{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T02:39:31Z","timestamp":1773887971359,"version":"3.50.1"},"reference-count":38,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["2012-322698"],"award-info":[{"award-number":["2012-322698"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["2012-322698"],"award-info":[{"award-number":["2012-322698"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018890","name":"Dutch Cardiovascular Alliance","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018890","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002996","name":"Netherlands Heart Foundation","doi-asserted-by":"publisher","award":["CVON2018-27"],"award-info":[{"award-number":["CVON2018-27"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002996","name":"Netherlands Heart Foundation","doi-asserted-by":"publisher","award":["01-001-2024-0601"],"award-info":[{"award-number":["01-001-2024-0601"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Atherosclerosis Plus"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1016\/j.athplu.2025.11.004","type":"journal-article","created":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T17:30:54Z","timestamp":1764869454000},"page":"53-61","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Innate immune cell function in statin-treated patients with severe hypercholesterolemia is comparable to normocholesterolemic individuals: A cross-sectional study"],"prefix":"10.1016","volume":"62","author":[{"given":"Harsh","family":"Bahrar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kim","family":"Steward","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liesbeth","family":"van Emst","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nils","family":"Rother","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeanine E.","family":"Roeters van Lennep","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihai G.","family":"Netea","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siroon","family":"Bekkering","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9197-8124","authenticated-orcid":false,"given":"Niels P.","family":"Riksen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"issue":"7855","key":"10.1016\/j.athplu.2025.11.004_bib1","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/s41586-021-03392-8","article-title":"The changing landscape of atherosclerosis","volume":"592","author":"Libby","year":"2021","journal-title":"Nature"},{"issue":"12","key":"10.1016\/j.athplu.2025.11.004_bib2","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/s41569-023-00894-y","article-title":"Trained immunity in atherosclerotic cardiovascular disease","volume":"20","author":"Riksen","year":"2023","journal-title":"Nat Rev Cardiol"},{"issue":"18","key":"10.1016\/j.athplu.2025.11.004_bib3","doi-asserted-by":"crossref","first-page":"2801","DOI":"10.1093\/cvr\/cvad003","article-title":"Bone marrow inflammatory memory in cardiometabolic disease and inflammatory comorbidities","volume":"119","author":"Mitroulis","year":"2024","journal-title":"Cardiovasc Res"},{"issue":"8","key":"10.1016\/j.athplu.2025.11.004_bib4","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1161\/ATVBAHA.114.303887","article-title":"Oxidized low-density lipoprotein induces long-term proinflammatory cytokine production and foam cell Formation via epigenetic reprogramming of monocytes","volume":"34","author":"Bekkering","year":"2014","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"8","key":"10.1016\/j.athplu.2025.11.004_bib5","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1161\/CIRCULATIONAHA.116.020838","article-title":"Oxidized phospholipids on Lipoprotein(a) elicit arterial Wall inflammation and an inflammatory monocyte response in humans","volume":"134","author":"Van Der Valk","year":"2016","journal-title":"Circulation"},{"issue":"8033","key":"10.1016\/j.athplu.2025.11.004_bib6","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/s41586-024-07993-x","article-title":"Early intermittent hyperlipidaemia alters tissue macrophages to fuel atherosclerosis","volume":"634","author":"Takaoka","year":"2024","journal-title":"Nature"},{"issue":"8033","key":"10.1016\/j.athplu.2025.11.004_bib7","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/s41586-024-07693-6","article-title":"Alternating high-fat diet enhances atherosclerosis by neutrophil reprogramming","volume":"634","author":"Lavillegrand","year":"2024","journal-title":"Nature"},{"issue":"6","key":"10.1016\/j.athplu.2025.11.004_bib8","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/s41569-019-0326-7","article-title":"Neutrophils as regulators of cardiovascular inflammation","volume":"17","author":"Silvestre-Roig","year":"2020","journal-title":"Nat Rev Cardiol"},{"issue":"7","key":"10.1016\/j.athplu.2025.11.004_bib9","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2020.108387","article-title":"BCG vaccination induces long-term functional reprogramming of human neutrophils","volume":"33","author":"Moorlag","year":"2020","journal-title":"Cell