Atherosclerosis最新文献

{"title":"Adjustment of the SMART risk score by bioactive adrenomedullin enables a more accurate prediction of mortality in patients with ASCVD","authors":"Berkan Kurt ,&nbsp;Matthias Rau ,&nbsp;Oliver Hartmann ,&nbsp;Andreas Bergmann ,&nbsp;Martin Reugels ,&nbsp;Susanne Just ,&nbsp;Florian A. Wenzl ,&nbsp;Julia Moellmann ,&nbsp;Jens Spießhöfer ,&nbsp;Andrea Milzi ,&nbsp;Kinan Kneizeh ,&nbsp;Kirsten Thiele ,&nbsp;Mathias Hohl ,&nbsp;Simina-Ramona Selejan ,&nbsp;Emiel P.C. van der Vorst ,&nbsp;Edgar Dahl ,&nbsp;Jörg Schröder ,&nbsp;Thomas F. Lüscher ,&nbsp;Nikolaus Marx ,&nbsp;Michael Lehrke ,&nbsp;Florian Kahles","doi":"10.1016/j.atherosclerosis.2025.120220","DOIUrl":"10.1016/j.atherosclerosis.2025.120220","url":null,"abstract":"<div><h3>Background and aims</h3><div>Bioactive adrenomedullin 1-52 (bio-ADM) is a novel biomarker for the assessment of endothelial function and prediction of adverse outcomes in patients with acute heart failure and cardiogenic shock. The SMART (Second Manifestations of Arterial Disease) risk score is a validated tool for risk assessment in patients with established atherosclerotic cardiovascular disease (ASCVD). Here we assessed whether bio-ADM adds incremental prognostic value to the SMART risk score in stable patients with ASCVD.</div></div><div><h3>Methods</h3><div>Circulating bio-ADM levels were measured in 452 stable patients with ASCVD. Endpoints evaluated were all-cause and cardiovascular mortality; follow up was 3 years.</div></div><div><h3>Results</h3><div>Bio-ADM was higher in non-survivors (n = 45; median 36.8 pg/mL) compared to survivors (n = 407; median 18.3 pg/mL; p &lt; 0.0001). Bio-ADM was found to be a strong predictor for all-cause mortality (Chi²: 44.58; C-index: 0.79) as well as cardiovascular death (Chi²: 33.29; C-index: 0.85) and proved to be superior to other markers including hs-Troponin T (Chi²: 7.77; C-index: 0.73) and eGFR_{CKD-EPI 2021} (Chi²: 25.10; C-index: 0.70). In multivariable analyses adjusting for age, sex, diabetes mellitus, hypertension, smoking, NT-proBNP, and eGFR_{CKD-EPI 2021}, bio-ADM remained independently associated with all-cause mortality (HR: 1.6; 95 % CI: 1.2–2.1; Chi²: 96.17; p &lt; 0.00001; C-index: 0.89) and cardiovascular death (HR: 1.7; 95 % CI: 1.1–2.5; Chi²: 57.71; p &lt; 0.00001; C-index: 0.88). Addition of bio-ADM to the SMART risk score meaningfully improved model performance in predicting mortality (SMART risk score: Chi²: 19.91; p = 0.0001; C-index: 0.69; SMART risk score + bio-ADM: Chi²: 54.51; p &lt; 0.00001; C-index: 0.81).</div></div><div><h3>Conclusions</h3><div>Bio-ADM levels are independently associated with mortality and provide incremental added value on top of the SMART risk score in stable patients with ASCVD.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"406 ","pages":"Article 120220"},"PeriodicalIF":4.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144170236","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":"Cardiometabolic determinants of aortic and carotid intima-media thickness in adolescence","authors":"Tomi T. Laitinen ,&nbsp;Hanna Mikola ,&nbsp;Katja Pahkala ,&nbsp;Juha Mykkänen ,&nbsp;Suvi P. Rovio ,&nbsp;Harri Niinikoski ,&nbsp;Tapani Rönnemaa ,&nbsp;Jorma S.A. Viikari ,&nbsp;Antti Jula ,&nbsp;Hanna Lagström ,&nbsp;Pia Salo ,&nbsp;Joel Nuotio ,&nbsp;Mika Ala-Korpela ,&nbsp;Markus Juonala ,&nbsp;Costan G. Magnussen ,&nbsp;Olli T. Raitakari","doi":"10.1016/j.atherosclerosis.2025.120218","DOIUrl":"10.1016/j.atherosclerosis.2025.120218","url":null,"abstract":"<div><h3>Background and aims</h3><div>Comprehensive longitudinal data in healthy populations on cardiometabolic determinants of arterial intima-media thickness (IMT), especially aortic IMT, in adolescence are lacking. We aimed to examine in detail how cardiometabolic risk factors associate with aortic and carotid intima-media thickness (IMT) in adolescence.</div></div><div><h3>Methods</h3><div>Participants (n = 522) were healthy individuals from Special Turku Coronary Risk Factor Intervention Project. IMT of the abdominal aorta and common carotid artery was measured repeatedly with ultrasonography at the age of 11, 13, 15, 17 and 19 years. Data on cardiometabolic risk markers were available beginning from early childhood.