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Sirtuins, as NAD + -dependent deacetylases, are widely found in eubacteria, archaea, and eukaryotes, and they play key roles in regulating cellular functions. Among these, SIRT7 stands out as a member discovered relatively late and studied less extensively. It is localized within the nucleus and displays enzymatic activity as an NAD + -dependent deacetylase, targeting a diverse array of acyl groups. The role of SIRT7 in important cellular processes like gene transcription, cellular metabolism, cellular stress responses, and DNA damage repair has been documented in a number of studies conducted recently. These studies have also highlighted SIRT7's strong correlation with human diseases like aging, cancer, neurological disorders, and cardiovascular diseases. In addition, a variety of inhibitors against SIRT7 have been reported, indicating that targeting SIRT7 may be a promising strategy for inhibiting tumor growth. The purpose of this review is to thoroughly look into the structure and function of SIRT7 and to explore its potential value in clinical applications, offering an essential reference for research in related domains., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Microtubules, complex cytoskeletal structures composed of tubulin proteins in eukaryotic cells, have garnered recent attention in cardiovascular research. Investigations have focused on the post-translational modifications of tubulin, including acetylation and detyrosination. Perturbations in microtubule homeostasis have been implicated in various pathological processes associated with cardiovascular diseases such as heart failure, ischemic heart disease, and arrhythmias. Thus, elucidating the intricate interplay between microtubule dynamics and cardiovascular pathophysiology is imperative for advancing preventive and therapeutic strategies. Several natural compounds have been identified to potentially modulate microtubules, thereby exerting regulatory effects on cardiovascular diseases. This review synthesizes current literature to delineate the roles of microtubules in cardiovascular diseases and assesses the potential of natural compounds in microtubule-targeted therapies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cardiovascular diseases as a primary driver of global morbidity and mortality. Despite the array of therapeutic avenues in clinical practice, predominantly pharmaceutical and surgical interventions, they often fall short of fully addressing the clinical exigencies of cardiovascular patients. In recent years, nanocarriers have shown great potential in the treatment and diagnose of cardiovascular diseases. They can enhance drug targeting and bioavailability while reducing side effects. Additionally, by improving imaging and detection technologies, they enhance early diagnosis and disease monitoring capabilities. These advancements in technology offer new solutions for precision medicine in cardiovascular diseases, advancing treatment efficacy and disease management. Crafted from biomaterials, metals, or their amalgamations, these nanocarriers approximate the dimensions of biologically active molecules like proteins and DNA. Cardiovascular nanomedicine, in its infancy, has only recently burgeoned. Yet, with continual refinement in nanocarrier architecture, drug delivery mechanisms, and therapeutic outcomes, the potential of nanomedical technologies in clinical contexts becomes increasingly evident. This review aims to consolidate the strides made in nanocarrier research concerning the treatment and diagnose of cardiovascular diseases., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cardiovascular diseases (CVDs) have a complex pathogenesis and pose a major threat to human health. Cardiomyocytes have a low regenerative capacity, and their death is a key factor in the morbidity and mortality of many CVDs. Cardiomyocyte death can be regulated by specific signaling pathways known as programmed cell death (PCD), including apoptosis, necroptosis, autophagy, pyroptosis, and ferroptosis, etc. Abnormalities in PCD can lead to the development of a variety of cardiovascular diseases, and there are also molecular-level interconnections between different PCD pathways under the same cardiovascular disease model. Currently, the link between programmed cell death in cardiomyocytes and cardiovascular disease is not fully understood. This review describes the molecular mechanisms of programmed death and the impact of cardiomyocyte death on cardiovascular disease development. Emphasis is placed on a summary of drugs and potential therapeutic approaches that can be used to treat cardiovascular disease by targeting and blocking programmed cell death in cardiomyocytes., Competing Interests: Declaration of Competing Interest I'd like to declare on behalf of my co-author that the work described was original research that has not been published previously and is not under consideration for publication elsewhere, in whole or in part. No conflict of interest exists in the submission of this manuscript, and all the authors listed have approved the manuscript that is closed., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The global incidence of cardiac diseases is increasing, imposing a substantial socioeconomic burden on healthcare systems. The pathogenesis of cardiovascular disease is complex and not fully understood, and the physiological function of the heart is inextricably linked to well-regulated cardiac muscle movement. Myosin light chain kinase (MLCK) is essential for myocardial contraction and diastole, cardiac electrophysiological homeostasis, vasoconstriction of vascular nerves and blood pressure regulation. In this sense, MLCK appears to be an attractive therapeutic target for cardiac diseases. MLCK participates in myocardial cell movement and migration through diverse pathways, including regulation of calcium homeostasis, activation of myosin light chain phosphorylation, and stimulation of vascular smooth muscle cell contraction or relaxation. Recently, phosphorylation of myosin light chains has been shown to be closely associated with the activation of myocardial exercise signaling, and MLCK mediates systolic and diastolic functions of the heart through the interaction of myosin thick filaments and actin thin filaments. It works by upholding the integrity of the cytoskeleton, modifying the conformation of the myosin head, and modulating innervation. MLCK governs vasoconstriction and diastolic function and is associated with the activation of adrenergic and sympathetic nervous systems, extracellular transport, endothelial permeability, and the regulation of nitric oxide and angiotensin II. Additionally, MLCK plays a crucial role in the process of cardiac aging. Multiple natural products/phytochemicals and chemical compounds, such as quercetin, cyclosporin, and ML-7 hydrochloride, have been shown to regulate cardiomyocyte MLCK. The MLCK-modifying capacity of these compounds should be considered in designing novel therapeutic agents. This review summarizes the mechanism of action of MLCK in the cardiovascular system and the therapeutic potential of reported chemical compounds in cardiac diseases by modifying MLCK processes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Transfer RNA-derived small RNAs (tsRNAs) are a class of small non-coding RNA (sncRNA) molecules derived from tRNA, including tRNA derived fragments (tRFs) and tRNA halfs (tiRNAs). tsRNAs can affect cell functions by participating in gene expression regulation, translation regulation, intercellular signal transduction, and immune response. They have been shown to play an important role in various human diseases, including cardiovascular diseases (CVDs). Targeted regulation of tsRNAs expression can affect the progression of CVDs. The tsRNAs induced by pathological conditions can be detected when released into the extracellular, giving them enormous potential as disease biomarkers. Here, we review the biogenesis, degradation process and related functional mechanisms of tsRNAs, and discuss the research progress and application prospects of tsRNAs in different CVDs, to provide a new perspective on the treatment of CVDs., Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for weight management require frequent dose titration, patient education, and insurance coverage navigation, which pharmacists are well equipped to manage. Data are lacking regarding the benefit of a pharmacist-managed service using GLP-1 RAs for weight loss in a high-risk cardiac population., Objective: This study aimed to evaluate the impact of a pharmacist-led weight loss service within a cardiology clinic using GLP-1 RAs and lifestyle counseling in patients with overweight and obesity., Practice Description: An outpatient cardiology clinic employs clinical pharmacists who use collaborative practice agreements to provide cardiovascular risk reduction services that did not include weight management at baseline., Practice Innovation: This is the first description of a pharmacist-led weight management clinic using solely GLP-1 RAs in a cardiology practice. Patients were referred to the clinical pharmacist, who initiated and titrated GLP-1 RA and provided lifestyle counseling., Evaluation Methods: This was a single-center, prospective, pre-post analysis of adults with a body mass index of at least 30 kg/m 2 or 27 kg/m 2 with a weight-related comorbidity, with a preceding failed dietary effort and insurance coverage for semaglutide (Wegovy, Novo Nordisk) or liraglutide (Saxenda, Novo Nordisk) and managed by a pharmacist. The primary outcome was patients achieving ≥ 5% weight loss at 6 months, assessed via descriptive statistics., Results: Between March 2022 and March 2023, 204 patients were