3p, which has been confirmed using the luciferase reporter assay. Upregulated circRNA PARG led to a reversal of LPS-simulated cells after transfection of miR-140-3p mimic. In general, a novel insight into understanding the important effects of circRNA PARG in sepsis is provided.

Association of Coffee Consumption With Atrial Fibrillation Risk: An Updated Dose-Response Meta-Analysis of Prospective Studies.

Background: Several published studies have examined the association of coffee consumption with atrial fibrillation (AF) risk, but their findings are still controversial. Therefore, we performed a systematic review and dose-response meta-analysis of prospective studies to determine the relationship between coffee consumption and the risk of incident AF. Methods: We systematically retrieved the PubMed and Embase databases until October 2021 for pertinent studies that reported the association of coffee consumption (caffeinated or decaffeinated coffee) with AF risk. A cubic spline random-effects model was used to fit the potential dose-response curve. The effect estimates were expressed as adjusted risk ratios (RRs) and 95% CIs. Results: A total of 10 prospective studies (11 cohorts) involving 30,169 AF events and 723,825 participants were included. In the dose-response analysis, there was a linear inverse association between coffee intake and risk of AF although not statistically significant (P non-linearity = 0.25). Compared with participants with no coffee consumption, the RRs (95% CI) of AF risk estimated directly from the dose-response curve were 1.01 (0.98-1.03), 1.00 (0.97-1.04), 0.99 (0.92-1.02), 0.95 (0.89-1.01), 0.94 (0.87-1.01), 0.89 (0.79-1.02), and 0.87 (0.76-1.02) for 1-7 cups of coffee per day, respectively. One cup per day increased in coffee consumption was associated with a 2% reduced risk of AF (RR = 0.98, 95% CI: 0.97-1.00, P = 0.02). Conclusions: Our evidence from this meta-analysis suggested that coffee consumption had a trend toward reducing the risk of AF in a dose-response manner. Further studies could be conducted to reinforce our findings.

An Updated Meta-Analysis of DOACs vs. VKAs in Atrial Fibrillation Patients With Bioprosthetic Heart Valve.

Background: Current guidelines recommend the utilization of direct-acting oral anticoagulants (DOACs) in patients with non-valvular atrial fibrillation (AF). However, the optimal anticoagulation strategy for AF patients with bioprosthetic heart valves (BPHV) remains controversial. Therefore, we conducted this meta-analysis to explore the effect of DOACs versus vitamin K antagonists (VKAs) in this population. Methods: We systematically searched the PubMed and Embase databases until November 2021 for studies reporting the effect of DOACs versus VKAs in AF patients with BPHV. Adjusted risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using the random-effects model with an inverse variance method. Results: We selected four randomized clinical trials and seven observational studies (2236 DOAC- and 6403 VKAs-users). Regarding the effectiveness outcomes, there were no significant differences between DOACs and VKAs in stroke or systemic embolism (RR = 0.74, 95%CI: 0.50-1.08), ischemic stroke (RR = 1.08, 95%CI: 0.76-1.55), all-cause death (RR = 0.98, 95%CI: 0.86-1.12), and cardiovascular death (RR = 0.85, 95%CI: 0.40-1.80). In terms of the safety outcomes, DOACs was associated with lower risks of major bleeding (RR = 0.70, 95%CI: 0.59-0.82) and intracranial bleeding (RR = 0.42, 95%CI: 0.26-0.70), but the risks of any bleeding (RR = 0.85, 95%CI: 0.65-1.13) and gastrointestinal bleeding (RR = 0.92, 95%CI: 0.73-1.17) are not significantly different when compared with VKAs. The subgroup analysis with follow-up as a covariate revealed that the DOACs had lower risks of SSE (RR = 0.59, 95%CI: 0.37-0.94) and major bleeding (RR = 0.69, 95%CI: 0.58-0.81) in patients with a mean follow-up of more than 24 months, but no statistical differences were found in patients with the follow-up less than 24 months (SSE: RR = 1.10, 95%CI: 0.92-1.32; major bleeding: RR = 0.91, 95%CI: 0.42-2.01). Conclusions: In AF with BPHV, patients on DOACs experienced a reduced risk of major bleeding and intracranial bleeding compared with VKAs, while the risks of stroke, cardiovascular death, and all-cause mortality were similar.

