Atherosclerosis最新文献

{"title":"PCSK9 inhibitor experiences and preferences of patients and healthcare professionals in decision-making: A mixed methods study.","authors":"Janneke W C M Mulder, Annette M H Galema-Boers, Leonieke W Kranenburg, Ken Redekop, Jeanine E Roeters van Lennep","doi":"10.1016/j.atherosclerosis.2024.119101","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.119101","url":null,"abstract":"<p><strong>Background and aims: </strong>This study investigated how patients experience and which outcomes matter to patients and healthcare professionals in the decision to initiate proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) as add-on lipid-lowering treatment (LLT).</p><p><strong>Methods: </strong>We performed a mixed methods study: very high-risk patients qualifying for PCSK9i reimbursement were interviewed about their experiences and preferences. Subsequently, patients using PCSK9i completed an anonymous online survey about their experiences. Additionally, healthcare professionals (HCPs) filled in an online survey about their PCSK9i prescription preferences and perceived patient preferences.</p><p><strong>Results: </strong>We interviewed 25 patients (median [IQR] age 58 [48-65] years, 56 % women, 64 % established cardiovascular disease) at different decision-making stages. The majority (72 %) chose efficacy over side-effects (16 %) and ease of use (12 %) as most important attribute of add-on LLT. Most patients (72 %) prefer shared decision-making. Subsequently, 170 patients using PCSK9i completed a survey (age 64 [56-69], 44 % women, 63 % established cardiovascular disease). Here again, the most important attribute (83 %) in deciding on add-on LLT was efficacy. Almost all (90 %) patients favoured shared decision-making. Of the 59 HCPs (age 44 [40-50], 49 % women, 78 % medical specialist), only 27 % indicated to consider patient preferences when selecting the PCSK9i type. HCPs identified patient characteristics influencing their PCSK9i prescription preferences.</p><p><strong>Conclusions: </strong>For patients and HCPs, efficacy was the most important aspect in choosing a PCSK9i. Even though shared decision-making is recommended by the guidelines and preferred by patients, in clinical practice only a minority of the HCPs apply this. To facilitate shared decision-making, future research should investigate the development and impact of a decision aid for patients.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"401 ","pages":"119101"},"PeriodicalIF":4.9,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998949","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":"Can fast wall shear stress computation predict adverse cardiac events in patients with intermediate non-flow limiting stenoses?","authors":"Vincenzo Tufaro, Ryo Torii, Jean-Paul Aben, Ramya Parasa, Bon-Kwon Koo, Roby Rakhit, Grigoris V Karamasis, Ibrahim H Tanboga, Ameer Hamid A Khan, Michael McKenna, Murat Cap, Mazen A Gamrah, Patrick W Serruys, Yoshinobu Onuma, Giulio G Stefanini, Daniel A Jones, Krishna Rathod, Anthony Mathur, Andreas Baumbach, Christos V Bourantas","doi":"10.1016/j.atherosclerosis.2024.119099","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.119099","url":null,"abstract":"<p><strong>Background and aims: </strong>Coronary angiography-derived wall shear stress (WSS) may enable identification of vulnerable plaques and patients. A new recently introduced software allows seamless three-dimensional quantitative coronary angiography (3D-QCA) reconstruction and WSS computation within a single user-friendly platform carrying promise for clinical applications. This study examines for the first time the efficacy of this software in detecting vulnerable lesions in patients with intermediate non-flow limiting stenoses.</p><p><strong>Methods: </strong>This multicentre retrospective study included patients who had coronary angiography showing at least one lesion with borderline negative fractional flow reserve (FFR: 0.81-0.85). In these lesions, 3D-QCA reconstruction and blood flow simulation were performed using the CAAS Workstation WSS prototype (Pie Medical Imaging, Maastricht, Netherlands). Time averaged and multidirectional WSS were extracted across the lesion at every 3 mm segments. The primary endpoint of the study was lesion-oriented clinical events (LOCE), defined as the composite of cardiac death, target lesion related myocardial infarction (MI) or clinically indicated target lesion revascularization.</p><p><strong>Results: </strong>352 patients (355 lesions) were included in the analysis. Over a median follow-up of 4.1 years, 57 LOCE were recorded. Lesions causing events had a larger area stenosis (AS) [59.4 (54.6-67.7)% vs 52.8 (43.8-60.1)%, p < 0.001], maximum time averaged WSS (TAWSS) [11.56 (8.25-13.64)Pa vs 7.73 (5.41-11.51)Pa, p < 0.001], mean TAWSS at the minimum lumen area (MLA) [9.30 (5.44-11.94)Pa vs 6.19 (3.96-9.00)Pa, p < 0.001] and maximum transverse WSS [0.30 (0.21-0.45)Pa vs 0.23 (0.17-0.32)Pa, p=0.002] than those remaining quiescent. In multivariable models, AS was the only independent predictor of LOCE. Kaplan-Meier curves demonstrated that lesions with elevated maximum TAWSS and AS had a higher rate of LOCE than those with low TAWSS and AS values (26 % vs 7 %, p < 0.001).