referred by their cardiologist, and 59 patients started treatment with semaglutide (Wegovy, Novo Nordisk) or liraglutide (Saxenda, Novo Nordisk). A total of 31 patients completed 6 months of treatment at time of study completion, and all achieved ≥ 5% weight loss at 6 months, with a mean weight loss of 12.6%. Glycated hemoglobin improved by 0.6%, low-density lipoprotein by 18 mg/dL, triglycerides by 29 mg/dL, systolic blood pressure by 9 mm Hg, and diastolic blood pressure by 2 mm Hg., Conclusion: Pharmacist-led management of GLP-1 RA in patients with obesity or overweight led to clinically meaningful weight loss and improvements in weight-related comorbidities., Competing Interests: Disclosure The authors declare no relevant conflicts of interest or financial relationships., (Copyright © 2023 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: The ODYSSEY OUTCOMES trial (NCT01663402) compared the effects of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo on major adverse cardiovascular events (MACE) in patients with recent acute coronary syndrome (ACS)., Objective: We assessed efficacy and safety of alirocumab versus placebo according to sex and lipoprotein(a) level., Methods: This prespecified analysis compared the effects of alirocumab versus placebo on lipoproteins, MACE (coronary heart disease death, non-fatal myocardial infarction, fatal/non-fatal ischemic stroke, unstable angina requiring hospitalization), death, total cardiovascular events, and adverse events in 4762 women and 14,162 men followed for a median of 2.8 years. In post-hoc analysis, we evaluated total cardiovascular events according to sex, baseline lipoprotein(a), and treatment., Results: Women were older, had higher baseline low-density lipoprotein cholesterol (LDL-C) levels (89.6 vs 85.3 mg/dL) and lipoprotein(a) (28.0 vs 19.3 mg/dL) and had more co-morbidities than men. At 4 months, alirocumab lowered LDL-C by 49.4 mg/dL in women and 54.0 mg/dL in men and lipoprotein(a) by 9.7 and 8.1 mg/dL, respectively (both p < 0.0001). Alirocumab reduced MACE, death, and total cardiovascular events similarly in both sexes. In the placebo group, lipoprotein(a) was a risk factor for total cardiovascular events in women and men. In both sexes, reduction of total cardiovascular events was greater at higher baseline lipoprotein(a), but this effect was more evident in women than men (p interaction =0.08). Medication adherence and adverse event rates were similar in both sexes., Conclusions: Alirocumab improves cardiovascular outcomes after ACS irrespective of sex. Reduction of total cardiovascular events was greater at higher baseline lipoprotein(a)., Competing Interests: Declaration of competing interest Vera A. Bittner reports grant support from Sanofi, Regeneron Pharmaceuticals, Amgen, Astra Zeneca, DalCor, Esperion, and Novartis; consulting fees from Pfizer; honoraria from Medscape; and fees for participating on Data Safety Monitoring Boards for the National Institutes of Health and for Verve Therapeutics. Gregory G. Schwartz reports research support (all paid to institution) from Sanofi; grants or contracts from AstraZeneca, Resverlogix, Silence Therapeutics, and The Medicines Company/Novartis (all paid to institution); support for attending meetings from University of Oxford, American Society of Preventive Cardiology, and Cardiovascular Clinical Trialists; and receipt of medical writing support from Novartis. Deepak L. Bhatt discloses the following relationships - Advisory Board: AngioWave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, Stasys; Board of Directors: AngioWave (stock options), Boston VA Research Institute, Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock), Society of Cardiovascular Patient Care, TobeSoft; Chair: Inaugural Chair, American Heart Association Quality Oversight Committee; Consultant: Broadview Ventures; Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute; Rutgers University (for the NIH-funded MINT Trial); Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today's Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees), Wiley (steering committee); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned to Lexicon; neither I nor Brigham and Women's Hospital receive any income from this patent); Research Funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, 89Bio; Royalties: Elsevier (Editor, Braunwald's Heart Disease); Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions; Trustee: American College of Cardiology; Unfunded Research: FlowCo, Takeda. Terrance Chua reports research grants from Sanofi. Asita De Silva reports no disclosures. Rafael Diaz reports research grants from Sanofi, DalCor Pharmaceuticals, Population Health Research Institute, Duke Clinical Research Institute, the TIMI group, Amgen, Cirius, Montreal Health Innovations Coordinating Center, and Lepetit; and personal fees, as a member of the Executive Steering Committee, from Amgen and Cirius. Genevieve Garon is an employee of Sanofi and may hold shares and/or stock options in the company. Shaun G. Goodman reports research grant support (e.g., steering committee or data and safety monitoring committee) and/or speaker/consulting honoraria (e.g., advisory boards) from: Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, Daiichi-Sankyo/American Regent, Eli Lilly, Esperion, Ferring Pharmaceuticals, GlaxoSmithKline, HLS Therapeutics, JAMP Pharma, Janssen/Johnson & Johnson, Merck, Novartis, Novo Nordisk A/C, Pendopharm, Pfizer, Regeneron, Sanofi, Servier, Valeo Pharma; and salary support/honoraria from the Heart and Stroke Foundation of Ontario/University of Toronto (Polo) Chair, Canadian Heart Research center and MD Primer, Canadian VIGOUR Centre, Cleveland Clinic Coordinating center for Clinical Research, Duke Clinical Research Institute, New York University Clinical Coordinating center, and PERFUSE Research Institute. Robert A. Harrington reports research grants from the Patient-Centered Outcomes Research Institute, National Institutes of Health, CSL and Janssen; consulting for Atropos Health, Bitterroot Bio, Bridge Bio, Bristol Myers Squibb, Foresight, Element science; and serving on the boards of directors for the American Heart Association (unpaid) and Cytokinetics. J. Wouter Jukema reports research grants from the Netherlands Heart Foundation, the Interuniversity Cardiology Institute of the Netherlands, and the European Commission Seventh Framework Programme; and research support from Amgen, Astellas, AstraZeneca, Daiichi- Sankyo, Lilly, Merck-Schering-Plough, Pfizer, Roche, and Sanofi. Jennifer McGinniss is an employee of Regeneron Pharmaceuticals, Inc. and holds share options in the company. Robert Pordy is an employee of Regeneron Pharmaceuticals, Inc., and may hold shares and/or stock options in the company. Michel Scemama is an employee of Sanofi may hold shares and/or stock options in the company. Harvey D. White reports grant support paid to the institution for serving on a Steering Committee for the ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) from Sanofi-Aventis and Regeneron Pharmaceuticals, for the ACCELERATE study (A Study of Evacetrapib in High-Risk Vascular Disease) from Eli Lilly and Company, for the STRENGTH trial (Outcomes Study to Assess Statin Residual Risk Reduction With EpaNova in High CV Risk Patients With Hypertriglyceridemia) from Omthera Pharmaceuticals, for the CAMELLIA-TIMI study (A Study to Evaluate the Effect of Long-term Treatment With BELVIQ [Lorcaserin HC] on the Incidence of Major Adverse Cardiovascular Events and Conversion to Type 2 Diabetes Mellitus in Obese and Overweight Subjects With Cardiovascular Disease or Multiple Cardiovascular Risk Factors) from Eisai Inc, for the HEART-FID study (Randomized Placebo-Controlled Trial of FCM as Treatment for Heart Failure With Iron Deficiency) from American Regent, and for the ISCHEMIA Trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) and the MINT Trial (Myocardial Ischemia and Transfusion) from the National Institutes of Health USA. He also received grants to the institution and personal fees as Steering Committee member for the dal-GenE study (Effect of Dalcetrapib vs Placebo on CV Risk in a Genetically Defined Population With a Recent ACS) from DalCor Pharma UK Inc, for the AEGIS-II study (The Safety and Tolerability of CSL112, a Reconstituted, Infusible, Plasma-Derived Human ApoA-I, After Acute Myocardial Infarction: The ApoA-I Event reducinG in Ischemic Syndromes I) from CSL Behring, for the SCORED trial (Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients With Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk) and the SOLOIST-WHF trial (Effect of Sotagliflozin on Cardiovascular Events in Patients With Type2 Diabetes Post Worsening Heart Failure) from Sanofi-Aventis Australia Pty Ltd, and for the CLEAR Outcomes Study (Evaluation of Major Cardiovascular Events in Patients With, or at High Risk for, Cardiovascular Disease Who Are Statin Intolerant Treated With Bempedoic Acid [ETC-1002] or Placebo) from Esperion Therapeutics Inc. Dr White was on the Advisory Boards for CSL Behring and Genentech, Inc. (an affiliate of F. Hoffmann-La Roche Ltd, “Roche”; Lytics Post-PCI Advisory Board at European Society of Cardiology. Ph. Gabriel Steg reports grants, personal fees, and non-financial support from Sanofi; grants and personal fees from Amarin, Servier and Bayer; personal fees from Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Idorsia, Pfizer, and Novartis. In addition, Dr Steg has a patent use of alirocumab to reduce risk after ACS (royalties to Sanofi) pending. Michael Szarek reports serving as a consultant or on advisory boards (or both) for CiVi, Resverlogix, Baxter, Esperion, Sanofi, and Regeneron Pharmaceuticals, Inc., (Copyright © 2024. Published by Elsevier Inc.)

