Treatment Of Ischemic Heart Disease Research Articles

Using proteomics to identify the mechanisms underlying the benefits of statins on ischemic heart disease

Ischemic heart disease (IHD) is the single leading cause of mortality globally. Statins are the mainstay for IHD treatment. However, the specific mechanisms underlying statins’ benefits on IHD have not been clarified. To examine the mechanisms through proteins, we used two-step Mendelian randomization (MR) approach. First, we examined the associations of genetically mimicked statins with 2923 proteins using genome-wide association of proteins from the UK Biobank Pharma Proteomics Project (UKB-PPP) to identify the proteins affected by statins, and replicated the findings using deCODE. Then we examined the associations of selected proteins with IHD risk using CARDIoGRAMplusC4D using MR, and replicated using FinnGen, and using another set of genetic instruments from deCODE. We selected proteins decreased or increased IHD risk and meanwhile increased or lowered by statins. We further examined the role of the selected protein(s) on common IHD comorbidities, including diabetes, chronic kidney disease (CKD), and kidney function (measured by estimated glomerular filtration rate (eGFR)). Nine proteins were affected by statins, including four proteins (PLA2G7, FGFBP1, ANGPTL1, and PTPRZ1) lowered by statins, and five proteins (EFNA4, COL6A3, ASGR1, PRSS8 and PCOLCE) increased by statins. Among these, PLA2G7 was related to higher risk of IHD after controlling for multiple testing. The associations were robust to different analytic methods and replication using another set of genetic instrument from deCODE, and using another GWAS of IHD from FinnGen. Genetically predicted PLA2G7 had null association with diabetes, CKD, and eGFR. We identified 9 proteins affected by statins, including 7 novel proteins which were not reported previously. PLA2G7 is on the pathway underlying statins’ benefits on IHD. The clarification of statins’ mechanisms had close relevance to precision medicine, and provided insights to the development of new treatment strategies.

The effect of macrophages and their exosomes in ischemic heart disease.

Ischemic heart disease (IHD) is a leading cause of disability and death worldwide, with immune regulation playing a crucial role in its pathogenesis. Various immune cells are involved, and as one of the key immune cells residing in the heart, macrophages play an indispensable role in the inflammatory and reparative processes during cardiac ischemia. Exosomes, extracellular vesicles containing lipids, nucleic acids, proteins, and other bioactive molecules, have emerged as important mediators in the regulatory functions of macrophages and hold promise as a novel therapeutic target for IHD. This review summarizes the regulatory mechanisms of different subsets of macrophages and their secreted exosomes during cardiac ischemia over the past five years. It also discusses the current status of clinical research utilizing macrophages and their exosomes, as well as strategies to enhance their therapeutic efficacy through biotechnology. The aim is to provide valuable insights for the treatment of IHD.

Integrated metabolomics and network pharmacology study on the mechanism of herbal pair of danggui-kushen for treating ischemia heart disease

DangGui-KuShen (DK) is a well-known classic traditional Chinese medicine recipe that improves blood circulation, eliminates moisture, and detoxifies, and is frequently used in the treatment of cardiovascular problems. Some protective effects of DK on cardiovascular disease have previously been identified, but its precise mechanism remains unknown. The goal of this study is to combine metabolomics and network pharmacology to investigate DK's protective mechanism in Ischemic Heart Disease(IHD) rat models. A combination of metabolomics and network pharmacology based on UPLC-Q-TOF/MS technology was used in this study to verify the effect of DK on IHD through enzyme-linked immunosorbent assay, HE staining, and electrocardiogram, and it was determined that DK improves the synergistic mechanism of IHD. In total, 22 serum differential metabolites and 26 urine differential metabolites were discovered, with the majority of them involved in phenylalanine, tyrosine, and tryptophan biosynthesis, glycine, serine, and threonine metabolism, arginine and proline metabolism, aminoacyl-tRNA biosynthesis, purine metabolism, and other metabolic pathways. Furthermore, using network pharmacology, a composite target pathway network of DangGui and KuShen for treating IHD was created, which is primarily associated to the tumor necrosis factor (TNF) signaling pathway, P53 signaling, and HIF-1 signaling pathways. The combined research indicated that the NF-B signaling pathway and the HIF-1 signaling pathway are critical in DK treatment of IHD. This study clearly confirms and expands on current knowledge of the synergistic effects of DG and KS in IHD.

