Serum copper and obesity among healthy adults in the National Health and Nutrition Examination Survey.

BACKGROUND: Copper (Cu) homeostasis are important processes in the cause of metabolic diseases, but the association between Cu and obesity remains unclear. METHODS: Participants were drawn from the 2011-2016 National Health and Nutrition Examination Survey (NHANES). Weighted logistic regression assessed the associations of serum Cu concentrations (tertiles) with obesity and central obesity in individuals without comorbidities. Obesity was defined as a BMI ≥30.0 kg/m2, and central obesity was defined as a waist circumference ≥80 cm for women and ≥95 cm for men. RESULTS: This cross-sectional study included 1,665 adults without comorbidities, representing 24,744,034 people (mean age 35.1 years, 48.5% female). High serum Cu levels (tertile 3: ≥19.19 µmol/L) were associated with higher odds of obesity (adjusted odds ratio [OR]: 4.48, 95% CI[confidence interval]: 2.44-8.32) and central obesity (OR: 2.36, 95% CI: 1.19-4.66) compared to low serum Cu levels (tertile 1: ≤15.64 µmol/L). The dose-response curve showed a nonlinear association between Cu levels and obesity (P-nonlinear = 0.02) and a linear association with central obesity (P-nonlinear = 0.21). CONCLUSION: This study suggests that higher serum Cu levels are associated with increased odds of obesity in healthy American adults.

Effects of sustained viral response on lipid in Hepatitis C: a systematic review and meta-analysis.

BACKGROUND: Direct-acting Antiviral Agents (DAAs) influence serum lipids of patients with Hepatitis C virus (HCV). This paper presents an analysis of the relevant literature to investigate the effects of DAAs in treating hepatitis C to achieve a sustained viral response (SVR) on lipid parameters. METHODS: PubMed,Web of science, Embase and Central databases were searched, with a deadline of September 2023. Studies on the effects of sustained viral response on lipid parameters after DAAs treatment for hepatitis C were selected. The required information was extracted from the included studies, and then the Stata 12.0 was used to analyze the data quantitatively. RESULTS: Of 32 studies, the results showed that total cholesterol (TC) levels increased from the end of treatment (WMD = 20.144, 95%CI = 3.404, 36.884,P = 0.018) to one year after treatment (WMD = 24.900, 95%CI = 13.669, 36.131, P < 0.001). From the end of treatment (WMD = 17.728, 95%CI = 4.375, 31.082, P = 0.009) to one year after treatment (WMD = 18.528, 95%CI = 7.622, 29.433, P < 0.001), the levels of low-density lipoprotein (LDL) were also increased. High-density lipoprotein (HDL) levels were elevated from 4 weeks after treatment (WMD = 6.665, 95%CI = 3.906, 9.424, P < 0.001) to 24 weeks after treatment (WMD = 3.159,95% CI = 0.176, 6.142, P = 0.038). Triglyceride (TG) levels showed no significant change after the treatment. CONCLUSIONS: Hepatitis C patients who achieved SVR on DAAs showed the increase of lipid levels and the improvement of hepatic inflammation indicators AST and ALT. This may provide evidence-based medical evidence for the follow-up and monitoring of blood lipids and hyperlipidemia treatment. REGISTRATION: PROSPERO CRD42020180793.

Screens in aging-relevant human ALS-motor neurons identify MAP4Ks as therapeutic targets for the disease.

Effective therapeutics is much needed for amyotrophic lateral sclerosis (ALS), an adult-onset neurodegenerative disease mainly affecting motor neurons. By screening chemical compounds in human patient-derived and aging-relevant motor neurons, we identify a neuroprotective compound and show that MAP4Ks may serve as therapeutic targets for treating ALS. The lead compound broadly improves survival and function of motor neurons directly converted from human ALS patients. Mechanistically, it works as an inhibitor of MAP4Ks, regulates the MAP4Ks-HDAC6-TUBA4A-RANGAP1 pathway, and normalizes subcellular distribution of RANGAP1 and TDP-43. Finally, in an ALS mouse model we show that inhibiting MAP4Ks preserves motor neurons and significantly extends animal lifespan.

