Prevention Of Atherosclerosis Research Articles

Impact of Direct Measurement of Small Dense Low-Density Lipoprotein Cholesterol for Long-Term Secondary Prevention in Patients with Stable Coronary Artery Disease.

This study investigated whether directly measured small dense low-density lipoprotein cholesterol (D-sdLDL-C) can predict long-term coronary artery disease (CAD) events compared with low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (apoB), and estimated small dense low-density lipoprotein cholesterol (E-sdLDL-C) determined by the Sampson equation in patients with stable CAD. D-sdLDL-C measured at Showa University between 2010 and 2022, and E-sdLDL-C were evaluated in 790 male and 244 female patients with stable CAD. CAD events, defined as sudden cardiac death, onset of acute coronary syndrome, and/or need for coronary revascularization, were monitored for 12 years. Cutoff lipid levels were determined by receiver operating characteristic curves. CAD events were observed in 238 male and 67 female patients. The Kaplan-Meier event-free survival curves showed that patients with D-sdLDL-C ≥32.1 mg/dL (0.83 mmol/L) had an increased risk for CAD events (P = 0.007), whereas risk in patients with E-sdLDL-C ≥36.2 mg/dL (0.94 mmol/L) was not increased. In the group with high D-sdLDL-C, the multivariable-adjusted hazard ratio (HR) was 1.47 (95% CI, 1.15-1.89), and it remained significant after adjustment for LDL-C, non-HDL-C, or apoB and in patients treated with statins. HRs for high LDL-C, non-HDL-C, or apoB were not statistically significant after adjustment for high D-sdLDL-C. Higher D-sdLDL-C was associated with enhanced risk of high LDL-C, non-HDL-C, and apoB (HR 1.73; 95% CI, 1.27-2.37). Higher D-sdLDL-C can predict long-term recurrence of CAD in stable CAD patients independently of apoB and non-HDL-C. D-sdLDL-C is an independent risk enhancer for secondary CAD prevention, whereas E-sdLDL-C is not. UMIN-CTR Clinical Trial Number: UMIN000027504.

Health economic analysis of polygenic risk score use in primary prevention of coronary artery disease – a system dynamics model

Health economic analysis of polygenic risk score use in primary prevention of coronary artery disease – a system dynamics model

Endothelial dysfunction in breast cancer survivors on aromatase inhibitors: changes over time

BackgroundBreast cancer is estimated to comprise about 290,560 new cases in 2022. Aromatase inhibitors (AIs) are recommended as adjuvant treatment for estrogen-receptor positive (ER+) breast carcinoma in postmenopausal women, which includes approximately two-thirds of all women with breast cancer. AIs inhibit the peripheral conversion of androgens to estrogen by deactivation of the aromatase enzyme, leading to a reduction in serum estrogen level in postmenopausal women with ER+ breast carcinoma. Estrogen is known for its cardiovascular (CV) protective properties through a variety of mechanisms including vasodilation of blood vessels and inhibition of vascular injury resulting in the prevention of atherosclerosis. In clinical trials and prospective cohorts, the long-term use of AIs can increase the risk for hypertension and hyperlipidemia. Studies demonstrate mixed results as to the impact of AIs on actual CV events and overall survival.MethodsA single arm longitudinal study of 14 postmenopausal women with ER+ breast cancer prescribed adjuvant AIs at the University of Minnesota (UMN). Subjects with a history of known tobacco use, hypertension, hyperlipidemia, and diabetes were excluded to eliminate potential confounding factors. Participants underwent routine labs, blood pressure assessments, and vascular testing at baseline (prior to starting AIs) and at six months. Vascular assessment was performed using the EndoPAT 2000 and HDI/PulseWave CR-2000 Cardiovascular Profiling System and pulse contour analysis on two occasions as previously described. Vascular measurements were conducted by one trained vascular technician. Assessments were performed in triplicate, and the mean indices were used for analyses. All subjects were on an AI at the follow-up visit. The protocol was approved by the UMN Institutional Review Board and all participants were provided written informed consent. Baseline and follow-up characteristics were compared using Wilcoxon signed-rank tests. Analyses were performed using R version 3.6.1 (R Foundation for Statistical Computing, Vienna, Austria).ResultsAfter six months of AI treatment, EndoPAT® ratio declined to a median 1.12 (Q1: 0.85, Q3: 1.86; p = 0.045; Figure 1) and median estradiol levels decreased to 2 pg/mL (Q1: 2, Q3: 3; p=0.052). There was no evidence of association between change in EndoPAT® and change in estradiol level (p = 0.91). There were no statistically significant changes in small or large arterial elasticity.ConclusionsWe hypothesize that long-term use of AI can lead to persistent endothelial dysfunction, and further investigation is necessary. In our study, patients were on AI for approximately 5-10 years. As a result, we do not have data on whether these changes, such as EndoPAT® ratio and the elasticity of small and large arterial, are reversible with discontinuation of AI. These findings set the stage for a larger study to more conclusively determine the association between AI exposure and cardiovascular outcomes. Further studies should evaluate for multivariate associations withmodifiable risk factors for CV disease.

