Impact of preoperative intra-aortic balloon pump on outcomes in coronary artery bypass grafting for unprotected left-main coronary artery disease.

Background: Preoperative intra-aortic balloon pump (IABP) before coronary artery bypass grafting (CABG) could improve operative outcomes by augmenting the diastolic coronary blood flow. Data on preoperative IABP use in patients with left-main coronary artery (LMCA) disease are limited. This study aimed to characterize patients who received preoperative IABP before CABG for LMCA and evaluate its effect on postoperative outcomes. Methods: This multicenter retrospective cohort study that included consecutive 914 patients who underwent CABG for unprotected LMCA disease from January 2015 to December 2019 in 14 tertiary referral centers. Patients were grouped according to the preoperative IABP insertion into patients with IABP (n=101) and without IABP (n=813). Propensity score matching adjusting for preoperative variables, with 1:1 match and a caliber of 0.03 identified 80 matched pairs. The primary outcomes used in propensity score matching were cardiac mortality and major adverse cardiac and cerebrovascular events (MACCE). Results: IABP was commonly inserted in patients with previous myocardial infarction (MI), chronic kidney disease, peripheral arterial disease, and congestive heart failure. IABP patients had higher EuroSCORE [ES >8%: 95 (11.86%) vs. 40 (39.60%), P<0.001] and SYNTAX {29 [interquartile range (IQR) 25-35] vs. 33 (IQR 26-36); P=0.02} scores. Preoperative cardiogenic shock and arrhythmia were more prevalent in patients with IABP, while acute coronary syndrome was more prevalent in patients without IABP. After matching, there was no difference in vasoactive inotropic score between groups [3.5 (IQR 1-7.5) vs. 6 (IQR 1-13.5), P=0.06], and lactate levels were nonsignificantly higher in patients with IABP [2.4 (IQR 1.4-4.5) vs. 3.1 (IQR 1.05-7.75), P=0.05]. There were no differences between groups in acute kidney injury [20 (25%) vs. 26 (32.5%), P=0.34], cerebrovascular accidents [3 (3.75%) vs. 4 (5%), P>0.99], heart failure [5 (6.25%) vs. 7 (8.75%), P=0.75], MI [7 (8.75%) vs. 8 (10%), P>0.99], major adverse cardiac and cerebrovascular events [10 (12.5%) vs. 17 (21.25%), P=0.21], and cardiac mortality [6 (7.50%) vs. 14 (17.50%), P=0.09]. Patients who received IABP had longer ventilation times [8.5 (IQR 6-23) vs. 15.5 (IQR 5-50.5) h, P=0.03] and intensive care unit (ICU) stays [3 (IQR 2-5) vs. 4 (IQR 2-7.5) days, P=0.01]. Conclusions: Preoperative IABP in patients with LMCA might not be associated with reduced cardiac mortality or hospital complications. IABP could increase the duration of mechanical ventilation and ICU stay, and its use should be individualized for each patient.

The role of natural products as PCSK9 modulators: A review.

A variety of mechanisms and drugs have been shown to attenuate cardiovascular disease (CVD) onset and/or progression. Recent researchers have identified a potential role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in modulating lipid metabolism and reducing plasma low density lipoprotein (LDL) levels. PCSK9 is the central protein in the metabolism of LDL cholesterol (LDL-C) owing to its major function in LDL receptor (LDLR) degradation. Due to the close correlation of cardiovascular disease with lipid levels, many in vivo and in vitro investigations are currently underway studying the physiological role of PCSK9. Furthermore, many studies are actively investigating the mechanisms of various compounds that influence lipid associated-disorders and their associated cardiovascular diseases. PCSK9 inhibitors have been shown to have significant impact in the prevention of emerging cardiovascular diseases. Natural products can effectively be used as PCSK9 inhibitors to control lipid levels through various mechanisms. In this review, we evaluate the role of phytochemicals and natural products in the regulation of PCSK9, and their ability to prevent cardiovascular diseases. Moreover, we describe their mechanisms of action, which have not to date been delineated.

Systematic Review and Meta-analysis of the Impact of Metabolic Surgery on Hepatic Stiffness.