</div></div><div><h3>Results</h3><div>Between ages 11 and 19 years, body mass index (BMI), waist circumference, systolic and diastolic blood pressure, serum total cholesterol, non-HDL-cholesterol, and apolipoprotein B levels, insulin and insulin resistance indicated by homeostasis model of insulin resistance (HOMA-IR), C-reactive protein, and smoking associated directly with aortic IMT. For carotid IMT, a direct association was found with BMI, waist circumference, systolic blood pressure and smoking. In multivariate analyses, BMI(β = 5.49, SE = 1.01, P &lt; 0.0001) and HOMA-IR (β = 16.79, SE = 7.45, P = 0.02) remained as determinants of aortic IMT. Correspondingly, BMI(β = 1.78, SE = 0.42, P &lt; 0.0001) and systolic blood pressure (β = 0.38, SE = 0.10, P = 0.0001) determined carotid IMT. Participants with longitudinal aortic or carotid IMT above/equal the 80th percentile had higher BMI measured from infancy than their peers with longitudinal IMT below the 80th percentile.</div></div><div><h3>Conclusions</h3><div>In adolescence, several cardiometabolic risk factors associate with aortic IMT while these links are less evident for carotid IMT. Aortic IMT may serve as a more sensitive marker than carotid IMT of early vascular remodeling.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"406 ","pages":"Article 120218"},"PeriodicalIF":4.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125256","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":"Air pollution and atherosclerosis","authors":"Anusha N. Seneviratne ,&nbsp;Mark R. Miller","doi":"10.1016/j.atherosclerosis.2025.119240","DOIUrl":"10.1016/j.atherosclerosis.2025.119240","url":null,"abstract":"<div><div>Air pollution is associated with considerable cardiovascular mortality and morbidity. The vascular disease atherosclerosis underlies many cardiovascular conditions, with atherosclerotic plaque rupture being a trigger for stroke and myocardial infarction. The acute and chronic effects of air pollution have the potential to exacerbate many different facets of atherosclerosis. This review provides an overview of how air pollution promotes the development of atherosclerosis. The review summaries the epidemiological evidence between exposure to air pollution and morphological measures of atherosclerosis such as carotid intimal media thickness, coronary artery calcification and aortic artery calcification, before summarising the biological mechanisms by which air pollution promotes atherosclerosis at the different stages of disease progression. We offer our perspective of the weight of evidence between air pollution to atherosclerosis and make recommendations for future research to advance this field. Given the ubiquity of air pollution exposure, we stress the need for urgency in efforts to tackle air pollution and emphasise the potential health gains from minimising the effects of air pollutants on this common and often fatal cardiovascular pathology.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"406 ","pages":"Article 119240"},"PeriodicalIF":4.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144115543","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":"H3K27Me3 abundance is associated with a decreased barrier function of endothelial cells by directly silencing VE-cadherin expression","authors":"Jolien Fledderus ,&nbsp;Byambasuren Vanchin ,&nbsp;Linda Brouwer ,&nbsp;Timara Kuiper ,&nbsp;Rianne M. Jongman ,&nbsp;M. van Meurs ,&nbsp;Martin C. Harmsen ,&nbsp;Guido Krenning","doi":"10.1016/j.atherosclerosis.2025.119242","DOIUrl":"10.1016/j.atherosclerosis.2025.119242","url":null,"abstract":"<div><h3>Background and aims</h3><div>Atherosclerosis develops mainly in predisposed, atheroprone regions characterised by the presence of disturbed flow i.e. oscillatory shear stress (OSS). OSS can induce endothelial cell (EC) activation, disruption of the EC barrier and increased permeability. The mechanisms that underly the loss of the EC barrier integrity are still incompletely understood. Enhancer of zeste homolog 2 (EZH2) and its epigenetic silencing mark H3K27Me3 are increased in the endothelium at atheroprone areas where EC barrier disruption is most prominent. Therefore, we hypothesized that increased H3K27Me3 abundance at atheroprone areas affects the barrier function of the endothelium.