Clinical Outcomes with GLP-1 Receptor Agonists in Patients with Heart Failure: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) reduce the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM). However, there remains uncertainty about the efficiency of GLP-1 RAs in patients with heart failure (HF). METHODS: Randomized placebo-controlled trials (RCTs) that reported the effect of GLP-1 RAs on prognosis in patients with HF were identified by searching databases. The primary outcome was defined as MACE. Trail Sequential Analysis (TSA) was used to evaluate the reality and authenticity. RESULTS: Nine RCTs involving 8920 patients with HF were included. GLP-1 RAs significantly reduced the risk of MACE compared with placebo (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.77-0.98) in HF coexisting with T2DM. The benefit was not observed in all-cause death (HR 0.99, 95% CI 0.84-1.15), hospitalization for heart failure (HR 1.04, 95% CI 0.89-1.22), cardiovascular death (HR 0.95, 95% CI 0.79-1.16), myocardial infarction (HR 0.88, 95% CI 0.71-1.08), stroke (HR 1.03, 95% CI 0.75-1.43) and death or hospitalization for HF (HR 1.07, 95% CI 0.78-1.46). GLP-1 RAs did not improve the change in LVEF (mean difference [MD]): - 0.86, p = 0.12, left-ventricular end-diastolic volume (LVEDV) (MD: 3.54, p = 0.11), left-ventricular end-systolic volume (LVESV) (MD: 2.78, p = 0.07) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) (MD: - 140.36, p = 0.08). However, GLP-1 RAs significantly increased the change in the 6-min walk test (MWT) distance (MD: 19.74, p = 0.002). In the subgroup analyses, human GLP-1 RAs, but not nonhuman GLP-1 RAs, reduced the risk of MACE in patients with HF (p interaction = 0.11). Grading of Recommendations Assessment, Development and Evaluation (GRADE) showed moderate certainty for MACE, all-cause death and hospitalization for HF. Trail Sequential Analysis revealed that there may be a high possibility of false positive results for MACE. CONCLUSION: Compared with placebo, GLP-1 RAs may reduce the risk of MACE in patients with HF coexisting with T2DM, with a more significant efficiency of human GLP-1 RAs. More RCTs are needed to assess the cardiovascular benefits of GLP-1 RAs in HF, regardless of T2DM. REGISTRATION: The protocol for this meta-analysis is registered on PROSPERO [CRD42022357886].

The regulation of circRNA and lncRNAprotein binding in cardiovascular diseases: Emerging therapeutic targets.

Noncoding ribonucleic acids (ncRNAs) are a class of ribonucleic acids (RNAs) that carry cellular information and perform essential functions. This class encompasses various RNAs, such as small nuclear ribonucleic acids (snRNA), small interfering ribonucleic acids (siRNA) and many other kinds of RNA. Of these, circular ribonucleic acids (circRNAs) and long noncoding ribonucleic acids (lncRNAs) are two types of ncRNAs that regulate crucial physiological and pathological processes, including binding, in several organs through interactions with other RNAs or proteins. Recent studies indicate that these RNAs interact with various proteins, including protein 53, nuclear factor-kappa B, vascular endothelial growth factor, and fused in sarcoma/translocated in liposarcoma, to regulate both the histological and electrophysiological aspects of cardiac development as well as cardiovascular pathogenesis, ultimately leading to a variety of genetic heart diseases, coronary heart disease, myocardial infarction, rheumatic heart disease and cardiomyopathies. This paper presents a thorough review of recent studies on circRNA and lncRNAprotein binding within cardiac and vascular cells. It offers insight into the molecular mechanisms involved and emphasizes potential implications for treating cardiovascular diseases.

A simple, flexible, and high-efficiency western blot analysis for age-related human induced neurons.

