Atherosclerosis最新文献

{"title":"Arterial imaging might optimize statin eligibility by current atherosclerotic cardiovascular disease risk calculation tools","authors":"Konstantinos G. Kyriakoulis, Aikaterini Komnianou, Kyriakos Dimitriadis, Anastasios Kollias","doi":"10.1016/j.atherosclerosis.2024.119093","DOIUrl":"10.1016/j.atherosclerosis.2024.119093","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"401 ","pages":"Article 119093"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations between plasma caspase-1 levels and cardiovascular disease, with the mediating role of metabolic syndrome","authors":"Yajuan Zhang ,&nbsp;Yumei Huang ,&nbsp;Shaobo Hu ,&nbsp;Gang Liu ,&nbsp;Tianshu Zeng ,&nbsp;An Pan ,&nbsp;Yunfei Liao","doi":"10.1016/j.atherosclerosis.2024.119090","DOIUrl":"10.1016/j.atherosclerosis.2024.119090","url":null,"abstract":"<div><h3>Aims</h3><div>This study aimed to explore the association between plasma caspase-1 levels and cardiovascular disease (CVD), as well as the potential mediating role of metabolic syndrome (Mets) in the association.</div></div><div><h3>Methods</h3><div>This study analyzed the UK Biobank Precision Proteomics Project (UKB-PPP), which detected plasma caspase-1 levels in participants. CVD was defined by ICD-9/ICD-10 codes. The Cox proportional hazards regression model was used to explore the hazard ratio (HR) of plasma caspase-1 levels with CVD. Mediation analysis was conducted to investigate the mediating effect of Mets and its components on this relationship.</div></div><div><h3>Results</h3><div>This study included a total of 41,499 participants. Among them, 4869 (11.7 %) participants were documented to have developed CVD during a median follow-up of 13.6 years. In the fully adjusted model, compared with individuals in the lowest tertile of plasma caspase-1 levels, the highest tertile was significantly associated with an increased risk of CVD (HR = 1.11, 95 % CI, 1.04–1.19). Per one-unit Normalized Protein eXpression (NPX) increment in plasma caspase-1 concentrations was associated with a 6 % higher risk of CVD (<em>p</em>＜0.001). The mediating effect of Mets was the largest, at 17.5 %, with its components hypertension, central obesity, hypertriglyceridemia, hyperglycemia and dyslipidemia mediated the effects by 13.52 %, 9.72 %, 7.35 %, 4.63 % and 2.74 %, respectively.</div></div><div><h3>Conclusions</h3><div>Higher plasma caspase-1 levels were associated with a higher risk of CVD. This association may be partially mediated by Mets and its components, suggesting that caspase-1 may increase the risk of CVD by increasing the occurrence of Mets.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"401 ","pages":"Article 119090"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cascade screening of a Pakistani consanguineous familial hypercholesterolemia cohort: Identification of seven new homozygous patients","authors":"Quratul Ain ,&nbsp;Jaka Sikonja ,&nbsp;Fouzia Sadiq ,&nbsp;Saeed Shafi ,&nbsp;Jan Kafol ,&nbsp;Tevz Gorjanc ,&nbsp;Ursa Sustar ,&nbsp;Jernej Kovac ,&nbsp;Mohammad Iqbal Khan ,&nbsp;Muhammad Ajmal ,&nbsp;Urh Groselj","doi":"10.1016/j.atherosclerosis.2025.119118","DOIUrl":"10.1016/j.atherosclerosis.2025.119118","url":null,"abstract":"<div><h3>Background and aims</h3><div>Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels from birth, significantly increasing the risk of premature cardiac events and mortality. In Pakistan, despite the potential burden of FH, comprehensive studies evaluating its genetic characteristics, cascade screening significance, and lipoprotein (a) [Lp(a)] levels remain scarce. Understanding these factors is crucial for effective diagnosis, risk assessment, and management of FH in the Pakistani population.</div></div><div><h3>Methods</h3><div>After the identification of index case with clinical homozygous FH, characterized by high LDL-C and high Lp(a) levels together with a positive personal and family history of cardiovascular disease, a cascade screening of 66 relatives from a consanguineous family was performed. Blood samples were obtained from all subjects for biochemical and genetic analysis. Simon Broome criteria was applied on children for clinical FH diagnosis. Dutch Lipid Clinic Network scores were calculated for individuals aged ≥16years. Genetic screening was performed using next-generation sequencing to analyse all coding regions and exon-intron borders of the following genes: <em>ALMS1, APOA1, APOB, APOA5, APOC2, APOC3, APOE, ABCA1, ABCG5, ABCG8, CREB3L3, GPIHBP1, LDLR, LDLRAP1, LIPA, LMF1, LPL</em>, and <em>PCSK9</em>. The identified variants were confirmed using Sanger sequencing.