</div></div><div><h3>Methods</h3><div>A knockdown model of EZH2 in human umbilical vein EC (HUVEC) was used for RNA-seq, to identify differentially expressed genes involved in EC barrier function. Additionally, the effect of OSS on endothelial gene expression was studied by applying laminar shear stress (LSS) on y-shaped slides as a model to mimic atheroprotective and atheroprone areas <em>in vivo</em>. Results were corroborated by a functional study of the barrier function using trans-endothelial electric resistance (TEER).</div></div><div><h3>Results</h3><div>An increased H3K27Me3 abundance is present in areas under OSS, this coincides with a decreased expression of VE-cadherin. Differentially expression (DE) analysis of EZH2^KD HUVEC <em>vs</em> control, revealed that EZH2 regulates genes involved in cell-cell adhesion and leukocyte transmigration. Chromatin immunoprecipitation (ChIP) of H3K27Me3 showed that H3K27Me3 directly silenced <em>CDH5</em> gene expression. Additionally, a reduction of EZH2 appears to increase EC barrier stability.</div></div><div><h3>Conclusions</h3><div>Decreased H3K27Me3 abundance in ECs is beneficial for the formation and integrity of the EC barrier.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"406 ","pages":"Article 119242"},"PeriodicalIF":4.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090502","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":"GRP75 inhibition attenuates arterial calcification.","authors":"Jonas Heyn, Andrea Gorgels, Nicolas Hense, Alexander Gombert, Eva Miriam Buhl, Lisa Stark, Sonja Vondenhoff, Joel Simon, Heidi Noels, Nikolaus Marx, Claudia Goettsch","doi":"10.1016/j.atherosclerosis.2025.119243","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2025.119243","url":null,"abstract":"<p><strong>Background and aims: </strong>Arterial calcification is a risk factor for cardiovascular mortality. The calcification process is driven by the osteogenic transition of vascular smooth muscle cells (SMCs), which release extracellular vesicles (EVs) that act as mineralization nucleation sites. While mitochondrial dysfunction and endoplasmic reticulum (ER) stress have been implicated in arterial calcification, the role of their contact sites remains unknown. Mitochondria-associated membranes (MAMs) are inter-organelle contacts connecting the outer mitochondrial membrane to the ER membrane through protein-protein interactions. This study investigated the role of Glucose-regulated protein 75 (GRP75), a MAM linker protein, in SMC calcification and EV cargo.</p><p><strong>Methods: </strong>Human coronary artery SMCs were cultured in osteogenic medium to induce calcification. MAMs were isolated from SMCs and human carotid artery by subcellular fractionation and visualized using transmission electron microscopy. SMC-derived EVs were isolated from the conditioned culture medium by ultracentrifugation. GRP75 inhibition was achieved using silencing RNA or the inhibitor MKT-077. Mitochondrial respiration and ER stress were analyzed using Seahorse analysis and Western blotting.</p><p><strong>Results: </strong>Calcifying SMCs expressed higher GRP75 mRNA (2.2-fold ± 0.7, p = 0.043) and protein (1.3-fold ± 0.2, p = 0.008) levels compared to control SMCs. GRP75 was enriched at MAMs, and electron microscopy imaging demonstrated closer mitochondria-ER contacts in both calcifying SMCs in vitro and human calcified carotid artery specimens. GRP75 inhibition by silencing RNA (-35 % ± 13 %, p < 0.001) or MKT-077 (-57 % ± 3 %, p < 0.001) attenuated matrix mineralization and reduced close mitochondria-ER contacts along with attenuating mitochondrial respiration capacity. Additionally, GRP75 was enriched in EVs released by calcifying SMCs (1.3-fold ± 0.1, p = 0.040).</p><p><strong>Conclusions: </strong>Our findings demonstrate that MAMs are altered in calcifying SMCs. GRP75 inhibition disrupted close mitochondria-ER contact formation, decreased mitochondrial respiration, modulated the osteogenic transition of SMCs, and reduced vascular calcification. Therefore, GRP75 could serve as a potential target for preventing arterial calcification.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"119243"},"PeriodicalIF":4.