Abstract 16244: Oncologic Disease and In-Stent Restenosis: A Nationwide Analysis

Introduction: Recent studies have shown that Ischemic Heart Disease (IHD) is leading cause of cardiovascular mortality in cancer patients. There is little information about In-Stent Restenosis (ISR), one complication of IHD treatment. ISR has been associated with the presence of underlying risk factors but there is no clear association between cancer and ISR. Methods: A retrospective cohort study was made selecting a sample of adult patients using the National Inpatient Sample (NIS) database from January 2017 to December 2019. Patients with cancer were identified and stratified by 5 main sites: lung, breast, gastrointestinal, prostate, and hematological tissue. Main outcome was odds of ISR in the oncologic population. Secondary outcomes were Major Adverse Cardiovascular Events (MACE) and mortality in patients with ISR, stratified by presence or absence of cancer. Univariate and multivariate analysis were done, adjusting for possible confounders. Results: A total of 90,900,000 adults were identified, of which 4,888,734 had cancer. From the adult population, 197350 patients with ISR were identified. Primary analysis revealed that cancer is not associated with increased odds of ISR but rather decreased, adjusted for other comorbidities, with an OR=0.181(IC95%=0.167-0.198, p=0.001). Paradoxically, secondary analysis of the ISR subpopulation showed statistically significant differences between cancer and non-cancer patients in the rate of composite MACE, and other cardiovascular outcomes such as Heart Failure, Atrial Fibrillation, and other arrhythmias (Table 1). Conclusions: The present study shows that cancer is associated with decreased odds for ISR, but in with patients with ISR cancer was associated with higher prevalence of composite MACE, mainly due to arrhythmias and heart failure. Further studies are needed to explain the dynamic relationship between cancer and endothelial dysfunction.

Plasma Proteomics to Identify Drug Targets for Ischemic Heart Disease

BackgroundIntegrated analyses of plasma proteomic and genetic markers in prospective studies can clarify the causal relevance of proteins and discover novel targets for ischemic heart disease (IHD) and other diseases. ObjectivesThe purpose of this study was to examine associations of proteomics and genetics data with IHD in population studies to discover novel preventive treatments. MethodsWe conducted a nested case-cohort study in the China Kadoorie Biobank (CKB) involving 1,971 incident IHD cases and 2,001 subcohort participants who were genotyped and free of prior cardiovascular disease. We measured 1,463 proteins in the stored baseline samples using the OLINK EXPLORE panel. Cox regression yielded adjusted HRs for IHD associated with individual proteins after accounting for multiple testing. Moreover, cis-protein quantitative loci (pQTLs) identified for proteins in genome-wide association studies of CKB and of UK Biobank were used as instrumental variables in separate 2-sample Mendelian randomization (MR) studies involving global CARDIOGRAM+C4D consortium (210,842 IHD cases and 1,378,170 controls). ResultsOverall 361 proteins were significantly associated at false discovery rate <0.05 with risk of IHD (349 positively, 12 inversely) in CKB, including N-terminal prohormone of brain natriuretic peptide and proprotein convertase subtilisin/kexin type 9. Of these 361 proteins, 212 had cis-pQTLs in CKB, and MR analyses of 198 variants in CARDIOGRAM+C4D identified 13 proteins that showed potentially causal associations with IHD. Independent MR analyses of 307 cis-pQTLs identified in Europeans replicated associations for 4 proteins (FURIN, proteinase-activated receptor-1, Asialoglycoprotein receptor-1, and matrix metalloproteinase-3). Further downstream analyses showed that FURIN, which is highly expressed in endothelial cells, is a potential novel target and matrix metalloproteinase-3 a potential repurposing target for IHD. ConclusionsIntegrated analyses of proteomic and genetic data in Chinese and European adults provided causal support for FURIN and multiple other proteins as potential novel drug targets for treatment of IHD.

Healing the Ischaemic Heart: A Critical Review of Stem Cell Therapies.