Flavonoids derived from plants offer a broad spectrum of therapeutic potential for addressing metabolic syndrome, particularly diabetes mellitus (DM), a prevalent non-communicable disease. Hyperglycemia in DM is a known risk factor for cardiovascular diseases (CVDs), which substantially impact global mortality rates. This review examines the potential effects of naringin, a citrus flavonoid, on both DM and its associated cardiovascular complications, including conditions like diabetic cardiomyopathy. The safety profile of naringin is summarized based on various pre-clinical studies. The data for this review was gathered from diverse electronic databases, including Medline, PubMed, ScienceDirect, SpringerLink, Google Scholar, and Emerald Insight. Multiple pre-clinical studies have demonstrated that naringin exerts hypoglycemic and cardioprotective effects by targeting various vascular mechanisms. Specifically, research indicates that naringin down-regulates the renin-angiotensin and oxidative stress systems while concurrently upregulating β-cell and immune system functions. Clinical trial outcomes also support the therapeutic potential of naringin in managing hyperglycemic states and associated cardiovascular issues. Moreover, toxicity studies have confirmed the safety of naringin in animal models, suggesting its potential for safe administration in humans. In conclusion, naringin emerges as a promising natural candidate for both antidiabetic and cardioprotective purposes, offering potential improvements in health outcomes. While naringin presents a new avenue for therapies targeting DM and CVDs, additional controlled and long-term clinical trials are necessary to validate its efficacy and safety for human use., Competing Interests: Declaration of competing interest The authors state that they have no known competing interests that could have appeared to influence the work recognized in this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been pivotal in the management of type 2 diabetes mellitus (T2DM) and in the reduction of major adverse cardiovascular events (MACE). Notably, large cardiovascular outcomes trials (CVOTs) demonstrate significant disparities in inclusion, based on sex, race, ethnicity, and geographical regions., Objectives: We examined the impact of GLP-1RA on MACE in patients with or without T2DM, based on sex, race, ethnicity, and geography., Methods: A literature search for placebo controlled randomized controlled trials on GLP-1RA treatment was conducted. Thorough data extraction and quality assessment were carried out, focusing on key outcome, and ensuring a robust statistical analysis using a random effects model to calculate log odds ratio (OR) with 95% confidence intervals (CIs)., Results: A total of 8 CVOTs comprising 71,616 patients were included. Compared with placebo, GLP-1RAs significantly reduced MACE in both sexes (females: logOR -0.19, (95% CI, -0.28 to -0.10), p < 0.01) versus (males: logOR -0.17, (95% CI, -0.23 to -0.10), p < 0.01), (p interaction NS), and among Asians (logOR -34 (95% CI, -0.53 to -0.15), p < 0.01), and Whites (logOR -17 (95% CI, -0.25 to -0.09), p < 0.01), with no difference in MACE among Blacks and Hispanics. Odds of MACE were also reduced in Asia (logOR -31 (95% CI, -0.50 to -0.11), p < 0.01), and Europe (logOR -27 (95% CI, -0.40 to -0.13), p < 0.01), but there was no statistical difference in MACE in North America and Latin America., Conclusion: Significant reductions in MACE with GLP-1RA treatment were demonstrated between both sexes and across certain ethnicities and certain geographical regions., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest relevant to the content of this manuscript., (Copyright © 2024. Published by Elsevier Inc.)

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Hyperlipidemia, particularly elevated low-density lipoprotein cholesterol (LDL-C) is one of the major risk factors for CVD. Major landmark cardiovascular outcome clinical trials demonstrated that LDL-C lowering medications reduce cardiovascular events, and the lower the LDL-C the better the outcome. This article discusses the evolution of LDL-C lowering medications starting from bile acid sequestrants (BAS), statin therapy, bempedoic acid, the proprotein convertase subtilisin kexin 9 (PCSK9) synthesis inhibitor, novel small interfering RNA-based therapy (inclisiran) to the most recent oral PCSK9 inhibitors (MK-0616) which is currently under phase 3 clinical trial studies., Competing Interests: Declaration of competing interest All authors declare no conflict of interest. This manuscript is not under consideration elsewhere., (Copyright © 2024 Elsevier Inc. All rights reserved.)

DNA origami is a cutting-edge nanotechnology approach that creates precise and detailed 2D and 3D nanostructures. The crucial feature of DNA origami is how it is created, which enables precise control over its size and shape. Biocompatibility, targetability, programmability, and stability are further advantages that make it a potentially beneficial technique for a variety of applications. The preclinical studies of sophisticated programmable nanomedicines and nanodevices that can precisely respond to particular disease-associated triggers and microenvironments have been made possible by recent developments in DNA origami. These stimuli, which are endogenous to the targeted disorders, include protein upregulation, pH, redox status, and small chemicals. Oncology has traditionally been the focus of the majority of past and current research on this subject. Therefore, in this comprehensive review, we delve into the intricate world of DNA origami, exploring its defining features and capabilities. This review covers the fundamental characteristics of DNA origami, targeting DNA origami to cells, cellular uptake, and subcellular localization. Throughout the review, we emphasised on elucidating the imperative for such a therapeutic platform, especially in addressing the complexities of cardiovascular disease (CVD). Moreover, we explore the vast potential inherent in DNA origami technology, envisioning its promising role in the realm of CVD treatment and beyond., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cardiovascular diseases (CVDs) are known as life-threatening illnessescaused by severe abnormalities in the cardiovascular system. They are a leading cause of mortality and morbidity worldwide.Nanotechnology integrated substantialinnovations in cardiovascular diagnostic and therapeutic at the nanoscale. This in-depth analysis explores cutting-edge methods for diagnosing CVDs, including nanotechnological interventions and crucial components for identifying risk factors, developing treatment plans, and monitoring patients' progress with chronic CVDs.Intensive research has gone into making nano-carriers that can image and treat patients. To improve the efficiency of treating CVDs, the presentreview sheds light on a decision-tree-based solution by investigating recent and innovative approaches in CVD diagnosis by utilizing nanoparticles (NPs). Treatment choices for chronic diseases like CVD, whose etiology might take decades to manifest, are very condition-specific and disease-stage-based. Moreover, thisreview alsobenchmarks the changing landscape of employing NPs for targeted and better drug administration while examining the limitations of various NPs in CVD diagnosis, including cost, space, time, and complexity. To better understand and treatment of cardiovascular diseases, the conversation moves on to the nano-cardiovascular possibilities for medical research.We also focus on recent developments in nanoparticle applications, the ways they might be helpful, and the medical fields where they may find future use. Finally, this reviewadds to the continuing conversation on improved diagnosis and treatment approaches for cardiovascular disorders by discussing the obstacles and highlighting the revolutionary effects of nanotechnology., Competing Interests: Declaration of competing interest The authors declared that they have no competing interests among them., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The impact of mitochondrial dysfunction on the pathogenesis of cardiovascular disease is increasing. However, the precise underlying mechanism remains unclear. Mitochondria produce cellular energy through oxidative phosphorylation while regulating calcium homeostasis, cellular respiration, and the production of biosynthetic chemicals. Nevertheless, problems related to cardiac energy metabolism, defective mitochondrial proteins, mitophagy, and structural changes in mitochondrial membranes can cause cardiovascular diseases via mitochondrial dysfunction. Mitofilin is a critical inner mitochondrial membrane protein that maintains cristae structure and facilitates protein transport while linking the inner mitochondrial membrane, outer mitochondrial membrane, and mitochondrial DNA transcription. Researchers believe that mitofilin may be a therapeutic target for treating cardiovascular diseases, particularly cardiac mitochondrial dysfunctions. In this review, we highlight current findings regarding the role of mitofilin in the pathogenesis of cardiovascular diseases and potential therapeutic compounds targeting mitofilin., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Propolis is a resinous compound that is obtained from honey bees. It consists of numerous chemical constituents that impart different therapeutic action. The heart is the core of the body and cardiovascular disease (CVD) is a burden for the human being. This article emphasizes how propolis is fruitful in the management of various CVDs., Scope and Approach: This review focuses on how various constituents of the propolis (such as terpenes, flavonoids, phenolics, etc.) impart cardio protective actions., Key Finding and Conclusion: With the support of various clinical trials and research outcomes, it was concluded that propolis owns niche cardio protective properties that can be a boon for various cardiac problems (both in preventive and therapeutic action) such as atherosclerosis, excessive angiogenesis, hypertension, and many more., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cardiovascular diseases (CVDs) constitute a predominant cause of both global mortality and morbidity. To address the challenges in the early diagnosis and management of CVDs, there is growing interest in the field of nanotechnology and nanomaterials to develop innovative diagnostic and therapeutic approaches. This review focuses on the recent advancements in nanotechnology-based diagnostic techniques, including cardiac immunoassays (CIA), cardiac circulating biomarkers, cardiac exosomal biomarkers, and molecular Imaging (MOI). Moreover, the article delves into the exciting developments in nanoparticles (NPs), biomimetic NPs, nanofibers, nanogels, and nanopatchs for cardiovascular applications. And discuss how these nanoscale technologies can improve the precision, sensitivity, and speed of CVD diagnosis and management. While highlighting their vast potential, we also address the limitations and challenges that must be overcome to harness these innovations successfully. Furthermore, this review focuses on the emerging opportunities for personalized and effective cardiovascular care through the integration of nanotechnology, ultimately aiming to reduce the global burden of CVDs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Aims: Inclisiran, an siRNA therapy, consistently reduces low-density lipoprotein cholesterol (LDL-C) with twice-yearly dosing. Potential cardiovascular benefits of implementing inclisiran at a population level, added to statins, were evaluated through simulation., Methods: For each participant in the ORION-10 and ORION-11 trials comparing inclisiran with placebo, baseline 10-year cardiovascular risk was estimated using the SMART equation. The time-adjusted LDL-C difference from baseline observed 90-540 days after baseline was assumed to persist and used to