A potential early-atheroprotective target: Irgm1 mediates lymphangiogenesis through LEC autophagy by Tfeb translocation

Lymphatic dysfunction is a pivotal pathological mechanism underlying the development of early atherosclerotic plaques. Potential targets of lymphatic function must be identified to realize the early prevention and treatment of atherosclerosis (AS). The immunity-related GTPase Irgm1 is involved in orchestrating cellular autophagy and apoptosis. However, the effect of Irgm1 on early AS progression, particularly through alterations in lymphatic function, remains unclear. In this study, we confirmed the protective effect of lymphangiogenesis on early-AS in vivo. Subsequently, an in vivo model of early AS mice with Irgm1 knockdown shows that Irgm1 reduces early atherosclerotic plaque burden by promoting lymphangiogenesis. Given that lymphatic endothelial cell (LEC) autophagy significantly contributes to lymphangiogenesis, Irgm1 may enhance lymphatic circulation by promoting LEC autophagy. Moreover, Irgm1 orchestrates autophagy in LECs by inhibiting mTOR and facilitating nuclear translocation of Tfeb. Collectively, these processes lead to lymphangiogenesis. Thus, this study establishes a link between Irgm1 and early AS, thus revealing a novel mechanism by which Irgm1 exerts an early protective influence on AS within the context of lymphatic circulation. The insights gained from this study have the potential to revolutionize the approach and management of AS onset.

Atherosclerosis Is a Smooth Muscle Cell-Driven Tumor-Like Disease.

Atherosclerosis, a leading cause of cardiovascular disease, involves the pathological activation of various cell types, including immunocytes (eg, macrophages and T cells), smooth muscle cells (SMCs), and endothelial cells. Accumulating evidence suggests that transition of SMCs to other cell types, known as phenotypic switching, plays a central role in atherosclerosis development and complications. However, the characteristics of SMC-derived cells and the underlying mechanisms of SMC transition in disease pathogenesis remain poorly understood. Our objective is to characterize tumor cell-like behaviors of SMC-derived cells in atherosclerosis, with the ultimate goal of developing interventions targeting SMC transition for the prevention and treatment of atherosclerosis. We used SMC lineage tracing mice and human tissues and applied a range of methods, including molecular, cellular, histological, computational, human genetics, and pharmacological approaches, to investigate the features of SMC-derived cells in atherosclerosis. SMC-derived cells in mouse and human atherosclerosis exhibit multiple tumor cell-like characteristics, including genomic instability, evasion of senescence, hyperproliferation, resistance to cell death, invasiveness, and activation of comprehensive cancer-associated gene regulatory networks. Specific expression of the oncogenic mutant KrasG12D in SMCs accelerates phenotypic switching and exacerbates atherosclerosis. Furthermore, we provide proof of concept that niraparib, an anticancer drug targeting DNA damage repair, attenuates atherosclerosis progression and induces regression of lesions in advanced disease in mouse models. Our findings demonstrate that atherosclerosis is an SMC-driven tumor-like disease, advancing our understanding of its pathogenesis and opening prospects for innovative precision molecular strategies aimed at preventing and treating atherosclerotic cardiovascular disease.