Ischaemic heart disease (IHD) remains the leading cause of mortality worldwide. Current pharmaceutical treatments focus on delaying, rather than preventing disease progression. The only curative treatment available is orthotopic heart transplantation, which is greatly limited by a lack of available donors and the possibility for immune rejection. As a result, novel therapies are consistently being sought to improve the quality and duration of life of those suffering from IHD. Stem cell therapies have garnered attention globally owing to their potential to replace lost cardiac cells, regenerate the ischaemic myocardium and to release protective paracrine factors. Despite recent advances in regenerative cardiology, one of the biggest challenges in the clinical translation of cell-based therapies is determining the most efficacious cell type for repair. Multiple cell types have been investigated in clinical trials; with inconsistent methodologies and isolation protocols making it difficult to draw strong conclusions. This review provides an overview of IHD focusing on pathogenesis and complications, followed by a summary of different stem cells which have been trialled for use in the treatment of IHD, and ends by exploring the known mechanisms by which stem cells mediate their beneficial effects on ischaemic myocardium.

Microbiota-related metabolites fueling the understanding of ischemic heart disease.

Up-to-date knowledge of gut microbial taxa associated with ischemic heart disease (IHD). Microbial metabolites for mechanistic dissection of IHD pathology. Microbiome-based therapies in IHD prevention and treatment.

SDF-1α-Releasing Microspheres Effectively Extend Stem Cell Homing after Myocardial Infarction

Ischemic heart disease (IHD) is one of the main focuses in today's healthcare due to its implications and complications, and it is predicted to be increasing in prevalence due to the ageing population. Although the conventional pharmacological and interventional methods for the treatment of IHD presents with success in the clinical setting, the long-term complications of cardiac insufficiency are on a continual incline as a result of post-infarction remodeling of the cardiac tissue. The migration and involvement of stem cells to the cardiac muscle, followed by differentiation into cardiac myocytes, has been proven to be the natural process, though at a slow rate. SDF-1α is a novel candidate to mobilize stem cells homing to the ischemic heart. Endogenous SDF-1α levels are elevated after myocardial infarction, but their presence gradually decreases after approximately seven days. Additional administration of SDF-1α-releasing microspheres could be a tool for the extension of the time the stem cells are in the cardiac tissue after myocardial infarction. This, in turn, could constitute a novel therapy for more efficient regeneration of the heart muscle after injury. Through this practical study, it has been shown that the controlled release of SDF-1α from biodegradable microspheres into the pericardial sac fourteen days after myocardial infarction increases the concentration of exogenous SDF-1α, which persists in the tissue much longer than the level of endogenous SDF-1α. In addition, administration of SDF-1α-releasing microspheres increased the expression of the factors potentially involved in the involvement and retention of myocardial stem cells, which constitutes vascular endothelial growth factor A (VEGFA), stem cell factor (SCF), and vascular cell adhesion molecules (VCAMs) at the site of damaged tissue. This exhibits the possibility of combating the basic limitations of cell therapy, including ineffective stem cell implantation and the ability to induce the migration of endogenous stem cells to the ischemic cardiac tissue and promote heart repair.

Recent advances in diagnosis and management of ischemic heart diseases in perspective of contemporary and Ayurveda medicine—a comprehensive review

Ischemic heart disease (IHD) or commonly known as coronary heart disease is considered as of the important cause of morbidity and mortality across the globe. This condition affects both the structure and function of heart muscle. Its prevalence should be considered since the advent of human life as even classical texts of Ayurveda have given ample emphasis on physiology and pathology of Hridroga (heart diseases). This is thus a topic of interest for the cardiologists, Ayurveda physicians, and general physicians. In order to cope with the transformations in the field of medicine, especially critical care, one must be well versed with the recent advances especially concerning this critical field of cardiology. The available classical literature regarding Hridroga and contemporary literature pertaining to IHD is reviewed in the present study with the help of robust search of different databases, published scientific works to present solid knowledge foundation for effective diagnosis, management, and research opportunities concerning filed of cardiology. The advances concerning the different clinical and preclinical trials on interventional drugs in treatment of IHD along with the different observational and exploratory studies done to understand the pathophysiology of Hridroga are highlighted in this article. Encouraging findings were achieved by the means of a thorough review put forth in the article which elaborates to highlight the recent advances in the research, diagnosis, management, and prevention of IHD in terms of both Ayurvedic and contemporary approaches.