estimate potential reduction in 10-year cardiovascular risk. Impact on 500,000 ORION-like individuals was simulated with Monte-Carlo., Results: Mean baseline LDL-C and predicted 10-year major vascular risk among patients randomized to inclisiran (n = 1288) versus placebo (n = 1264) were 2.66 mmol/L versus 2.60 mmol/L and 24.9% versus 24.6%, respectively. Placebo-corrected time-adjusted absolute reduction in LDL-C with inclisiran was -1.32 mmol/L (95% CI -1.37 to -1.26; p < 0.001), which predicted a 10-year cardiovascular risk of 18.1% with inclisiran versus 24.7% with placebo (absolute difference [95% CI], -6.99% [-7.33 to -6.66]; p < 0.001) NNT 15. Extrapolating to 500,000 inclisiran-treated individuals, the model predicted large population shifts towards lower quintiles of risk with fewer remaining in high-risk categories; 3350 to 471 (≥80% risk), 11,793 to 3332 (60-<80% risk), 52,142 to 22,665 (40-<60% risk), 197,752 to 141,014 (20-<40% risk), and more moving into the lowest risk category (<20%) from 234,963 to 332,518., Conclusions: Meaningful gains in population health might be achieved over 10 years by implementing at-scale approaches capable of providing substantial and sustained reductions in LDL-C beyond those achievable with statins., Competing Interests: Declaration of competing interest Kausik K. Ray reports unrestricted research grants to Imperial College London from Amgen, Daiichi Sankyo, Regeneron, Sanofi, and SC, EC or advisory board honoraria from Novartis, Esperion, Daiichi Sankyo, Abbott, Bayer, Eli Lilly, Silence Therapeutics, CSL Behring, New Amsterdam Pharma, Sanofi, Amgen, Novo Nordisk, BI, Scribe, Vaxxinity, CRISPR, AZ, Kowa, and Cargene, honoraria for CME and non-CME from Novartis, Novo Nordisk, BI, AZ, Viatris, Daiichi Sankyo, Amgen, and Sanofi, and stock options from PEMI-31; Laura H. Gunn has no conflict of interests to declare; Lorena Garcia Conde is an employee of Novartis; Frederick J. Raal reports receiving advisory board fees and lecture fees from Amgen, Sanofi-Aventis, Regeneron Pharmaceuticals, The Medicines Company, and Novartis; R. Scott Wright reports receiving advisory board fees from Boehringer Ingelheim and past fees for consulting on lipid issues with The Medicines Company; Nathalie H. Gosselin is an employee of Certara, consulting division; Lawrence A. Leiter reports grant support paid to his institution, advisory board fees, and fees for CME from Amgen and Novartis, fees for serving on a steering committee, and advisory board fees from Esperion, grant support paid to his institution, and fees for serving on a steering committee from Kowa, The Medicines Company, and Novartis; advisory board fees and fees for CME from Amarin, Astra Zeneca, HLS, Merck, Pfizer, and Sanofi; Wolfgang Koenig reports receiving consulting fees and lecture fees from AstraZeneca, Novartis, and Amgen, consulting fees from Pfizer, The Medicines Company, Novartis, DalCor Pharmaceuticals, Kowa, Corvidia Therapeutics, Esperion, Genentech, OMEICOS, Novo Nordisk, LIB Therapeutics, New Amsterdam Pharma, TenSixteen Bio, and Daiichi Sankyo, lecture fees from Berlin-Chemie, Bristol-Myers Squibb, and Sanofi, and grant support and provision of reagents from Singulex, Abbott, Roche Diagnostics, and Dr Beckmann Pharma; Gregory G. Schwartz reports receiving research support, paid to his institution from AstraZeneca, Resverlogix, Sanofi, Silence Therapeutics, and The Medicines Company, and a patent (62/806313) on a method for reducing cardiovascular risk assigned in full to the University of Colorado; Ulf Landmesser reports receiving lecture fees and advisory fees from AstraZeneca, Amgen, Sanofi, Berlin Chemie, and Abbott, advisory fees from The Medicines Company, and grant support, lecture fees, and advisory fees from Bayer and Novartis., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Statins are the leading lipid-lowering drugs, reducing blood cholesterol by controlling its synthesis. Side effects are linked to the use of statins, in particular statin-associated muscle symptoms (SAMS). Some data suggest that vitamin D supplementation could reduce SAMS., Objective: The purpose of this study was to evaluate the potential benefits of vitamin D supplementation in a randomized controlled trial., Methods: Men (n = 23) and women (n = 15) (50.5 ± 7.7 years [mean ± SD]) in primary cardiovascular prevention, self-reporting or not SAMS, were recruited. Following 2 months of statin withdrawal, patients were randomized to supplementation (vitamin D or placebo). After 1 month of supplementation, statins were reintroduced. Before and 2 months after drug reintroduction, muscle damage (creatine kinase and myoglobin) was measured. Force (F), endurance (E) and power (P) of the leg extensors (ext) and flexors (fle) and handgrip strength (FHG) were also measured with isokinetic and handheld dynamometers, respectively. The Short Form 36 Health Survey (SF-36) questionnaire and a visual analog scale (VAS) were administrated to assess participants' self-reported health-related quality of life and SAMS intensity, respectively. Repeated-measures analysis was used to investigate the effects of time, supplementation, and their interaction, according to the presence of SAMS., Results: Despite no change for objective measures, subjective measures worsened after reintroduction of statins, independent of supplementation (VAS, SF-36 mental component score, all p < 0.05). However, no interaction between time and supplementation according to the presence of SAMS was observed for any variables., Conclusions: Vitamin D supplementation does not appear to mitigate SAMS., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023. Published by Elsevier Inc.)

Marine-based dietary oils (MDOs), which are naturally obtained from different sources, have been scientifically recommended as potent functional bioactives owing to their therapeutic biological activities; however, they have exhibited plenty of health benefits. Though they are very sensitive to light, temperature, moisture, and oxygen, as well as being chemically unstable and merely oxidized, this may limit their utilization in food and pharmaceutical products. Miro- and nanoencapsulation techniques are considered to be the most promising tactics for enhancing the original characteristics, physiochemical properties, and therapeutic effects of entrapped MDOs. This review focuses on the biomacromolecule-stabilized micro/nanocarriers encompassing a wide range of MDOs. The novel-equipped polysaccharides and protein-based micro/nanocarriers cover microemulsions, microcapsules, nanoemulsions, and nanoliposomes, which have been proven to be encouraging candidates for the entrapment of diverse kinds of MDOs. In addition, the current state-of-the-art loading of various MDOs through polysaccharide and protein-based micro/nanocarriers has been comprehensively discussed and tabulated in detail. Biomacromolecule-stabilized nanocarriers, particularly nanoemulsions and nanoliposomes, are addressed as propitious nanocargos for protection of MDOs in response to thought-provoking features as well as delivering the successful, meticulous release to the desired sites. Gastrointestinal fate (GF) of biopolymeric micro/nanocarriers is fundamentally based on their centrifugation, dimension, interfacial, and physical properties. The external surface of epithelial cells in the lumen is the main site where the absorption of lipid-based nanoparticles takes place. MDO-loaded micro- and nanocarriers with biological origins or structural modifications have shown some novel applications that could be used as future therapies for cardiovascular disorders, thanks to today's cutting-edge medical technology. In the future, further investigations are highly needed to open new horizons regarding the application of polysaccharide and protein-based micro/nanocarriers in food and beverage products with the possibility of commercialization in the near future for industrial use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Blood cholesterol has firmly been established as a crucial risk factor for the development of atherosclerotic cardiovascular disease (ASCVD) by elegant epidemiological studies. Naturally, means to reduce blood cholesterol level took the centerstage of research in this field. After initial lukewarm results with nicotinic acid, fibrates and some other agents, statins emerged as the most effective class of medicine to reduce blood cholesterol; in particular, the most atherogenic low density lipoprotein cholesterol (LDL-C). Also, they are very safe and well tolerated. As ASCVD comes in various stages, statins have also been tried in different settings, e.g., primary prevention, secondary prevention, as part of coronary intervention strategy, familial hypercholesterolemia, etc. Almost in all clinical scenarios, statins proved themselves to impart clinical benefit. Though side effects of statins are outweighed by their benefits, nonetheless clinicians should detect the side effects early to avoid major problems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financialinterests or personal relationships that could have appeared to influencethe work reported in this paper., (Copyright © 2023 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Cardiovascular disease (CVD) remains the leading cause of death and disability worldwide. While many factors can contribute to CVD, atherosclerosis is the cardinal underlying pathology, and its development is associated with several metabolic risk factors including dyslipidemia and obesity. Recent studies have definitively demonstrated a link between low-grade systemic inflammation and two relevant metabolic abnormalities: hypercholesterolemia and obesity. Interestingly, both metabolic disorders are also associated with endothelial dysfunction/activation, a proinflammatory and prothrombotic phenotype of the endothelium that involves leukocyte infiltration into the arterial wall, one of the earliest stages of atherogenesis. This article reviews the current literature on the intricate relationship between hypercholesterolemia and obesity and the associated systemic inflammation and endothelial dysfunction, and discusses the effectiveness of present, emerging and in-development pharmacological therapies used to treat these metabolic disorders with a focus on their effects on the associated systemic inflammatory state and cardiovascular risk., Competing Interests: Declaration of Competing Interest No potential conflicts of interest relevant to this article were reported., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The management of LDL-C levels is pivotal in the prevention of cardiovascular morbidity, particularly among patients at high risk or those intolerant to statins. Bempedoic acid emerges as a novel agent in this therapeutic arena., Objectives: This systematic review and meta-analysis endeavor to quantify the effectiveness of Bempedoic acid in attenuating LDL-C levels and explore its impact on cardiovascular morbidity, emphasizing its role as an adjunctive or alternative therapy in statin-intolerant or high-risk patients., Methods: A comprehensive search spanning PubMed, Google Scholar, and Cochrane Library databases furnished studies for this review. The inclusion was critiqued based on predefined PICOS parameters, ensuring a robust analytical framework., Results: Bempedoic acid showcased a significant plunge in LDL-C levels (MD -20.69 %, 95 % CI [-23.20, -18.19]), outperforming placebo and ezetimibe monotherapy. The cardioprotective effect was further echoed with a reduced risk of major adverse cardiac events (MACE) in the Bempedoic acid cohort (RR 0.86, 95 % CI [0.80, 0.94]). However, a dive into the safety profile revealed no substantial augmentation in adverse events, affirming its tolerance and efficacy., Conclusions: Bempedoic acid represents a potent therapeutic ally, affirming its capacity to significantly pare down LDL-C levels and curtail cardiovascular events. Its favorable safety profile