Cardiac rehabilitation using intensive lifestyle habituation combined with outdoor exercise in an urban forest environment for primary and secondary prevention of coronary artery disease: a feasibility test

Background: We aimed to examine the feasibility of intensive lifestyle habituation with a subsequent home program, including forest-based exercise, as an alternative approach to conventional cardiac rehabilitation for both primary and secondary prevention of coronary artery disease (CAD).Methods: A total of 28 participants were included in a 1-week intensive education program aimed at fostering desirable lifestyle habits in the study: 17 patients who underwent percutaneous coronary intervention and 11 participants at high risk of CAD. Subsequently, they engaged in a self-directed, home-based program that included unstructured exercise in an urban forest. The terrain of the urban forest was analyzed to estimate metabolic equivalent levels and to assess safety and accessibility for patient exercise.Results: Throughout the program, no adverse cardiac events were reported. Additionally, risk factors for CAD—including body composition, blood sugar levels, hemodynamic variables, total cholesterol levels, and cardiorespiratory endurance—showed significant improvement in both groups.Conclusions: Intensive lifestyle habituation and unstructured, self-directed exercise in the forest were as effective and safe as conventional cardiac rehabilitation for patients with CAD. The study demonstrated that an urban forest could serve as a safe exercise environment in both primary and secondary prevention strategies for CAD.

JCS 2023 Guideline on the Primary Prevention of Coronary Artery Disease.

JCS 2023 Guideline on the Primary Prevention of Coronary Artery Disease.

The potential molecular mechanism underlying gypenoside amelioration of atherosclerosis in ApoE−/− mice: A multi-omics investigation

Gypenosides (Gyp) are bioactive components of Gynostemma pentaphyllum that have a variety of pharmacological properties. Extracts of G. pentaphyllum have been found to be effective in the reduction of blood sugar and lipids and prevention of atherosclerosis. Here, the functions of Gyp and the mechanisms underlying their effects on atherosclerosis were investigated. Mice were allocated to three groups, namely, the control (C57BL/6), atherosclerosis model (ApoE−/− mice with high-fat diet), and Gyp-treated groups. Differentially expressed mRNAs, miRNAs, circRNA, and differential metabolites among the groups were analyzed. The results showed that “Fatty acid metabolism”, “Fatty acid elongation”, “Cytokine-cytokine receptor interaction”, and “PI3K-Akt signaling pathway”, amongst others, were involved in treatment process. Differentially expressed genes, including Fabp1, Apoe, FADS1, ADH1, SYNPO2, and Lmod1were also identified. Mmu-miR-30a and mmu-miR-30e showed reduced expression in atherosclerosis models but were increased following Gyp treatment, suggesting involvement in the effects of Gyp. In addition, chr5:150604177-150608440 were found to interact with mmu-miR-30a and mmu-miR-30e to regulate their abundance. In terms of metabolomics, Gyp may regulate biological processes involving PGD2 and PGJ2, potentially alleviating atherosclerosis. In conclusion, Gyp appeared to have complex effects on atherosclerosis, most of which were positive. These results support the use of Gyp in the treatment of atherosclerosis.

The novel vaccines targeting interleukin-1 receptor type I

ObjectiveThere is mounting evidence indicating that atherosclerosis represents a persistent inflammatory process, characterized by the presence of inflammation at various stages of the disease. Interleukin-1 (IL-1) precisely triggers inflammatory signaling pathways by binding to interleukin-1 receptor type I (IL-1R1). Inhibition of this signaling pathway contributes to the prevention of atherosclerosis and myocardial infarction. The objective of this research is to develop therapeutic vaccines targeting IL-1R1 as a preventive measure against atherosclerosis and myocardial infarction. MethodsILRQβ-007 and ILRQβ-008 vaccines were screened, prepared and then used to immunize high-fat-diet fed ApoE-/- mice and C57BL/6J mice following myocardial infarction. Progression of atherosclerosis in ApoE-/- mice was assessed primarily by oil-red staining of the entire aorta and aortic root, as well as by detecting the extent of macrophage infiltration. The post-infarction cardiac function in C57BL/6J mice were evaluated using cardiac ultrasound and histological staining. ResultsILRQβ-007 and ILRQβ-008 vaccines stimulated animals to produce high titers of antibodies that effectively inhibited the binding of interleukin-1β and interleukin-1α to IL-1R1. Both vaccines effectively reduced atherosclerotic plaque area, promoted plaque stabilization, decreased macrophage infiltration in plaques and influenced macrophage polarization, as well as decreasing levels of inflammatory factors in the aorta, serum, and ependymal fat in ApoE-/- mice. Furthermore, these vaccines dramatically improved cardiac function and macrophage infiltration in C57BL/6J mice following myocardial infarction. Notably, no significant immune-mediated damage was observed in immunized animals. ConclusionThe vaccines targeting the IL-1R1 would be a novel and promising treatment for the atherosclerosis and myocardial infarction.