Network pharmacology approach and experimental verification of Dan-Shen Decoction in the treatment of ischemic heart disease

Context Dan-Shen Decoction, which is composed of Danshen, Tanxiang and Sharen, has a good therapeutic effect on ischemic heart disease (IHD). However, systematic research on the exact mechanism of action of Dan-Shen Decoction is still lacking. The anti-IHD effect of Dan-Shen Decoction was examined in this study using a systematic pharmacological method. Objective This study validates the efficacy and explores the potential mechanisms of Dan-Shen Decoction in treating IHD by integrating network pharmacology analyses and experimental verification. Materials and methods The active components, critical targets and potential mechanisms of Dan-Shen Decoction against IHD were predicted by network pharmacology and molecule docking. H9c2 cells were pretreated with various 1 µg/mL Dan-Shen Decoction for 2 h before induction with 1000 µmol/L CoCl2 for 24 h. The cell viability was detected by CCK8, and protein expression was detected by western blots. Results The network pharmacology approach successfully identified 69 active components in Dan-Shen Decoction, and 122 potential targets involved in the treatment of IHD. The in vitro experiments indicate that the anti-IHD effect of Dan-Shen Decoction may be closely associated with targets such as AKT1 and MAPK1, as well as biological processes such as cell proliferation, inflammatory response, and metabolism. Conclusions This study not only provides new insights into the mechanism of Dan-Shen Decoction against IHD, but also provides important information and new research ideas for the discovery of anti-IHD compounds from traditional Chinese medicine.

Exploring the Potential Mechanism of Danshen in the Treatment of Concurrent Ischemic Heart Disease and Depression Using Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation

Objective: This study aimed to explore the potential targets and mechanism of action of Danshen in treating concurrent ischemic heart disease (IHD) and depression using network pharmacology, molecular docking, and molecular dynamics simulation (MDS). Methods: The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to obtain active ingredients and targets of Danshen. Candidate targets for IHD and depression were obtained from the Genecards and DisGeNet databases. The protein–protein interaction (PPI) network was constructed using the STRING database and the Cytoscape 3.8.2 software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using the Metascape database and the GlueGO package of the Cytoscape 3.8.2 software. Molecular docking was performed using Autodock 1.5.6 and Vina, and the MDS was completed using GROMACS 5.1.2. Results: We obtained 65 active ingredients of Danshen with 131 candidate targets and 39 intersection targets of the active ingredients and diseases. Luteolin, tanshinone IIA, and salviolone were the core active ingredients, and AKT1, TNF, IL-6, MMP9, CASP3, IL-10, PTGS2, STAT3, PPARG, IL-4, EGFR, MAPK14, NOS3, and EDN1 were the core targets. The GO and KEGG pathway enrichment analyses revealed that the intersection targets were mainly enriched in positive regulation of protein phosphorylation, blood circulation, IL-17 signaling pathway, VEGF signaling pathway, and JAK/STAT signaling pathway. The molecular docking revealed that the core active ingredients had a good affinity for the core targets. The results of MDS revealed that the protein-ligand complexes were stable. Conclusions: This study used network pharmacology to analyze the potential mechanism of action of Danshen in the treatment of concurrent IHD and depression. Additionally, the study provided a theoretical basis for further studying the pharmacological mechanisms and targets of Danshen.

Abstract 15056: Cardiac P62/sqstm1 Deficiency Exacerbates Hypoxic Stress vi a Impaired Hypoxia Inducible Factor 1α Signaling

Ischemic heart disease (IHD), a major cause of heart failure, is characterized by metabolic dysfunction and myocardial cell death. Cellular hypoxia activates hypoxia inducible factor 1α (HIF1α) to initiate metabolic, angiogenic, and growth-factor related responses. Under normoxia, HIF1α is degraded by prolyl hydroxylase (PHD) domain-containing proteins via the proteasome. Due to the short half-life of HIF1α (&lt;5mins), PHD inhibitors are utilized to stabilize HIF1α and improve cardiac function in pre-clinical models of ischemia/infarction. However, evidence exists that PHD inhibitors exert off-target effects. Based on prior studies in cancer cells demonstrating that the autophagy adaptor protein p62 prevents HIF1α degradation, we hypothesized that p62 stabilizes cardiac HIF1α and provides cardioprotection from hypoxia. We generated mice with tamoxifen-inducible cardiomyocyte-specific p62 deletion (p62icKO mice; 8 week male and female) and exposed them to 7% O 2 for 6h. Hypoxia increased cardiac mRNA expression of Sqstm1 , Bnip3 , and Hmox1 in wild-type (WT) but not p62icKO mice. Underscoring functional relevance, ejection fraction and fractional shortening were less, oxidative stress was elevated, and apoptosis was greater, in p62icKO vs. WT mice exposed to hypoxia. Mechanisms were evaluated using cultured H9c2 cardiomyoblasts exposed to 21% (normoxia) or 1% (hypoxia) O 2 for 24h. Hypoxia increased both HIF1α and p62 protein expression. To determine the role of p62, H9c2 cells were transfected with p62 or scrambled (ctrl) siRNA for 48h, followed by 24 h hypoxia. Hypoxia-induced HIF1α protein accrual and expression of HIF1α downstream targets Egln1 , Vegfa , Bnip3 and Hmox1 mRNA was attenuated in H9c2 cells transfected with p62 vs. control siRNA. These data indicate p62 stabilizes cardiac HIF1α and regulates its transcriptional activation. Thus, p62 could be a novel therapeutic target for treatment of IHD.

