Cardiovascular pharmacogenetics

Ischemic stroke is a heterogeneous condition influenced by a combination of genetic and environmental factors. Recent advancements have explored genetics in relation to various aspects of ischemic stroke, including the alteration of individual stroke occurrence risk, modulation of treatment response, and effectiveness of post-stroke functional recovery. This article aims to review the recent findings from genetic studies related to various clinical and molecular aspects of ischemic stroke. The potential clinical applications of these genetic insights in stratifying stroke risk, guiding personalized therapy, and identifying new therapeutic targets are discussed herein...

BACKGROUND: Statins are one of the most prescribed medications in developed countries as the treatment of choice for reducing cholesterol and preventing cardiovascular diseases. However, a large proportion of patients experience adverse drug reactions, especially myotoxicity. Among the factors that influence the diversity of response, pharmacogenetics emerges as a relevant factor of influence in inter-individual differences in response to statins and can be useful in the prevention of adverse drug effects...

Cancer is a widespread disease in our nation, characterized by a high occurrence rate. The use of tumor medications has been linked to an increased chance of cardiovascular complications, including a notable occurrence of heart toxicity. This has caused significant concern among healthcare professionals. This article provides a comprehensive compilation of drugs recognized for their potential to cause heart toxicity. Furthermore, extensive research has been conducted to investigate and categorize the effects of heart toxicity, with the purpose of promoting awareness, facilitating early intervention, and ultimately reducing the occurrence of heart toxicity...

PURPOSE: Inconclusive and limited results have been reported on the clinical utility of CYP2C19 genotyping in stroke/TIA patients of non-East Asian ancestries. We herein performed an updated systematic review and meta-analysis to quantitatively estimate the association of CYP2C19 loss-of function (LOF) status with efficacy and safety of clopidogrel-based antiplatelet therapy in non-East Asian patients affected by stroke or TIA. METHODS: A comprehensive search was performed up to July 2023 using PubMed, Web of Knowledge, and Cochrane Library databases...

PURPOSE OF REVIEW: Advances in pharmacogenomics have paved the way for personalized medicine. Cardiovascular diseases still represent the leading cause of mortality in the world. The aim of this review is to summarize the background, rationale, and evidence of pharmacogenomics in cardiovascular medicine, in particular, the use of antiplatelet drugs, anticoagulants, and drugs used for the treatment of dyslipidemia. RECENT FINDINGS: Randomized clinical trials have supported the role of a genotype-guided approach for antiplatelet therapy in patients with coronary heart disease undergoing percutaneous coronary interventions...

BACKGROUND: Once thought to be primarily a result of lifestyle, it is now known that obesity has significant genetic components. Dozens of genes have been linked to obesity, and office-based genetic testing for obesity-associated genes is now readily available. As both pharmacotherapy and genetic testing for obesity become more accessible, pharmacogenetic personalization is becoming a reality. In this case report, a patient with a PLXNA4 polymorphism had a superior weight loss response to phentermine/topiramate therapy than has previously been reported in the literature...

BACKGROUND: Sufentanil and ropivacaine when used as epidural anesthetics effectively reduce maternal pain during labor. From previous reports, rs2242480 single nucleotide polymorphisms (SNPs) can alter sufentanil metabolism, which affects analgesic efficacy. METHODS: We randomly divided 573 eligible mothers into groups A and B (in a 1 : 3 ratio). The control group (group A) was given sufentanil at the usual 0.5 mg/L-1 dose + 0.15% ropivacaine hydrochloride mixture in 10 ml...

Antiplatelet therapy is the cornerstone of antithrombotic prevention in patients with established atherosclerosis, since it has been proven to reduce coronary, cerebrovascular, and peripheral thrombotic events. However, the protective effect of antiplatelet agents is counterbalanced by an increase of bleeding events that impacts on patients' mortality and morbidity. Over the last years, great efforts have been made toward personalized antithrombotic strategies according to the individual bleeding and ischemic risk profile, aiming to maximizing the net clinical benefit...

BACKGROUND: Beta-blockers are essential agents in the management of cardiovascular diseases, such as heart failure, acute myocardial infarction (MI), and cardiac arrhythmias. However, there are diurnal variations in the cardioprotective effects of the subgroups as a result of their different pharmacokinetic, pharmacodynamic, and pharmacogenetic profiles. OBJECTIVE: We aimed to compare metoprolol and bisoprolol in terms of electrocardiogram (ECG) outcomes. METHODS: A retrospective cross-sectional study was conducted at Prince Sultan Cardiac Center...

Background: This study analyzed real-world data from 2004 to 2023 to evaluate the toxicity profile of tyrosine receptor kinase (TRK) inhibitor therapy. Method: A retrospective analysis of US FDA Adverse Event Reporting System data was conducted to identify adverse events in patients receiving TRK inhibitor therapy. Result: Entrectinib demonstrated toxicities primarily in the cardiovascular and nervous systems, followed by the renal and urinary system. Common adverse effects included dizziness, renal impairment, constipation, heart failure and taste disorders...