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131848","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":"Evinacumab and reduced lipoprotein apheresis in pediatric homozygous familial hypercholesterolemia: a retrospective study on LDL-C","authors":"Charlotte Nigmann ,&nbsp;Manuela Neyer ,&nbsp;Sophie Draxler-Dworzak ,&nbsp;Margot Baumgartner-Kaut ,&nbsp;Thomas Müller-Sacherer ,&nbsp;Klaus Arbeiter ,&nbsp;Susanne Greber-Platzer","doi":"10.1016/j.atherosclerosis.2025.119234","DOIUrl":"10.1016/j.atherosclerosis.2025.119234","url":null,"abstract":"<div><h3>Background and aims</h3><div>Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by severely elevated low-density lipoprotein cholesterol (LDL-C) from birth, leading to accelerated atherosclerotic cardiovascular disease and premature death if untreated. Evinacumab, a monoclonal antibody targeting angiopoietin-like 3 (ANGPTL3), offers an LDL receptor-independent pathway to lower LDL-C. This study aimed to evaluate the effect of evinacumab on lipid levels and its potential to reduce lipoprotein apheresis (LA) frequency in children and adolescents with HoFH.</div></div><div><h3>Methods</h3><div>This was a single-center, retrospective, observational study of six patients aged 10–19 years who had genetically confirmed HoFH and were treated with stable doses of lipid-lowering therapy (LLT) and evinacumab with or without LA at the Medical University of Vienna. Demographic characteristics, lipid levels, and treatment details were collected.</div></div><div><h3>Results</h3><div>At the first visit, LDL-C levels ranged from 521 to 870 mg/dL (13.5–22.5 mmol/L). With stable LLT plus LA, pre-LA LDL-C levels were reduced to 212–352 mg/dL (5.5–9.1 mmol/L) and, after evinacumab was added, further reductions to 90–201 mg/dL (2.3–5.2 mmol/L) were observed. However, during periods of reduced LA frequency, pre-LA LDL-C levels increased to 105–216 mg/dL (2.7–5.6 mmol/L), exceeding the target of 115 mg/dL (3.0 mmol/L) in three out of four patients. LA frequency reduction from weekly to three times per month was only possible in one patient, but no patients had termination of LA.</div></div><div><h3>Conclusions</h3><div>Evinacumab effectively lowers LDL-C in children and adolescents with HoFH. However, its ability to facilitate long-term reduction in LA frequency was not shown and remains unclear.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"406 ","pages":"Article 119234"},"PeriodicalIF":4.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083724","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":"Racial differences in aortic perivascular adipose tissue volume and its association with arterial stiffness in middle-aged men","authors":"Akira Sekikawa,&nbsp;Mengyi Li,&nbsp;Michel Clifton,&nbsp;Kelly Shield,&nbsp;Jiatong Li,&nbsp;Andrea Kozai,&nbsp;Murat Sari,&nbsp;Tina Costacou,&nbsp;Mindy Coccari,&nbsp;Emma Barinas-Mitchell","doi":"10.1016/j.atherosclerosis.2025.119246","DOIUrl":"10.1016/j.atherosclerosis.2025.119246","url":null,"abstract":"<div><h3>Background and aims</h3><div>Ectopic fat depots, such as aortic perivascular adipose tissue (aPVAT), are emerging as key factors in cardiovascular health. Individuals of African ancestry have lower ectopic fat levels, including visceral adipose tissue (VAT), than European ancestry. However, racial differences in aPVAT volume and its association with arterial stiffness remain unclear.</div></div><div><h3>Methods</h3><div>This cross-sectional study examined 325 men aged 40–49 (252 White, 73 African American). aPVAT and VAT were quantified using electron-beam computed tomography, and carotid-femoral pulse wave velocity (cfPWV), the gold standard measure of arterial stiffness, was assessed using a noninvasive testing device. Participant characteristics, aPVAT, and cfPWV were compared by race. Multivariable linear regression models evaluated the association between race and aPVAT and between aPVAT and cfPWV, adjusting for cardiovascular risk and lifestyle factors, body mass index (BMI), and VAT. Interaction terms were included to test race-specific effects.</div></div><div><h3>Results</h3><div>African Americans had significantly lower aPVAT volume than White Americans (42.7 cm³ vs. 49.1 cm³, <em>p</em> = 0.01). This difference became non-significant after adjusting for VAT. aPVAT was positively associated with cfPWV, independent of VAT, BMI, and other confounders (β = 1.52 cm/s, p = 0.04), with no race-specific interactions (<em>p</em> = 0.41). cfPWV did not differ significantly between racial groups (<em>p</em> = 0.64).