MiRNA in Ischemic Heart Disease and Its Potential as Biomarkers: A Comprehensive Review.

Ischemic heart disease (IHD) constitutes the leading global cause of mortality and morbidity. Although significant progress has been achieved in the diagnosis, treatment, and prognosis of IHD, more robust diagnostic biomarkers and therapeutic interventions are still needed to circumvent the increasing incidence of IHD. MicroRNAs (miRNAs) are critical regulators of cardiovascular function and are involved in various facets of cardiovascular biology. While the knowledge of the role of miRNAs in IHD as diagnostic biomarkers has improved, research emphasis on how miRNAs can be effectively used for diagnosis and prognosis of IHD is crucial. This review provides an overview of the biology, therapeutic and diagnostic potential, as well as the caveats of using miRNAs in IHD based on existing research.

Reactive Oxygen Species Scavenging Nanomedicine for the Treatment of Ischemic Heart Disease.

Ischemic heart disease (IHD) is the leading cause of disability and mortality worldwide. Reactive oxygen species (ROS) have been shown to play key roles in the progression of diabetes, hypertension, and hypercholesterolemia, which are independent risk factors that lead to atherosclerosis and the development of IHD. Engineered biomaterial-based nanomedicines are under extensive investigation and exploration, serving as smart and multifunctional nanocarriers for synergistic therapeutic effect. Capitalizing on cell/molecule-targeting drug delivery, nanomedicines present enhanced specificity and safety with favorable pharmacokinetics and pharmacodynamics. Herein, the roles of ROS in both IHD and its risk factors are discussed, highlighting cardiovascular medications that have antioxidant properties, and summarizing the advantages, properties, and recent achievements of nanomedicines that have ROS scavenging capacity for the treatment of diabetes, hypertension, hypercholesterolemia, atherosclerosis, ischemia/reperfusion, and myocardial infarction. Finally, the current challenges of nanomedicines for ROS-scavenging treatment of IHD and possible future directions are discussed from a clinical perspective.

Clinical Patterns of Traditional Chinese Medicine for Ischemic Heart Disease Treatment: A Population-Based Cohort Study.

Background and objectives: Traditional Chinese medicines (TCMs) are widely prescribed to relieve ischemic heart disease (IHD); however, no cohort studies have been conducted on the use of TCMs for patients with IHD. The aim of the study was to analyze TCM prescription patterns for patients with IHD. Materials and Methods: The retrospective population-based study employed a randomly sampled cohort of 4317 subjects who visited TCM clinics. Data were obtained from the National Health Insurance Research Database (NHIRD) of Taiwan for the period covering 2000 to 2017. Data analysis focused on the top ten most commonly prescribed formulae and single TCMs. We also examined the most common two- and three-drug combinations of TCM in single prescriptions. Demographic characteristics included age and sex distributions. Analysis was performed on 22,441 prescriptions. Results: The majority of TCM patients were male (53.6%) and over 50 years of age (65.1%). Zhi-Gan-Cao-Tang (24.76%) was the most frequently prescribed formulae, and Danshen (28.89%) was the most frequently prescribed single TCM for the treatment of IHD. The most common two- and three-drug TCM combinations were Xue-Fu-Zhu-Yu-Tang and Danshen” (7.51%) and “Zhi-Gan-Cao-Tang, Yang-Xin-Tang, and Gua-Lou-Xie-Bai-Ban-Xia-Tang” (2.79%). Conclusions: Our results suggest that most of the frequently prescribed TCMs for IHD were Qi toning agents that deal with cardiovascular disease through the promotion of blood circulation. The widespread use of these drugs warrants large-scale, randomized clinical trials to investigate their effectiveness and safety.