Screening, risk stratification and CT imaging for assessment of coronary artery disease

Early treatment of cardiovascular risk factors and characterization of coronary plaques is essential to collect prognostic information about coronary artery disease (CAD) and prevent cardiovascular events. Discussion of the most important risk factors of CAD, basic diagnostic of CAD, prevention, and prognostic factors of CAD with focus on cardiac computed tomography (CT). Prevalence and prognostic impact of CAD risk factors; description of specific assessment of risk profiles; estimation of pretest probability; conventional prevention of CAD; prognostic assessment of CAD using the Calcium Scoring and coronary CT angiography. Assessment of risk profiles and estimation of pretest probability for obstructive coronary stenosis necessitates athorough evaluation of medical history and laboratory values. The composition and extent of calcified and noncalcified plaques in CT exams based on the criteria of the Coronary Artery Disease-Reporting and Data System give important prognostic information about the risk of cardiovascular events, which increases with high plaque burden and vice versa. Initial imaging with CT for evaluation of CAD leads to areduction of invasive coronary angiographies and catheter-associated complications. Besides early detection of cardiovascular risk factors, the additional assessment of plaque burden and significant stenosis in CT gives further prognostic information to facilitate effective therapies to prevent cardiovascular events and in the case of low plaque burden avoid invasive coronary angiography. However, systmatic screening using Calcium Scoring is not established yet due to insufficient data, although it could potentially be used for an early risk stratification in patients with multiple risk factors.

Role of interleukin 6 signaling pathway in the anti-inflammatory effects of statins on coronary artery disease: Evidence from Mendelian randomization analysis

BackgroundStatins are currently widely used in the prevention of coronary artery disease (CAD) primarily for lipid-lowering with a potential anti-inflammatory effect. However, it is not clear if their potential anti-inflammatory effects are mediated through the interleukin 6 (IL-6) signaling pathway. MethodsUsing the Mendelian randomization (MR) approach followed by multivariable MR analyses, we examined the extent to which the effects of statins on CAD might be mediated through the IL-6 signaling pathway. ResultsOur observations showed that HMG-CoA reductase, using LDL levels as a proxy, had a significant effect on upstream IL-6 (βMR = 0.47, P-IVW = 0.01) and nominally significant effects on IL-6RA (βMR = 0.22, P-IVW = 0.047) and APOB (βMR = 0.82, P-IVW = 1.8 × 10–33). While the IL-6 signaling cascade (IL-6RA βMR = −0.06, P-IVW = 3.45 × 10–20 and IL-6 βMR = −0.03, P-IVW = 0.09) and the anti-inflammatory effect of HMG-CoA reductase (βMR = −0.31, P-IVW = 0.01) was found to influence the risk of CAD, the multivariable MR (MVMR) model indicated that the anti-inflammatory effect of HMG-CoA reductase is not likely to be mediated through the IL-6 signaling cascade, including APOB and IL-6RA (MVMRβ = 0.23, P = 0.688). ConclusionsOur findings suggest that statins may use inflammatory mechanisms independent of the IL-6 signaling pathway to prevent CAD. This result could potentially affect the definition of the target population for statin use.

Study of the mechanism of action of sand therapy on atherosclerosis based on the two-phase flow-Casson model.