BACKGROUND: Bariatric surgery is one of the effective therapeutic options for people with obesity and obesity-related co-morbidities. In addition to weight-related co-morbid diseases, including diabetes, hypertension, and hypercholesterolemia, non-alcoholic fatty liver disease (NAFLD) is common in patients with morbid obesity. Bariatric surgery is one of the therapeutic options in the management of NAFLD. Hence, this review focused on the potential role of bariatric surgery on hepatic elasticity measured through shear wave elastography. METHODS: A systematic literature search was performed, and the studies regarding heterogeneity were evaluated using the random-effects model. RESULTS: The meta-analysis on 6 trials (3-12 months follow-up) including 350 participants showed a significant reduction of liver elasticity after surgery (WMD: -1.149, 95% CI: -1.767, -0.532, p < 0.001; I2:81.55%). CONCLUSION: Bariatric surgery is associated with decreased liver elasticity. This improvement could be related to weight loss or other mechanisms of bariatric surgery.

The Atrial FibriLlatiOn (FLOW-AF) Registry in the Middle East and North Africa: Patient Characteristics, Treatment Patterns and Outcomes.

INTRODUCTION: Limited data on atrial fibrillation (AF) are available from the Middle East and North Africa region (MENA). The aim of the FLOW-AF registry was to evaluate the characteristics, treatment patterns, and clinical and economic outcomes of patients with newly diagnosed non-valvular atrial fibrillation (NVAF) in MENA. METHODS: This multi-center, prospective, observational study (the FLOW-AF registry) enrolled patients newly diagnosed with NVAF across Egypt, Lebanon, Kingdom of Saudi Arabia, and United Arab Emirates. The data collection occurred at enrollment (baseline) and after 6- and 12-months (follow-up). Baseline data included demographics, AF characteristics, medical history, and anti-thrombotic treatment patterns. Clinical events, healthcare resource utilization, and direct costs were collected at follow-up. RESULTS: The study enrolled a total of 1418 patients (52.7% males and 47.3% females). The mean age of the patients was 64.5 years and 90.6% were white. The mean (standard deviation) CHA2DS2-VASc and HAS-BLED risk scores were 2.7 (1.6) and 1.6 (1.2), respectively. Non-vitamin K antagonist oral anticoagulants, antiplatelet therapy, and vitamin K antagonists were prescribed to 65.8%, 16.4%, and 12.9% patients, respectively. During follow-up, the following rates of clinical outcomes were observed: bleeding events (1.7%), transient ischemic attack (1.7%), all-cause mortality (1.7%), stroke (0.6%), myocardial infarction (0.2%), and systemic embolism (0.08%). CONCLUSIONS: This MENA patient population was younger and had lower mean baseline CHA2DS2-VASc and HAS-BLED scores. The rates of clinical outcomes over 1-year in this study were low. Longer follow-up is required to comprehensively assess clinical outcomes in this patient population.

Targeting PCSK9 as a key player in lipid metabolism: exploiting the therapeutic and biosensing potential of aptamers.

The degradation of low-density lipoprotein receptor (LDLR) is induced by proprotein convertase subtilisin/kexin type 9 (PCSK9), resulting in elevated plasma concentrations of LDL cholesterol. Therefore, inhibiting the interactions between PCSK9 and LDLR is a desirable therapeutic goal for managing hypercholesterolemia. Aptamers, which are RNA or single-stranded DNA sequences, can recognize their targets based on their secondary structure. Aptamers exhibit high selectivity and affinity for binding to target molecules. The systematic evolution of ligands by exponential enrichment (SELEX), a combination of biological approaches, is used to screen most aptamers in vitro. Due to their unique advantages, aptamers have garnered significant interest since their discovery and have found extensive applications in various fields. Aptamers have been increasingly utilized in the development of biosensors for sensitive detection of pathogens, analytes, toxins, drug residues, and malignant cells. Furthermore, similar to monoclonal antibodies, aptamers can serve as therapeutic tools. Unlike certain protein therapeutics, aptamers do not elicit antibody responses, and their modified sugars at the 2'-positions generally prevent toll-like receptor-mediated innate immune responses. The focus of this review is on aptamer-based targeting of PCSK9 and the application of aptamers both as biosensors and therapeutic agents.