underscores its suitability, especially among those with statin intolerance or individuals categorized within the high-risk vascular bracket, necessitating a paradigm shift in current lipid management strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Bioinformatics is an interconnected subject of science dealing with diverse fields including biology, chemistry, physics, statistics, mathematics, and computer science as the key fields to answer complicated physiological problems. Key intention of bioinformatics is to store, analyze, organize, and retrieve essential information about genome, proteome, transcriptome, metabolome, as well as organisms to investigate the biological system along with its dynamics, if any. The outcome of bioinformatics depends on the type, quantity, and quality of the raw data provided and the algorithm employed to analyze the same. Despite several approved medicines available, cardiovascular disorders (CVDs) and cancers comprises of the two leading causes of human deaths. Understanding the unknown facts of both these non-communicable disorders is inevitable to discover new pathways, find new drug targets, and eventually newer drugs to combat them successfully. Since, all these goals involve complex investigation and handling of various types of macro- and small- molecules of the human body, bioinformatics plays a key role in such processes. Results from such investigation has direct human application and thus we call this filed as translational bioinformatics. Current book chapter thus deals with diverse scope and applications of this translational bioinformatics to find cure, diagnosis, and understanding the mechanisms of CVDs and cancers. Developing complex yet small or long algorithms to address such problems is very common in translational bioinformatics. Structure-based drug discovery or AI-guided invention of novel antibodies that too with super-high accuracy, speed, and involvement of considerably low amount of investment are some of the astonishing features of the translational bioinformatics and its applications in the fields of CVDs and cancers., (Copyright © 2024. Published by Elsevier Inc.)

Considering the worldwide mortality and morbidity of cardiovascular diseases (CVDs), the necessity of using multiple pills due to the chronicity of this condition, and the importance of medication adherence in these patients, we conducted this systematic review and meta-analysis to assess the polypill effect on adherence in patients with established CVD and at high risk. To accomplish this review, we searched various databases to access grey literature and several electronic databases to find randomized controlled trials (RCTs) assessing polypills compared to individual pills from January 2000 to October 2022. The outcomes were primarily medication adherence, secondarily systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C) serum level, and serious adverse events (SAEs). Ultimately, 2820 studies were detected and narrowed to 8 RCTs based on the eligibility criteria. In this study, involving 7364 patients, there was a significant improvement in medication adherence in the polypill group compared to the individual pills group (Risk Ratio [RR] = 1.29; [95%CI: 1.10; 1.50]). Out of secondary outcomes, SBP was significantly decreased (Mean Difference [MD] = -1.72 mmHg; [95%CI: -2.40; 1.03]), but LDL-C serum level (MD = -0.65 mg/dl; [95%CI: -4.47; 3.16]) and SAE (RR = 1.08; [95%CI: f0.98; 1.20]) did not have a notable difference in polypill compared to individual pills., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Hypertriglyceridemia is a type of dyslipidemia characterized by high triglyceride levels in the blood and increases the risk of cardiovascular disease. Conventional management includes antilipidemic medications such as statins, lowering LDL and triglyceride levels as well as raising HDL levels. However, the treatment may be stratified using omega-3 fatty acid supplements such as eicosatetraenoic acid (EPA) and docosahexaenoic acid (DHA), aka fish oil derivatives. Studies have shown that fish oil supplements reduce the risk of cardiovascular diseases; however, the underlying mechanism and the extent of reduction in CVD need more clarification. Our paper aims to review the clinical trials and observational studies in the current literature, investigating the use of fish oil and its benefits on the cardiovascular system as well as the proposed underlying mechanism., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Recent Food and Drug Administration approvals of glucagon-like peptide 1 (GLP-1) receptor agonists linked to substantial weight loss have generated interest in demand projections. However, a longitudinal analysis in a large, diverse, current, real-world database has not been published., Objectives: The study objective was to determine user frequency of GLP-1 receptor agonist products overall and by type 2 diabetes (T2D), cardiovascular disease (CVD), and overweight or obese status. Secondary objective was monthly growth rate estimation by product since first appearance in University of California Health., Methods: This retrospective cohort study included patients who were dispensed a GLP-1 receptor agonist from 2014 to 2022 in the University of California Health Data Warehouse. Exponential growth rates were estimated using a log-linear regression model., Results: Between 2014 and 2018, only Trulicity and Victoza exceeded 5000 annual users. Ozempic users increased from 569 in 2019 to 7667 in 2020. Use accelerated with more than 13,310 users in 2021 to surpass Trulicity. Ozempic count was 22,891 in 2022. Wegovy rose from 989 in 2021 to 2992 in 2022. Mounjaro increased to 1508 users in 2022. Although generally similar trends were observed for T2D, CVD, and overweight or obese subgroups, the ascent of Ozempic as most frequently used was more apparent in the overweight or obese group. The monthly growth rates were 83.9% for Ozempic, 119.2% for Wegovy, 84.8% for Rybelsus, 53.3% for Saxenda, 12.9% for Adlyxin, 78.8% for Trulicity, and 254.3% for Mounjaro., Conclusion: This first cohort study of weight loss-associated GLP-1 receptor agonists in a large, diverse, state-wide health system demonstrated a rapid increased use that represents a clear and likely durable transition in utilization for this category. Informed decision making and longitudinal studies are needed to ensure evidence-concordant prescribing and supply stability., Competing Interests: Disclosure The authors declare no relevant conflicts of interest or financial relationships., (Copyright © 2023 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Optimal medical therapy (OMT) in patients with coronary artery disease (CAD) and/or heart failure (HF) is underused despite the established benefits of these medications. Cardiac rehabilitation (CR) may be one place where OMT could be promoted. We sought to describe the prevalence and characteristics of OMT use in patients with CAD or HF undergoing CR. We included patients with CAD (myocardial infarction, percutaneous coronary intervention, coronary artery bypass grafting, angina) and HF enrolled in our CR program. For patients with CAD, we defined OMT to consist of aspirin or other antiplatelets, statins, and beta-blockers (BB). For patients with HF or EF ≤ 40%, OMT included BB, spironolactone, and either Angiotensin Converting Enzyme inhibitors (ACEi)/angiotensin receptor blockers or angiotensin receptor neprilysin inhibitor (ARNI). For CAD patients with normal EF, OMT also included ACEi/ARB/ARNI if they also had diabetes type 2. From January 2015 to December 2019, 828 patients were referred to CR and 743 attended. Among 612 patients (mean age: 65, 23% female) with CAD, 483 (79%) patients were on OMT. Of the 131 HF patients (mean age: 64, 21% female) enrolled in CR, only 23 (18%) met all 3 OMT criteria, whereas most patients were on only 1 (93 %) or 2 (76%) HF specific medications. Spironolactone was the least prescribed (22%) medication. Over the study period, we observed a steady increase in the use of ARNI (2015: 0% vs 2019: 27%, p < 0.01). Among the individuals, 69 patients experienced both CAD and HF, while only 7 patients were under OMT for both CAD and HF. Most patients attending CR with CAD are receiving OMT, but most patients with HF are not. Although OMT has improved over time, there remains room for improvement, particularly among patients with HF., Competing Interests: Declaration of Competing Interest The authors have no relevant conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The term "cardiovascular diseases" (CVD) refers to various ailments that affect the heart and blood vessels, including myocardial ischemia, congenital heart defects, heart failure, rheumatic heart disease, hypertension, peripheral artery disease, atherosclerosis, and cardiomyopathies. Despite significant breakthroughs in preventative measures and treatment choices, CVDs significantly contribute to morbidity and mortality, imposing a considerable financial burden. Oxidative stress (OS) is a fundamental contributor to the development and progression of CVDs, resulting from an inherent disparity in generating reactive oxygen species. The disparity above significantly contributes to the aberrant operation of the cardiovascular system. To tackle this issue, therapeutic intervention primarily emphasizes the nuclear erythroid 2-related factor 2 (Nrf2), a transcription factor crucial in regulating endogenous antioxidant defense systems against OS. The Nrf2 exhibits potential as a promising target for effectively managing CVDs. Significantly, an emerging field of study is around the utilization of natural substances to stimulate the activation of Nrf2, hence facilitating the promotion of cardioprotection. This technique introduces a new pathway for treating CVD. The substances above elicit their advantageous effects by mitigating the impact of OS via initiating Nrf2 signaling. The primary objective of our study is to provide significant insights that can contribute to advancing treatment methods, including natural products. These strategies aim to tackle the obstacles associated with CVDs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Bempedoic acid is an oral adenosine triphosphate citrate lyase (ACL) inhibitor that lowers low-density lipoprotein cholesterol (LDL-C) blood levels. The Cholesterol Lowering via Bempedoic acid, an ACL-Inhibiting Regimen (CLEAR) Outcomes study demonstrated that bempedoic acid reduced cardiovascular (CV) risk in patients at high risk for CV events who were unwilling or unable to take guideline-recommended doses of statins., Objective: To describe detailed safety information from CLEAR Outcomes, including events in the United States (US) prescribing information based on previous phase 3 hyperlipidemia studies., Methods: CLEAR Outcomes was a double-blind trial conducted in 13,970 patients randomized to oral bempedoic acid 180 mg daily or placebo and followed for a median of 3.4 years., Results: In patients who received at least one dose (7,001 bempedoic acid, 6,964 placebo), treatment emergent adverse events (AE) occurred in 86.3 % and 85 % of patients, respectively. COVID-19 was the most frequently reported AE in both groups. Changes in serum creatinine, blood urea nitrogen, hemoglobin, aminotransaminases, and uric acid were consistent with the known safety profile of bempedoic acid. Gout or gouty arthritis occurred in 3.2 % of bempedoic acid and 2.2 % of placebo patients. AE associated with tendinopathies, including tendon rupture, occurred in 2 % of patients in both treatment groups. Cholelithiasis occurred in 2.2 % of bempedoic acid and 1.2 % of placebo patients; AE related to gallbladder disease were similar between treatment groups., Conclusions: Bempedoic acid was well-tolerated compared with placebo. Safety data from the long-term CLEAR Outcomes study reinforce the positive benefit-risk profile of bempedoic acid., (Copyright © 2023. Published by Elsevier Inc.)