Is the Risk of Diabetes Lower in Patients With Atrial Fibrillation Treated With Direct Oral Anticoagulant Compared to Warfarin?

Background: The use of anticoagulants is an established strategy to prevent stroke, embolism, and cardiovascular mortality in patients with atrial fibrillation (AF), but its role in the prevention of incident diabetes is unclear. We aimed to investigate this question by using participant data from cohort studies. Methods: We conducted a meta-analysis of participants to investigate the impact of direct oral anticoagulants (DOACs) on the risk of new-onset diabetes in AF patients. The collection of related data was performed in the PubMed and EMBASE databases until December 2021, including studies associated with evaluating the correlation between DOACs and incident diabetes. The hazard ratios (HRs) and 95% confidence intervals (CIs) were adjusted by the random-effects model with an inverse variance method. Results: Two cohort studies with a total of 24,434 patients were included in this study (warfarin: n = 6,906; DOACs: n = 17,528). Compared with warfarin, the use of DOACs could reduce the incident diabetic risk in AF patients (HR = 0.75, 95%CI: 0.68-0.82). Investigations about the effects of three major classes of DOACs showed that the individual use of dabigatran (HR = 0.76, 95%CI: 0.64-0.90), rivaroxaban (HR = 0.74, 95%CI: 0.64-0.87), apixaban (HR = 0.74, 95%CI: 0.60-0.92) and the combined use of rivaroxaban and apixaban (HR = 0.74, 95%CI: 0.66-0.84) could reduce the risk of new-onset diabetes compared with warfarin. This risk reduction effect could be observed in both male and female groups (HR = 0.73, 95%CI: 0.64-0.84, P < 0.00001; HR = 0.82, 95%CI: 0.82-0.99, P = 0.04). Conclusions: Treatment with DOACs compared with warfarin reduced the risk of new-onset diabetes in both male and female patients with AF.

Association of Depression, Antidepressants With Atrial Fibrillation Risk: A Systemic Review and Meta-Analysis.

Background: Depression is a possible influence factor for the increased risk of incident atrial fibrillation (AF). Although several investigations have assessed their association, the results are still controversial. Therefore, we conducted a meta-analysis to evaluate the association between depression or using antidepressants and AF. Methods: We systemically performed the literature retrieval from two electronic databases PubMed and EMBASE until March 2022 to extract relevant data. The hazard ratios (HRs) and odds ratios (OR) from included studies with 95% confidence intervals (CIs) were adjusted into the risk ratio (RR) and pooled by using the random-effects model. Results: Totally 9 studies about the associations between depression or antidepressants and incident AF risk were included in this meta-analysis. Among them, 5 studies specifically analyzed the impact of antidepressants on the risk of AF. The outcomes of our analysis indicated that depression or depressive symptoms could increase AF risk (RR = 1.15, 95% CI, 1.03-1.27, P < 0.01). In addition, the use of antidepressants can also increase AF risk (RR = 1.16, 95% CI, 1.07-1.25, P < 0.001). These results remained unchanged when we remove the source of heterogeneity or adjust the analysis model into the fixed-effects model. Conclusions: Based on existing investigations, both depression and the use of antidepressants are closely related to the increase of incident AF risk.

Impact of COPD or Asthma on the Risk of Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Background: Respiratory diseases related to chronic pulmonary ventilation dysfunction are mainly composed of chronic obstructive pulmonary disease (COPD) and asthma. Our meta-analysis aimed to illustrate the association of COPD or asthma with risk of atrial fibrillation (AF). Methods: We systematically searched the databases of the PubMed, Embase, and Cochrane library until December 2021 for studies focusing on the relationship between COPD or asthma and AF risk. Due to the potential heterogeneity across studies, the random-effects model was used to pool the studies. Results: Our meta-analysis included 14 studies. Based on the random-effects model, the pooled analysis showed that COPD (risk ratio[RR] = 1.74, 95% confidence interval [CI]: 1.70-1.79) and asthma (RR = 1.08, 95% CI: 1.04-1.12) were significantly associated with an increased risk of AF. The results did not change after each study was excluded. Conclusion: Our current data suggested that COPD or asthma with associated with an increased risk of AF.

