Inverse Variance Method Research Articles

Causal relationship between benign prostatic hyperplasia and prostate cancer: a bidirectional Mendelian randomization analysis.

Our aim is to explore the relation between benign prostatic hyperplasia (BPH) and prostate cancer (PCa) from a genetic level utilizing Mendelian randomization (MR). The IEU genome-wide association studies database was surveyed for single nucleotide polymorphisms (SNPs) associated with BPH, PCa, and PCa (validation cohort). Single nucleotide polymorphisms were subjected to stringent quality control based on rigorous screening criteria. BPH and PCa risk were evaluated using the inverse-variance weighted method (IVW), MR-Egger, simple mode, weighted median, and weighted mode. Horizontal pleiotropy of single nucleotide polymorphisms was assessed using the MR-Egger intercept test, while heterogeneity was evaluated using Cochran's Q test. Reverse causality was assessed by evaluating PCa as the exposure and BPH as the outcome. A validation database was used to verify the exposure and outcome. The risk of PCa increased significantly with genetically predicted BPH (IVW: OR [95% CI] = 1.3849 × 107 [2330, 8.2294 × 1010], P = 2.0814 × 10-4). In reverse MR analysis, PCa also increased the risk of BPH (IVW: OR [95% CI] = 1.0011 [1.0003, 1.0019], P = 0.0031). The findings were consistent with the MR analysis results of the PCa validation cohort. Sensitivity analyses indicated the presence of heterogeneity but no horizontal pleiotropy. The study presents proof of a significant bidirectional causal relationship between genetically predicted BPH and an increased risk of PCa. Key message Three research questions and three bullet points What is already known on this topic? Observational studies suggest a controversial relationship between BPH and PCa. MR allows investigation of causality using genetic variants as instrumental variables (IVs). What does this study add? The study presents proof of a significant bidirectional causal relationship between genetically predicted BPH and an increased risk of PCa. How this study might affect research, practice, or policy? Recognizing the bidirectional relationship between BPH and PCa, men diagnosed with BPH may benefit from more stringent PCa screening protocols.

Sex differences in survival following acute coronary syndrome with and without standard modifiable risk factors.

This meta-analysis investigates the sex differences in mortality risk between the acute coronary syndrome (ACS) population without standard modifiable risk factors (SMuRF-less) and those with at least one standard modifiable risk factor (SMuRF), and analyses mortality rates between males and females within the SMuRF-less cohort. The MEDLINE and Embase databases were searched for cohort studies with sex-stratified outcomes for SMuRF-less versus SMuRF patients with ACS till 15 December 2023. The analysis of variables reported in proportions was carried out by utilizing a meta-analysis with a generalized linear mixed model while continuous variables were analyzed by a meta-analysis of means, using an inverse variance method. Eight studies were included in the current paper, with 82,395 SMuRF-less ACS patients and 607,558 SMuRF ACS patients. Excess in-hospital mortality found in SMuRF-less ACS, compared to those with SMuRFs, were only observed in females (RR 1.56, 95%CI 1.08-2.25, p = 0.029), but not in males (RR 1.59, 95%CI 0.90-2.80, p = 0.088). On longer follow-up, the 1- and 2-year post-ACS mortality rates were similar across the SMuRF-less and SMuRF cohorts, for both sexes. The subgroup analysis of SMuRF-less ACS individuals revealed that SMuRF-less females had higher in-hospital (RR 1.52, 95%CI 1.30-1.78, p = 0.002), 1-year (RR 1.51, 95%CI 1.34-1.71, p = 0.005) and 2-year mortality risks (RR 1.40, 95%CI 1.13-1.75, p = 0.016) compared to the SMuRF-less male counterparts. Paradoxical excess mortality in SMuRF-less ACS, compared to those with SMuRFs, was only observed in females. Females without cardiovascular risk factors are at the highest risk of short- and medium-term mortality following ACS.

Abstract 4143239: Extracorporeal Shockwave Therapy Improves Physical Outcomes and Quality of Life In Patients With Symptomatic Peripheral Arterial Disease: Results from a Meta-analysis of Randomized Controlled Trials