BACKGROUND: Arteriosclerosis obliterans (ASO) is the leading cause of nontraumatic lower-extremity amputations. Multiple researches have suggested that circular RNAs (circRNAs) played vital regulatory functions in cancer and cardiovascular disease. Nevertheless, the underlying effect and pathological mechanism of circRNAs in the formation and progression of ASO are still indistinct. METHODS AND RESULTS: This study used microarray analysis to investigate the expression portrait of circRNAs in normal lower extremity arteries and ASO arteries...

PURPOSE: The main dose-limiting toxicity of anthracyclines is cardiotoxicity. Clonal hematopoiesis (CH), somatic mutations in hematopoietic stem or progenitor cells in patients without hematologic malignancy, is also associated with risk for adverse cardiovascular events and worse outcomes overall. We hypothesize that CH increases risk for doxorubicin-induced cardiotoxicity (DIC). METHODS: We conducted a retrospective cohort study in patients treated with doxorubicin for cancer (N = 100)...

PURPOSE: Patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib are at risk of developing cardiovascular side effects (CVSEs). The molecular determinants of CVSEs have not been fully elucidated. We interrogated genetic polymorphisms in the Bruton Tyrosine Kinase (BTK) signaling pathway for their association with ibrutinib-related CVSEs. EXPERIMENTAL DESIGN: We conducted a retrospective/prospective observational pharmacogenetic study of 50 patients with newly diagnosed or relapsed CLL who received ibrutinib at a starting daily dose of 420 mg for at least six months...

BACKGROUND: Clinical pharmacogenetics is a rapidly growing field that focuses on the study of genetic variations and their impact on drug metabolism, efficacy, and safety. Angiotensin II receptor blockers (ARBs) are commonly used to treat hypertension in Iraq but not all patients respond equally to these drugs. AIM: This article aims to review the current evidence on the clinical pharmacogenetics of ARBs in Iraq and its implications for personalized medicine. MATERIALS AND METHODS: We conducted a literature review of studies on the genetic variations that affect the response to ARBs in Iraq...

BACKGROUND: To observe the level of serum Sema7A in acute aortic dissection (AAD) and its diagnostic value for AAD. RESEARCH DESIGN AND METHODS: Patients with sudden chest pain including AAD, acute myocardial infarction (AMI) or pulmonary embolism (PE) were enrolled. Patients without chest pain or cardiovascular diseases were included as the controls. Serum Sema7A and plasma D-dimer were detected and compared in each group. RESULTS: 85 AAD patients, 55 AMI patients, 15 PE patients, and 30 controls were enrolled...

The study of anaemia is a well-developed discipline where the concepts of precision medicine have, in part, been researched extensively. This review discusses the treatment of erythropoietin (EPO) deficiency anaemia and resistance in cases of chronic kidney disease (CKD). Traditionally, erythropoietin-stimulating agents (ESAs) and iron supplementation have been used to manage anaemia in cases of CKD. However, these treatments pose potential risks, including cardiovascular and thromboembolic events. Newer treatments have emerged to address these risks, such as slow-release and low-dosage intravenous iron, oral iron supplementation, and erythropoietin-iron combination therapy...

PURPOSE: This study was designed to investigate the impact of single-nucleotide polymorphism-encoded cytochrome P450 enzymes (CYP3A4/5) on clinical outcomes of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF) based on pharmacokinetics and pharmacodynamics (PK/PD) aspects. METHOD: A prospective study enrolling 165 rivaroxaban-treated patients with NVAF was conducted. Genotyping of CYP3A4 (rs2242480, rs2246709, rs3735451, and rs4646440) and CYP3A5 (rs776746) was performed to explore their impact on the trough plasma concentrations (Ctrough ) of rivaroxaban, coagulation indicators at the Ctrough including activated partial thromboplastin time (APTT) and prothrombin time (PT), and clinical outcomes...

BACKGROUND: Familial Hypercholesterolemia (FH) is a hereditary condition that causes a rise in blood cholesterol throughout a person's life. FH can result in myocardial infarction and even sudden death if not treated. FH is thought to be caused mainly by variants in the gene for the low-density lipoprotein receptor (LDLR). This study aimed to investigate the genetic variants in FH patients, verify their pathogenicity, and comprehend the relationships between genotype and phenotype. Also, review studies assessed the relationship between the LDLR null variants and the reaction to lipid-lowering therapy...

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Genome-wide association studies (GWAS) have identified many single nucleotide polymorphisms (SNPs) appearing in non-coding genomic regions in CVDs. The SNPs may alter gene expression by modifying transcription factor (TF) binding sites and lead to functional consequences in cardiovascular traits or diseases. To understand the underlying molecular mechanisms, it is crucial to identify which variations are involved and how they affect TF binding...

O-GlcNAcylation is a post-translational modification that directly couples the processes of nutrient sensing, metabolism, and signal transduction, affecting protein function and localization, since the O-linked N-acetylglucosamine moiety comes directly from the metabolism of glucose, lipids, and amino acids. De addition and removal of O-GlcNAc of target proteins is mediated by two highly conserved enzymes: O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA), respectively. Deregulation of O-GlcNAcylation has been reported to be associated with various human diseases such as cancer, diabetes, and cardiovascular diseases...