Atherosclerosis最新文献

{"title":"Identification of salivary inflammatory non coding RNA biomarkers for coronary artery disease through epicardial adipose tissue gene network analysis","authors":"Anandhi Sekar Arthi Sri ,&nbsp;Vishnu Priya Veeraraghavan ,&nbsp;Shankargouda Patil ,&nbsp;A. Thirumal Raj","doi":"10.1016/j.atherosclerosis.2025.120486","DOIUrl":"10.1016/j.atherosclerosis.2025.120486","url":null,"abstract":"<div><h3>Background and aim</h3><div>Epicardial adipose tissue (EAT), due to its proximity to the myocardium, contributes inflammatory profile in CAD onset and progression. Emerging evidence highlights the role of EAT-derived non-coding RNAs in modulating disease pathways. However, identifying EAT-specific biomarkers remains challenging for routine diagnosis. Therefore, this study aimed to identify non-invasive, multi-source biomarkers from EAT, plasma, and saliva, and their regulatory miRNAs and lncRNAs, through network analysis, regulatory mapping, and experimental validation.</div></div><div><h3>Methods</h3><div>Differential expression analyses identified upregulated genes and miRNAs in EAT. Protein interaction network was constructed for overlapping upregulated genes and downregulated miRNA targets along with inflammatory-related genes. Clustering, ontology, and topological analyses were performed to pinpoint hub biomarkers and regulatory non-coding RNAs. Key candidate molecules were then experimentally validated using saliva and plasma samples from a cohort of CAD patients (n = 30) and healthy controls (n = 30).</div></div><div><h3>Results</h3><div>A total of 840 upregulated and 1817 downregulated genes were identified in EAT with 36 upregulated and 82 downregulated miRNAs. Among 343 overexpressed inflammatory genes, CD8A, IL7R, and CCL5 emerged as hub biomarkers. Regulatory analysis uncovered 18 miRNAs and 548 lncRNAs influencing these hubs. Notably, hsa-miR-582–3p exhibited the highest number of lncRNA interactions and was significantly downregulated in saliva and plasma of CAD patients (<em>p</em> &lt; 0.05).</div></div><div><h3>Conclusions</h3><div>Our study establishes a link between EAT inflammation and salivary expression profiles, highlighting hsa-miR-582–3p as a promising non-invasive salivary biomarker for CAD. This integrative approach provides a valuable foundation for developing multi-source diagnostics in cardiovascular clinical settings.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"409 ","pages":"Article 120486"},"PeriodicalIF":5.7,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144866461","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":"Antiplatelet therapy with clopidogrel versus aspirin in atherosclerotic cardiovascular disease: a systematic review and meta-analysis","authors":"Maximilian Tscharre ,&nbsp;David Mutschlechner ,&nbsp;Kurt Huber ,&nbsp;Thomas Gremmel","doi":"10.1016/j.atherosclerosis.2025.120478","DOIUrl":"10.1016/j.atherosclerosis.2025.120478","url":null,"abstract":"<div><h3>Background and aims</h3><div>Whether single antiplatelet therapy (SAPT) with clopidogrel offers superior ischemic efficacy and a more favourable bleeding profile than aspirin in atherosclerotic cardiovascular disease is unclear.</div></div><div><h3>Methods</h3><div>A systematic search on the main databases Medline, Web of Science, and Embase until April 21, 2024 was performed. Only randomized trials were eligible for this analysis. As primary endpoint we analyzed major adverse cardiovascular events (MACE), defined as a composite of all-cause mortality, non-fatal myocardial infarction (MI) and non-fatal stroke. As secondary endpoints we investigated the individual primary endpoints as well as the rate of total and severe bleeding events. The analysis was carried out using the odds ratio (OR) as outcome measure. Due to the expected heterogeneity across studies, a random-effects model was fitted to the data.