Coronary Arterial Function and Disease in Women With No Obstructive Coronary Arteries.

Ischemic heart disease (IHD) is the leading cause of mortality in women. While traditional cardiovascular risk factors play an important role in the development of IHD in women, women may experience sex-specific IHD risk factors and pathophysiology, and thus female-specific risk stratification is needed for IHD prevention, diagnosis, and treatment. Emerging data from the past 2 decades have significantly improved the understanding of IHD in women, including mechanisms of ischemia with no obstructive coronary arteries and myocardial infarction with no obstructive coronary arteries. Despite this progress, sex differences in IHD outcomes persist, particularly in young women. This review highlights the contemporary understanding of coronary arterial function and disease in women with no obstructive coronary arteries, including coronary anatomy and physiology, mechanisms of ischemia with no obstructive coronary arteries and myocardial infarction with no obstructive coronary arteries, noninvasive and invasive diagnostic strategies, and management of IHD.

Ischemic Heart Disease Selectively Modifies the Right Atrial Appendage Transcriptome.

Background: Although many pathological changes have been associated with ischemic heart disease (IHD), molecular-level alterations specific to the ischemic myocardium and their potential to reflect disease severity or therapeutic outcome remain unclear. Currently, diagnosis occurs relatively late and evaluating disease severity is largely based on clinical symptoms, various imaging modalities, or the determination of risk factors. This study aims to identify IHD-associated signature RNAs from the atrial myocardium and evaluate their ability to reflect disease severity or cardiac surgery outcomes.Methods and Results: We collected right atrial appendage (RAA) biopsies from 40 patients with invasive coronary angiography (ICA)-positive IHD undergoing coronary artery bypass surgery and from 8 patients ICA-negative for IHD (non-IHD) undergoing valvular surgery. Following RNA sequencing, RAA transcriptomes were analyzed against 429 donors from the GTEx project without cardiac disease. The IHD transcriptome was characterized by repressed RNA expression in pathways for cell–cell contacts and mitochondrial dysfunction. Increased expressions of the CSRNP3, FUT10, SHD, NAV2-AS4, and hsa-mir-181 genes resulted in significance with the complexity of coronary artery obstructions or correlated with a functional cardiac benefit from bypass surgery.Conclusions: Our results provide an atrial myocardium-focused insight into IHD signature RNAs. The specific gene expression changes characterized here, pave the way for future disease mechanism-based identification of biomarkers for early detection and treatment of IHD.

Abstract 12866: Ischemic Heart Disease Selectively Modifies The Right Atrial Appendage Transcriptome

Introduction: Although many pathological changes have been associated with ischemic heart disease (IHD), molecular-level alterations specific to the ischemic myocardium and their potential to reflect disease severity or therapeutic outcome remain unclear. Currently, diagnosis occurs relatively late and evaluating disease severity is largely based on clinical symptoms, various imaging modalities, or the determination of risk factors. Objectives: This study aims to identify IHD-associated signature RNAs from the atrial myocardium and evaluate their ability to reflect disease severity or cardiac surgery outcomes. Methods: We collected right atrial appendage (RAA) biopsies from 40 patients with invasive coronary angiography (ICA)-positive IHD undergoing coronary artery bypass surgery and from 8 patients ICA-negative for IHD (non-IHD) undergoing valvular surgery. Following RNA sequencing, RAA transcriptomes were analyzed against those 429 donors from the GTEx project without cardiac background. Results: The IHD transcriptome was characterized using repressed RNA expressions in pathways for cell-cell contacts and mitochondrial dysfunction. Specifically, we identified the increased expressions of the CSRNP3 , FUT10 , SHD , NAV2-AS4 , and hsa-mir-181 genes to correlate with the complexity of coronary artery obstructions or with a functional cardiac benefit from bypass surgery. Conclusions: Our results provide an atrial myocardium-focused insight into IHD signature RNAs. The specific gene expression changes we characterized here pave the way for disease mechanism-based identification of biomarkers allowing for the early detection and treatment of IHD.