</p><p><strong>Conclusions: </strong>For non-flow limiting lesions with borderline negative FFR, fast WSS computation using a dedicated software is feasible and holds potential for cardiovascular risk stratification.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"401 ","pages":"119099"},"PeriodicalIF":4.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999040","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":"Risk of atherosclerosis-related diseases in polymyositis and dermatomyositis patients: A large-scale population-based study.","authors":"Lior Fisher, Niv Ben-Shabat, Omer Gendelman, Kassem Sharif, Scott Ehrenberg, Uria Shani, Yonatan Shneor Patt, Nour Karra, Abdulla Watad, Howard Amital, Arnon Cohen, Israel Dudkiewicz","doi":"10.1016/j.atherosclerosis.2024.119100","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.119100","url":null,"abstract":"<p><strong>Background and aims: </strong>Several systemic autoimmune diseases predispose to the enhancement of Atherosclerotic Cardiovascular Disease (ASCVD). These findings underline the role of inflammation in atherogenesis. Dermatomyositis (DM) and polymyositis (PM) are polygenic autoimmune disorders involving mainly skeletal muscles. The association between PM/DM and ASCVD has not been well addressed and explored. We aimed to investigate the association between PM/DM and ASCVD events, we examined the incidence, mortality, and interaction of disease-modifying agents, autoantibodies, and traditional cardiovascular disease (CVD) risk factors in a large population-based sample.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study using the electronic database of Clalit Health Services (CHS), the largest health organization in Israel. All DM and PM patients diagnosed between 2000 and 2016 were included and matched with healthy controls by age and sex in a 1:5 ratio. Follow-up continued until the first diagnosis of ASCVD or death. The incidence of ASCVD was compared between the groups using univariate and multivariate models adjusting for baseline cardiovascular risk factors.</p><p><strong>Results: </strong>The study population included 1899 PM/DM patients and 7676 controls. The mean age at the index date was 32.5 years (SD ± 19 years), and the female proportion was 60.3 %, similar for both groups. Traditional cardiovascular risk factors were similar in both groups. The Median follow-up time was 8.4 years (3.6-12.8) in the PM/DM group compared to 8.6 (3.7-12.9) in the control group. 47 (3.0 %) PM/DM patients were diagnosed with ischemic heart disease (IHD) compared to 1.8 % (140) in the controls, yielding a multivariate HR (95%CI) of 1.61 (1.15-2.25). Multivariate HR for cerebrovascular accident (CVA) in the PM/DM group was (95%CI) 2.45 (1.63-3.70). Multivariate HR for ASCVD. (95%CI) was 1.75 (1.35-2.27) in the PM/DM group. APLA-associated antibodies presence was more associated with ASCVD among PM/DM groups than non-ASCVD PM and DM patients (OR 2.33, 95 % CI 1.41-3.86, p < 0.001).</p><p><strong>Conclusions: </strong>Our study demonstrates that PM and DM are associated with an increased risk of IHD and CVA. Furthermore, PM and DM patients positive for APLA-associated antibodies exhibited excessive rates of ASCVD. These findings support the increased need for awareness and surveillance of cardiological, neuronal, and vascular outcomes in patients suffering from PM/DM.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"401 ","pages":"119100"},"PeriodicalIF":4.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998955","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":"Evaluation of a machine learning-based metabolic marker for coronary artery disease in the UK Biobank.","authors":"Kyle Gibson, Iain S Forrest, Ben O Petrazzini, Áine Duffy, Joshua K Park, Waqas Malick, Robert S Rosenson, Ghislain Rocheleau, Daniel M Jordan, Ron Do","doi":"10.1016/j.atherosclerosis.2024.119103","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.119103","url":null,"abstract":"<p><strong>Background and aims: </strong>An in silico quantitative score of coronary artery disease (ISCAD), built using machine learning and clinical data from electronic health records, has been shown to result in gradations of risk of subclinical atherosclerosis, coronary artery disease (CAD) sequelae, and mortality. Large-scale metabolite biomarker profiling provides increased portability and objectivity in machine learning for disease prediction and gradation. However, these models have not been fully leveraged. We evaluated a quantitative score of CAD derived from probabilities of a machine learning model trained on metabolomic data.</p><p><strong>Methods: </strong>We developed a CAD-predictive learning model using metabolic data from 93,642 individuals from the UK Biobank (median [IQR] age, 57 [14] years; 39,796 [42 %] male; 5640 [6 %] with diagnosed CAD), and assessed its probabilities as a quantitative metabolic risk score for CAD (M-CAD; range 0 [lowest probability] to 1 [highest probability]) in participants of the UK Biobank. The relationship of M-CAD with arterial stiffness index, ejection fraction, CAD sequelae, and mortality was assessed.