</div></div><div><h3>Results</h3><div>In total, 6 randomized trials comprising 33,508 patients (16,824 on clopidogrel, 16,684 on aspirin) were analyzed. Clopidogrel as compared to aspirin significantly reduced MACE (OR 0.85 [95 %CI 0.77–0.94], p &lt; 0.001, I² = 26 %). The reduction was driven by a decrease in non-fatal MI (OR 0.73 [95 %CI 0.60–0.90], p = 0.01, I² = 28 %) and stroke (OR 0.86 [95 %CI 0.74–1.00], p = 0.05, I² = 8 %), without increasing the rates of total (OR 1.04 [95 %CI 0.83–1.31], p = 0.73, I² = 72 %) or severe bleeding (OR 0.89 [95 %CI 0.83–1.18], p = 0.43, I² = 50 %). No effect on all-cause mortality was detectable (OR 0.96 [95 %CI 0.87–1.06], p = 0.41, I² = 0 %).</div></div><div><h3>Conclusion</h3><div>In patients with atherosclerotic cardiovascular disease, SAPT with clopidogrel is associated with lower MACE rates as compared to aspirin without increasing the risk of bleeding.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"409 ","pages":"Article 120478"},"PeriodicalIF":5.7,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144880160","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":"Plaque remodelling as a surrogate for major adverse cardiac events.","authors":"G B John Mancini","doi":"10.1016/j.atherosclerosis.2025.120481","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2025.120481","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"120481"},"PeriodicalIF":5.7,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940505","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":"Regarding \"Modifications of coronary plaque phenotype on lipid-lowering therapies and risk of cardiovascular events\": a compelling hypothesis warranting cautious interpretation.","authors":"Artur Dziewierz, Beata Bobrowska, Renata Rajtar-Salwa","doi":"10.1016/j.atherosclerosis.2025.120482","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2025.120482","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"120482"},"PeriodicalIF":5.7,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940549","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 of ANGPTL proteins and complexes with progression of coronary artery calcification and coronary events","authors":"Günther Silbernagel ,&nbsp;Halle Higbie ,&nbsp;Tanja Meininger ,&nbsp;Deven Lemen ,&nbsp;Hongxia Li ,&nbsp;Yan Q. Chen ,&nbsp;Yi Wen ,&nbsp;Eugene Y. Zhen ,&nbsp;Yue-Wei Qian ,&nbsp;Polina Korovianskaia ,&nbsp;Hans J. Trampisch ,&nbsp;Hubert Scharnagl ,&nbsp;Winfried März ,&nbsp;Andreas Stang ,&nbsp;Raimund Erbel ,&nbsp;Robert J. Konrad ,&nbsp;Börge Schmidt","doi":"10.1016/j.atherosclerosis.2025.120485","DOIUrl":"10.1016/j.atherosclerosis.2025.120485","url":null,"abstract":"<div><h3>Background and aims</h3><div>Angiopoietin-like protein 8 (ANGPTL8) forms complexes with ANGPTL3 and ANGPTL4 to regulate lipoprotein lipase (LPL) activity, and decreased LPL activity is an established cardiovascular risk factor. Serum levels of ANGPTL4/8 and C-terminal domain-containing ANGPTL4 (CD-ANGPTL4) are positively associated with cardiovascular death, however, the underlying mechanisms remain incompletely understood. The present study investigated relationships of ANGPTL3, ANGPTL3/8, CD-ANGPTL4, and ANGPTL4/8 with coronary artery calcification (CAC) progression (using Agatston scores) and incident coronary events.</div></div><div><h3>Methods</h3><div>ANGPTL3, ANGPTL3/8, CD-ANGPTL4, and ANGPTL4/8, were measured using dedicated immunoassays in participants of the Heinz Nixdorf Recall (HNR) study, an unselected, population-based cohort of subjects free from cardiovascular disease at baseline. CAC measurements were performed at baseline and after 5 years in 2887 participants, and there was follow-up for coronary events (median duration 18.8 years).