</div></div><div><h3>Results</h3><div>Cascade screening identified seven homozygous and 25 heterozygous FH patients with pathogenic variant in the <em>LDLR</em> gene (NM_000527.5: c.2416dupG: p. Val806GlyfsTer11). Additionally, heterozygous variants of uncertain significance were identified in 4 other subjects.</div></div><div><h3>Conclusion</h3><div>This study underscores the high effectiveness of cascade screening in consanguineous families and societies that could lead to early detection and prevention.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"402 ","pages":"Article 119118"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143142558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling feature importance biases in linear regression: Implications for protein-centric cardiovascular research","authors":"Yoshiyasu Takefuji","doi":"10.1016/j.atherosclerosis.2024.119049","DOIUrl":"10.1016/j.atherosclerosis.2024.119049","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"401 ","pages":"Article 119049"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-related differences in response to lomitapide in HoFH: A subanalysis of the Pan-European Lomitapide retrospective observational study","authors":"Chiara Pavanello ,&nbsp;Patrizia Suppressa ,&nbsp;Sofia Castiglione ,&nbsp;Alessia Di Costanzo ,&nbsp;Daniele Tramontano ,&nbsp;Luigi Rizzi ,&nbsp;Kim Steward ,&nbsp;Laura Calabresi ,&nbsp;Marcello Arca ,&nbsp;Jeanine Roeters van Lennep ,&nbsp;Laura D'Erasmo","doi":"10.1016/j.atherosclerosis.2024.119089","DOIUrl":"10.1016/j.atherosclerosis.2024.119089","url":null,"abstract":"<div><h3>Background and aims</h3><div>Homozygous familial hypercholesterolemia (HoFH) is a hereditary lipid metabolism disorder characterized by severe elevation of low-density lipoprotein cholesterol (LDL-C) and heightened risk of premature atherosclerotic cardiovascular disease (ASCVD). Lomitapide, an inhibitor of microsomal triglyceride transfer protein, has shown promise in reducing LDL-C levels, albeit with variable response in real-world settings. Sex-based differences in treatment efficacy and safety remain unclear.</div></div><div><h3>Methods and Results</h3><div>This <em>post-hoc</em> analysis of the Pan-European Lomitapide Study investigated sex-specific disparities in the efficacy and safety of lomitapide in HoFH patients (N=38 women and N=37 men). Data were collected from HoFH patients receiving lomitapide across Europe.</div><div>Clinical characteristics, lipid profile, and adverse events were compared between women and men.</div><div>Results indicate comparable baseline characteristics and cardiovascular risk factors between sexes. While LDL-C reduction was comparable at each time point between the two groups, women exhibited a trend towards greater reduction compared to men, particularly evident at 6 months (−53.0% vs −32.9% <em>p</em>=0.051). Annual LDL-C reduction did not differ between sexes (−4.83% ± 7.02 vs −4.03% ± 9.74 <em>p</em>=0.526).</div><div>No differences in the median lomitapide dose or the intensity of concomitant lipid lowering therapies were observed between sexes.</div><div>Notably, gastrointestinal disturbances were more prevalent in women (78 events in women vs 32 in men, <em>p</em>=0.0002), although most adverse events were manageable.</div><div>Event-free survival curves for ASCVD did not significantly differ between sexes (<em>p</em>=0.363).</div></div><div><h3>Conclusions</h3><div>Lomitapide demonstrates comparable efficacy in reducing LDL-C levels in men and women with HoFH, with potential sex-specific variations in tolerability.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"401 ","pages":"Article 119089"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using omics data and genome editing methods to decipher GWAS loci associated with coronary artery disease","authors":"Arnaud Chignon ,&nbsp;Guillaume Lettre","doi":"10.1016/j.atherosclerosis.2024.118621","DOIUrl":"10.1016/j.atherosclerosis.2024.118621","url":null,"abstract":"<div><div>Coronary artery disease (CAD) is due to atherosclerosis, a pathophysiological process that involves several cell-types and results in the accumulation of lipid-rich plaque that disrupt the normal blood flow through the coronary arteries to the heart. Genome-wide association studies have identified 1000s of genetic variants robustly associated with CAD or its traditional risk factors (e.g. blood pressure, blood lipids, type 2 diabetes, smoking). However, gaining biological insights from these genetic discoveries remain