Direct Oral Anticoagulants vs. Warfarin in Latin American Patients With Atrial Fibrillation: Evidence From Four post-hoc Analyses of Randomized Clinical Trials.

Background: Several studies have investigated the effect of direct oral anticoagulants (DOACs) in Latin American patients with atrial fibrillation (AF), but the results remain controversial. Therefore, we aimed to compare the efficacy and safety of DOACs vs. warfarin in Latin American patients with AF. Methods: We systematically searched the PubMed and Embase databases until November 2021 for studies that compared the effect of DOACs vs. warfarin in Latin patients with AF. Adjusted hazard ratios (HRs) and 95% CIs were pooled by a random-effects model using an inverse variance method. Results: Four post-hoc analyses of randomized clinical trials (RCTs) involving 42,411 DOACs and 29,270 warfarin users were included. In Latin American patients with AF, for the effectiveness outcomes, the use of DOACs compared with warfarin was significantly associated with decreased risks of stroke or systemic embolism (SSE) (HR = 0.78; 95%CI.64-0.96), stroke (HR = 0.75; 95%CI.57-0.99), hemorrhagic stroke (HR = 0.14; 95%CI.05-0.36), all-cause death (HR = 0.89; 95% CI.80-1.00), but not ischemic stroke and cardiovascular death. For the safety outcomes, compared with warfarin, the use of DOACs was associated with reduced risks of major or non-major clinically relevant (NMCR) bleeding (HR = 0.70; 95% CI.57-0.86), major bleeding (HR = 0.70; 95%CI.53-0.92), intracranial hemorrhage (ICH) (HR = 0.42; 95%CI.24-0.74), or any bleeding (HR = 0.70;95% CI.62-0.78), but not gastrointestinal bleeding. In non-Latin American patients with AF, for the effectiveness outcomes, the use of DOACs compared with warfarin was significantly associated with decreased risks of SSE (HR = 0.87; 95%CI.75-1.00), hemorrhagic stroke (HR = 0.41; 95%CI.28-0.60), cardiovascular death (HR = 0.87; 95% CI.81-0.94), all-cause death (HR = 0.90; 95% CI.85-0.94). Conversely, the risk of myocardial infarction increased (HR = 1.34; 95% CI 1.13-1.60), but not ischemic stroke. For the safety outcomes, compared with warfarin, the use of DOACs was associated with reduced risks of major or NMCR bleeding (HR = 0.75; 95%CI.61-0.92), major bleeding (HR = 0.76; 95%CI.63-0.92), ICH (HR = 0.42; 95%CI.36-0.52), and any bleeding (HR = 0.81; 95% CI.71-0.92), but not gastrointestinal bleeding. Conclusion: Current pooled data from the four post-hoc analyses of RCTs suggested that compared with warfarin, DOACs appeared to have significant reductions in SSE, stroke, hemorrhagic stroke, all-cause death, major or NMCR bleeding, major bleeding, ICH, and any bleeding, but comparable risks of ischemic stroke, cardiovascular death, and gastrointestinal bleeding in Latin American patients with AF. DOACs appeared to have significant reductions in SSE, hemorrhagic stroke, all-cause death, cardiovascular death, major or NMCR bleeding, major bleeding, ICH, and any bleeding, and increased the risk of myocardial infarction, but comparable risks of stroke, ischemic stroke, and gastrointestinal bleeding in non-Latin American patients with AF.

Non-Vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Patients with Atrial Fibrillation with Coronary or Peripheral Artery Disease.

The efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) with coronary or peripheral artery disease (CAD or PAD) remain largely unresolved. We, therefore, conducted a meta-analysis to explore the effect of NOACs compared with warfarin in these populations.We systematically searched the Cochrane Library, PubMed, and Embase databases for randomized controlled trials (RCTs) involving NOACs versus warfarin in AF patients with CAD or PAD. A random-effect model was selected to pool the risk ratios (RRs) and 95% confidence intervals (CIs).A total of 7 RCTs were included. In AF patients with CAD, compared with warfarin use, the use of NOACs was associated with reduced risks of stroke/systemic embolism (RR 0.82; 95% CI 0.70-0.96) and intracranial hemorrhage (RR 0.41; 95% CI 0.26-0.63), but NOACs versus warfarin showed similar risks of all-cause death (RR 0.95; 95% CI 0.86-1.05), cardiovascular death (RR 0.95; 95% CI 0.80-1.13), stroke (RR 0.80; 95% CI 0.64-1.00), myocardial infarction (RR 1.00; 95% CI 0.83-1.21), and major bleeding (RR 0.82; 95% CI 0.65-1.04). Among patients with AF and PAD, NOACs versus warfarin had similar risks for stroke (RR 0.93; 95% CI 0.61-1.42), myocardial infarction (RR 1.10; 95% CI 0.64-1.90), all-cause death (RR 0.91; 95% CI 0.70-1.19), major bleeding (RR 1.12; 95% CI 0.70-1.81), and intracranial hemorrhage (RR 0.54; 95% CI 0.16-1.85).NOACs seem to be at least as effective and safe as warfarin in AF patients with CAD. whereas NOACs versus warfarin have similar efficacy and safety in patients with PAD.

Dose-response relationship of cardiorespiratory fitness with incident atrial fibrillation.

The dose-response association between cardiorespiratory fitness and risk of atrial fibrillation (AF) is still not well known. Therefore, we performed a comprehensive meta-analysis to investigate the dose-response association between cardiorespiratory fitness and incident AF. We performed a comprehensive search in the databases of PubMed, Cochrane library, and Ovid from inception through August 2019. A one-stage robust error meta-regression method was used to summarize the dose-response association between cardiorespiratory fitness and AF. A total of 9 studies were included in this meta-analysis. In the categorical analysis, compared with the lowest level of cardiorespiratory fitness, both the intermediate (RR = 0.68, 95% CI 0.57-0.82) and highest (RR = 0.60, 95% CI 0.51-0.72) levels of cardiorespiratory fitness were associated with a decreased risk of AF. In the dose-response analysis, per 1 metabolic equivalent increase in cardiorespiratory fitness was associated with a decreased risk of AF (RR = 0.91, 95% CI 0.86-0.95). There was an inverse relationship between cardiorespiratory fitness and risk of AF with evidence of linearity (Pnon-linearity = 0.43). Current evidence suggests that there is an inverse relationship between cardiorespiratory fitness and risk of AF, manifesting as a higher level of cardiorespiratory fitness is associated with a decreased risk of AF.

Non-vitamin K antagonist oral anticoagulants in Asian patients with atrial fibrillation: evidences from the real-world data.

The role of non-vitamin K antagonist oral anticoagulants (NOACs) in stroke prevention remains unclear in Asian patients with atrial fibrillation (AF). Therefore, we performed a meta-analysis to compare the efficacy and safety outcomes of NOACs in Asian patients with AF from the real-world settings. The PubMed and Embase databases were systematically searched to identify eligible observational studies until June 2019. The odds ratios (OR) and 95% confidence intervals (CIs) were calculated and then pooled by a random-effects model. A total of 18 observational studies were included. Compared with warfarin, dabigatran (OR, 0.56, 95% CI 0.43-0.73), rivaroxaban (OR, 0.54, 95% CI 0.44-0.67), apixaban (OR, 0.41, 95% CI 0.35-0.48), and edoxaban (OR, 0.19, 95% CI 0.14- 0.25) reduced the risk of major bleeding, while dabigatran (OR, 0.78, 95% CI 0.71-0.85), rivaroxaban (OR, 0.74, 95% CI 0.68-0.82), and edoxaban (OR, 0.29, 95% CI 0.22-0.39) were associated with reduced risks of stroke or systemic embolism. In addition, dabigatran versus apixaban was associated with increased risks of ischemic stroke and gastrointestinal bleeding, while rivaroxaban versus apixaban was associated with elevated risks of stroke or systemic embolism, ischemic stroke, intracranial hemorrhage, and gastrointestinal bleeding. In Asian patients with AF, NOACs are non-inferior to warfarin for stroke prevention, and apixaban may be a better choice compared with dabigatran or rivaroxaban.