</div></div><div><h3>Results</h3><div>Median Agatston scores increased over 5 years from 6.70 (t₀) to 24.75 (t₁), and 315 participants experienced a coronary event. Concentrations of ANGPTL3 and ANGPTL3/8 were not associated with Agatston score progression. ANGPTL3 was associated with incident coronary events, whereas ANGPTL3/8 was not. In contrast, CD-ANGPTL4 and ANGPTL4/8 were positively associated with both Agatston score progression and incident coronary events.</div></div><div><h3>Conclusions</h3><div>Associations of ANGPTL3 and ANGPTL3/8 with coronary atherosclerosis progression and incident coronary events were inconsistent, while CD-ANGPTL4 and ANGPTL4/8 were associated with both coronary atherosclerosis progression and incident coronary events. Associations of ANGPTL4/8 and CD-ANGPTL4 with cardiovascular events may reflect progression of coronary atherosclerosis conferred by diabetes, inflammation, or the potential intrinsic effects of CD-ANGPTL4 and ANGPTL4/8.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"409 ","pages":"Article 120485"},"PeriodicalIF":5.7,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858513","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":"Enhanced coronary physiology assessment with endothelial shear stress predicts residual cardiovascular risk in older patients with myocardial infarction","authors":"Alessandro Candreva ,&nbsp;Umberto Morbiducci ,&nbsp;Andrea Erriquez ,&nbsp;Maurizio Lodi Rizzini ,&nbsp;Karol Calò ,&nbsp;Filippo Maria Verardi ,&nbsp;Stefano Clò ,&nbsp;Jacopo Farina ,&nbsp;Frank Ruschitzka ,&nbsp;Barbara E. Stähli ,&nbsp;Gianluca Campo ,&nbsp;Simone Biscaglia ,&nbsp;Diego Gallo","doi":"10.1016/j.atherosclerosis.2025.120476","DOIUrl":"10.1016/j.atherosclerosis.2025.120476","url":null,"abstract":"<div><h3>Background</h3><div>The relationship between traditional risk factors, translesional hemodynamics, and plaque vulnerability remains incompletely understood. Endothelial shear stress (ESS) has recently emerged among the key players determining lesions instability and cardiovascular risk.</div></div><div><h3>Aims</h3><div>We aimed to evaluate the prognostic value of ESS-based quantities and their interplay with anatomical and clinical factors in predicting adverse cardiovascular events in older patients with multivessel coronary artery disease (MVD).</div></div><div><h3>Methods</h3><div>This post hoc analysis of the Functional Assessment in Elderly MI Patients with Multivessel Disease (FIRE) trial included older patients (≥75 years) with acute myocardial infarction (MI) and MVD undergoing percutaneous coronary intervention (PCI). ESS was assessed by angiography-based computational fluid dynamics simulations and the topological shear variation index (TSVI), recently emerged as predictor of future MI measurable within a clinical framework, was computed in non-culprit coronary lesions with negative functional assessment left untreated. The primary endpoint was major adverse cardiovascular events (MACE) at one year, defined as a composite of all-cause death, non-fatal MI, stroke, and ischemia-driven revascularization. Multivariate Cox regression and causal inference analysis were used to assess the prognostic role of anatomo-functional metrics alongside traditional risk factors.</div></div><div><h3>Results</h3><div>A total of 335 FIRE trial patients were analyzed. The median percentage area stenosis (%AS), lesion length, time-averaged ESS, and TSVI were 57.2 %, 12.3 mm, 2.9 Pa, and 59.2 m^-1, respectively. Severe lesions were associated with a higher risk of the primary outcome (hazard ratio, HR, 1.024, 95 % confidence interval, CI, 1.002–1.046, p = 0.031). Longer lesions were significantly linked to an increased risk of all-cause death (HR 1.042, 95 % CI 1.009–1.077, p = 0.013), while TSVI was associated with higher risk of MI (HR 1.006, 95 % CI 1.000–1.012, p = 0.014) and ischemia-driven revascularization (HR 1.006, 95 % CI 1.000–1.012, p = 0.021). The inclusion of %AS, lesion length, and TSVI significantly improved multivariate outcome prediction. Causal inference analysis indicated that TSVI had a strong causal association with both MI and revascularization, with an information content at least equal to that of %AS.