Cardiovascular diseases (CVDs) are considered as the leading cause of death worldwide. CVD continues to be a major cause of death and morbidity despite significant improvements in its detection and treatment. Therefore, it is strategically important to be able to precisely characterize an individual's sensitivity to certain illnesses. The discovery of genes linked to cardiovascular illnesses has benefited from linkage analysis and genome-wide association research. The last 20 years have seen significant advancements in the field of molecular genetics, particularly with the development of new tools like genome-wide association studies. In this article we explore the profound impact of genetic variations on disease development, prognosis, and therapeutic responses. And the significance of genetics in cardiovascular risk assessment and the ever-evolving realm of genetic testing, offering insights into the potential for personalized medicine in this domain. Embracing the future of cardiovascular care, the article explores the implications of pharmacogenomics for tailored treatments, the promise of emerging technologies in cardiovascular genetics and therapies, including the transformative influence of nanotechnology. Furthermore, it delves into the exciting frontiers of gene editing, such as CRISPR/Cas9, as a novel approach to combat cardiovascular diseases. And also explore the potential of stem cell therapy and regenerative medicine, providing a holistic view of the dynamic landscape of cardiovascular genomics and its transformative potential for the field of cardiovascular medicine., Competing Interests: Declaration of Competing Interest The author has indicated that they have no competing interests or conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Antiplatelet therapy plays a critical role in the prevention and treatment of major cardiovascular diseases triggered by thrombosis. Since the 1900s, significant progress in reducing morbidity and death caused by cardiovascular diseases has been made. However, despite the development and approval of drugs that specifically target the platelet, including inhibitors for cycloxygenase-1, P2Y 12 receptor, integrin αIIbβ3, phosphodiesterases, and protease-activated receptor 1, the risk of recurrent thrombotic events remains high, and the increased risk of bleeding is a major concern. Scientific advances in our understanding of the role of platelets in haemostasis and thrombosis have revealed novel targets, such as protease-activated receptor 4 (PAR4), glycoprotein Ib (GPIb)-V-IX complex, glycoprotein VI, and 12-lipoxygenase. The antithrombotic effects and safety of the pharmacologic inhibition of these targets are currently under investigation in clinical studies. This review provides an overview of drugs in early development to target the platelet and those in current use in clinical practice. Furthermore, it describes the emerging drug targets being developed and studied to reduce platelet activity and outlines potential novel therapeutic targets in the platelet., Competing Interests: Declaration of competing interests M.H. is a consultant and equity holder and consultant for Veralox therapeutics and Cereno Scientific. M.H. is an inventor and holds patents for ML355 and CS585. All other authors declare no competing interests for the work reported in this manuscript., (Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Despite the best pharmacologic tools available, cardiovascular diseases (CVDs) remain a major cause of morbidity and mortality in developed countries. After 2 decades of research, new therapeutic targets, such as angiopoietin-like proteins (ANGPTLs), are emerging. ANGPTLs belong to a family of 8 members, from ANGPTL1 to ANGPTL8; they have structural homology with angiopoietins and are secreted in the circulation. ANGPTLs display a multitude of physiological and pathologic functions; they contribute to inflammation, angiogenesis, cell death, senescence, hematopoiesis, and play a role in repair, maintenance, and tissue homeostasis. ANGPTLs-particularly the triad ANGPTL3, 4, and 8-have an established role in lipid metabolism through the regulation of triacylglycerol trafficking according to the nutritional status. Some ANGPTLs also contribute to glucose metabolism. Therefore, dysregulation in ANGPTL expression associated with abnormal circulating levels are linked to a plethora of CVD and metabolic disorders including atherosclerosis, heart diseases, diabetes, but also obesity and cancers. Because ANGPTLs bind to different receptors according to the cell type, antagonists are therapeutically inadequate. Recently, direct inhibitors of ANGPTLs, mainly ANGPTL3, have been developed, and specific monoclonal antibodies and antisense oligonucleotides are currently being tested in clinical trials. The aim of the current review is to provide an up-to-date preclinical and clinical overview on the function of the 8 members of the ANGPTL family in the cardiovascular system, their contribution to CVD, and the therapeutic potential of manipulating some of them., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Whether the effect of a combination strategy rather than increasing doses of one drug to lower low-density lipoprotein cholesterol (LDL-C) levels is consistent across baseline LDL-C levels remains uncertain., Methods: In the RACING trial, which showed a non-inferiority of moderate-intensity statin with ezetimibe (rosuvastatin 10 mg with ezetimibe 10 mg) to high-intensity statin (rosuvastatin 20 mg) for the primary outcome (3-year composite of cardiovascular death, major cardiovascular event, or stroke), the heterogeneity in treatment effect according to baseline LDL-C levels was assessed for the primary and secondary outcomes (clinical efficacy and safety)., Results: Of 3780 participants, 2817 participants (74.5%) had LDL-C <100 mg/dL, and 963 participants (25.5%) had LDL-C ≥100 mg/dL. The treatment effect of combination therapy versus high-intensity statin monotherapy was similar among the lower LDL-C subset (8.8% vs. 10.2%; hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.67 to 1.08, p = 0.19) and the higher LDL-C subset (10.8% vs. 9.6 %; HR 1.14, 95% CI 0.76 to 1.7, p = 0.53) without a significant interaction (interaction p = 0.22). Of the secondary outcomes, the 1-, 2-, and 3-year achievement of LDL-C <70 mg/dL was greater in the combination therapy group regardless of baseline LDL-C levels., Conclusions: Among ASCVD patients, there was no heterogeneity in the effect of moderate-intensity statin plus ezetimibe combination therapy in the higher and lower baseline LDL-C levels for the 3-year composite of cardiovascular outcomes., Competing Interests: Declaration of competing interest Byeong-Keuk Kim has received speaker's fees from Medtronic and Abbott Vascular, Myeong-Ki Hong has received speaker's fees from Medtronic, Abbott Vascular, and Pfizer, Yangsoo Jang has received institutional research grants from Biotronik and Hanmi, and Jung-Sun Kim has received proctoring fees from Abbott Vascular. All other authors declare no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Glucagon-like peptide-1 receptor agonists (GLP1RA) are incretin agents initially designed for the treatment of type 2 diabetes mellitus but because of pleiotropic actions are now used to reduce cardiovascular disease in people with type 2 diabetes mellitus and in some instances as approved treatments for obesity. In this review we highlight the biology and pharmacology of GLP1RA. We review the evidence for clinical benefit on major adverse cardiovascular outcomes in addition to modulation of cardiometabolic risk factors including reductions in weight, blood pressure, improvement in lipid profiles, and effects on kidney function. Guidance is provided on indications and potential adverse effects to consider. Finally, we describe the evolving landscape of GLP1RA and including novel glucagon-like peptide-1-based dual/polyagonist therapies that are being evaluated for weight loss, type 2 diabetes mellitus, and cardiorenal benefit., (Copyright © 2023 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: There is limited evidence regarding long-term effects of prenatal docosahexaenoic acid (DHA) supplementation on offspring cardiometabolic health (CMH). Inconsistent results may be attributable to variants of fatty acid desaturase (FADS) genes., Objective: We aimed to evaluate the effect of prenatal DHA supplementation on offspring CMH and investigate effect modification by maternal FADS2 single nucleotide polymorphism (SNP) rs174602., Methods: We used follow-up data from a double-blind, randomized controlled trial in Mexico in which pregnant females received 400 mg/d of algal DHA or placebo from midgestation until delivery. The study sample included 314 offspring with data at age 11 y and maternal FADS genetic data (DHA: n = 160; Placebo: n = 154). We derived a Metabolic Syndrome (MetS) score from body mass index, HDL, triglycerides, fasting glucose concentrations, and systolic blood pressure. Generalized linear models were used to evaluate the effect of the intervention on offspring MetS score and test interactions between treatment group and genotype, adjusting for maternal, offspring, and household factors., Results: Offspring MetS score did not differ significantly by treatment group. We observed evidence of effect modification by maternal SNP rs174602 (P = 0.001); offspring of maternal TT genotype who received DHA had lower MetS score relative to the placebo group (DHA (mean ± standard error of the mean (SEM)): -0.21 ± 0.11, n = 21; Placebo: 0.05 ± 0.11, n = 23; Δ= -0.26 (95% CI: -0.55, 0.04), P = 0.09); among CC maternal genotype carriers, offspring of mothers who received DHA had higher MetS score (0.18 ± 0.06, n = 62) relative to the placebo group (-0.05 ± 0.06, n = 65, Δ=0.24 (0.06, 0.41), P < 0.01)., Conclusion: The effect of prenatal DHA supplementation on offspring MetS score differed by maternal FADS SNP rs174602. These findings further support incorporating genetic analysis of FADS polymorphisms in DHA supplementation trials., Clinical Trial Details: This trial was registered at clinicaltrials.gov as NCT00646360., Competing Interests: Conflicts of interest Usha Ramakrishnan is a member of the Journal’s Editorial Board., (Copyright © 2023. Published by Elsevier Inc.)