Introduction: Extracorporeal shockwave therapy (ESWT) is a non-invasive procedure that may be useful to treat symptomatic peripheral arterial disease (PAD). Trials comparing ESWT with control groups have shown promising results. Methods: PubMed, Cochrane, EMBASE, and Google Scholar were searched for randomized controlled trials reporting the efficacy of extracorporeal shockwave therapy versus control in patients with symptomatic PAD. Data from eligible studies was analyzed using the Review Manager 5.4 software. Mean difference (MD) and 95% Confidence intervals (CI) were calculated for continuous outcomes. Inverse variance method and a random effects model were used for pooled estimates. A p-value < 0.05 (Z-test) was considered significant. Results: 5 randomized controlled trials with 264 patients were included in our analysis. A significant increase in the mean walking distance (MD: 54.13, 95% CI 9.34 to 98.92, p=0.02), pain-free walking distance (MD: 54.13, 95% CI 14.19, 57.88, p= 0.001), SF-36 physical component summary (MD: 11.97, 95% CI 0.26 to 23.69, p=0.05), EQ-5D-3L index score (MD; 0.08, 95% CI: 0.00 to 0.15, p=0.05) and VascuQoL index ((MD: 0.48, 95% CI 0.03 to 0.92, p= 0.04) was seen with ESWT. A slightly higher ankle brachial pressure index was seen in the control group (MD: -0.01, 95% CI: -0.02 to -0.00, p=0.04). There was no difference in SF-36 physical functioning domain score (MD: 18.58, 95% CI: -0.29 to 37.45, p=0.05) and SF-36 bodily pain score (MD: 9.17, 95% CI: -2.885 to 21.19, p=0.13). Conclusions: There was significant improvement in walking distances, exertional symptoms, and quality of life with ESWT. However, ESWT did not translate to an increase in post-treatment ankle-brachial index which was slightly higher in the control group. There is a need for larger randomized controlled trials to substantiate the efficacy of ESWT in treating symptomatic PAD.

Abstract 4145880: Incidence and Outcomes of Acute Myocardial Infarction (AMI) in Hematological Malignancy Patients: Systematic review and Meta-analysis

Background: Patients with hematological malignancies may face increased cardiovascular risks, including acute myocardial infarction (AMI). This systematic review and meta-analysis aims to evaluate the incidence and outcomes of AMI in patients with hematological malignancies compared with the general population. Methods: A comprehensive literature search was conducted using the PubMed, Embase, and Google Scholar databases. Random effect models were utilized to calculate Mantel-Haenszel odds ratios (ORs) with 95% confidence intervals (CIs). The inverse variance method with DerSimonian–Laird (DL) of Tau2 was used to calculate standardized mean differences (SMDs) with CIs. Statistical significance was set at p < 0.05. The primary endpoint was the incidence of AMI, while secondary outcomes included in-hospital mortality, length of hospital stay, likelihood of undergoing invasive procedures, total hospital costs, bleeding events, and stroke outcomes. Results: Twenty-six articles, including approximately 6.33 million patients with hematological malignancies, were included in the meta-analysis. Hematological malignancies were not associated with an increased incidence of AMI compared with the general population (OR = 0.91; 95% CI 0.80 to 1.03; p<0.001). AMI in hematological malignancies was associated with an increased risk of in-hospital mortality (OR = 1.71; 95% CI 1.57 to 1.86; p<0.001), bleeding event (OR = 1.30; 95% CI 1.12 to 1.60; p<0.001), and stroke (OR = 1.24; 95% CI 1.09 to 1.42) compared with AMI in the general population. Patients admitted due to AMI in hematologic malignancies also experienced an increased length of stay (SMD = 0.25; 95% CI 0.20 to 0.28; p<0.001) compared with AMI in the general population. There was no significant difference between the two groups in terms of the likelihood of undergoing invasive procedures (OR = 0.62; 95% CI 0.56 to 0.69) or total hospital expenditure (SMD = 0.09; 95% CI -0.01 to 0.19). Conclusion: While hematological malignancies do not appear to increase the incidence of acute myocardial infarction (AMI), patients who experience AMI episodes are at higher odds of in-hospital complications.

Abstract 4148096: Discrimination Abilities of Euroscore and SYNTAX score for Prognostic Outcomes in patients with Stable Coronary Artery Disease: A Systematic Review and Meta-analysis

Introduction: There is a lack of good risk prediction models in patients with stable coronary artery disease (SCAD). We conducted a meta-analysis of validation studies to compare and determine the discrimination abilities of Euroscore (ES) and Syntax score (SS) for prognostic outcomes in patients with SCAD. Methods: A comprehensive literature search was conducted across MEDLINE, Cochrane and Embase from inception till May 2024. All studies that reported C-statistic/AUC for predicting all cause mortality, cardiac death or Major adverse cardiovascular events (MACE) for patients with stable coronary artery disease (SCAD) were included in the analysis. Studies lacking confidence intervals (CI) for C-statistic or those which reported C-statistics in patients with acute coronary syndromes or mixed SCAD and ACS patients were excluded. A generic inverse variance method was used to pool C-statistics and their corresponding standard errors (SEs). The SEs were calculated from CI wherever needed. A pooled C statistic of >0.8 was considered to be a good discrimination ability. Results: A total of 5 studies with a patient population of 5903 were included in the meta-analysis. For ES, the pooled C-statistic for all cause mortality (n=2666) was 0.69[0.51-0.87] while for cardiac death (n=2666) it was 0.77[0.60-0.71]. The discrimination ability of ES for MACE as reported by one study (n=305) was 0.54[0.49-0.60]. For SS, the summary AUC for all cause mortality (n=2936) was 0.77[0.69-0.85] while for cardiac death (n=305) it was 0.52[0.46-0.57]. The pooled AUC of SS for occurrence of MACE(n=2666) was 0.56[0.45-0.66]. Conclusion: None of the two scores have a a good discrimination ability for risk stratification in SCAD patients. The predictive accuracy of SS is comparatively better than ES for all cause mortality. However, ES performs better for predicting cardiac death. Better risk prediction models with large scale external validations are needed.