</div></div><div><h3>Conclusions</h3><div>TSVI, rather than absolute ESS magnitude, plays a key role in predicting acute events in older MI patients with MVD. Integrating ESS-based factors with traditional clinical and anatomical factors significantly enhances risk prediction and helps refine management strategies for this challenging patient population.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"409 ","pages":"Article 120476"},"PeriodicalIF":5.7,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144890200","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":"Occurrence of coronary events in the absence of traditional risk factors: Understanding residual risk","authors":"Natalie Arnold ,&nbsp;Alina Goßling ,&nbsp;Jessica Weimann ,&nbsp;Benjamin Bay ,&nbsp;Tanja Zeller ,&nbsp;Marco M. Ferrario ,&nbsp;Luigi Palmieri ,&nbsp;Philippe Amouyel ,&nbsp;Marie Moitry ,&nbsp;Jean Ferrières ,&nbsp;Hermann Brenner ,&nbsp;Abdonas Tamosiunas ,&nbsp;Sofia Malyutina ,&nbsp;Satu Männistö ,&nbsp;Wojciech Drygas ,&nbsp;Guido Grassi ,&nbsp;Sameline Grimsgaard ,&nbsp;Allan Linneberg ,&nbsp;Stefan Söderberg ,&nbsp;Licia Iacoviello ,&nbsp;Wolfgang Koenig","doi":"10.1016/j.atherosclerosis.2025.120475","DOIUrl":"10.1016/j.atherosclerosis.2025.120475","url":null,"abstract":"<div><h3>Background and aims</h3><div>The major predictors of future coronary heart disease (CHD) events in individuals without traditional modifiable cardiovascular risk factors (CVRFs) remain unknown. We investigated the association between circulating biomarkers, reflecting residual risk, with incident CHD in a general population, according to the presence of five CVRFs (hypertension, diabetes mellitus, hypercholesterolemia, smoking and obesity) at baseline.</div></div><div><h3>Methods</h3><div>Overall 212,598 CHD-free individuals from 21 European population-based cohorts were stratified by CVRF burden into three groups, having zero (n = 35,707), one (n = 68,548) or ≥2 (n = 108,343) risk factors at baseline. Five biomarkers (triglycerides (TGs), high-sensitivity C-reactive protein (hsCRP), cystatin C, N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin I) were assessed in a subset with available measurements.</div></div><div><h3>Results</h3><div>During a median follow-up of 13.97 years, 17,499 participants developed incident CHD with 453 events occurring among individuals without CVRFs. Although increased concentrations of all biomarkers were related to incident CHD, significant risk modulation by CVRFs was seen only for TGs and, to a lesser extent, for hsCRP. The fully-adjusted sub-distribution Hazard Ratios (95 % CI) were for TGs (≥vs &lt; 1.70 mmol/L) 1.66 (1.29–2.15) in those without CVRFs versus 1.35 (1.21–1.49)/1.14 (1.07–1.20) in those with 1 or ≥2 risk factors (p_interaction&lt;0.01) and for hsCRP (≥vs &lt; 2 mg/L) 1.39 (1.02–1.90) versus 1.42 (1.26–1.61) or 1.22 (1.13–1.32), respectively (<em>p</em>_interaction = 0.092).</div></div><div><h3>Conclusion</h3><div>Even in the absence of CVRFs, elevated triglycerides and hsCRP were significantly associated with an increased risk of CHD. These results highlight the importance of residual risk assessment using those biomarkers in individuals deemed metabolically healthy by conventional standards.