{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:39:13Z","timestamp":1791563953406,"version":"4.3.4"},"reference-count":29,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008678","name":"Leipzig University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008678","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008799","name":"Foundation for Pathobiochemistry and Molecular Diagnostics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008799","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004337","name":"Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004337","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011102","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["602202"],"award-info":[{"award-number":["602202"]}],"id":[{"id":"10.13039\/100011102","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["atherosclerosis-journal.com","clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Atherosclerosis"],"published-print":{"date-parts":[[2021,10]]},"DOI":"10.1016\/j.atherosclerosis.2021.09.026","type":"journal-article","created":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T02:19:09Z","timestamp":1632363549000},"page":"62-67","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":40,"special_numbering":"C","title":["Association of plasma trimethylamine N-oxide levels with atherosclerotic cardiovascular disease and factors of the metabolic syndrome"],"prefix":"10.1016","volume":"335","author":[{"given":"Clemens","family":"Ringel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9766-7439","authenticated-orcid":false,"given":"Julia","family":"Dittrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Gaudl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5382-0083","authenticated-orcid":false,"given":"Paul","family":"Schellong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl Friedrich","family":"Beuchel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronny","family":"Baber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Beutner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrej","family":"Teren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7247-282X","authenticated-orcid":false,"given":"Christoph","family":"Engel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Wirkner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Thiele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"B\u00fcttner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"L\u00f6ffler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Scholz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Thiery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uta","family":"Ceglarek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.atherosclerosis.2021.09.026_bib1","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/0026-0495(92)90140-6","article-title":"The exogenous origin of trimethylamine in the mouse","volume":"41","author":"Al-Waiz","year":"1992","journal-title":"Metabolism"},{"key":"10.1016\/j.atherosclerosis.2021.09.026_bib2","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nature09922","article-title":"Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease","volume":"472","author":"Wang","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.atherosclerosis.2021.09.026_bib3","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1093\/eurheartj\/ehu002","article-title":"Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide","author":"Wang","year":"2014","journal-title":"Eur. Heart J."},{"key":"10.1016\/j.atherosclerosis.2021.09.026_bib4","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/nm.3145","article-title":"Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis","volume":"19","author":"Koeth","year":"2013","journal-title":"Nat. Med."},{"key":"10.1016\/j.atherosclerosis.2021.09.026_bib5","doi-asserted-by":"crossref","first-page":"21307","DOI":"10.1073\/pnas.1215689109","article-title":"Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme","volume":"109","author":"Craciun","year":"2012","journal-title":"Proc. Natl. Acad. Sci. Unit. States Am."},{"key":"10.1016\/j.atherosclerosis.2021.09.026_bib6","doi-asserted-by":"crossref","first-page":"4268","DOI":"10.1073\/pnas.1316569111","article-title":"Carnitine metabolism to trimethylamine by an unusual Rieske-type oxygenase from human microbiota","volume":"111","author":"Zhu","year":"2014","journal-title":"Proc. Natl. Acad. Sci. Unit. States Am."