High-throughput western blot (WB) analysis can be used to obtain more consistent, comparable, and informative data from precious samples and materials with extremely limited availability, such as various age-related, subtype-specific human induced neurons (hiNs). In this study, p-toluenesulfonic acid (PTSA), an odorless tissue fixative, was used to inactivate horseradish peroxidase (HRP) and develop a high-throughput WB method. PTSA-treated blots demonstrated rapid and efficient HRP inactivation without detectable protein loss or epitope damage. With a brief PTSA treatment (1 min at room temperature [RT]) before every subsequent probing, 10 dopaminergic hiN proteins could be sequentially, sensitively, and specifically detected in the blot. The resulting WB data confirmed the age-associated and neuron-specific features of hiNs and revealed a significant reduction in two Parkinson's disease-associated proteins, UCHL1 and GAP43, in normal aging dopaminergic neurons. Overall, this study developed a unique and high-efficiency WB analysis method for capturing robust and useful data from limited, precious samples.

Evaluation of blood-based PRO-C3 testing as a diagnostic marker for staging liver fibrosis: A systematic review and meta-analysis.

BACKGROUND AND AIM: With the global increase in chronic liver disease and cirrhosis, there is an increasing need to identify non-invasive biomarkers to measure the severity of disease progression while reducing reliance on pathological biopsies. This study aimed to comprehensively evaluate the diagnostic value of PRO-C3 as a biomarker for staging liver fibrosis in patients with viral hepatitis or fatty liver disease. METHODS: Articles published until January 6, 2023, were searched in the PubMed, Embase, MEDLINE, Web of Science, and Cochrane Library databases. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to evaluate the quality of the included studies. Pooled sensitivity, specificity, diagnostic odds ratio, and likelihood ratios were integrated using a random-effects model, and a summary receiver operating characteristic curve was constructed. Publication bias was also detected. Subgroup and meta-regression analyses, as well as sensitivity analysis, were also performed. RESULTS: Fourteen studies with 4315 patients were included. Summary area under the curve of PRO-C3 for the identification of significant fibrosis (≥ F2) and advanced fibrosis (≥ F3) was 0.80 (95% confidence interval: 0.76-0.83). Subgroup and meta-regression analyses suggested that disease type and sample size may be the primary factors of heterogeneity in PRO-C3 diagnosis of ≥ F2, while study design, study sample type, and enzyme-linked immunosorbent assay kit brand may be the primary sources of heterogeneity in PRO-C3 diagnosis of ≥ F3. CONCLUSIONS: PRO-C3 demonstrated clinically meaningful diagnostic accuracy when used alone as a non-invasive biomarker for diagnosing the liver fibrosis stage in individuals with viral hepatitis or fatty liver disease.

Is There a Sex Difference in the Prognosis of Hypertrophic Cardiomyopathy? A Systematic Review and Meta-Analysis.

Background It is still unclear whether there is a sex difference in the prognosis of patients with hypertrophic cardiomyopathy (HCM). Therefore, we performed a meta-analysis to elucidate the association between sex and adverse outcomes in patients with HCM. Methods and Results The PubMed, Cochrane Library, and Embase databases were used to search for studies on sex differences in prognosis in patients with HCM up to August 17, 2021. Summary effect sizes were calculated using a random effects model. The protocol was registered in PROSPERO (International prospective register of systematic reviews) (registration number- CRD42021262053). A total of 27 cohorts involving 42 365 patients with HCM were included. Compared with male subjects, female subjects had a higher age at onset (mean difference=5.61 [95% CI, 4.03-7.19]), a higher left ventricular ejection fraction (standard mean difference=0.09 [95% CI, 0.02-0.15]) and a higher left ventricular outflow tract gradient (standard mean difference=0.23 [95% CI, 0.18-0.29]). The results showed that compared with male subjects with HCM, female subjects had higher risks of HCM-related events (risk ratio [RR]=1.61 [95% CI, 1.33-1.94], I2=49%), major cardiovascular events (RR=3.59 [95% CI, 2.26-5.71], I2=0%), HCM-related death (RR=1.57 [95% CI, 1.34-1.82], I2=0%), cardiovascular death (RR=1.55 [95% CI, 1.05-2.28], I2=58%), noncardiovascular death (RR=1.77 [95% CI, 1.46-2.13], I2=0%) and all-cause mortality (RR=1.43 [95% CI, 1.09-1.87], I2=95%), but not atrial fibrillation (RR=1.13 [95% CI, 0.95-1.35], I2=5%), ventricular arrhythmia (RR=0.88 [95% CI, 0.71-1.10], I2=0%), sudden cardiac death (RR=1.04 [95% CI, 0.75-1.42], I2=38%) or composite end point (RR=1.24 [95% CI, 0.96-1.60], I2=85%). Conclusions Based on current evidence, our results show significant sex-specific differences in the prognosis of HCM. Future guidelines may emphasize the use of a sex-specific risk assessment for the diagnosis and management of HCM.