challenging because of linkage disequilibrium and the difficulty to interpret the functions of non-coding regulatory elements in the human genome. In this review, we present different statistical methods (e.g. Mendelian randomization) and molecular datasets (e.g. expression or protein quantitative trait loci) that have helped connect CAD-associated variants with genes, biological pathways, and cell-types or tissues. We emphasize that these various strategies make predictions, which need to be validated in orthologous systems. We discuss specific examples where the integration of omics data with GWAS results has prioritized causal CAD variants and genes. Finally, we review how targeted and genome-wide genome editing experiments using the CRISPR/Cas9 toolbox have been used to characterize new CAD genes in human cells. Researchers now have the statistical and bioinformatic methods, the molecular datasets, and the experimental tools to dissect comprehensively the loci that contribute to CAD risk in humans.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"401 ","pages":"Article 118621"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143155175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AI-derived automated quantification of cardiac chambers and myocardium from non-contrast CT: Prediction of major adverse cardiovascular events in asymptomatic subjects","authors":"Aryabod Razipour ,&nbsp;Kajetan Grodecki ,&nbsp;Nipun Manral ,&nbsp;Jolien Geers ,&nbsp;Heidi Gransar ,&nbsp;Aakash Shanbhag ,&nbsp;Robert J.H. Miller ,&nbsp;Alan Rozanski ,&nbsp;Daniel S. Berman ,&nbsp;Piotr J. Slomka ,&nbsp;Damini Dey","doi":"10.1016/j.atherosclerosis.2024.119098","DOIUrl":"10.1016/j.atherosclerosis.2024.119098","url":null,"abstract":"<div><h3>Background and aims</h3><div>The significance of left ventricular mass and chamber volumes from non-contrast computed tomography (CT) for predicting major adverse cardiovascular events (MACE) has not been studied. Our objective was to evaluate the role of artificial intelligence-enabled multi-chamber cardiac volumetry from non-contrast CT for long-term risk stratification in asymptomatic subjects without known coronary artery disease.</div></div><div><h3>Methods</h3><div>Our study included 2022 asymptomatic individuals (55.6 ± 9.0 years; 59.2 % male) from the EISNER (Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) trial. Multi-chamber cardiac volumetry was performed using deep-learning algorithms from routine non-contrast CT scans for coronary artery calcium scoring. MACE was defined as cardiac death, acute coronary syndrome, and late (&gt;180 days) revascularization.</div></div><div><h3>Results</h3><div>A total of 215 individuals (11 %) suffered MACE at a mean follow-up of 13.9 ± 3 years. Individuals with MACE had higher left ventricular mass (115.1g vs. 105.2g, p &lt; 0.001). In a multivariable analysis adjusted for cardiovascular risk factors and medications, left ventricular mass (HR 2.76, <em>p&lt;</em>0.001) and coronary artery calcium score (HR 1.34, <em>p&lt;</em>0.001) were independent predictors of long-term MACE. Adding left ventricular mass to the coronary calcium score improved the Receiver Operating Characteristic Area Under the Curve (AUC 0.753 vs 0.767, <em>p=</em>0.031) with continuous net reclassification index of 18 % (<em>p=</em>0.011). Left ventricular mass (HR 3.89, <em>p&lt;</em>0.001), but not the coronary artery calcium score predicted cardiovascular death.</div></div><div><h3>Conclusions</h3><div>Left ventricular mass quantified automatically by AI from routine non-contrast CT independently predicted long-term MACE over and above the coronary calcium score in asymptomatic participants without known coronary artery disease.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"401 ","pages":"Article 119098"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to: “Unveiling feature importance biases in linear regression: Implications for protein-centric cardiovascular research”","authors":"Holger Kirsten,&nbsp;Markus Scholz","doi":"10.1016/j.atherosclerosis.2024.119084","DOIUrl":"10.1016/j.atherosclerosis.2024.119084","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"401 ","pages":"Article 119084"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The low-density lipoprotein receptor: Emerging post-transcriptional regulatory mechanisms","authors":"Klevis Ndoj ,&nbsp;Amber Meurs ,&nbsp;Dimitra Papaioannou ,&nbsp;Katrine Bjune ,&nbsp;Noam Zelcer","doi":"10.1016/j.atherosclerosis.2024.119082","DOIUrl":"10.1016/j.atherosclerosis.2024.119082","url":null,"abstract":"<div><div>Cholesterol