},{"key":"10.1016\/j.atherosclerosis.2021.09.026_bib7","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.cmet.2012.12.011","article-title":"Trimethylamine-N-Oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation","volume":"17","author":"Bennett","year":"2013","journal-title":"Cell Metabol."},{"key":"10.1016\/j.atherosclerosis.2021.09.026_bib8","doi-asserted-by":"crossref","first-page":"551","DOI":"10.3109\/00498258709043962","article-title":"The metabolism of 14c-labelled trimethylamine and its n-oxide in man","volume":"17","author":"Al-Waiz","year":"1987","journal-title":"Xenobiotica"},{"key":"10.1016\/j.atherosclerosis.2021.09.026_bib9","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1161\/ATVBAHA.114.303252","article-title":"Comparative genome-wide association studies in mice and humans for trimethylamine N-Oxide, a proatherogenic metabolite of choline and L-carnitine","volume":"34","author":"Hartiala","year":"2014","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"10.1016\/j.atherosclerosis.2021.09.026_bib10","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.115.002767","article-title":"Trimethylamine N-oxide promotes vascular inflammation through signaling of mitogen-activated protein kinase and nuclear factor-\u03bab","volume":"5","author":"Seldin","year":"2016","journal-title":"J. Am. Heart Assoc."},{"key":"10.1016\/j.atherosclerosis.2021.09.026_bib11","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.bbrc.2016.11.017","article-title":"Trimethylamine N-oxide induces inflammation and endothelial dysfunction in human umbilical vein endothelial cells via activating ROS-TXNIP-NLRP3 inflammasome","volume":"481","author":"Sun","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.atherosclerosis.2021.09.026_bib12","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.cell.2016.02.011","article-title":"Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk","volume":"165","author":"Zhu","year":"2016","journal-title":"Cell"},{"key":"10.1016\/j.atherosclerosis.2021.09.026_bib13","first-page":"1575","article-title":"Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk","volume":"36","author":"Tang","year":"2013","journal-title":"N. England J. Med. Massachusetts Med. Soc."},{"issue":"7","key":"10.1016\/j.atherosclerosis.2021.09.026_bib14","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.116.004947","article-title":"Gut microbiota metabolites and risk of major adverse cardiovascular disease events and death: a systematic review and meta-analysis of prospective studies","volume":"6","author":"Heianza","year":"2017","journal-title":"J. Am. Heart Assoc."},{"key":"10.1016\/j.atherosclerosis.2021.09.026_bib15","article-title":"Gut microbe-generated metabolite trimethylamine N -oxide and the risk of diabetes: a systematic review and dose-response meta-analysis","volume":"1\u201312","author":"Zhuang","year":"2019","journal-title":"Obes. Rev."},{"key":"10.1016\/j.atherosclerosis.2021.09.026_bib16","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.atherosclerosis.2015.10.091","article-title":"Plasma levels of trimethylamine-N-oxide are confounded by impaired kidney function and poor metabolic control","volume":"243","author":"Mueller","year":"2015","journal-title":"Atherosclerosis"},{"key":"10.1016\/j.atherosclerosis.2021.09.026_bib17","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1515\/cclm-2016-0374","article-title":"Intra-individual variation of plasma trimethylamine-N-oxide (TMAO), betaine and choline over 1 year","volume":"55","author":"K\u00fchn","year":"2017","journal-title":"Clin. Chem. Lab. Med."},{"key":"10.1016\/j.atherosclerosis.2021.09.026_bib18","doi-asserted-by":"crossref","DOI":"10.1186\/s12889-015-1983-z","article-title":"The LIFE-Adult-Study: objectives and design of a population-based cohort study with 10,000 deeply phenotyped adults in Germany","volume":"15","author":"Loeffler","year":"2015","journal-title":"BMC Publ. Health"},{"key":"10.1016\/j.atherosclerosis.2021.09.026_bib19","doi-asserted-by":"crossref","DOI":"10.1093\/ije\/dyaa075","article-title":"Cohort profile: the Leipzig research center for civilization diseases\u2013heart study (LIFE-Heart)","author":"Scholz","year":"2020","journal-title":"Int. J. Epidemiol."},{"key":"10.1016\/j.atherosclerosis.2021.09.026_bib20","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.ahj.2015.11.006","article-title":"Multivessel versus culprit lesion only percutaneous revascularization plus potential staged revascularization in patients with acute myocardial infarction complicated by cardiogenic shock: design and rationale of CULPRIT-SHOCK trial","volume":"172","author":"Thiele","year":"2016","journal-title":"Am. Heart J."