Association between triglyceride glucose index and arterial stiffness and coronary artery calcification: a systematic review and exposure-effect meta-analysis.

BACKGROUND: The triglyceride and glucose (TyG) index has been linked to various cardiovascular diseases. However, it's still unclear whether the TyG index is associated with arterial stiffness and coronary artery calcification (CAC). METHODS: We conducted a systematic review and meta-analysis of relevant studies until September 2022 in the PubMed, Cochrane Library, and Embase databases. We used a random-effects model to calculate the pooled effect estimate and the robust error meta-regression method to summarize the exposure-effect relationship. RESULTS: Twenty-six observational studies involving 87,307 participants were included. In the category analysis, the TyG index was associated with the risk of arterial stiffness (odds ratio [OR]: 1.83; 95% CI 1.55-2.17, I2 = 68%) and CAC (OR: 1.66; 95% CI 1.51-1.82, I2 = 0). The per 1-unit increment in the TyG index was also associated with an increased risk of arterial stiffness (OR: 1.51, 95% CI 1.35-1.69, I2 = 82%) and CAC (OR: 1.73, 95% CI 1.36-2.20, I2 = 51%). Moreover, a higher TyG index was shown to be a risk factor for the progression of CAC (OR = 1.66, 95% CI 1.21-2.27, I2 = 0, in category analysis, OR = 1.47, 95% CI 1.29-1.68, I2 = 41% in continuity analysis). There was a positive nonlinear association between the TyG index and the risk of arterial stiffness (Pnonlinearity < 0.001). CONCLUSION: An elevated TyG index is associated with an increased risk of arterial stiffness and CAC. Prospective studies are needed to assess causality.

Recent advances in recurrent hepatocellular carcinoma therapy.

Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer, accounting for 75%-85% of cases. Although treatments are given to cure early-stage HCC, up to 50%-70% of individuals may experience a relapse of the illness in the liver after 5 years. Research on the fundamental treatment modalities for recurrent HCC is moving significantly further. The precise selection of individuals for therapy strategies with established survival advantages is crucial to ensuring better outcomes. These strategies aim to minimize substantial morbidity, support good life quality, and enhance survival for patients with recurrent HCC. For individuals with recurring HCC after curative treatment, no approved therapeutic regimen is currently available. A recent study presented novel approaches, like immunotherapy and antiviral medication, to improve the prognosis of patients with recurring HCC with the apparent lack of data to guide the clinical treatment. The data supporting several neoadjuvant and adjuvant therapies for patients with recurring HCC are outlined in this review. We also discuss the potential for future clinical and translational investigations.

Chemical screens in aging-relevant human motor neurons identify MAP4Ks as therapeutic targets for amyotrophic lateral sclerosis.