Effect of anticoagulation therapy in older patients with chronic kidney disease and atrial fibrillation: A meta-analysis.

BACKGROUND: The role of anticoagulation therapy for stroke prevention in older atrial fibrillation (AF) patients with chronic kidney disease (CKD) remains unclear. Therefore, we conducted a meta-analysis to explore the efficacy and safety of anticoagulation therapy in this population. METHODS: The Cochrane Library, PubMed, and Embase databases were systematically searched for studies reporting the effect of anticoagulation therapy in older patients with AF and CKD. The risk ratios (RRs) and 95% confidence intervals (CIs) were regarded as the risk estimates. A random-effects model selected was to evaluate the treatment outcomes. The presentations were based on the Preferred Reporting Items for reporting systematic reviews and meta-analyses statement. RESULTS: A total of 7 studies with 24,794 older patients with AF and CKD were included. The follow-up of the included studies ranged from 0.9 to 9.0 years. In older patients with no dialysis, compared with nonanticoagulants, anticoagulants reduced the risk of all-cause death (RR 0.66, 95% CI 0.54-0.79), but had comparable risks of ischemic stroke/transient ischemic attack (TIA, RR 0.91, 95% CI 0.46-1.79) and bleeding (RR 1.17, 95% CI 0.86-1.60). In older patients with dialysis, compared with nonanticoagulants, anticoagulants increased the risk of bleeding (RR 1.37, 95% CI 1.09-1.74), but had similar risks of ischemic stroke/TIA (RR 1.18, 95% CI 0.88-1.58) and death (RR 0.87, 95% CI 0.60-1.27). CONCLUSION: Compared with nonanticoagulation, anticoagulation therapy is associated with a reduced risk of death in older AF patients with nondialysis, but an increased risk of bleeding in older patients with dialysis.

Non-Vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Asians With Atrial Fibrillation: Meta-Analysis of Randomized Trials and Real-World Studies.

Background and Purpose- Several randomized trials and real-world studies have reported the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in Asian patients with atrial fibrillation; and therefore, this meta-analysis was aimed to compare the effects of NOACs with warfarin for atrial fibrillation stroke prevention in Asians. Methods- The PubMed and Embase databases were searched from January 2009 to February 2019 for studies on comparisons of NOACs versus warfarin in Asians. Risk ratios (RRs) with 95% CIs were pooled using a random-effects model. Results- Five NOAC trials and 21 observational cohorts were included. For the NOAC trials, compared with warfarin, NOACs was associated with reduced risks of stroke or systemic embolism (RR, 0.73; 95% CI, 0.59-0.90), all-cause death (RR, 0.83; 95% CI, 0.73-0.95), major bleeding (RR, 0.59; 95% CI, 0.48-0.72), and intracranial bleeding (RR, 0.36; 95% CI, 0.26-0.49). For the real-world data, compared with warfarin, NOACs was associated with decreased rates of stroke or systemic embolism (RR, 0.75; 95% CI, 0.68-0.82), ischemic stroke (RR, 0.70; 95% CI, 0.59-0.83), myocardial infarction (RR, 0.74; 95% CI, 0.58-0.93), all-cause death (RR, 0.67; 95% CI, 0.59-0.77), major bleeding (RR, 0.63; 95% CI, 0.55-0.73), intracranial bleeding (RR, 0.50; 95% CI, 0.43-0.59), and gastrointestinal bleeding (RR, 0.65; 95% CI, 0.51-0.84). The results did not change in the subgroup analyses based on the type and dose of NOACs. Conclusions- Based on published NOAC trials and real-world studies, the use of NOACs is noninferior to warfarin in Asians with atrial fibrillation irrespective of the NOAC type and dose.