Abstract 4137175: Functional Mitral Regurgitation as a Predictor of Atrial Fibrillation Recurrence Following Catheter Ablation: A Systematic Review and Meta-Analysis

Background: Recent studies showed that functional mitral valve regurgitation (FMR) was associated with higher long-term mortality in chronic heart failure patients and poorer outcomes in those with atrial fibrillation (AF), including a higher risk of atrial cardiomyopathy. However, the effect of baseline FMR on outcomes post-AF catheter ablation remains unclear due to inconsistent evidence. Methods: We systematically reviewed studies from Medline and EMBASE databases from inception to April 2024. Eligible studies must report the association between baseline FMR and risk of AF recurrence post-AF catheter ablation compared to individuals without FMR. Relative Risk (RR) or hazard ratio (HR) and 95% CIs were retrieved from each study and combined using the generic inverse variance method. Results: Our meta-analysis included 7 cohort studies and found that baseline FMR was associated with a higher risk of AF recurrence compared to those without FMR. The pooled risk ratios (RR) were 1.40 (95% CI 1.11-1.78, I2 = 31%, p = 0.005). No publication bias was identified on the funnel plot. Conclusions: Our pooled analysis found that patients with FMR who underwent AF catheter ablation had a higher risk of AF recurrence compared to those without FMR. Further research is needed to explore the underlying mechanisms and their clinical implications. Keyword: Functional mitral regurgitation, Atrial fibrillation, Catheter ablation, Atrial fibrillation recurrence, Systematic review, Meta-analysis

BIOS-05. PEPTIDE-BASED VACCINES VERSUS DENDRITIC CELL-BASED VACCINE THERAPIES FOR PATIENTS WITH GLIOBLASTOMA: A NETWORK META-ANALYSIS OF CONTROLLED CLINICAL TRIALS

Abstract BACKGROUND Glioblastoma (GBM) is the most prevalent primary CNS malignancy in adults, often with a bleak prognosis. Reports suggest the efficacy of dendritic cell vaccines (DCV) and peptide vaccines in extending overall survival (OS). We aimed to compare their efficacy using network meta-analysis (NMA). METHODS We systematically searched PubMed, Cochrane database, SCOPUS, and Clinicaltrials.gov up to February 2024 for controlled trials on DCV or peptide vaccines for GBM. NMA was conducted using the frequentist approach to obtain direct and indirect comparisons of each vaccine. Pairwise analyses were performed using the inverse variance method, comparing each vaccine’s efficacy. PEPvIII-KLH and Rindopepimut were merged into “Peptide-based vaccines” [PEP], and standard of care (SOC) and (Placebo + SOC) were merged. Primary outcome: hazard ratio (HR) of overall survival with 95% confidence intervals. RESULTS Analysis included 5 studies with 451 patients (vaccine arm) and 445 controls, with SOC/[Placebo + SOC] as reference. Common effects model showed DCV + SOC significantly reduced the HR to 0.3385 [0.1753; 0.6539], while the peptide-based vaccine + SOC reduced the HR to 0.8276 [0.6960; 0.9840]. In the random effects model, DCV + SOC had an HR of 0.3132 [0.0839; 1.1688], and the peptide-based vaccine + SOC had an HR of 0.3888 [0.1383; 1.0928]. Heterogeneity: tau^2 = 0.6473, tau = 0.8045, I^2 = 77.7% [39.5%; 91.8%]. In a pairwise meta-analysis comparing the DCV+SOC and SOC/[Placebo + SOC] consisting of 2 trials, the common and random effects models both estimated an HR of 0.3385 [0.1753; 0.6539, I^2 = 0.0%]. Comparing the PEP+SOC and SOC/[Placebo + SOC] based on 3 trials, the common effect model estimated an HR of 0.8276 [0.6960; 0.9840], while the random effects model estimated an HR of 0.3874 [0.1360; 1.1039, I^2 = 84.4%]. CONCLUSION Based on current evidence, DCV vaccines perform better than peptide-based vaccines in reducing mortality in GBM patients. Further trials are required to validate their efficacies.

Efficacy and safety of sacituzumab govitecan Trop-2-targeted antibody-drug conjugate in solid tumors and UGT1A1*28 polymorphism: a systematic review and meta-analysis.