},{"key":"10.1016\/j.atherosclerosis.2021.09.026_bib21","doi-asserted-by":"crossref","first-page":"3338","DOI":"10.1016\/j.jchromb.2010.10.016","article-title":"Quantification of acetylcholine, choline, betaine, and dimethylglycine in human plasma and urine using stable-isotope dilution ultra performance liquid chromatography-tandem mass spectrometry","volume":"878","author":"Kirsch","year":"2010","journal-title":"J. Chromatogr. B: Analyt. Technol. Biomed. Life Sci."},{"key":"10.1016\/j.atherosclerosis.2021.09.026_bib22","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.jpba.2015.02.040","article-title":"Development and validation of a simple UHPLC-MS\/MS method for the simultaneous determination of trimethylamine N-oxide, choline, and betaine in human plasma and urine","volume":"109","author":"Ocque","year":"2015","journal-title":"J. Pharmaceut. Biomed. Anal."},{"key":"10.1016\/j.atherosclerosis.2021.09.026_bib23","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.ejim.2016.08.017","article-title":"Trimethylamine-N-oxide (TMAO) predicts fatal outcomes in community-acquired pneumonia patients without evident coronary artery disease","volume":"36","author":"Ottiger","year":"2016","journal-title":"Eur. J. Intern. Med."},{"key":"10.1016\/j.atherosclerosis.2021.09.026_bib24","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.jchromb.2012.10.038","article-title":"Validation of an LC-MS\/MS method for the quantification of choline-related compounds and phospholipids in foods and tissues","volume":"911","author":"Xiong","year":"2012","journal-title":"J. Chromatogr. B: Analyt. Technol. Biomed. Life Sci."},{"key":"10.1016\/j.atherosclerosis.2021.09.026_bib25","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0735-1097(02)02663-3","article-title":"Level of kidney function as a risk factor for atherosclerotic cardiovascular outcomes in the community","volume":"41","author":"Manjunath","year":"2003","journal-title":"J. Am. Coll. Cardiol."},{"key":"10.1016\/j.atherosclerosis.2021.09.026_bib26","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.jbiosc.2014.03.001","article-title":"Dietary trimethylamine N-oxide exacerbates impaired glucose tolerance in mice fed a high fat diet","volume":"118","author":"Gao","year":"2014","journal-title":"J. Biosci. Bioeng."},{"key":"10.1016\/j.atherosclerosis.2021.09.026_bib27","doi-asserted-by":"crossref","first-page":"86","DOI":"10.3390\/jcm6090086","article-title":"Gut microbiota-dependent trimethylamine-N-oxide and serum biomarkers in patients with T2DM and advanced CKD","volume":"6","author":"Al-Obaide","year":"2017","journal-title":"J. Clin. Med."},{"key":"10.1016\/j.atherosclerosis.2021.09.026_bib28","first-page":"21","article-title":"Gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) potentially increases the risk of obesity in adults: an exploratory systematic review and dose-response meta- analysis","author":"Dehghan","year":"2020","journal-title":"Obes. Rev."},{"key":"10.1016\/j.atherosclerosis.2021.09.026_bib29","doi-asserted-by":"crossref","first-page":"25","DOI":"10.7150\/ijms.13800","article-title":"Systematic review of metabolic syndrome biomarkers: a panel for early detection, management, and risk stratification in the West Virginian population","author":"Srikanthan","year":"2016","journal-title":"Int. J. Med. Sci."}],"container-title":["Atherosclerosis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021915021013708?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021915021013708?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T16:26:19Z","timestamp":1762187179000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0021915021013708"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10]]},"references-count":29,"alternative-id":["S0021915021013708"],"URL":"https:\/\/doi.org\/10.1016\/j.atherosclerosis.2021.09.026","relation":{},"ISSN":["0021-9150"],"issn-type":[{"value":"0021-9150","type":"print"}],"subject":[],"published":{"date-parts":[[2021,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Association of plasma trimethylamine N-oxide levels with atherosclerotic cardiovascular disease and factors of the metabolic syndrome","name":"articletitle","label":"Article Title"},{"value":"Atherosclerosis","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.atherosclerosis.2021.09.026","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}]}}