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"409 ","pages":"Article 120475"},"PeriodicalIF":5.7,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144860537","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":"Long-term clinical outcomes according to first responsive dose of acetylcholine in patients with coronary artery spasm","authors":"Woo Jin Ahn ,&nbsp;Seung-Woon Rha ,&nbsp;Byoung Geol Choi ,&nbsp;Se Yeon Choi ,&nbsp;Jae Kyeong Byun ,&nbsp;Youjin Lee ,&nbsp;Manda Satria Chesario ,&nbsp;Melly Susanti ,&nbsp;Wonsang Chu ,&nbsp;Jieun Lee ,&nbsp;Soohyung Park ,&nbsp;Eun Jin Park ,&nbsp;Dong Oh Kang ,&nbsp;Cheol Ung Choi ,&nbsp;Chang Gyu Park ,&nbsp;Dong Joo Oh","doi":"10.1016/j.atherosclerosis.2025.120473","DOIUrl":"10.1016/j.atherosclerosis.2025.120473","url":null,"abstract":"<div><h3>Background</h3><div>Coronary artery spasm (CAS) has become a focus of recent prognostic studies. However, research evaluating prognosis based on the initial dose of acetylcholine (ACH) at which patients first respond is lacking. This study aims to investigate long-term clinical outcomes according to the first responsive dose of ACH in patients with CAS.</div></div><div><h3>Methods</h3><div>A total of 3783 patients with positive intracoronary provocation testing with ACH were categorized into three groups based on the dose at which they first exhibited a positive spasm response: A1 (20 μg), A2 (50 μg), and A3 (100 μg). The primary endpoint was major adverse cardiovascular events (MACE), and secondary endpoints included major adverse cardiovascular and cerebrovascular events (MACCE1) and MACCE1 with recurrent angina (MACCE2). Kaplan-Meier survival analysis and multivariate Cox regression were used to assess the relationship between the initial responsive dose and the clinical outcomes up to 10 years.</div></div><div><h3>Results</h3><div>The prevalence of coronary artery stenosis was greater in the A1 group (61.6 %) compared to the A2 group (61.1 %) and the A3 group (56.8 %). The A1 group showed a higher incidence of MACE (10.8 %) compared to the A2 group (3.7 %) and the A3 group (3.5 %, P = 0.003). MACCE2 was also more frequent in the A1 group (38.2 %) than in the A2 group (28.9 %) and the A3 group (26.4 %, P = 0.036). Consistently, in multivariable Cox regression, the A1 group demonstrated a higher risk of both MACE (HR 2.43, 95 % CI 1.01–5.81, P = 0.047) and MACCE2 (HR 1.62, 95 % CI 1.09–2.39, P = 0.016) compared to the A3 group.</div></div><div><h3>Conclusion</h3><div>The initial responsive dose of ACH is a potential predictor of long-term clinical outcomes in patients with CAS. Patients who respond at lower doses may have a higher risk of adverse events, indicating the need for tailored therapeutic strategies based on ACH responsiveness.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"409 ","pages":"Article 120473"},"PeriodicalIF":5.7,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144829673","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":"Pharmacological activation of Nrf2: Cardioprotective effects of statins and metformin against dyslipidemia-induced oxidative stress","authors":"Sinenhlanhla X.H. Mthembu ,&nbsp;Sithandiwe E. Mazibuko-Mbeje ,&nbsp;Khanyisani Ziqubu ,&nbsp;Sonia Silvestri ,&nbsp;Patrick Orlando ,&nbsp;Bongani B. Nkambule ,&nbsp;Christo J.F. Muller ,&nbsp;Luca Tiano ,&nbsp;Phiwayinkosi V. Dludla","doi":"10.1016/j.atherosclerosis.2025.120474","DOIUrl":"10.1016/j.atherosclerosis.2025.120474","url":null,"abstract":"<div><div>Oxidative stress plays a central role in dyslipidemia-related cardiovascular complications, driving cellular damage and disease progression. The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is a critical defense mechanism against oxidative stress, helping to protect cardiac function under pathological conditions. This review explores the potential of enhancing Nrf2 activation as a therapeutic strategy to mitigate oxidative damage in cardiovascular diseases associated with dyslipidemia. While statins and metformin are primarily known for their