</p><p><strong>Results: </strong>The model predicted CAD with an area under the receiver-operating-characteristic curve of 0.712. Arterial Stiffness Index increased by 0.19 and ejection fraction decreased by 0.2 % per 0.1 increase in M-CAD. Both incident and recurrent myocardial infarction increased stepwise over M-CAD quartiles (odds ratio (OR) 15.3 [4.2 %] and 12.5 [0.2 %]) in top quartiles as compared to the first quartile of incident and recurrent MI respectively). Likewise, the hazard ratio and prevalence of all-cause mortality, CVD-associated mortality, and CAD-associated mortality increased stepwise over M-CAD deciles (2.98 [14 %], 9.34 [4.3 %], 26.7 [2.7 %] in the top deciles as compared to the first decile of all-cause, CVD, and CAD mortality respectively).</p><p><strong>Conclusions: </strong>Metabolic-based machine learning can be used to build a quantitative risk score for CAD that is associated with atherosclerotic burden, CAD sequelae and mortality.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"401 ","pages":"119103"},"PeriodicalIF":4.9,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969520","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":"VLDL triglycerides and cholesterol in non-alcoholic fatty liver disease and myocardial infarction.","authors":"Lærke Kristine Kyhl, Børge Grønne Nordestgaard, Anne Tybjærg-Hansen, George Davey Smith, Sune Fallgaard Nielsen","doi":"10.1016/j.atherosclerosis.2024.119094","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.119094","url":null,"abstract":"<p><strong>Background and aims: </strong>Myocardial infarction is a leading cause of death in individuals with non-alcoholic fatty liver disease (NAFLD). The two diseases share elevated very low-density lipoproteins (VLDL) carrying both triglycerides and cholesterol; however, in NAFLD mainly triglycerides accumulate in liver cells while in myocardial infarction mainly cholesterol accumulates in the atherosclerotic plaque. We hypothesized that VLDL triglycerides preferentially associate with risk of NAFLD, while VLDL cholesterol preferentially associates with risk of myocardial infarction.</p><p><strong>Methods: </strong>We examined 25,428 individuals without clinically diagnosed NAFLD or myocardial infarction at baseline, nested within 109,776 individuals from the prospective Copenhagen General Population Study and followed these individuals for a mean of 10 years. VLDL triglycerides, VLDL cholesterol, and low-density lipoprotein (LDL) cholesterol were determined using nuclear magnetic resonance spectrometry.</p><p><strong>Results: </strong>Continuously higher VLDL triglycerides were associated with continuously higher risk of NAFLD; however, this was not the case for VLDL cholesterol, LDL cholesterol, or apolipoprotein B. In contrast, continuously higher VLDL cholesterol, LDL cholesterol, and plasma apolipoprotein B were all associated with continuously higher risk of myocardial infarction. Compared to individuals with both VLDL triglycerides and VLDL cholesterol ≤66th percentile, the hazard ratios for NAFLD in individuals with VLDL triglycerides >66th percentile were 1.61(95 % confidence intervals:1.25-2.06) at high VLDL cholesterol and 1.41(0.90-2.21) at low VLDL cholesterol. Corresponding hazard ratios for myocardial infarction in individuals with VLDL cholesterol >66th percentile were 1.51(1.36-1.67) at high VLDL triglycerides and 1.42(1.18-1.69) at low VLDL triglycerides.</p><p><strong>Conclusions: </strong>VLDL triglycerides predominated in NAFLD while VLDL cholesterol predominated in myocardial infarction; however, VLDL cholesterol was also elevated slightly in NAFLD while VLDL triglycerides was also elevated in myocardial infarction.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"401 ","pages":"119094"},"PeriodicalIF":4.9,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999017","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":"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":"https://doi.org/10.1016/j.atherosclerosis.2024.119093","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"401 ","pages":"119093"},"PeriodicalIF":4.9,"publicationDate":"2024-12-14","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":"Sex-related differences in response to lomitapide in HoFH: A subanalysis of the Pan-European Lomitapide retrospective observational study.","authors":"Chiara Pavanello, Patrizia Suppressa, Sofia Castiglione, Alessia Di Costanzo, Daniele Tramontano, Luigi Rizzi, Kim Steward, Laura Calabresi, Marcello Arca, Jeanine Roeters van Lennep, Laura D'Erasmo","doi":"10.1016/j.atherosclerosis.2024.119089","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.119089","url":null,"abstract":"<p><strong>Background and aims: </strong>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.</p><p><strong>Methods and results: </strong>This post-hoc 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. Clinical characteristics, lipid profile, and adverse events were compared between women and men. 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% p=0.051). Annual LDL-C reduction did not differ between sexes (-4.83% ± 7.02 vs -4.03% ± 9.74 p=0.526). No differences in the median lomitapide dose or the intensity of concomitant lipid lowering therapies were observed between sexes. Notably, gastrointestinal disturbances were more prevalent in women (78 events in women vs 32 in men, p=0.0002), although most adverse events were manageable. Event-free survival curves for ASCVD did not significantly differ between sexes (p=0.363).