Rep"},{"issue":"1","key":"10.1016\/j.athplu.2025.11.004_bib10","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1152\/physrev.00031.2021","article-title":"Trained immunity: adaptation within innate immune mechanisms","volume":"103","author":"Dom\u00ednguez-Andr\u00e9s","year":"2023","journal-title":"Physiol Rev"},{"issue":"1\u20132","key":"10.1016\/j.athplu.2025.11.004_bib11","article-title":"Metabolic induction of trained immunity through the mevalonate pathway","volume":"172","author":"Bekkering","year":"2018","journal-title":"Cell"},{"issue":"1","key":"10.1016\/j.athplu.2025.11.004_bib12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cmet.2019.05.014","article-title":"Treatment with statins does not revert trained immunity in patients with familial hypercholesterolemia","volume":"30","author":"Bekkering","year":"2019","journal-title":"Cell Metab"},{"issue":"2","key":"10.1016\/j.athplu.2025.11.004_bib13","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1159\/000355628","article-title":"Long-lasting effects of BCG vaccination on both heterologous Th1\/Th17 responses and innate trained immunity","volume":"6","author":"Kleinnijenhuis","year":"2014","journal-title":"J Innate Immun"},{"key":"10.1016\/j.athplu.2025.11.004_bib14","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2024.1459593","article-title":"Impact of COVID-19, lockdowns and vaccination on immune responses in a HIV cohort in the Netherlands","volume":"15","author":"Otten","year":"2024","journal-title":"Front Immunol"},{"issue":"6","key":"10.1016\/j.athplu.2025.11.004_bib15","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1093\/clinchem\/18.6.499","article-title":"Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge","volume":"18","author":"Friedewald","year":"1972","journal-title":"Clin Chem"},{"issue":"2","key":"10.1016\/j.athplu.2025.11.004_bib16","doi-asserted-by":"crossref","first-page":"618","DOI":"10.4049\/jimmunol.165.2.618","article-title":"Cutting edge: repurification of lipopolysaccharide eliminates signaling through both human and murine toll-like receptor 2","volume":"165","author":"Hirschfeld","year":"2000","journal-title":"J Immunol"},{"issue":"11","key":"10.1016\/j.athplu.2025.11.004_bib17","doi-asserted-by":"crossref","first-page":"3237","DOI":"10.1002\/art.27667","article-title":"Engagement of fatty acids with toll\u2010like receptor 2 drives interleukin\u20101\u03b2 production via the ASC\/caspase 1 pathway in monosodium urate monohydrate crystal\u2013induced gouty arthritis","volume":"62","author":"Joosten","year":"2010","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.athplu.2025.11.004_bib18","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2014.00448","article-title":"Granule protein processing and regulated secretion in neutrophils","volume":"5","author":"Sheshachalam","year":"2014","journal-title":"Front Immunol"},{"issue":"12","key":"10.1016\/j.athplu.2025.11.004_bib19","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1136\/annrheumdis-2018-213223","article-title":"Cleaved N-terminal histone tails distinguish between NADPH oxidase (NOX)-dependent and NOX-independent pathways of neutrophil extracellular trap formation","volume":"77","author":"Pieterse","year":"2018","journal-title":"Ann Rheum Dis"},{"issue":"1\u20132","key":"10.1016\/j.athplu.2025.11.004_bib20","article-title":"Western diet triggers NLRP3-Dependent innate immune reprogramming","volume":"172","author":"Christ","year":"2018","journal-title":"Cell"},{"issue":"12","key":"10.1016\/j.athplu.2025.11.004_bib21","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1161\/CIRCULATIONAHA.120.046464","article-title":"Hyperglycemia induces trained immunity in macrophages and their precursors and promotes atherosclerosis","volume":"144","author":"Edgar","year":"2021","journal-title":"Circulation"},{"issue":"7407","key":"10.1016\/j.athplu.2025.11.004_bib22","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nature11260","article-title":"Myocardial infarction accelerates atherosclerosis","volume":"487","author":"Dutta","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.athplu.2025.11.004_bib23","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1016\/j.immuni.2024.07.021","article-title":"BCG vaccination alters the epigenetic landscape of progenitor cells in human bone marrow to influence innate immune responses","volume":"57","author":"Sun","year":"2024","journal-title":"Immunity"},{"issue":"nov11 1","key":"10.1016\/j.athplu.2025.11.004_bib24","doi-asserted-by":"crossref","first-page":"a2423","DOI":"10.1136\/bmj.a2423","article-title":"Efficacy of statins in familial hypercholesterolaemia: a long term cohort study","volume":"337","author":"Versmissen","year":"2008","journal-title":"BMJ"},{"issue":"10","key":"10.1016\/j.athplu.2025.11.004_bib25","doi-asserted-by":"crossref","first-page":"5591","DOI":"10.1172\/JCI133935","article-title":"BCG vaccination in humans inhibits systemic inflammation in a sex-dependent manner","volume":"130","author":"Koeken","year":"2020","journal-title":"J Clin Investig"},{"issue":"47","key":"10.1016\/j.athplu.2025.11.004_bib26","doi-asserted-by":"crossref","first-page":"4953","DOI":"10.1093\/eurheartj\/ehad649","article-title":"Neutrophil