Abstract 14113: Age-Related Demographic Trends in Mortality Due to Ischemic Heart Disease in the United States From 1999 to 2019

Introduction: United States Ischemic heart disease (IHD) mortality has decreased recently. mortality trends for demographic groups across different ages have not been well described. Hypothesis: Different age groups have different IHD mortality trends Methods: WWe performed a nationwide analysis using the CDC WONDER database to evaluate IHD mortality trends from 1999 to 2019. Crude mortality rates per 100,000 were evaluated by sex, race, ethnicity and ten-year age groups. We used Joinpoint linear regression to assess average annual percentage change (AAPC) in IHD-related mortality. Results: From 1999 to 2019, IHD mortality decreased from 189.8 to 110.0/100,000 (AAPC -2.9%, 95% CI -3.3 to -2.6%) nationally. Compared to the 65-74 year age group (AAPC -1.7%, 95% CI -1.9 to -1.4%), decline in IHD-related mortality was lower for 35-44 year (-0.4%, 95% CI -0.4 - 0.0%; p &lt; 0.001), 45-54 year (-0.4%, 95% CI -0.5 to -0.3%; p &lt; 0.001), and 55-64 year (-0.5%, 95% CI -0.8% to -0.2%; p &lt; 0.001) age groups but similar for the 75-84 year group and higher for ≥85 year age group. Black populations had the highest mortality rates among men and women across all age groups except men ≥85 years old. All the studied groups had significant decreases in mortality between 2002 and 2010. From 2010 to 2019, all groups had significant decreases in mortality except for 35-44 year-old minority groups (black women AAPC -0.7%, 95% CI -2.3% to 1.0%; black men -0.6%, 95% CI -1.7% to 0.6%; Hispanic women 0.9, 95% CI -1.7% to 3.6%; Hispanic men 0.3%, 95% CI -0.9% to 1.5%) (Figure). Conclusions: U.S. populations &lt;65 years old have had slower declines in IHD-related mortality than those ≥65 years, and black populations continue to have the highest IHD-related mortality across almost all age groups. Since 2010, black and Hispanic populations between 35 and 44 years old have not had significant decreases in IHD-related mortality. Greater focus on prevention and treatment of IHD in younger and minority populations is needed.

Abstract 12079: Demographic and State-Level Trends in Mortality Due to Ischemic Heart Disease in the United States From 1999 to 2019

Introduction: Mortality from ischemic heart disease (IHD) in the United States (U.S.) has decreased recently, yet variation in IHD-related mortality trends for different demographic across U.S. states is not well described. Hypothesis: IHD mortality differs based on geography, gender, ethnicity, and race. Methods: We performed analysis using CDC WONDER database to evaluate IHD mortality trends in the U.S. between 1999 and 2019. Age-adjusted mortality rates (AAMR) per 100,000 people were evaluated and stratified by sex, race, and state. Joinpoint regression was used to assess annual rates of change in IHD-related mortality. Results: From 1999 to 2019, AAMR due to IHD decreased from 194.6/100,000 to 88.0/100,000 nationally. Black men had the highest AAMR, and Hispanic white women had the lowest AAMR throughout this period. AAMR for white men decreased nationally by 51.4% from 251.2 to 122.1; 59.1% for white women from 150.5 to 61.5; 51.8% for black men from 278.7 to 134.2; 59.9% for black women from 188 to 75.4; 54.3% for Hispanic men from 200.1 to 91.4; and 63.1% for Hispanic women from 133.1 to 49.0 (Figure). Relative decreases in AAMR across states ranged from 27.0%-70.9% for white men, 30.9%-68.9% for white women, 7.3%-80.9% for black men, 27.2%-74.7% for black women, 30.5%-79.8% for Hispanic men, and 35.8%-76.8% for Hispanic women. Based on the regression model, the annual average percent decline in IHD-related AAMR for all groups has decreased since 2011 (Figure). Conclusions: AAMR due to IHD in the U.S. has decreased from 1999 to 2019 for all demographic groups, though the rate of decline has lessened since 2011. There is significant geographic variation in reductions of IHD-related AAMR across U.S. states. These findings indicate that race, ethnicity, and geography are strongly associated with trends in mortality due to IHD. Given the ongoing disparities in mortality, further investigation into geographic differences in prevention and treatment of IHD is needed.