Impact of bariatric surgery on circulating irisin levels: a systematic review and meta­analysis.

This systematic review and meta-analysis evaluated changes in circulating irisin levels after bariatric surgery. A systematic search was performed across Embase, Scopus, PubMed, and Web of Science for this study. The meta-analysis was conducted using Comprehensive Meta-Analysis (CMA) V4 software. The overall effect size was depicted through a random-effects meta-analysis and the leave-one-out method. The meta-analysis, which included 13 studies with a total of 407 participants, showed a statistically non-significant reduction in circulating irisin levels following bariatric surgery (SMD: - 0.089, 95% CI - 0.281, 0.102, 95% PI: - 0.790, 0.611, p = 0.360; I2:70.56). Our research found no significant change in irisin levels after bariatric surgery. Moreover, these findings were not associated with the type of surgery or the duration of follow-up.

Cell Therapies and Gene Therapy for Diabetes: Current Progress.

The epidemic of diabetes continues to be an increasing problem, and there is a need for new therapeutic strategies. There are several promising drugs and molecules in synthetic medicinal chemistry that are developing for diabetes. In addition to this approach, extensive studies with gene and cell therapies are being conducted. Gene therapy is an existing approach in treating several diseases, such as cancer, autoimmune diseases, heart disease and diabetes. Several reports have also suggested that stem cells have the differentiation capability to functional pancreatic beta cell development in vitro and in vivo, with the utility to treat diabetes and prevent the progression of diabetes-related complications. In this current review, we have focused on the different types of cell therapies and vector-based gene therapy in treating or preventing diabetes.

Identification of Critical Genes Differentiating Stable and Unstable Atherosclerotic Plaques: A Bioinformatic and Computational Analysis.

BACKGROUND: Identification of biomarkers to distinguish between stable and unstable plaque formation would be very useful to predict plaque vulnerability. METHODS: We downloaded microarray profiles of gene set enrichment (GSE) accession numbers including GSE71226 and GSE20680 (group A: containing healthy vs stable plaque samples) and GSE62646 and GSE34822 (group B: containing stable vs unstable plaque samples) from Gene expression omnibus (GEO) database. Differentially expressed genes were compared in both data sets of each group. RESULTS: Ten and 12 key genes were screened in groups A and B, respectively. Gene Ontology (GO) enrichment was applied by the plugin "BiNGO" (Biological networks gene ontology tool) of the Cytoscape. The key genes were mostly enriched in the biological process of positive regulation of the cellular process. The protein-protein interaction and co-expression network were analyzed by the STRING (search tool for the retrieval of interacting genes/proteins) and GeneMANIA (gene multiple association network integration algorithm) plugin of Cytoscape, respectively, which showed that Epidermal growth factor (EGF), Heparin-binding EGF like growth factor (HBEGF), and Matrix metalloproteinase 9 (MMP9) were at the core of the network. Further validation of key genes using two datasets showed that Phosphodiesterase 5A (PDE5A) and Protein S (PROS1) were decreased in unstable plaques, while Suppressor of cytokine signaling (SOCS3), HBEGF, and Leukocyte immunoglobulin-like receptor B4 (LILRB4) were increased. CONCLUSION: The present study used several datasets to identify key genes associated with stable and unstable atherosclerotic plaque.

Toward a Universal Definition of Etiologies in Heart Failure: Categorizing Causes and Advancing Registry Science.

Heart failure (HF) is a well-described final common pathway for a broad range of diseases however substantial confusion exists regarding how to describe, study, and track these underlying etiologic conditions. We describe (1) the overlap in HF etiologies, comorbidities, and case definitions as currently used in HF registries led or managed by members of the global HF roundtable; (2) strategies to improve the quality of evidence on etiologies and modifiable risk factors of HF in registries; and (3) opportunities to use clinical HF registries as a platform for public health surveillance, implementation research, and randomized registry trials to reduce the global burden of noncommunicable diseases. Investment and collaboration among countries to improve the quality of evidence in global HF registries could contribute to achieving global health targets to reduce noncommunicable diseases and overall improvements in population health.

Repressive H3K27me3 drives hyperglycemia-induced oxidative and inflammatory transcriptional programs in human endothelium.