Effective therapeutics is much needed for amyotrophic lateral sclerosis (ALS), an adult-onset neurodegenerative disease mainly affecting motor neurons. By screening chemical compounds in human patient-derived and aging-relevant motor neurons, we identify a neuroprotective compound and show that MAP4Ks may serve as therapeutic targets for treating ALS. The lead compound broadly improves survival and function of motor neurons directly converted from human ALS patients. Mechanistically, it works as an inhibitor of MAP4Ks, regulates the MAP4Ks-HDAC6-TUBA4A-RANGAP1 pathway, and normalizes subcellular distribution of RANGAP1 and TDP-43. Finally, in an ALS mouse model we show that inhibiting MAP4Ks preserves motor neurons and significantly extends animal lifespan.

Periodontal disease is associated with the risk of cardiovascular disease independent of sex: A meta-analysis.

Objectives: Studies have established a link between periodontal disease and cardiovascular disease (CVD), but it is unclear whether there is a sex difference in their association. Methods: The PubMed, Embase, and Cochrane databases were searched until June, 21 2022. Cardiovascular outcomes included any CVD, myocardial infarction (MI), coronary heart disease (CHD), or stroke. Studies reported the prevalence of CVD in patients with periodontal disease and the relationship between periodontal disease and CVD. The study is registered with PROSPERO (CRD42022333663). The level of evidence and recommendations is assessed by the Grading of Recommendations for Assessment, Development and Evaluation (GRADE). Results: Twenty-six studies were included. In patients with periodontal disease, the prevalence of CVD was 7.2% [9 studies; 95% confidence interval (CI): 2.7-13.6%], and prevalence for CHD, hypertension, stroke, and heart failure was 6.6, 25.3, 1, and 1.1%, respectively. There was a significant association between periodontal disease and CVD in men [odds ratio (OR) = 1.22; 95% CI: 1.12-1.34] and women (OR = 1.11; 95% CI: 1.05-1.17), with no significant sex difference (P > 0.05). Conclusion: Cardiovascular disease is relatively common in patients with periodontal disease, and an increased risk of CVD is associated with periodontal disease independent of sex. Interventions targeting periodontal disease may be beneficial for CVD. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022333663.

Atrial fibrillation and breast cancer-Vicious twins? A systematic review and meta-analysis.

Background: Epidemiological studies suggest a bidirectional association between atrial fibrillation and breast cancer. This study aimed to conduct a meta-analysis to elucidate the prevalence of atrial fibrillation among breast cancer patients, and the bidirectional association between atrial fibrillation and breast cancer. Methods: PubMed, the Cochrane Library, and Embase were searched to identify studies reporting the prevalence, incidence, and bidirectional association between atrial fibrillation and breast cancer. The study was registered with PROSPERO (CRD42022313251). Levels of evidence and recommendations were assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: Twenty-three studies (17 retrospective cohort studies, 5 case-control studies and 1 cross-sectional study) involving 8,537,551 participants were included. Among patients with breast cancer, the prevalence of atrial fibrillation was 3% (11 studies; 95% CI: 0.6 to 7.1%) and the incidence was 2.7% (6 studies; 95% CI: 1.1 to 4.9%). Breast cancer was associated with increased risk of atrial fibrillation (5 studies; hazard ratio [HR]: 1.43, 95% CI: 1.12 to 1.82, I2 = 98%). Atrial fibrillation was also significantly associated elevated risk of breast cancer (5 studies HR: 1.18, 95% CI: 1.14 to 1.22, I2 = 0%). Grade assessment shown low certainty of the evidence for the risk of atrial fibrillation and moderate certainty of the evidence for the risk of breast cancer. Conclusion: Atrial fibrillation is not uncommon in patients with breast cancer and vice versa. There is a bidirectional association between atrial fibrillation (low certainty) and breast cancer (moderate certainty).

Association between weight loss and outcomes in patients undergoing atrial fibrillation ablation: a systematic review and dose-response meta-analysis.