counts and cardiovascular disease","volume":"44","author":"Luo","year":"2023","journal-title":"Eur Heart J"},{"issue":"5","key":"10.1016\/j.athplu.2025.11.004_bib27","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1161\/ATVBAHA.123.316246","article-title":"Impact of impaired cholesterol homeostasis on neutrophils in atherosclerosis","volume":"43","author":"Tucker","year":"2023","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"18","key":"10.1016\/j.athplu.2025.11.004_bib28","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1161\/CIRCULATIONAHA.110.961714","article-title":"Hyperlipidemia-Triggered neutrophilia promotes early atherosclerosis","volume":"122","author":"Drechsler","year":"2010","journal-title":"Circulation"},{"key":"10.1016\/j.athplu.2025.11.004_bib29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.atherosclerosis.2020.12.016","article-title":"The association of serum lipid and lipoprotein levels with total and differential leukocyte counts: results of a cross-sectional and longitudinal analysis of the UK Biobank","volume":"319","author":"Tucker","year":"2021","journal-title":"Atherosclerosis"},{"issue":"6","key":"10.1016\/j.athplu.2025.11.004_bib30","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1165\/rcmb.2002-0257OC","article-title":"Oxidized low-density lipoprotein activates migration and degranulation of human granulocytes","volume":"29","author":"Sedgwick","year":"2003","journal-title":"Am J Respir Cell Mol Biol"},{"key":"10.1016\/j.athplu.2025.11.004_bib31","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.freeradbiomed.2016.01.004","article-title":"Oxidized LDL induced extracellular trap formation in human neutrophils via TLR-PKC-IRAK-MAPK and NADPH-oxidase activation","volume":"93","author":"Awasthi","year":"2016","journal-title":"Free Radic Biol Med"},{"issue":"6245","key":"10.1016\/j.athplu.2025.11.004_bib32","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1126\/science.aaa8064","article-title":"Neutrophil extracellular traps license macrophages for cytokine production in atherosclerosis","volume":"349","author":"Warnatsch","year":"2015","journal-title":"Science"},{"issue":"10","key":"10.1016\/j.athplu.2025.11.004_bib33","doi-asserted-by":"crossref","first-page":"2598","DOI":"10.1161\/ATVBAHA.120.316389","article-title":"Hypercholesterolemia impairs clearance of neutrophil extracellular traps and promotes inflammation and atherosclerotic plaque progression","volume":"41","author":"Dhawan","year":"2021","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"1","key":"10.1016\/j.athplu.2025.11.004_bib34","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1161\/CIRCRESAHA.116.308537","article-title":"Pleiotropic effects of statins on the cardiovascular System","volume":"120","author":"Oesterle","year":"2017","journal-title":"Circ Res"},{"issue":"7","key":"10.1016\/j.athplu.2025.11.004_bib35","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.115.002113","article-title":"Rho\u2010GTPase and atherosclerosis: pleiotropic effects of statins","volume":"4","author":"Cai","year":"2015","journal-title":"J Am Heart Assoc"},{"issue":"2","key":"10.1016\/j.athplu.2025.11.004_bib36","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1093\/jleuko\/qiad032","article-title":"Rac2 regulates immune complex-mediated granule polarization and exocytosis in neutrophils","volume":"114","author":"Ilarraza","year":"2023","journal-title":"J Leukoc Biol"},{"issue":"2","key":"10.1016\/j.athplu.2025.11.004_bib37","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1161\/CIRCRESAHA.119.315800","article-title":"Catecholamines induce trained immunity in monocytes in vitro and in vivo","volume":"127","author":"van der Heijden","year":"2020","journal-title":"Circ Res"},{"key":"10.1016\/j.athplu.2025.11.004_bib38","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.60939","article-title":"Reprogramming of bone marrow myeloid progenitor cells in patients with severe coronary artery disease","volume":"9","author":"Noz","year":"2020","journal-title":"eLife"}],"container-title":["Atherosclerosis Plus"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2667089525000537?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2667089525000537?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T22:06:14Z","timestamp":1773871574000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2667089525000537"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":38,"alternative-id":["S2667089525000537"],"URL":"https:\/\/doi.org\/10.1016\/j.athplu.2025.11.004","relation":{},"ISSN":["2667-0895"],"issn-type":[{"value":"2667-0895","type":"print"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Innate immune cell function in statin-treated patients with severe hypercholesterolemia is comparable to normocholesterolemic individuals: A cross-sectional study","name":"articletitle","label":"Article Title"},{"value":"Atherosclerosis Plus","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.athplu.2025.11.004","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}]}}