Sacituzumab govitecan (SG) is a promising Trop-2-targeted antibody-drug conjugate (ADC) approved for the treatment of metastatic triple-negative breast cancer (TNBC). Early phase clinical trials have demonstrated good clinical activity and safety profile of SG in various tumor types, albeit with differing response rates and durations. The aim of this systematic review and meta-analysis was to evaluate the clinical efficacy and toxicity of SG and the influence of UGT1A1*28 genotype in clinical trials involving solid tumors. A systematic review of the literature from publicly available databases was performed on February 15, 2024 whereby studies published till 15 February 2024 were retrieved according to PRISMA guidelines [PROSPERO #CRD42022359943]. Data extracted included tumor type, sample size, demographic information, SG dose, UGT1A1*28 status, toxicity events, duration of follow-up, response, and survival outcomes. Risks of bias analysis was refereed using the Joanna Briggs Institute quality assessment tool for the cohort and RCT studies using 11 and 13 parameters, respectively. Statistical analysis was performed using the DerSimonian and Laird inverse variance methods. Heterogeneity was assessed using the I2 statistic and Χ2 tests. P value < 0.05 was considered as statistical significance. Eleven eligible clinical trials comprised of 1578 patients harboring various tumor types including TNBC, lung, genitourinary and gastrointestinal malignancies were included in the systematic review and meta-analysis. Pooled incidences of severe adverse events were minimal at <10%, with the exception of grade 3-4 neutropenia at 37.4%. The median PFS and OS across all studies were 4.9 (95%CI: 4.0-5.8) months and 9.6 (95%CI: 7.6-11.6) months, respectively. Objective response rate across all studies evaluated was 17.1% (95%CI: 12.0-22.1). Our systematic review and meta-analysis confirmed that SG confers good clinical activity in certain solid tumor types and was tolerable with minimal adverse events. The potential utility of UGT1A1*28 genotyping in predicting clinical response and outcomes could not be determined due to the limited number of studies with available UGT1A1 genotype data.

Association and mediation pathways of maternal hyperglycaemia and liability to gestational diabetes with neonatal outcomes: A two-sample Mendelian randomization study.

Maternal hyperglycemia is linked to adverse neonatal outcomes. However, current evidence was insufficient for mechanistic pathways. We aim to use two-sample Mendelian randomization (MR) to obtain a comprehensive understanding of the causal association and mediation pathways. Genetic variants of fasting glucose (FG), insulin sensitivity index (ISI), glycated haemoglobin (HbA1c), gestational diabetes mellitus (GDM) and type 2 diabetes (T2D) were used as instruments (N = 50 404-898 130). The associations with offspring birthweight, gestational duration, spontaneous preterm and post-term birth were assessed by the inverse-variance weighted method, using summary statistics of European genome-wide association studies (N = 131 279-210 248). Sensitivity analyses, including multivariable MR removing pleiotropic effect from maternal body mass index (BMI), assessed the robustness. Mediation via placental weight and maternal hypertension were assessed via a two-step MR design. FG (0.46 SD per mmol/L, 95% confidence interval [95% CI]: 0.32, 0.61) and GDM liability (0.18 SD per log odds, 95% CI: 0.08, 0.18) were positively associated with birthweight, with consistent findings for HbA1c, T2D liability and ISI. These associations were mediated by placental weight (proportion mediated: 32.8% to 77.7%). Higher HbA1c, GDM and T2D liability were associated with preterm birth (odds ratios for GDM: 1.07, 95% CI: 1.01, 1.14) and shorter gestational duration, whilst the association for T2D attenuated after adjusted for maternal BMI and gestational hypertension. Maternal hyperglycemia is associated with higher birthweight (possibly indicating macrosomia), mediated via increased placental growth. GDM and T2D liability are related to preterm birth, whilst the association for T2D liability is driven by maternal adiposity.

Midwife-Led Versus Obstetrician-Led Perinatal Care for Low-Risk Pregnancy: A Systematic Review and Meta-Analysis of 1.4 Million Pregnancies