BACKGROUND: Obesity is an strong risk factor for atrial fibrillation (AF), and obesity can affect the prognosis of AF. However, the role of weight loss on outcomes after ablation remains unclear. OBJECTIVES: This study aims to determine the relationship between weight loss and outcomes in patients with AF ablation, as well as the potential dose-response relationship. METHODS: The Cochrane Library, PubMed, and Embase databases were searched to identify studies that reported a relationship between weight loss and ablation up to August 17, 2021. Relative risks (RRs) were pooled using random-effects models. RESULTS: One randomized, open-labeled clinical trial and seven cohort studies involving 1283 patients were included. The mean body mass index of all included studies was over 30 kg/m2. The clinical trial showed a non-significant benefit of weight loss intervention on AF recurrence (Odd risk [OR] = 1.02, 95% confidence interval [CI] 0.70-1.47). Meta-analysis based on observational studies showed that the recurrence rate of AF after ablation was significantly reduced (RR = 0.43, 95% CI 0.22-0.81, I2 = 97%) in relatively obese patients with weight loss compared with the control group. Each 10% reduction in weight was associated with a decreased risk of AF recurrence after ablation (RR = 0.54, 95% CI 0.33-0.88) with high statistical heterogeneity (I2 = 76%). An inverse linear association (Pnon-linearity = 0.27) between AF relapse and increasing weight loss was found. CONCLUSIONS: Our results first suggest an inverse dose-response association between weight loss and risk of recurrent AF after ablation, with moderate certainty.

AcrPred: A hybrid optimization with enumerated machine learning algorithm to predict Anti-CRISPR proteins.

CRISPR-Cas, as a tool for gene editing, has received extensive attention in recent years. Anti-CRISPR (Acr) proteins can inactivate the CRISPR-Cas defense system during interference phase, and can be used as a potential tool for the regulation of gene editing. In-depth study of Anti-CRISPR proteins is of great significance for the implementation of gene editing. In this study, we developed a high-accuracy prediction model based on two-step model fusion strategy, called AcrPred, which could produce an AUC of 0.952 with independent dataset validation. To further validate the proposed model, we compared with published tools and correctly identified 9 of 10 new Acr proteins, indicating the strong generalization ability of our model. Finally, for the convenience of related wet-experimental researchers, a user-friendly web-server AcrPred (Anti-CRISPR proteins Prediction) was established at http://lin-group.cn/server/AcrPred, by which users can easily identify potential Anti-CRISPR proteins.

Efficacy and Safety of Sofosbuvir-based Regimens in Hepatitis C Patients With Decompensated Cirrhosis: A Systematic Review and Meta-analysis.

Background and Aims: Decompensated cirrhotic patients with hepatitis C (HCV) are often under-represented in clinical trials. We aimed to evaluate pooled data on the efficacy and safety of sofosbuvir (SOF)-based regimens in these patients. Methods: We conducted a systemic review and meta-analysis by searching multiple databases for studies published from October 2010 to October 2020. Outcomes of interest were sustained virologic response (SVR) and safety of SOF-based regimens in decompensated HCV patients. Two reviewers independently performed the study selection and data extraction. Results: We included 33 studies that enrolled 5,302 HCV patients. The pooled SVR rate in decompensated patients with SOF-based regimens was 85.1% (95% CI: 82.8-87.3). Patients on SOF/velpatasvir±ribavirin achieved a significantly higher SVR (91.0%, 95% CI: 87.7-93.9) than that of SOF/ledipasvir±ribavirin [(86.3%, 95% CI: 84.6-87.8); p=0.004)], or on SOF/daclatasvir±ribavirin (82.4%, 95% CI: 78.2-86.2%; p<0.001). Adding ribavirin to SOF-based regimens (pooled SVR 84.9%, 95% CI: 81.7-87.9) did not significantly increase the SVR [(83.8% (95% CI: 76.8-89.8%; p=0.76)] in decompensated patients, which was also true in subgroup analyses for each regimen within the same treatment duration. However, adding ribavirin significantly increased the frequency of adverse events from 52.9% (95% CI: 28.0-77.1) to 89.2% (95% CI: 68.1-99.9) and frequency of severe events. The pooled incidence of hepatocellular carcinoma and case-fatality of decompensated patients were 3.1% (95% CI: 1.5-5.0) and 4.6% (95% CI: 3.1-6.3), respectively. The overall heterogeneity was high. There was no publication bias. Conclusions: The analysis found that 12 weeks of SOF/velpatasvir without ribavirin is the preferred therapy, with a significantly higher SVR compared with other SOF-based regimens in decompensated HCV patients.