BACKGROUND: Histone modifications play a critical role in chromatin remodelling and regulate gene expression in health and disease. Histone methyltransferases EZH1, EZH2, and demethylases UTX, JMJD3, and UTY catalyse trimethylation of lysine 27 on histone H3 (H3K27me3). This study was designed to investigate whether H3K27me3 triggers hyperglycemia-induced oxidative and inflammatory transcriptional programs in the endothelium. METHODS: We studied human aortic endothelial cells exposed to high glucose (HAEC) or isolated from individuals with diabetes (D-HAEC). RT-qPCR, immunoblotting, chromatin immunoprecipitation (ChIP-qPCR), and confocal microscopy were performed to investigate the role of H3K27me3. We determined superoxide anion (O2-) production by ESR spectroscopy, NF-κB binding activity, and monocyte adhesion. Silencing/overexpression and pharmacological inhibition of chromatin modifying enzymes were used to modulate H3K27me3 levels. Furthermore, isometric tension studies and immunohistochemistry were performed in aorta from wild-type and db/db mice. RESULTS: Incubation of HAEC to high glucose showed that upregulation of EZH2 coupled to reduced demethylase UTX and JMJD3 was responsible for the increased H3K27me3. ChIP-qPCR revealed that repressive H3K27me3 binding to superoxide dismutase and transcription factor JunD promoters is involved in glucose-induced O2- generation. Indeed, loss of JunD transcriptional inhibition favours NOX4 expression. Furthermore, H3K27me3-driven oxidative stress increased NF-κB p65 activity and downstream inflammatory genes. Interestingly, EZH2 inhibitor GSK126 rescued these endothelial derangements by reducing H3K27me3. We also found that H3K27me3 epigenetic signature alters transcriptional programs in D-HAEC and aortas from db/db mice. CONCLUSIONS: EZH2-mediated H3K27me3 represents a key epigenetic driver of hyperglycemia-induced endothelial dysfunction. Targeting EZH2 may attenuate oxidative stress and inflammation and, hence, prevent vascular disease in diabetes.

Bariatric Surgery Improves Serum CD40L Levels as a Predictor of Cardiovascular Risk: Systematic Review and Meta-analysis.

CD40 and its ligand have been recently implicated in the pathogenesis of cardiovascular disease (CVD). This meta-analysis examined the effect of bariatric surgery in reducing circulating CD40L levels. A systematic review was performed using Embase, Google Scholar, PubMed, Scopus, and Web of Science. The meta-analysis was provided by Comprehensive Meta-Analysis (CMA) V4 software. The overall effect size was detected by a random-effects meta-analysis and the leave-one-out approach. Random-effects meta-analysis of 7 studies including 191 subjects showed a significant reduction in CD40L after bariatric surgery (standardized mean difference (SMD), - 0.531; 95% CI, - 0.981, - 0.082; p = 0.021; I2, 87.00). Circulating levels of CD40L are decreased after bariatric surgery which may represent a mechanism for improvement of metabolic profile.

RNA interference-based therapies for atherosclerosis: Recent advances and future prospects.

Atherosclerosis represents a pathological state that affects the arterial system of the organism. This chronic, progressive condition is typified by the accumulation of atheroma within arterial walls. Modulation of RNA molecules through RNA-based therapies has expanded the range of therapeutic options available for neurodegenerative diseases, infectious diseases, cancer, and, more recently, cardiovascular disease (CVD). Presently, microRNAs and small interfering RNAs (siRNAs) are the most widely employed therapeutic strategies for targeting RNA molecules, and for regulating gene expression and protein production. Nevertheless, for these agents to be developed into effective medications, various obstacles must be overcome, including inadequate binding affinity, instability, challenges of delivering to the tissues, immunogenicity, and off-target toxicity. In this comprehensive review, we discuss in detail the current state of RNA interference (RNAi)-based therapies.

The protective effects of statins in traumatic brain injury.