The main role of cholesteryl ester transfer protein (CETP) is the transfer of cholesteryl esters and triglycerides between high-density lipoprotein (HDL) particles and triglyceride-rich lipoprotein and low-density lipoprotein (LDL) particles. There is a long history of investigations regarding the inhibition of CETP as a target for reducing major adverse cardiovascular events. Initially, the potential effect on cardiovascular events of CETP inhibitors was hypothesized to be mediated by their ability to increase HDL cholesterol, but, based on evidence from anacetrapib and the newest CETP inhibitor, obicetrapib, it is now understood to be primarily due to reducing LDL cholesterol and apolipoprotein B. Nevertheless, evidence is also mounting that other roles of HDL, including its promotion of cholesterol efflux, as well as its apolipoprotein composition and anti-inflammatory, anti-oxidative, and anti-diabetic properties, may play important roles in several diseases beyond cardiovascular disease, including, but not limited to, Alzheimer's disease, diabetes, and sepsis. Furthermore, although Mendelian randomization analyses suggested that higher HDL cholesterol is associated with increased risk of age-related macular degeneration (AMD), excess risk of AMD was absent in all CETP inhibitor randomized controlled trial data comprising over 70,000 patients. In fact, certain HDL subclasses may, in contrast, be beneficial for treating the retinal cholesterol accumulation that occurs with AMD. This review describes the latest biological evidence regarding the relationship between HDL and CETP inhibition for Alzheimer's disease, type 2 diabetes mellitus, sepsis, and AMD., Competing Interests: Declaration of Competing Interest N.M. is Founder and Chief Executive Officer of Mobius Scientific, Inc. M.D. is Vice President of Research & Development for NewAmsterdam Pharma. M.R.D. as an employee of Midwest Biomedical Research has received consulting fees from NewAmsterdam Pharma. J.J.P.K. is founder and Chief Science Officer of NewAmsterdam Pharma, and Emeritus Professor of Medicine at the University of Amsterdam, The Netherlands. K.D. and P.C.N.R. have no relevant conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Background and Aims: Despite lipid lowering therapy (LLT), reaching LDL-C targets in patients with familial hypercholesterolemia (FH) remains challenging. Our aim was to determine attainment of LDL-C target levels and reasons for not reaching these in female and male FH patients., Methods: We performed a cross-sectional study of heterozygous FH patients in five hospitals in the Netherlands and Norway. Clinical characteristics and information about LLT, lipid levels and reasons for not being on LDL-C treatment target were retrospectively collected from electronic medical records., Results: We studied 3178 FH patients (53.9% women), median age 48.0 (IQR 34.0-59.9) years. Median LDL-C before treatment and on-treatment was higher in women compared to men (6.2 (IQR 5.1-7.3) and 6.0 (IQR 4.9-7.2) mmol/l (p=0.005) and 3.0 (IQR 2.4-3.8) and 2.8 (IQR 2.3-3.5) mmol/L (p<0.001)), respectively. A minority of women (26.9%) and men (28.9%) reached LDL-C target. In patients with CVD, 17.2% of women and 25.8% of men reached LDL-C target. Women received less often high-intensity statins and ezetimibe. Most common reported reasons for not achieving the LDL-C target were insufficient effect of maximum LLT (women 17.3%, men 24.3%) and side effects (women 15.2%, men 8.6%)., Conclusions: In routine practice, only a minority of women and men with FH achieved their LDL-C treatment target. Extra efforts have to be made to provide FH patients with reliable information on the safety of statins and their long-term effects on CVD risk reduction. If statin treatment is insufficient, alternative lipid lowering therapies such as ezetimibe or PCSK9-inhibitors should be considered., Competing Interests: Declaration of competing competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Overweight and obesity are highly prevalent worldwide and are associated with cardiovascular disease (CVD) risk factors, including systematic inflammation, dyslipidemia, and hypertension. Alpha-linolenic acid (ALA) is a plant-based essential polyunsaturated fatty acid associated with reduced CVD risks. This systematic review and meta-analysis aimed to investigate the effects of supplementation with ALA compared with the placebo on CVD risk factors in people with obesity or overweight (International Prospective Register of Systematic Reviews Registration No. CRD42023429563). This review included studies with adults using oral supplementation or food or combined interventions containing vegetable sources of ALA. All studies were randomly assigned trials with parallel or crossover designs. The Cochrane Collaboration tool was used for assessing the risk of bias (Version 1). PubMed, Web of Science, Embase, and Cochrane library databases were searched from inception to April 2023. Nineteen eligible randomized controlled trials, including 1183 participants, were included in the meta-analysis. Compared with placebo, dietary ALA supplementation significantly reduced C-reactive protein concentration (standardized mean difference [SMD] = -0.38 mg/L; 95% confidence interval [CI]: -0.72, -0.04), tumor necrosis factor-α concentration (SMD = -0.45 pg/mL; 95% CI: -0.73, -0.17), triglyceride in serum (SMD = -4.41 mg/dL; 95% CI: -5.99, -2.82), and systolic blood pressure (SMD = -0.37 mm Hg; 95% CI: -0.66, -0.08); but led to a significant increase in low-density lipoprotein cholesterol concentrations (SMD = 1.32 mg/dL; 95% CI: 0.05, 2.59). ALA supplementation had no significant effect on interleukin-6, diastolic blood pressure, total cholesterol, or high-density lipoprotein cholesterol (all P ≥ 0.05). Subgroup analysis revealed that ALA supplementation at a dose of ≥3 g/d from flaxseed and flaxseed oil had a more prominent effect on improving CVD risk profiles, particularly where the intervention duration was ≥12 wk and where the baseline CVD profile was poor., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Anticoagulant drugs that are currently used to prevent and/or treat thrombosis have some limitations that hinder their ability to meet specific clinical requirements. While these drugs effectively reduce the rates of thrombotic events, they simultaneously increase the risk of bleeding. Moreover, their risk-to-benefit balance is problematic in some patients, such as those with severe chronic kidney disease or those at high bleeding risk. A novel anticoagulation method, FXI inhibition has emerged as a promising alternative. It demonstrates a strong rationale for the prevention and treatment of venous thromboembolism and the potential fulfillment of unmet clinical needs in the cardiovascular field. A number of FXI inhibitors are currently undergoing clinical investigation. The objective of this review is to provide an overview of early results of research on FXI inhibitors in the cardiovascular setting, offering valuable insights into their potential role in shaping the future of anticoagulation., Competing Interests: Declaration of Competing Interest Santagata D. MD: no conflict to disclose. Professor Donadini M.P. MD, PhD: no conflict to disclose. Professor Ageno W. MD: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Bayer, BMS/Pfizer, Viatris, Leo Pharma, Sanofi. Participation on a Data Safety Monitoring Board or Advisory Board for Bayer, Norgine, Leo Pharma, Sanofi, Techdow., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Mimicry of host proteins is a strategy employed by pathogens to hijack host functions. Domain and motif mimicry was explored in the experimental and predicted SARS-CoV-2-human interactome. The host first interactor proteins were also added to capture the continuum of the interactions. The domains and motifs of the proteins were annotated using NCBI CD Search and ScanProsite, respectively. Host and pathogen proteins with a common host interactor and similar domain/motif constitute a mimicry pair indicating global structural similarity (domain mimicry pair; DMP) or local sequence similarity (motif mimicry pair; MMP). 