Sex differences in mortality and hospitalization in heart failure with preserved and mid-range ejection fraction: a systematic review and meta-analysis of cohort studies.

Introduction: The influence of sex on the prognosis of heart failure with preserved or intermediate ejection fraction (HFpEF and HFmrEF) remains uncertain. This study aimed to investigate whether sex differences impact the prognosis of patients diagnosed with HFpEF and HFmrEF. Methods: A comprehensive search across three databases (PubMed, the Cochrane Library, and Embase) was conducted to identify sex-related prognostic cohort studies focusing on HFpEF and HFmrEF. Risk estimates were synthesized using the random effects model. The analysis included 14 cohorts comprising 41,508 HFpEF patients (44.65% males) and 10,692 HFmrEF patients (61.79% males). Results: Among HFpEF patients, men exhibited significantly higher rates of all-cause mortality (13 studies; hazard ratio (HR): 1.24, 95% confidence interval (CI): 1.15 to 1.33)) and cardiovascular disease mortality (5 studies; HR: 1.22, 95% CI: 1.14 to 1.31) compared to women. However, no significant difference was observed in HF admissions. For HFmrEF patients, men displayed notably higher all-cause mortality (HR: 1.21, 95% CI: 1.12 to 1.31) but no significant differences in cardiovascular mortality or HF admissions. Discussion: These findings suggest that male patients diagnosed with HFpEF and HFmrEF may face a more unfavorable prognosis in terms of all-cause mortality. Variations were noted in cardiovascular mortality and HF admissions, indicating potential complexities in sex-related prognostic factors within these heart failure categories. In summary, male patients with HFpEF and HFmrEF may have a more unfavorable prognosis.

Fibroblast growth factor-23 and the risk of cardiovascular diseases and mortality in the general population: A systematic review and dose-response meta-analysis.

Background: In the past decade, fibroblast growth factor 23 (FGF23) has been recognized as an important biomarker of cardiovascular diseases. This study aimed to assess the relationship between FGF23 and the risk of cardiovascular diseases (CVDs) in general populations. Methods: The protocol was registered prospectively in PROSPERO (CRD42021281837) and two authors independently searched for relevant studies in the PubMed, EMBASE, and Cochrane Library databases. The random effects model was applied. Results: In total, 29 prospective studies involving 135,576 participants were included. In the general population, the category analysis revealed that elevated FGF23 levels were related to increased risks of myocardial infarction (MI) (RR: 1.40, 95%CI: 1.03-1.89), stroke (RR: 1.20, 95%CI: 1.02-1.43), heart failure (HF) (RR: 1.37, 95%CI: 1.23-1.52), CVD events (RR: 1.22, 95%CI: 0.99-1.51), cardiovascular mortality (RR: 1.46, 95%CI: 1.29-1.65), and all-cause mortality (RR: 1.50, 95%CI: 1.29-1.74). In the continuous analysis, per doubling of FGF23 was associated with increased risks of MI (RR: 1.08, 95%CI: 0.94-1.25), stroke (RR: 1.21, 95%CI: 0.99-1.48), HF (RR: 1.24, 95%CI: 1.14-1.35), CVD events (RR: 1.12, 95%CI: 0.99-1.27), cardiovascular mortality (RR: 1.43, 95%CI: 1.09-1.88), all-cause mortality (RR: 1.37, 95%CI: 1.15-1.62). Furthermore, the dose-response analysis demonstrated a potentially non-linear relationship between FGF23 and stroke, HF, and all-cause mortality. In contrast, a potentially linear relationship between FGF23 and cardiovascular mortality was observed (p for non-linearity = 0.73). Conclusion: The present study suggests that increased serum FGF23 levels are positively related to CVD events and mortality in the general population. The clinical application of FGF23 levels to predict CVD risk requires further research.