Sand therapy is a non-pharmacological physiotherapy method that uses the natural environment and resources of Xinjiang to treat through the heat transfer and magnetic effects of sand. Employing the two-phase flow-Casson blood flow model, we investigate the mechanism of atherosclerosis prevention via sand therapy, offering a biomechanical theoretical rationale for the prevention of atherosclerosis through sand therapy via the prism of computational fluid dynamics (CFD). Sand therapy experiments were conducted to obtain popliteal artery blood flow velocity, and blood was considered as a two-phase flow composed of plasma and red blood cells, and CFD method was applied to analyze the hemodynamic effects of Casson's blood viscosity model before and after sand therapy. (1) The blood flow velocity increased by 0.24 m/s and 0.04 m/s at peak systolic and diastolic phases, respectively, after sand therapy; the axial velocity of blood vessels increased by 28.56% after sand therapy. (2) The average red blood cell viscosity decreased by 0.00014 Pa ⋅ s after sand therapy. (3) The low wall shear stress increased by 1.09Pa and the high wall shear stress reached 41.47Pa after sand therapy. (4) The time-averaged wall shear stress, shear oscillation index and relative retention time were reduced after sand therapy. The increase of blood flow velocity after sand therapy can reduce the excessive deposition of cholesterol and other substances, the decrease of erythrocyte viscosity is beneficial to the migration of erythrocytes to the vascular center, the increase of low wall shear stress has a positive effect on the prevention of atherosclerosis, and the decrease of time-averaged wall shear stress, shear oscillation index and relative retention time can reduce the occurrence of thrombosis.

A Study to Assess the Knowledge regarding Prevention of Coronary Artery Disease among the Students of Selected Colleges of Guwahati, Assam and with a View to Develop an Information Booklet on Prevention of CAD

A Study to Assess the Knowledge regarding Prevention of Coronary Artery Disease among the Students of Selected Colleges of Guwahati, Assam and with a View to Develop an Information Booklet on Prevention of CAD

Silicon in prevention of atherosclerosis and other age-related diseases.

Researchers' interest in silicon as an element important for the functioning of the animal and human body began in the 1970s. Soluble compounds of silicon bioavailable from water and food seem to have important meaning for life processes occurring in the body. So far, researchers have focused on the significance of silicon for the development of bones and connective tissue, and its role in preventing neurodegenerative diseases and atherosclerosis. Despite numerous studies, the role of silicon as an active element in the human body is poorly understood. Since the involvement of lipid oxidation and inflammatory processes in the pathogenesis of atherosclerosis is well known, this article summarizes and discusses the current research and scientific observations regarding silicon, primarily in terms of its beneficial influence on redox and anti-inflammatory reactions and the lipid profile. The association of silicon with the stabilization of the structure of glycosaminoglycans and their protein complexes may also support the anti-atherosclerotic effect. The authors attempted to collect and present existing publications that could confirm the beneficial role of dietary silicon in the prevention of age-related diseases and explain the potential mechanisms of its action.

The negative effects of statin drugs on cardiomyocytes: current review of laboratory and experimental data (mini-review).

Statin drugs have long been used as a key component of lipid-lowering therapy, which is necessary for the prevention and treatment of atherosclerosis and cardiovascular diseases. Many studies focus on finding and refining new effects of statin drugs. In addition to the main lipid-lowering effect (blocking cholesterol synthesis), statin drugs have a number of pleiotropic effects, including negative effects. The main beneficial effects of statin drugs on the components of the cardiovascular system are: anti-ischemic, antithrombotic, anti-apoptotic, antioxidant, endothelioprotective, anti-inflammatory properties, and a number of other beneficial effects. Due to these effects, statin drugs are considered one of the main therapeutic agents for the management of patients with cardiovascular pathologies. To date, many review manuscripts have been published on the myotoxicity, hepatotoxicity, nephrotoxicity, neurotoxicity and diabetogenic effects of statins. However, there are no review manuscripts considering the negative effect of statin drugs on myocardial contractile cells (cardiomyocytes). The purpose of this review is to discuss the negative effects of statin drugs on cardiomyocytes. Special attention is paid to the cardiotoxic action of statin drugs on cardiomyocytes and the mechanisms of increased serum levels of cardiac troponins. In the process of preparing this review, a detailed analysis of laboratory and experimental data devoted to the study of the negative effects of statin drugs on cardiomyocytes was carried out. The literature search was carried out with the keywords: statin drugs, negative effects, mechanisms, cardiac troponins, oxidative stress, apoptosis. Thus, statin drugs can have a number of negative effects on cardiomyocytes, in particular, increased oxidative stress, endoplasmic reticulum stress, damage to mitochondria and intercalated discs, and inhibition of glucose transport into cardiomyocytes. Additional studies are needed to confirm and clarify the mechanisms and clinical consequences of the negative effects of statin drugs on cardiomyocytes.