Traumatic brain injury (TBI), often referred to as the "silent epidemic", is the most common cause of mortality and morbidity worldwide among all trauma-related injuries. It is associated with considerable personal, medical, and economic consequences. Although remarkable advances in therapeutic approaches have been made, current treatments and clinical management for TBI recovery still remain to be improved. One of the factors that may contribute to this gap is that existing therapies target only a single event or pathology. However, brain injury after TBI involves various pathological mechanisms, including inflammation, oxidative stress, blood-brain barrier (BBB) disruption, ionic disturbance, excitotoxicity, mitochondrial dysfunction, neuronal necrosis, and apoptosis. Statins have several beneficial pleiotropic effects (anti-excitotoxicity, anti-inflammatory, anti-oxidant, anti-thrombotic, immunomodulatory activity, endothelial and vasoactive properties) in addition to promoting angiogenesis, neurogenesis, and synaptogenesis in TBI. Supposedly, using agents such as statins that target numerous and diverse pathological mechanisms, may be more effective than a single-target approach in TBI management. The current review was undertaken to investigate and summarize the protective mechanisms of statins against TBI. The limitations of conducted studies and directions for future research on this potential therapeutic application of statins are also discussed.

Identification and analysis of the molecular targets of statins in colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer in the world. According to several types of research, statins may impact the development and treatment of CRC. This work aimed to use bioinformatics to discover the relationship between statin targets and differentially expressed genes (DEGs) in CRC patients and determine the possible molecular effect of statins on CRC suppression. We used CRC datasets from the GEO database to select CRC-related DEGs. DGIdb and STITCH databases were used to identify gene targets of subtypes of statin. Further, we identified the statin target of CRC DEGs hub genes by using a Venn diagram of CRC DEGs and statin targets. Funrich and enrichr databases were carried out for the KEGG pathway and gene ontology (GO) enrichment analysis, respectively. GSE74604 and GSE10950 were used to identify CRC DEGs. After analyzing datasets,1370 genes were identified as CRC DEGs, and 345 targets were found for statins. We found that 35 genes are CRC DEGs statin targets. We found that statin targets in CRC were enriched in the receptor and metallopeptidase activity for molecular function, cytoplasm and plasma membrane for cellular component, signal transduction, and cell communication for biological process genes were substantially enriched based on FunRich enrichment. Analysis of the KEGG pathways revealed that the overexpressed DEGs were enriched in the IL-17, PPAR, and Toll-like receptor signaling pathways. Finally, CCNB1, DNMT1, AURKB, RAC1, PPARGC1A, CDKN1A, CAV1, IL1B, and HSPD1 were identified as hub CRC DEGs statin targets. The genetic and molecular aspects of our findings reveal that statins might have a therapeutic effect on CRC.

Regulatory impact of statins on macrophage polarization: mechanistic and therapeutic implications.

Statins, also known as HMG-CoA reductase inhibitors, are widely prescribed drugs for the prevention and treatment of cardiovascular diseases. In addition to their lipid-lowering effects, these compounds have been found to possess immune-modulating properties. Macrophages, which are crucial phagocytic cells in the body, can be divided into two main subsets: M1 (proinflammatory) and M2 (anti-inflammatory). While there is evidence suggesting that statins exert an anti-inflammatory action on macrophages and promote their polarization towards the M2 subset, recent studies have identified the proinflammatory impact of statins on macrophages, leading to polarization towards the M1 subset. For example, statins have been shown to inhibit NF-κB activation to promote anti-inflammatory responses. On the other hand, statins can induce NFκB/AP-1 activation and increase IL-1ß secretion in macrophages to promote pro-inflammatory responses. This review aims to provide a comprehensive overview of both in vivo and in vitro studies that have investigated the effects of statins on macrophage polarization and inflammatory responses in various diseases. Furthermore, this review seeks to evaluate the underlying mechanisms involved in these effects. By summarizing the existing evidence, this review contributes to our understanding of the complex interactions between statins and macrophages in different disease contexts.

Clinical features, socioeconomic status, management, short and long-term outcomes of patients with acute myocardial infarction: Phase I results of PEACE MENA registry.