</p><p><strong>Conclusions: </strong>Lomitapide demonstrates comparable efficacy in reducing LDL-C levels in men and women with HoFH, with potential sex-specific variations in tolerability.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"401 ","pages":"119089"},"PeriodicalIF":4.9,"publicationDate":"2024-12-13","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":"Sphingoid Base Diversity.","authors":"Thorsten Hornemann","doi":"10.1016/j.atherosclerosis.2024.119091","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.119091","url":null,"abstract":"<p><p>Sphingolipids (SL) are crucial components of cellular membranes and play pivotal roles in various biological processes, including cell growth, differentiation, apoptosis, and stress responses. All SL contain a sphingoid base (SPB) backbone which is the shared and class-defining element. SPBs are heterogeneous in length and structure. This review summarizes our current understanding on minor SPBs and the role of the serine palmitoyltransferase (SPT) in particular of its subunits SPTLC3 and SPTSSA/B in forming a spectrum of structurally and metabolically distinct SPBs. Some minor SPBs, such as 1-deoxysphingolipids (1-deoxySL) are neurotoxic and associated with neurological disorders such as hereditary sensory neuropathy type 1 (HSAN1) and diabetic neuropathy. Furthermore, the review discusses the pathological implications of atypical SPBs in cardiometabolic conditions such as obesity, type 2 diabetes or cardiomyopathy, where the induction of the SPTLC3 subunit alters the SPB profile and contributes to disease progression. Understanding these, often neglected aspects of the sphingolipid metabolism provides potential therapeutic targets for metabolic and neurodegenerative diseases, emphasizing the need for continued research in this area.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"119091"},"PeriodicalIF":4.9,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998912","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":"Orally administrated acetate inhibits atherosclerosis progression through AMPK activation via GPR43 in plaque macrophages.","authors":"Toshiaki Wada, Takafumi Senokuchi, Yudan Shi, Tatsuya Furusho, Yutaro Morita, Maeda Sarie, Satoko Hanatani, Kazuki Fukuda, Norio Ishii, Takeshi Matsumura, Yukio Fujiwara, Yoshihiro Komohara, Eiichi Araki, Naoto Kubota","doi":"10.1016/j.atherosclerosis.2024.119088","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.119088","url":null,"abstract":"<p><strong>Background and aims: </strong>Oral administration of acetic acid, a short-chain fatty acid, has been shown to efficiently reduce obesity and insulin resistance in both experimental animals and humans. The anti-atherosclerotic effect of acetate is expected owing to its anti-inflammatory and anti-oxidative stress characteristics; however, this remains to be fully understood.</p><p><strong>Methods: </strong>For 12 weeks, apolipoprotein E-deficient mice were administered 0.6 % sodium acetate water or vehicle water. Plaque formation and progression were investigated using histological analysis of dissected aortic root sections. Flow cytometry and gene expression analyses were employed to assess plaque macrophage characteristics and functional states. In vitro tests were performed on mouse peritoneal primary macrophages and bone marrow-derived macrophages isolated from wild-type or GPR43-deficient mice.</p><p><strong>Results: </strong>Atherosclerotic plaque formation was inhibited in acetate-treated ApoE-deficient mice, and AMPK activation was directly validated in plaque macrophages. Acetate inhibited macrophage proliferation, reactive oxygen species production, and pro-inflammatory molecule expression, all of which were reversed by AMPK inhibition. Bone marrow transplantation study revealed the role of GPR43-mediated AMPK activation by acetic acid in anti-atherosclerotic effect.</p><p><strong>Conclusions: </strong>Oral acetate administration suppressed arteriosclerosis formation and progression in ApoE-deficient mice. Acetate inhibited macrophage proliferation, inflammatory cytokine release, and reactive oxygen species production via GPR43-mediated AMPK activation in macrophages, ameliorating plaque formation and progression.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"401 ","pages":"119088"},"PeriodicalIF":4.9,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871237","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, Yumei Huang, Shaobo Hu, Gang Liu, Tianshu Zeng, An Pan, Yunfei Liao","doi":"10.1016/j.atherosclerosis.2024.119090","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.119090","url":null,"abstract":"<p><strong>Aims: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 (p＜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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"401 ","pages":"119090"},"PeriodicalIF":4.9,"publicationDate":"2024-12-11","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}