Background: The optimum model of perinatal care for low-risk pregnancies has been a topic of debate. Obstetrician-led care tends to perform unnecessary interventions, whereas the quality of midwife-led care has been subject to debate. This review aimed to assess whether midwife-led care reduces childbirth intervention and whether this comes at the expense of maternal and neonatal wellbeing. Methods: PubMed, Scopus, Cochrane Library, and Web of Science were systematically searched for relevant studies. Studies were checked for eligibility by screening the titles, abstracts, and full texts. We performed meta-analyses using the inverse variance method using RevMan software version 5.3. We pooled data using the risk ratio and mean difference with the 95% confidence interval. Results: This review included 44 studies with 1,397,320 women enrolled. Midwife-led care carried a lower risk of unplanned cesarean and instrumental vaginal deliveries, augmentation of labor, epidural/spinal analgesia, episiotomy, and active management of labor third stage. Women who received midwife-led care had shorter hospital stays and lower risks of infection, manual removal of the placenta, blood transfusion, and intensive care unit (ICU) admission. Furthermore, neonates delivered under midwife-led care had lower risks of acidosis, asphyxia, transfer to specialist care, and ICU admission. Postpartum hemorrhage, perineal tears, APGAR score &lt; 7, and other outcomes were comparable between the two models of management. Conclusions: Midwife-led care reduced childbirth interventions with favorable maternal and neonatal outcomes in most cases. We recommend assigning low-risk pregnancies to midwife-led perinatal care in health systems with infrastructure allowing for smooth transfer when complications arise. Further research is needed to reflect the situation in low-resource countries.

Gastroesophageal reflux disease, mood swings, and frozen shoulder: A two-sample, two-step Mendelian randomization study.

A Mendelian randomization (MR) study was undertaken to establish a causal link between gastroesophageal reflux disease (GERD) and frozen shoulder (FS), examining whether the risk of GERD with FS is mediated through mood fluctuations. Genetic loci from populations of independent European ancestry were selected as instrumental variables for GERD, FS, and mood swings. The primary analysis employed the inverse-variance weighted method supplemented by 3 additional analytical methods. This was conducted using two-sample and two-step MR analyses. This study explored the correlation and mediating effects of mood swings between GERD and FS. Our study employed heterogeneity and horizontal diversity, and sensitivity analysis was conducted using the leave-one-out method to explore the robustness of the results. In the two-sample MR analysis, for every 1-unit increase in the log-transformed odds ratio (OR) of GERD, the corresponding OR increased to 1.844 (inverse-variance weighting: OR = 1.844, 95% confidence interval: 1.47-2.30, P < .001). In the two-step MR analysis, we found that mood swings played a mediating role in the association between GERD and FS. We assessed this mediating effect using the delta method (b = 0.181, SE = 0.059, OR = 1.199, 95% confidence interval: 1.072-1.349). Analysis of the data using the above methods indicated that GERD is a risk factor for FS, and mood swings mediate between the 2. Therefore, GERD and mood swings should be included in the health management of patients with FS.

Prevalence and Risk Factors of Heart Failure in Patients Diagnosed with Hyperthyroidism: A Systematic Review and Meta-analysis.

Objectives: Hyperthyroidism has a significant impact on the cardiovascular system, causing thyrotoxic cardiomyopathy, which is characterized by atrial fibrillation, left ventricular hypertrophy and diastolic dysfunction, and may lead to heart failure. This study aimed to investigate the prevalence and associated risk factors for heart failure in patients with hyperthyroidism. Methods: A systematic literature search was conducted on PubMed, SCOPUS and Ovid SP up until April 2023. Pooled prevalence and pooled odds ratio for risk factors were calculated using the generic inverse variance method. Results: Studies involving 30,889 patients were included in this meta-analysis. The overall prevalence of heart failure in patients with hyperthyroidism was 8% (95% confidence interval [CI]: 6-11%). Further analyses revealed that the prevalence of heart failure in patients who underwent treatment with radioactive iodine ablation, antithyroid medication and thyroidectomy was 8% (95% CI: -1 to 16%), 6% (95% CI: 2 to 11%) and 4% (95% CI: -2 to 10%), respectively. The risk factors of heart failure in hyperthyroidism include atrial fibrillation, chronic kidney disease, anaemia, hypertension, history of stroke or transient ischaemic attack, history of coronary artery disease and diabetes mellitus. Conclusion: Heart failure occurs in 8% of patients with hyperthyroidism, with the most common risk factor being atrial fibrillation.

Prognostic Value of Neutrophil-to-Eosinophil Ratio (NER) in Cancer: A Systematic Review and Meta-Analysis.

The identification of reliable prognostic biomarkers is crucial for optimizing cancer treatment strategies, especially in the era of personalized medicine. This systematic review and meta-analysis evaluate the prognostic significance of the neutrophil-to-eosinophil ratio (NER) in various cancer types, with a focus on its association with overall survival (OS) and progression-free survival (PFS). We conducted a systematic literature search across PubMed, Scopus, and Web of Science databases for studies published up to 28 July 2024. We performed the meta-analyses with the generic inverse variance method with a random effects model and reported hazard ratios (HR) with 95% confidence intervals (CI). The comprehensive literature search identified 10 studies comprising 2351 patients. Pooled analyses demonstrated that elevated pretreatment NER levels were significantly correlated with poorer OS (HR: 1.74, 95% CI: 1.28-2.36, p < 0.001) and PFS (HR: 1.53, 95% CI: 1.21-1.95, p < 0.001). Subgroup analyses confirmed a consistent adverse association between high NER and OS across various tumor types and geographic locations, although results from studies conducted in the Far East did not reach statistical significance. This meta-analysis demonstrates that elevated NER is associated with poorer OS and PFS in cancer patients, suggesting its potential utility as a non-invasive prognostic marker. Further validation in large, prospective studies is warranted to establish NER's role in guiding personalized treatment strategies across diverse oncologic contexts.