</div></div><div><h3>Conclusions</h3><div>African Americans had lower aPVAT volume than White Americans, primarily explained by differences in VAT. The positive relationship between aPVAT and cfPWV underscores the potential role of aPVAT in arterial stiffness across racial groups. Longitudinal studies are needed to explore causality and mechanisms underlying these associations.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"406 ","pages":"Article 119246"},"PeriodicalIF":4.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125255","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":"Special issue: Decoding atherosclerosis: Epigenetics and functional genomics.","authors":"Casey E Romanoski, Minna U Kaikkonen","doi":"10.1016/j.atherosclerosis.2025.119230","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2025.119230","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"119230"},"PeriodicalIF":4.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109492","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":"Effectiveness of long-term weight reduction following bariatric surgery on cardiovascular risk.","authors":"Shin-Ichiro Miura","doi":"10.1016/j.atherosclerosis.2025.119245","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2025.119245","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"119245"},"PeriodicalIF":4.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126209","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":"Association of Lipoprotein(a) with cardiovascular events among individuals with autoimmune conditions","authors":"Pamela L. Alebna ,&nbsp;Mathew Ambrosio ,&nbsp;Maxwell Martin ,&nbsp;Sarah Martey ,&nbsp;Jared A. Spitz ,&nbsp;Garima Sharma ,&nbsp;Benjamin Van Tassell ,&nbsp;Dave L. Dixon ,&nbsp;W. Gregory Hundley ,&nbsp;Fadi N. Salloum ,&nbsp;Anurag Mehta","doi":"10.1016/j.atherosclerosis.2025.119244","DOIUrl":"10.1016/j.atherosclerosis.2025.119244","url":null,"abstract":"<div><h3>Background</h3><div>Autoimmune conditions are associated with systemic inflammation, which elevates the risk of major adverse cardiovascular events (MACE). Systemic inflammation can increase plasma lipoprotein(a) [Lp(a)] levels by activating the interleukin-6 response element within the <em>LPA</em> gene promoter region. However, the association between elevated plasma Lp(a) and MACE risk in individuals with autoimmune conditions remains unclear.</div></div><div><h3>Methods</h3><div>We analyzed data from 353,035 UK Biobank participants without cardiovascular disease, including 11,229 individuals with autoimmune conditions such as systemic lupus erythematosus, rheumatoid arthritis, psoriasis, multiple sclerosis, and others. Cox proportional hazards regression models and Kaplan-Meier survival curves assessed the association between elevated Lp(a) (≥125 nmol/L), autoimmune status, and time to MACE (myocardial infarction, stroke, cardiovascular death).</div></div><div><h3>Results</h3><div>Over a median follow-up of 14 years, 19,091 MACEs occurred. Autoimmune conditions (HR, 1.30; 95 % CI, 1.20–1.41; P &lt; 0.001) and elevated Lp(a) (HR, 1.24; 95 % CI, 1.18–1.30; P &lt; 0.001) were independently associated with increased MACE risk. The interaction between autoimmune conditions and elevated Lp(a) was not significant (p = 0.40). Compared to participants with neither risk factor, those with both autoimmune conditions and elevated Lp(a) had the highest MACE risk (HR, 1.77; 95 % CI, 1.46–2.15; P &lt; 0.001). Elevated MACE risk was also observed in individuals with only elevated Lp(a) (HR, 1.23; 95 % CI, 1.17–1.29; P &lt; 0.001) or only autoimmune conditions (HR, 1.28; 95 % CI, 1.18–1.40; P &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>Autoimmune disease status and elevated Lp(a) level have an independent and additive joint association with MACE risk. This may have implications for Lp(a) lowering therapy use in high-risk primary prevention populations.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"406 ","pages":"Article 119244"},"PeriodicalIF":4.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090503","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}