Influenza vaccination is associated with a decreased risk of atrial fibrillation: A systematic review and meta-analysis.

Background: Evidence from longitudinal studies has shown that influenza infection is linked to an increased risk of arrhythmia. Therefore, we aimed to assess the role of influenza vaccination in arrhythmia prevention. Materials and methods: The PubMed, Embase, and Cochrane Library databases were searched to identify studies that investigated the potential effects of the influenza vaccine on arrhythmia risk published until October 25th, 2021. The study was registered with PROSPERO (CRD42022300815). Results: One RCT with 2,532 patients and six observational studies with 3,167,445 patients were included. One RCT demonstrated a non-significant benefit of the influenza vaccine against arrhythmias [odds ratio (OR) = 0.43, 95% confidence interval (CI): 0.11-1.64; P = 0.20] in patients after myocardial infarction or those with high-risk stable coronary heart disease. A meta-analysis based on observational studies showed that vaccination was associated with a significantly lower risk of arrhythmia (OR: 0.82, 95% CI: 0.70-0.97; P = 0.02; I 2 = 76%). Additionally, subgroup analysis showed a decreased risk of atrial fibrillation (AF) (OR: 0.94, 95% CI: 0.90-0.98; P = 0.006; I 2 = 0%) and a non-significant but positive trend concerning ventricular arrhythmias (VAs) (OR: 0.68, 95% CI: 0.42-1.11; P = 0.12; I 2 = 85%) after influenza vaccination. Conclusion: Based on the current evidence, influenza vaccination may be associated with a reduced risk of arrhythmia, especially AF. Influenza vaccination may be an effective tool for the prevention of arrhythmias. The effect of influenza vaccination on the risk of VAs and arrhythmias in patients at low risk for cardiovascular diseases should be further studied. Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42022300815].

Relationship between serum growth differentiation factor 15, fibroblast growth factor-23 and risk of atrial fibrillation: A systematic review and meta-analysis.

Background and objective: Growth differentiation factor-15 (GDF-15) and fibroblast growth factor-23 (FGF-23) are considered predictors of the incidence of cardiovascular diseases. The present meta-analysis aimed to elucidate the associations between GDF-15 and FGF-23 in the risk of atrial fibrillation (AF). Methods: An electronic search was conducted in the Cochrane Library, PubMed, and Embase databases from inception until February 27, 2021. The study protocol was registered in the PROSPERO database (CRD42020182226). Results: In total, 15 studies that enrolled 36,017 participants were included. Both serum FGF-23 and GDF-15 were elevated in patients with AF. Analysis of categorical variables showed higher serum FGF-23 levels were associated with an increased risk of AF [relative risk (RR) = 1.28, 95% confidence interval (CI): 1.05-1.56]. In contrast, this association was not found with GDF-15 (RR = 0.91, 95% CI: 0.20-4.04). In dose-response analysis, a linear positive association was noted between serum FGF-23 levels and the risk of AF (P nonlinear = 0.9507), with a RR elevation of 7% for every 20 pg/ml increase in the serum FGF-23 levels (95% CI: 1.02-1.13). No remarkable relationship was found between serum GDF-15 levels and the risk of AF, and the overall RR for the association between a 100 ng/L increment in GDF-15 levels and AF was 1.01 (95% CI: 0.998-1.02). Conclusion: Our study showed a positive linear correlation between serum FGF-23 levels and the risk of AF. However, no significant association was found between GDF-15 and the risk of AF. Further studies are warranted to clarify whether serum FGF-23 levels may be considered in predicting the risk of AF.Systematic Review Registration: http:www.york.ac.uk/inst/crd, identifier CRD42020182226.