Prognostic Impact and Prevalence of Cachexia in Patients With Heart Failure: A Systematic Review and Meta-Analysis.

Cachexia, defined as the combination of weight loss, weakness, fatigue, anorexia and abnormal biochemical markers based on Evans' criteria, is known to exacerbate the prognosis of heart failure (HF) patients. This systematic review and meta-analysis investigates the prognostic impact and prevalence of cachexia, as defined by Evans' criteria, in patients with HF. PubMed, Cochrane Library, Scopus and Web of Science were searched from inception until December 2023, including HF patients for whom the Evans' criteria were applied to explore the prevalence and prognostic impact of cachexia. This study employed a meta-analyses using the random-effects model and inverse-variance method that was adhered to the revised 2020 PRISMA guidelines for systematic reviews and meta-analyses (CRD42023446443). Six prospective or retrospective studies of 2252 patients with HF were included, whereby all-cause mortality was significantly greater in patients with cachexia with low heterogeneity among studies (HR: 1.60, 95% CI 1.31-1.95, p < 0.001; I2 = 0%). For the studies that used full, uniformly defined Evans' criteria, among 1844 patients, mortality remained greater in patients with cachexia (HR: 1.58, 95% CI 1.27-1.97, p < 0.001; I2 = 0%). In a subgroup analysis among 1714 of HF with reduced ejection fraction, the results were consistent (HR: 1.57, 95% CI 1.28-1.92, p < 0.001; I2 = 0%). Additionally, 10 studies comprising 2862 patients indicated a 31% risk of cachexia in HF (95% CI 21-43%, I2 = 94%). Cachexia is an independent predictor for increased all-cause mortality among patients with HF with a notable prevalence of 31%. Interventions aiding in improving fatigue, anorexia and exercise capacity could help improve the quality of life of this clinical population.

Colchicine in patients with coronary disease undergoing coronary artery bypass surgery: a meta-analysis of randomized controlled trials

Abstract Background Recent randomized evidence has shown that low dose colchicine lowers the risk of cardiovascular events in patients with chronic coronary artery disease (CAD). Colchicine has also been used in coronary artery bypass grafting (CABG) with individual studies suggesting protective effects for postoperative atrial fibrillation (POAF). We performed a meta-analysis of studies assessing the effect of colchicine on outcomes in CABG surgery. Purpose To determine the potential of colchicine for reducing post-operative atrial fibrillation or other adverse events in patients undergoing CABG. Methods We systematically searched three libraries (MEDLINE, Web of Science and The Cochrane Library) selecting all randomized control trials (RCT) including patients who underwent CABG and were randomized for pre- or perioperative administration of colchicine versus standard of care. Primary outcome was incidence of POAF. Inverse variance method (DerSimonian&amp;Laird) and random effects model were performed. The leave-one-out analysis was carried out as a sensitivity analysis to address possible outliers. Results From 205 screened studies, five met the inclusion criteria and were selected. The data from 839 patients were included in the final analysis. Included studies were published between 2014 and 2022. The perioperative administration of colchicine was associated with reduction of POAF rates after CABG when compared to standard of care (relative risk; RR= 0.54, 95% confidence interval; CI, 0.40-0.73, p&amp;lt;0.01 – Fig. 1). The leave-one-out analysis confirmed the robustness of the analysis, with minimal variations of the confidence interval (Fig. 2). Conclusions This meta-analysis of randomized studies suggests that the perioperative administration of colchicine is associated with significant reduction of POAF rates after CABG.Forest plotLeave-one-out analysis

Cardiovascular prevention with GLP1 agonists in high or very-high cardiovascular risk irrespective of diabetes

