{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T06:57:08Z","timestamp":1788245828486,"version":"build-2803163510"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T00:00:00Z","timestamp":1626393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,8,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Trimethyllysine (TML) is involved in carnitine synthesis, serves as a precursor of trimethylamine N-oxide (TMAO) and is associated with cardiovascular events in patients with established coronary heart disease (CHD). We prospectively examined circulating TML as a predictor of all-cause and cardiovascular mortality in community-dwelling adults and patients with CHD.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>By Cox regression modelling, risk associations were examined in 6393 subjects in the community-based Hordaland Health Study (HUSK). A replication study was conducted among 4117 patients with suspected stable angina pectoris in the Western Norway Coronary Angiography Cohort (WECAC). During a mean follow-up of 10.5\u2009years in the HUSK-cohort, 884 (13.8%) subjects died, of whom 287 from cardiovascular causes. After multivariable adjustments for traditional cardiovascular risk factors, the hazard ratio (HR) [95% confidence interval (95% CI)] for all-cause mortality comparing the 4th vs. 1st TML-quartile was 1.66 (1.31\u20132.10, P\u2009&amp;lt;\u20090.001). Particularly strong associations were observed for cardiovascular mortality [HR (95% CI) 2.04 (1.32\u20133.15, P\u2009=\u20090.001)]. Corresponding risk-estimates in the WECAC (mean follow-up of 9.8\u2009years) were 1.35 [1.10\u20131.66, P\u2009=\u20090.004] for all-cause and 1.45 [1.06\u20131.98, P\u2009=\u20090.02] for cardiovascular mortality. Significant correlations between plasma TML and TMAO were observed in both cohorts (rs \u2265 0.42, P\u2009&amp;lt;\u20090.001); however, additional adjustments for TMAO did not materially influence the risk associations, and no effect modification by TMAO was found.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Elevated TML-levels were associated with increased risk of all-cause and cardiovascular mortality both in subjects with and without established CHD.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ehjopen\/oeab007","type":"journal-article","created":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T18:09:07Z","timestamp":1626458947000},"source":"Crossref","is-referenced-by-count":10,"title":["Trimethyllysine predicts all-cause and cardiovascular mortality in community-dwelling adults and patients with coronary heart disease"],"prefix":"10.1093","volume":"1","author":[{"given":"Espen \u00d8","family":"Bj\u00f8rnestad","sequence":"first","affiliation":[{"name":"Department of Cardiology, Stavanger University Hospital , Gerd-Ragna Bloch Thorsens gate 8, 4011 Stavanger, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3096-8165","authenticated-orcid":false,"given":"Indu","family":"Dhar","sequence":"additional","affiliation":[{"name":"Mohn Nutrition Research Laboratory, Department of Clinical Science, University of Bergen , Postboks 7804, 5020 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gard F T","family":"Svingen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Haukeland University Hospital , Jonas Lies vei 65, 5021 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva R","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Haukeland University Hospital , Jonas Lies vei 65, 5021 Bergen, Norway"},{"name":"Department of Clinical Science, University of Bergen , Postboks 7804 NO-5020 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mads M","family":"Svenningsson","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Haukeland University Hospital , Jonas Lies vei 65, 5021 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grethe S","family":"Tell","sequence":"additional","affiliation":[{"name":"Department of Global Public Health and Primary Care, University of Bergen , \u00c5rstadveien 17, 5020 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per M","family":"Ueland","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, University of Bergen , Postboks 7804 NO-5020 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stein","family":"\u00d8rn","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Stavanger University Hospital , Gerd-Ragna Bloch Thorsens gate 8, 4011 Stavanger, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Sulo","sequence":"additional","affiliation":[{"name":"Centre for Disease Burden, Division of Mental and Physical Health, Norwegian Institute of Public Health, Zander Kaaesgate 7, 5015 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9888-4278","authenticated-orcid":false,"given":"Reijo","family":"Laaksonen","sequence":"additional","affiliation":[{"name":"Finnish Cardiovascular Research Center, University of Tampere, Tampere University Hospital, Arvo Ylp\u00f6n Katu 34, 33520 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ottar","family":"Nyg\u00e5rd","sequence":"additional","affiliation":[{"name":"Mohn Nutrition Research Laboratory, Department of Clinical Science, University of Bergen , Postboks 7804, 5020 Bergen, Norway"},{"name":"Department of Cardiology, Haukeland University Hospital , Jonas Lies vei 65, 5021 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,7,16]]},"reference":[{"key":"2024021711215810600_oeab007-B1","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1161\/CIRCRESAHA.120.316242","article-title":"Gut microbiota and cardiovascular disease","volume":"127","author":"Witkowski","year":"2020","journal-title":"Circ Res"},{"key":"2024021711215810600_oeab007-B2","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1016\/j.jacc.2019.03.024","article-title":"Intestinal microbiota in cardiovascular health and disease: JACC 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