BACKGROUND: The Program for the Evaluation and Management of Cardiac Events in the Middle East and North Africa (PEACE MENA) is a prospective registry program in Arabian countries that involves in patients with acute myocardial infarction (AMI) or acute heart failure (AHF). METHODS: This prospective, multi-center, multi-country study is the first report of the baseline characteristics and outcomes of inpatients with AMI who were enrolled during the first 14-month recruitment phase. We report the clinical characteristics, socioeconomic, educational levels, and management, in-hospital, one month and one-year outcomes. RESULTS: Between April 2019 and June 2020, 1377 patients with AMI were enrolled (79.1% males) from 16 Arabian countries. The mean age (± SD) was 58 ± 12 years. Almost half of the population had a net income < $500/month, and 40% had limited education. Nearly half of the cohort had a history of diabetes mellitus, hypertension, or hypercholesterolemia; 53% had STEMI, and almost half (49.7%) underwent a primary percutaneous intervention (PCI) (lowest 4.5% and highest 100%). Thrombolytics were used by 36.2%. (Lowest 6.45% and highest (90.9%). No reperfusion occurred in 13.8% of patients (lowest was 0% and highest 72.7%).Primary PCI was performed less frequently in the lower income group vs. high income group (26.3% vs. 54.7%; P<0.001). Recurrent ischemia occurred more frequently in the low-income group (10.9% vs. 7%; P = 0.018). Re-admission occurred in 9% at 1 month and 30% at 1 year, whereas 1-month mortality was 0.7% and 1-year mortality 4.7%. CONCLUSION: In the MENA region, patients with AMI present at a young age and have a high burden of cardiac risk factors. Most of the patients in the registry have a low income and low educational status. There is heterogeneity among key performance indicators of AMI management among various Arabian countries.

The Effect of Beta-Blocker Post-Myocardial Infarction With Ejection Fraction >40% Pooled Analysis From Seven Arabian Gulf Acute Coronary Syndrome Registries.

The use of beta-blockers (BB) in reduced left ventricular ejection fraction (LVEF) post-myocardial infarction (MI) is associated with reduced 1-year mortality, while their role in patients with mid-range and preserved LVEF post-MI remains controversial. We studied 31,620 patients who presented with acute coronary syndrome (ACS) enrolled in seven Arabian Gulf registries between 2005 and 2017. Patients with LVEF ≤40% were excluded. The remaining cohort was divided into two groups: BB group (n = 15,541) and non-BB group (n = 2,798), based on discharge medications. Patients in the non-BB group were relatively younger (55.3 vs. 57.4, P = .004) but higher risk at presentation; with higher Global Registry of Acute Coronary Events (GRACE) score (119.2 vs 109.2, P < .001), higher percentage of cardiogenic shock (3.5 vs 1.4%, P < .001), despite lower prevalence of comorbidities, such as hypertension and hyperlipidemia. BB use was associated with lower 1-year mortality in a multivariate logistic regression analysis, adjusting for major confounders [adjusted odds ratio (OR): 0.71 (95% CI 0.51-0.99)]. This remained the case in a sensitivity analysis using propensity score matching [adjusted OR: 0.34 (95% CI 0.16-0.73)]. In this study, using Arabian Gulf countries registries, the use of BB after ACS with LVEF >40% was independently associated with lower 1-year mortality.

Does Gender Affect the Outcomes of Myocardial Revascularization for Left-Main Coronary Artery Disease?

Currently, gender is not considered in the choice of the revascularization strategy for patients with unprotected left main coronary artery (ULMCA) disease. This study analyzed the effect of gender on the outcomes of percutaneous coronary intervention (PCI) vs coronary artery bypass grafting (CABG) in patients with ULMCA disease. Females who had PCI (n = 328) were compared with females who had CABG (n = 132) and PCI in males (n = 894) was compared with CABG (n = 784). Females with CABG had higher overall hospital mortality and major adverse cardiovascular events (MACE) than females with PCI. Male patients with CABG had higher MACE; however, mortality did not differ between males with CABG vs PCI. In female patients, follow-up mortality was significantly higher in CABG patients, and target lesion revascularization was higher in patients with PCI. Male patients had no difference in mortality and MACE between groups; however, MI was higher with CABG, and congestive heart failure was higher with PCI. In conclusion, women with ULMCA disease treated with PCI could have better survival with lower MACE compared with CABG. These differences were not evident in males treated with either CABG or PCI. PCI could be the preferred revascularization strategy in women with ULMCA disease.