Abstract Introduction Patients with established cardiovascular disease have an increased risk of stroke and myocardial infarction, even in the absence of atrial fibrillation. Several trials have analyzed the effect of glucagon-like peptide-1 receptor (GLP1) agonists in patients with high cardiovascular risk and lately this effect has been studied even in the absence of diabetes. Methods A meta-analysis of randomized clinical trials (RCT) comparing GLP1 agonists with placebo was performed. The primary objective of the study was to analyze the composite endpoint of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke (MACE). As secondary objectives, cardiovascular death, non-fatal myocardial infarction and non-fatal stroke have been studied separately. The meta-analysis was performed using the inverse variance method, using the fixed effects model when there was no heterogeneity and the random effects model when heterogeneity is significant. In the case of significant heterogeneity in the primary objective, a stratified analysis with exposure time have been performed to explain this outcome. Results A sum of 9 randomized controlled trials were included where a GLP1 agonist such as albiglutide, dulaglutide, exenatide, liraglutide, lixinatide or semaglutide was compared with placebo. 77684 patients were incorporated, while 39497 were treated with a GLP1 agonist. The mean age was of 63.7 years (SD ± 1.97 years), 60080 (77.3%) suffered from diabetes and 60552 (77.9%) from cardiovascular disease. As showed in figure 1, the GLP1 agonists showed a reduction of 13% of the MACE (RR: 0.87, 95% CI 0.81-0.92; p&amp;lt;0.001). Heterogeneity could be explained by exposure time and concentration in the blood, considering that it disappears within each group when applying this condition. Treatment with GLP1 agonist also reduced cardiovascular death by 12% (RR: 0.88, 95% CI 0.82-0.94; p&amp;lt;0.001), non-fatal strokes by 14% (RR: 0.86, 95%CI 0.79-0.95; p&amp;lt;0.001) and non-fatal miocardial infarction by 13% (RR: 0.87, 95% CI 0.78-0.97; p&amp;lt;0.001). Conclusion Treatment with a GLP1 agonist reduced the incidence of the MACE by 13% and cardiovascular death by 12%, as well as it decreased the incidence of nonfatal stroke by 14% and of nonfatal myocardial infarction by 13% in different RCTs involving patients with high or very-high cardiovascular risk with or without diabetes.

Heart failure and renal outcomes in patient treated with GLP1 agonists

Abstract Introduction Glucagon-like peptide-1 receptor (GLP1) agonists are emerging as a primordial treatment for diabetes and to reduce cardiovascular burden, both of them factors that play an important role in the developing of renal chronic disease and heart failure, and vice versa. The debut of renal chronic disease and the manifestation of acute renal injury/failure can lead to the discontinuation of treatment, which in patients suffering from heart failure who tend to be polymedicated could end up in lessening their survival. Methods A metanalysis of randomized clinical trials (RCT) comparing GLP1 agonists with placebo was performed. The endpoint of the study was to analyze all-cause mortality, hospitalization or urgent medical visit for heart failure, a kidney outcome composite, which is slightly heterogenic depending on the RCT, and the manifestation of acute renal injury/failure as an adverse effect or that lead to the discontinuation of treatment. The meta-analysis was performed using the inverse variance method, using the fixed effects model when there was no heterogeneity and the random effects model when heterogeneity is significant. Results A sum of 9 randomized controlled trial were included where a GLP1 agonists such as albiglutide, dulaglutide, exenatide, liraglutide, lixinatide or semaglutide compared with placebo. 77684 patients were incorporated, while 39497 were treated with a GLP1 agonists. The mean age was of 63.7 years (SD ± 1.97 years), 60080 (77.3%) suffered from diabetes, 60552 (77.9%) from cardiovascular disease and 14367 from chronic heart failure (18.4%). The mean eGFR was 77.3 mL/min (SD ± 3.3 mL/min). As showed in the forest plots, treatment with GLP1 agonists reduced all-cause mortality by 12% (RR: 0.88, 95% CI 0.83-0.92; p&amp;lt;0.001), hospitalization or urgent medical visit for heart failure by 10% (RR: 0.90, 95% CI 0.83-0.98; p&amp;lt;0.001), the kidney composite outcome by 22% (RR: 0.78, 95% CI 0.70-0.87; p&amp;lt;0.001), while it showed no statistical reduction in acute renal injury/failure (RR: 0.89, 95% CI 0.79-1.01; p=0.069). Conclusion Treatment with a GLP1 agonists reduced the incidence of all-cause mortality by 12%. In addition, hospitalization or urgent medical visit for heart failure was decreased by 10%. In terms of renal asessment, the composite of kidney function was reduced by 22%, while the manifestation of acute renal injury/failure, though no statistical signification was accomplished, showed some evidence of beneficial effect but more RCTs are needed to prove it. Hence, GLP1 analogues appear as a possible new pillar of treatment for heart failure and renal disease in determined patients.