lipid- and glucose-lowering effects, emerging evidence suggests that they also influence Nrf2 activation. These drugs do not directly activate Nrf2 but rather modulate its activity by reducing oxidative stress and improving mitochondrial function, offering dual protection against cardiovascular dysfunction. By examining the relationship between oxidative stress, Nrf2 activation, and commonly used therapies, this review proposes a novel approach to enhance cardiovascular protection in patients with metabolic disorders, offering insights into new therapeutic avenues to improve outcomes in cardiovascular diseases associated with metabolic conditions.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"409 ","pages":"Article 120474"},"PeriodicalIF":5.7,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144866458","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":"Apolipoprotein CIII in statin-treated type 2 diabetic patients: Its implications for plaque progression and instability: The pre-specified analysis from the OPTIMAL randomized controlled trial","authors":"Satoshi Kitahara ,&nbsp;Yu Kataoka ,&nbsp;Stephen J. Nicholls ,&nbsp;Sayaka Funabashi ,&nbsp;Kiyomasa Nakatsuka ,&nbsp;Kunihiro Nishimura ,&nbsp;Hisashi Makino ,&nbsp;Masaki Matsubara ,&nbsp;Miki Matsuo ,&nbsp;Yoko Omura-Ohata ,&nbsp;Ryo Koezuka ,&nbsp;Mayu Tochiya ,&nbsp;Tamiko Tamanaha ,&nbsp;Tsutomu Tomita ,&nbsp;Kyoko Honda-Kohmo ,&nbsp;Michio Noguchi ,&nbsp;Kota Murai ,&nbsp;Takamasa Iwai ,&nbsp;Kenichiro Sawada ,&nbsp;Hideo Matama ,&nbsp;Teruo Noguchi","doi":"10.1016/j.atherosclerosis.2025.120470","DOIUrl":"10.1016/j.atherosclerosis.2025.120470","url":null,"abstract":"<div><h3>Aims</h3><div>Apolipoprotein CIII (ApoCIII) has a variety of proatherogenic properties. Given that hyperglycemia induces ApoCIII transcription, this apolipoprotein may promote coronary atherosclerosis in type 2 diabetic patients. We aimed to elucidate whether ApoCIII affects plaque progression and instability in statin-treated type 2 diabetic patients.</div></div><div><h3>Methods and results</h3><div>The OPTIMAL study was a prospective randomized controlled trial that employed serial NIRS/IVUS imaging to evaluate the efficacy of glycemic control on coronary atherosclerosis in 94 statin-treated type 2 diabetic patients (UMIN000036721). Of these, 78 patients with both ApoCIII levels and NIRS/IVUS images at baseline and week 48 were analyzed.</div><div>Any increase in ApoCIII levels at week 48 was observed in 47.4 % of study participants. On-treatment LDL-C levels did not differ among participants with and without any increase in ApoCIII levels (1.76 ± 0.55 vs. 1.74 ± 0.55 mmol/L, p = 0.91). Serial changes in IVUS-derived atheroma volume were similar between two groups (−0.7 ± 2.2 vs. −2.4 ± 1.6 mm³, p = 0.51). However, greater progression in NIRS-derived maxLCBI_4mm was observed in those with any increase in ApoCIII levels (91.2 ± 24.8 vs. −44.2 ± 23.5, p &lt; 0.001). Even after adjusting for clinical characteristics, maxLCBI_4mm in participants with any increase in ApoCIII levels still progressed (87.0 ± 24.9 vs. −44.2 ± 23.5, p &lt; 0.001). Moreover, maxLCBI_4mm less likely regressed in patients with any increase in ApoCIII levels (16.2 vs. 80.5 %, p &lt; 0.001). Even in those achieving on-treatment LDL-C&lt;1.4 mmol/L, maxLCBI_4mm progressed in association with any increase in ApoCIII levels.</div></div><div><h3>Conclusion</h3><div>Circulating ApoCIII promoted the accumulation of lipidic plaque components in statin-treated type 2 diabetic patient, suggesting ApoCIII as a residual risk that requires therapeutic intervention.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"409 ","pages":"Article 120470"},"PeriodicalIF":5.7,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144842423","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}