593 DMPs and 7,02,472 MMPs were determined. AAA, DEXDc and Macro domains were frequent among DMPs whereas glycosylation, myristoylation and RGD motifs were abundant among MMP. The proteins involved in mimicry were visualised as a SARS-CoV-2 mimicry interaction network. The host proteins were enriched in multiple CVD pathways indicating the role of mimicry in COVID-19 associated CVDs. Bridging nodes were identified as potential drug targets. Approved antihypertensive and anti-inflammatory drugs are proposed for repurposing against COVID-19 associated CVDs. The SARS-CoV-2 mimicry data has been updated in ImitateDB (http://imitatedb.sblab-nsit.net/SARSCoV2Mimicry). Determination of key mechanisms, proteins, pathways, drug targets and repurposing candidates is critical for developing therapeutics for SARS CoV-2 associated CVDs., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sonika Bhatnagar reports financial support was provided by Indian Council of Medical Research., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Sodium-glucose cotransport 2 inhibitors (SGLT2i) are a class of drugs initially approved by the Food and Drug Association (FDA) as antihyperglycemic agents for patients with type 2 diabetes mellitus (DM). However, lately, these agents (Canagliflozin, Empagliflozin, Ertugliflozin, Sotagliflozin, and Dapagliflozin) have become better known for their cardiovascular (CV) and reno-protective effects. In this comprehensive review and analysis, we display the advancement of Sodium Glucose Cotransport Inhibitors have shown in cardiology, specifically heart failure in a concise, yet thorough manner., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Underlying molecular mechanisms of the kidney protective effects of sodium glucose co-transporter 2 (SGLT2) inhibitors are not fully elucidated. Therefore, we studied the association between urinary epidermal growth factor (uEGF), a mitogenic factor involved in kidney repair, and kidney outcomes in patients with type 2 diabetes (T2D). The underlying molecular mechanisms of the SGLT2 inhibitor canagliflozin on EGF using single-cell RNA sequencing from kidney tissue were examined. Urinary EGF-to-creatinine ratio (uEGF/Cr) was measured in 3521 CANagliflozin cardioVascular Assessment Study (CANVAS) participants at baseline and week 52. Associations of uEGF/Cr with kidney outcome were assessed using multivariable-adjusted Cox regression models. Single-cell RNA sequencing was performed using protocol kidney biopsy tissue from ten young patients with T2D on SGLT2i, six patients with T2D on standard care only, and six healthy controls (HCs). In CANVAS, each doubling in baseline uEGF/Cr was associated with a 12% (95% confidence interval 1-22) decreased risk of kidney outcome. uEGF/Cr decreased after 52 weeks with placebo and remained stable with canagliflozin (between-group difference +7.3% (2.0-12.8). In young persons with T2D, EGF mRNA was primarily expressed in the thick ascending loop of Henle. Expression in biopsies from T2D without SGLT2i was significantly lower compared to HCs, whereas treatment with SGLT2i increased EGF levels closer to the healthy state. In young persons with T2D without SGLT2i, endothelin-1 emerged as a key regulator of the EGF co-expression network. SGLT2i treatment was associated with a shift towards normal EGF expression. Thus, decreased uEGF represents increased risk of kidney disease progression in patients with T2D. Canagliflozin increased kidney tissue expression of EGF and was associated with a downstream signaling cascade linked to tubular repair and reversal of tubular injury., (Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

While the prevalence of diabetes continues to rise worldwide, with 537 million adults aged 20-79-years-old having diabetes in 2021, the development of new therapeutic classes improving not only glycemic control but also kidney function and cardiovascular prevention has revolutionized patient care. Today, the treatment of diabetes is no longer just the treatment of blood sugar level. In this context, the individualized therapeutic strategy has been completely reviewed, with in particular sulfamides indicated much later in the therapeutic strategy, while SGLT2 inhibitors are indicated very early in patients with kidney disease and/or with ischemic heart disease or chronic heart failure, and GLP-1 analogues in obese patients and/or in primary or secondary cardiovascular prevention. As for lifestyle rules and metformin, they remain the cornerstone of treatment. Knowledge of antidiabetic effects in terms of efficacy and hypoglycemic risk, of cardiovascular, nephroprotective and weight effects is essential to optimize the management of diabetic patients today., (Copyright © 2023 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Although chemotherapy drugs are extensively utilized in cancer therapy, their administration for treatment of patients has faced problems that regardless of chemoresistance, increasing evidence has shown concentration-related toxicity of drugs. Doxorubicin (DOX) is a drug used in treatment of solid and hematological tumors, and its function is based on topoisomerase suppression to impair cancer progression. However, DOX can also affect the other organs of body and after chemotherapy, life quality of cancer patients decreases due to the side effects. Heart is one of the vital organs of body that is significantly affected by DOX during cancer chemotherapy, and this can lead to cardiac dysfunction and predispose to development of cardiovascular diseases and atherosclerosis, among others. The exposure to DOX can stimulate apoptosis and sometimes, pro-survival autophagy stimulation can ameliorate this condition. Moreover, DOX-mediated ferroptosis impairs proper function of heart and by increasing oxidative stress and inflammation, DOX causes cardiac dysfunction. The function of DOX in mediating cardiac toxicity is mediated by several pathways that some of them demonstrate protective function including Nrf2. Therefore, if expression level of such protective mechanisms increases, they can alleviate DOX-mediated cardiac toxicity. For this purpose, pharmacological compounds and therapeutic drugs in preventing DOX-mediated cardiotoxicity have been utilized and they can reduce side effects of DOX to prevent development of cardiovascular diseases in patients underwent chemotherapy. Furthermore, (nano)platforms are used comprehensively in treatment of cardiovascular diseases and using them for DOX delivery can reduce side effects by decreasing concentration of drug. Moreover, when DOX is loaded on nanoparticles, it is delivered into cells in a targeted way and its accumulation in healthy organs is prevented to diminish its adverse impacts. Hence, current paper provides a comprehensive discussion of DOX-mediated toxicity and subsequent alleviation by drugs and nanotherapeutics in treatment of cardiovascular diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Accumulating evidence suggests that inflammation plays an important role in the pathophysiology of the initiation and progression of cardiovascular and metabolic diseases (CVMDs). Anti-inflammation strategies and those that promote inflammation resolution have gradually become potential therapeutic approaches for CVMDs. Resolvin D2 (RvD2), a specialized pro-resolving mediator, exerts anti-inflammatory and pro-resolution effects through its receptor GPR18, a G protein-coupled receptor. Recently, the RvD2/GPR18 axis has received more attention due to its protective role in CVMDs, including atherosclerosis, hypertension, ischaemiareperfusion, and diabetes. Here, we introduce basic information about RvD2 and GPR18, summarize their roles in different immune cells, and review the therapeutic potential of the RvD2/GPR18 axis in CVMDs. In summary, RvD2 and its receptor GPR18 play an important role in the occurrence and development of CVMDs and are potential biomarkers and therapeutic targets., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Statins are the cornerstone of lipid-lowering therapy (LLT) for reduction of low-density lipoprotein cholesterol (LDLc) levels and high percentage of patients require LLT combinations or alternative treatments for adequate LDLc control., Methods: We performed an intention-to-treat meta-analysis of published data of phase III trials evaluating LLT efficacy on major adverse cardiovascular events (MACE). The primary endpoint was MACE incidence, as reported in each trial, and secondary analyses included myocardial infarction, stroke and mortality., Results: Eleven clinical trials and 135,688 patients were included; seven trials tested high intensity LLT and 4 LLT combinations. Intensive LLT reduced MACE risk by 15% (12.03% vs. 13.79%, HR: 0.85 95% CI 0.80-0.90; p<0.001). The number needed to treat was 56 patients. Meta-regression analyses showed a linear correlation between absolute LDLc reductions and the risk of MACE. Significant reductions in myocardial infarction (HR: 0.83, 95% CI 0.80-0.86) and stroke (HR: 0.81, 95% CI 0.75-0.87) were observed. Cardiovascular death rate was 3.32% in LLT treatment arm vs. 3.56% in controls, resulting in a HR: 0.94 (95% CI 0.88-0.99; p = 0.03); no effect on all-cause mortality was observed (HR: 0.97 95% CI 0.93-1.01; p = 0.09). The sensitivity analyses verified the lack of heterogeneity, except for MACE that was mainly driven by the divergent results of the 2 trials. Small study effect was detected for the assessment of mortality., Conclusions: Current evidence consistently supports the efficacy of available intensity LLT for LDLc decrease on MACE and cardiovascular mortality reduction., (Copyright © 2023. Published by Elsevier Inc.)