Peer support interventions improve disease self-management after coronary heart disease diagnosis: a systematic review and meta-analysis

Abstract Background Patients with coronary heart disease (CHD) diagnoses often experience impacts on patient-reported outcomes (quality of life, depression, disease self-management and self-efficacy) at a time when secondary prevention is required. Peer support has proven benefits for these issues in many chronic conditions but synthesis of the evidence in CHD populations has not been undertaken. Purpose In this systematic review and meta-analysis, we aimed to explore the impact of peer support interventions on health-related quality of life, depression, anxiety, self-management and self-efficacy in CHD. Methods Electronic databases were searched from inception to November 2023 (MEDLINE, Embase, PsycINFO, CINAHL, Scopus, PubMed [non-MEDLINE], Web of Science, and the Cochrane Central Register of Controlled Trials). Randomised controlled trials (RCTs) evaluating peer support interventions (that enable experience sharing and/or support by others with the same condition) in populations with diagnosed CHD were eligible for inclusion. Risk of bias was assessed using the Cochrane risk of bias tool. Meta-analyses were undertaken in RevMan Version: 7.4.0 using the inverse variance method and a random effects model. Results In total, 16 papers reporting 14 unique RCTs were included. The total sample (n=1793) was 65% male with a mean age of 54.5±13.0 years. The diagnosis of the samples varied between studies, including coronary artery bypass graft(s), first time or newly diagnosed myocardial infarction and percutaneous coronary intervention. By 6-months follow-up, peer support interventions demonstrated no statistically significant improvements in health-related quality of life (SMD -0.38, 95% CI -1.84, 1.08), depression (SMD -0.09, 95% CI -0.26, 0.08) and anxiety (SMD -0.85, 95% CI -1.83, 0.14). Whereas, improvements occurred in disease self-management (SMD 1.49, 95% CI 0.66, 2.32) and self-efficacy in both short term (by 6-months, SMD 0.57, 95% CI 0.37, 0.77) and longer term (6-12 months, SMD 0.67, 95% CI 0.29, 1.05). Peer support interventions varied widely in format and several studies were of poor quality. Conclusion Peer support interventions benefit patient-reported outcomes of disease self-management and self-efficacy up to 6 and 12 months, but not for other patient reported outcomes after CHD diagnosis. More exploration is needed of content, delivery and focus of peer support interventions to maximise effectiveness for CHD secondary prevention.

Causal Associations Between the Gut Microbiota and Hypertension-Related Traits Through Mendelian Randomization: A Cross-Sectional Cohort Study.

Previous studies have suggested a link between the gut microbiome and hypertension-related traits like blood pressure. However, these reports are often limited by weak causal evidence. This study investigates the potential causal association between gut microbiota and hypertension-related traits using Mendelian randomization with summary data from genome-wide association studies. The inverse-variance weighted method revealed that the Clostridium innocuum group (Odds ratio [OR]: 1.0047, 95% confidence interval [CI]: 1.0004-1.0090, p=0.0336), Eubacterium fissicatena group (OR: 1.0047, 95% CI: 1.0005-1.0088, p=0.0266), Lachnospiraceae FCS020 group (OR: 1.0063, 95% CI: 1.0004-1.0122, p=0.0361), and Olsenella (OR: 1.0044, 95% CI: 1.0001-1.0088, p=0.0430) were associated with an increased risk of hypertension. Conversely, Flavonifractor (OR: 0.9901, 95% CI: 0.9821-0.9982, p=0.0166), Parabacteroides (OR: 0.9874, 95% CI: 0.9776-0.9972, p=0.0121), and Senegalimassilia (OR: 0.9907, 95% CI: 0.9842-0.9974, p=0.0063) were associated with a decreased risk of hypertension. External validation with the Guangdong Gut Microbiome Project confirmed a negative correlation between Parabacteroides and hypertension, potentially through metabolic pathways. These findings provide further evidence supporting the hypothesis that microbes and their metabolites play a role in blood pressure regulation.

Evaluating the connection between mean platelet volume (MPV) and peripheral arterial disease risk: a meta-analysis

Background: Numerous studies have been conducted to evaluate the role of Mean Platelet Volume (MPV) in relation to Peripheral Artery Disease (PAD). However, the results of these studies have been inconsistent regarding the significance of MPV as an indicator for PAD. Objective: This meta-analysis aimed to clarify the role of MPV in PAD by collecting and analyzing data from various studies. The goal was to provide a more definitive assessment of whether MPV levels could serve as a reliable indicator for PAD Methods: We conducted a meta-analysis from July to August 2024, utilizing data from three major databases: Scopus, Embase, and PubMed. We gathered data on MPV levels from studies comparing PAD patients with control groups. The meta-analysis included cumulative effect estimates, with analysis performed using the inverse variance method to synthesize data and evaluate the overall effect of MPV on PAD. Results: Nine studies were included in this meta-analysis, comprising 1,214 PAD cases and 6,568 controls. Our analysis demonstrated that MPV was a significant marker in PAD, with PAD patients having higher MPV levels compared to controls (MD: 0.46; 95%CI: 0.25, 0.66; p Egger: 0.0911; p Heterogeneity &lt;0.0001; p &lt;0.0001). Conclusion: Our findings support that MPV is an important indicator in the context of PAD. Further study is needed to explore the clinical applications of MPV in PAD and to establish standardized thresholds for its use in clinical practice. Keyword: diagnosis, mean platelet volume, peripheral disease, predictor