Efficacy and potential mechanism of atherosclerosis prevention by the active components of leech based on network pharmacology combined with animal experiments

IntroductionLeeches are flesh-eating and bloodsucking parasitic worms. They are being used as a traditional Chinese medicine for centuries in activating blood and dissolving statis, dreging the meridims and tick. Hirudin, an active peptide product present in leech, has blood anticoagulant property and can assist in the treatment of thrombosis and diseases related to blood circulation. The efficacy and potential mechanism of action of leeches in such diseases should be further explored. Materials and methodsFirst, network pharmacology was used to screen the predicted potential targets of the active constituents of leech and AS. The common targets of the active constituents of leech and AS were obtained using Venn diagram. Further, the drug-active-constituent–target network diagram, protein–protein interaction, and GO and KEGG pathway enrichment analyses were used to construct the active-constituent–AS target–pathway network diagram. Subsequently, the protein–drug molecule docking model was drawn. Finally, the results of network pharmacology were validated using a mouse model of AS. ResultsIn total, 34 active constituents of leech and 1172 AS-related gene targets were selected, took the drug action targets and potential disease targets to get the common targets, and took the top 10 of degree value as the main active constituents for the treatment of atherosclerosis. There were 89 common targets and 12 core targets. The main targets included MAPK, EGFR, PIK3CB, etc. Potential regulatory pathways included cancer pathways, EGFR tyrosine kinase inhibitor resistance, Rap1 signaling pathway, PPAR signaling pathway, PI3K-Akt signaling pathway, C-type lectin receptor signaling pathway, and AGE-RAGE signaling pathway in diabetic complications. Animal experiments using mouse model of AS confirmed that AS plaques were smaller after treatment with leeches. SRC level was measured using western blotting. Expression of SRC in myocardial tissue was remarkably lower in the mice treated with leech than in the mice from model group fed on high-fat chow. ConclusionsTo the best of our knowledge, this is the first study to explore the mechanism of action of the active components of leech in AS prevention. The active components of leeches play a coordinated role in preventing AS through multicomponent, multitarget, and multichannel mechanism of action related to inflammatory response, oxidative stress, and lipid metabolism. This study provided a reference for subsequent cellular and animal experiments.

Correlation between the serum FABP4, ANGPTL3, and ANGPTL4 levels and coronary artery disease.

Lipid metabolism related factors, such as angiopoietin-like protein 3 (ANGPTL3), angiopoietin-like 4 (ANGPTL4), fatty acid-binding protein 4 (FABP4) are newly discovered factors that can affect coronary artery disease (CAD). In this study, we aimed to investigate the relationship between CAD and these lipid metabolism factors. ANGPTL3, ANGPTL4, and FABP4 may provide a new method for the control of CAD risk factors and the prevention and treatment of CAD. We enrolled 284 consecutive inpatients with suspected CAD and divided them into CAD and non-CAD groups based on the coronary angiography results. Serum ANGPTL3, ANGPTL4, FABP4, and tumor necrosis factor-α (TNF-α) levels were estimated using the enzyme-linked immunosorbent assay. Multivariate logistic regression was used to assess the risk factors for CAD. The receiver operating characteristic curve was used to determine the cutoff and diagnostic values. The serum TNF-α, FABP4, ANGPTL3, and ANGPTL4 values showed a significant difference between the CAD and non-CAD groups (p < .05). After adjusting for confounding factors, the FABP4, ANGPTL3, and ANGPTL4 levels were independently associated with CAD (p < .05). The ANGPTL3 expression level was an independent risk factor for CAD in patients with hypertension, but not in those without hypertension. The ANGPTL3 > 67.53 ng/mL, ANGPTL4 > 29.95 ng/mL, and FABP4 > 1421.25 ng/L combination had the highest diagnostic value for CAD. ANGPTL3, ANGPTL4, and FABP4 were identified as independent risk factors for CAD and have valuable clinical implications for the diagnosis and treatment of CAD.