is a vital component of cellular membranes and is an essential molecule in mammalian physiology. Yet dysregulation of hepatic cholesterol metabolism and an increase in plasma cholesterol is linked to development of atherosclerotic cardiovascular disease. Maintaining tight regulation of cholesterol homeostasis is therefore essential, elegantly highlighted by the control of hepatic low-density lipoprotein receptor (LDLR) abundance and associated lipoprotein clearance. The LDLR was discovered in the 1970's in the seminal work of Brown and Goldstein. This was followed by the development of statins, which promote hepatic clearance of LDL via the LDLR pathway. The discovery two decades ago of Proprotein Convertase Subtilisin–Kexin Type 9 (PCSK9), a secreted protein that binds to the LDLR ectodomain and promotes its degradation, and the clinical development of PCSK9 inhibitors has ushered an effort to uncover additional mechanisms that govern the function and abundance of the LDLR. In recent years this has led to the identification of novel post-transcriptional and post-translational mechanisms that govern the LDLR. This review focuses on these emerging regulatory mechanisms and specifically discusses: (1) Regulation of the <em>LDLR</em> mRNA by RNA-binding proteins and microRNAs, (2) Ubiquitin-dependent degradation of the LDLR protein by the E3 ubiquitin ligases inducible degrader of the LDLR (IDOL) and GOLIATH (RNF130), (3) Control of the LDLR pathway by the asialoglycoprotein receptor 1 (ASGR1), and (4) The role of LDLR ectodomain shedding mediated by membrane-type 1 matrix metalloprotease (MT1-MMP), Bone morphogenetic protein 1 (BMP1), and <strong>γ</strong>-secretase. Understanding the contribution of these emerging mechanisms to regulation of the LDLR is important for the development of novel LDLR-focused lipid-lowering strategies.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"401 ","pages":"Article 119082"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-culprit plaque healing on serial OCT imaging and future outcome in patients with acute coronary syndromes","authors":"Boling Yi ,&nbsp;Luping He ,&nbsp;Dirui Zhang ,&nbsp;Ming Zeng ,&nbsp;Chen Zhao ,&nbsp;Wei Meng ,&nbsp;Yuhan Qin ,&nbsp;Ziqian Weng ,&nbsp;Yishuo Xu ,&nbsp;Minghao Liu ,&nbsp;Xi Chen ,&nbsp;Shuangtong Shao ,&nbsp;Qianhui Sun ,&nbsp;Wentao Wang ,&nbsp;Man Li ,&nbsp;Yin Lv ,&nbsp;Xing Luo ,&nbsp;Xiaoxuan Bai ,&nbsp;Xiuzhu Weng ,&nbsp;Jason L. Johnson ,&nbsp;Haibo Jia","doi":"10.1016/j.atherosclerosis.2024.119092","DOIUrl":"10.1016/j.atherosclerosis.2024.119092","url":null,"abstract":"<div><h3>Background and aims</h3><div>Histologic studies indicated that healed plaque, characterized by a multilayered pattern, is indicative of prior atherothrombosis and subsequent healing. However, longitudinal in vivo data on healed plaque formation in non-culprit plaques are limited. This study aimed to investigate serial changes and clinical significance of new layered pattern formation in non-culprit plaques in patients with acute coronary syndromes (ACS) using serial optical coherence tomography (OCT) imaging.</div></div><div><h3>Methods</h3><div>ACS patients who underwent two OCTs at baseline and 1-year follow-up were included. Serial changes in morphologic characteristics of non-culprit plaques were evaluated. New layered pattern was defined as a new signal-rich layer on the plaque surface at follow-up that was not present at baseline.</div></div><div><h3>Results</h3><div>Among 553 non-culprit plaques observed in 222 patients, 82 (14.8 %) exhibited a new layered pattern at follow-up. Thin-cap fibroatheroma, macrophage, and thrombus were identified as independent predictors of the new layered pattern. Plaques with new layered pattern formation showed a greater significant reduction in luminal area and lipid content, as well as a greater increase in fibrous cap thickness compared to those without. The incidence of 6-year non-culprit-related major adverse cardiac events was higher in patients with new layered pattern than in those without (25.4 % vs. 10.8 %, <em>p</em> = 0.011), mainly due to clinically driven coronary revascularization.</div></div><div><h3>Conclusions</h3><div>Plaque destabilization and subsequent healing frequently occur in non-culprit plaques after ACS. The formation of a new layered pattern may contribute to temporary plaque stabilization, but results in luminal stenosis and worse clinical outcomes.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"401 ","pages":"Article 119092"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}