Drug target Mendelian randomization supports apolipoprotein C3-lowering for lipoprotein-lipid levels reductions and cardiovascular diseases prevention

Background and aimsInhibitors of apolipoprotein C-III (apoC3) are currently approved for the reduction of triglyceride levels in patients with Familial Chylomicronemia Syndrome. We used drug target Mendelian randomization (MR) to assess the effect of genetically predicted decrease in apoC3 blood protein levels on cardiometabolic traits and diseases. MethodsWe quantified lifelong reductions in apoC3 blood levels by selecting all genome wide significant and independent (r2<0.1) single nucleotide polymorphisms (SNPs) in the APOC3 gene region ±1 Mb, from three genome-wide association studies (GWAS) of apoC3 blood protein levels (deCODE, n = 35,378, Fenland, n = 10,708 and ARIC, n = 7213). We included the largest GWASes on 18 cardiometabolic traits and 9 cardiometabolic diseases as study outcomes. ResultsA one standard deviation lowering in apoC3 blood protein levels was associated with lower triglycerides, apolipoprotein B, low-density lipoprotein cholesterol, alanine aminotransferase, and glomerular filtration rate as well as higher high-density lipoprotein cholesterol levels. ApoC3 lowering was also associated with lower risk of acute pancreatitis (odds ratio [OR] = 0.91 95% CI = 0.82 to 1.00), aortic stenosis (OR = 0.82 95% CI = 0.73 to 0.93), and coronary artery disease (OR = 0.86 95% CI = 0.80 to 0.93), and was associated with increased parental lifespan (0.06 95% CI = 0.03–0.09 years). These results were concordant across robust MR methods, the three protein datasets and upon adjustment for APOA1, APOA4 and APOA5 using a multivariable MR framework. ConclusionsThese results provide evidence that apoC3 lowering could result in widespread benefits for cardiometabolic health and encourage the launch of trials on apoC3 inhibition for coronary artery disease prevention.

Association between anti-Helicobacter pylori immunoglobulin G status and coronary artery disease among hypertensives: Myth or fact?

Abstract Background: Chronic persistent inflammation associated with Helicobacter pylori (H. pylori) infection accelerates vascular complications which are prone to cause atherogenesis and coronary artery disease (CAD). This study was undertaken to assess the significance of the association between H. pylori immunoglobulin G (IgG) serostatus and the occurrence of CAD among hypertensives. Materials and Methods: A total of 90 hypertensive subjects without stroke and CAD symptoms were tested for serum H. pylori IgG. Their electrocardiogram and echocardiogram (ECHO) outcomes were analyzed after 3 months. Results: Among the 90 subjects, 52 (57.8%) were H. pylori IgG positive. The adjusted odds ratio for abnormal ECHO outcome and H. pylori IgG positivity was 2.494. There was a positive correlation between H. pylori IgG positivity, sedentary lifestyle, alcoholism, and elevated serum C-reactive protein and abnormal ECHO findings suggestive of CAD. Conclusions: This study found a positive correlation between H. pylori IgG seropositivity and abnormal ECHO outcomes. The prevention of CAD with antimicrobial therapy for H. pylori is simple and innovative. Lifestyle modification and hand hygiene can obviate the adverse circumstances of CAD to some extent.

Single-nucleus RNA sequencing reveals that macrophages and smooth muscle cells promote carotid atherosclerosis progression through mitochondrial autophagy.

Carotid atherosclerotic plaques are the manifestation of atherosclerosis in the carotid arteries and can significantly increase the incidence of cerebrovascular disease. Macrophages and smooth muscle cells are crucial for their development. To reveal the mechanism of carotid atherosclerotic plaque formation, we performed single-nucleus RNA sequencing of the carotid plaque tissue and identified 11 cell types, and the macrophages were divided into 5 different macrophage subpopulations. The macrophages and smooth muscle cells in the patients with symptomatic carotid atherosclerotic plaques caused intraplaque cell death via the mitochondrial autophagic pathway, resulting in plaque instability and rupture, which in turn led to clinical cardiovascular and cerebrovascular events. The findings provide new insights into carotid atherosclerosis formation, and this may provide new directions for the prevention and treatment of carotid atherosclerosis.