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Our objective was to examine Hcy\u2010thiolactone, a chemically reactive metabolite generated by methionyl\u2010<jats:styled-content style=\"fixed-case\">tRNA<\/jats:styled-content> synthetase and cleared by the kidney, as a risk predictor of incident acute myocardial infarction (<jats:styled-content style=\"fixed-case\">AMI<\/jats:styled-content>) in the Western Norway B\u2010Vitamin Intervention Trial.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Single centre, prospective double\u2010blind clinical intervention study, randomized in a 2 \u00d7 2 factorial design.<\/jats:p><\/jats:sec><jats:sec><jats:title>Subjects and methods<\/jats:title><jats:p>Patients with suspected <jats:styled-content style=\"fixed-case\">CAD<\/jats:styled-content> (<jats:italic>n<\/jats:italic> = 2049, 69.8% men; 61.2\u2010year\u2010old) were randomized to groups receiving daily (i) folic acid (0.8 mg)\/vitamin B<jats:sub>12<\/jats:sub> (0.4 mg)\/vitamin B<jats:sub>6<\/jats:sub> (40 mg); (ii) folic acid\/vitamin B<jats:sub>12<\/jats:sub>; (iii) vitamin B<jats:sub>6<\/jats:sub> or (iv) placebo. Urinary Hcy\u2010thiolactone was quantified at baseline, 12 and 38 months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Baseline urinary Hcy\u2010thiolactone\/creatinine was significantly associated with plasma <jats:styled-content style=\"fixed-case\">tH<\/jats:styled-content>cy, ApoA1, glomerular filtration rate, potassium and pyridoxal 5\u2032\u2010phosphate (positively) and with age, hypertension, smoking, urinary creatinine, plasma bilirubin and kynurenine (negatively). During median 4.7\u2010years, 183 patients (8.9%) suffered an <jats:styled-content style=\"fixed-case\">AMI<\/jats:styled-content>. In Cox regression analysis, Hcy\u2010thiolactone\/creatinine was associated with <jats:styled-content style=\"fixed-case\">AMI<\/jats:styled-content> risk (hazard ratio = 1.58, 95% confidence interval = 1.10\u20132.26, <jats:italic>P<\/jats:italic> = 0.012 for trend; adjusted for age, gender, <jats:styled-content style=\"fixed-case\">tH<\/jats:styled-content>cy). This association was confined to patients with pyridoxic acid below median (adjusted <jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content> = 2.72, 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> = 1.47\u20135.03, <jats:italic>P<\/jats:italic> = 0.0001; <jats:italic>P<\/jats:italic><jats:sub>interaction<\/jats:sub> = 0.020). B\u2010vitamin\/folate treatments did not affect Hcy\u2010thiolactone\/creatinine and its <jats:styled-content style=\"fixed-case\">AMI<\/jats:styled-content> risk association.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Hcy\u2010thiolactone\/creatinine ratio is a novel <jats:styled-content style=\"fixed-case\">AMI<\/jats:styled-content> risk predictor in patients with suspected <jats:styled-content style=\"fixed-case\">CAD<\/jats:styled-content>, independent of traditional risk factors and <jats:styled-content style=\"fixed-case\">tH<\/jats:styled-content>cy, but modified by vitamin B<jats:sub>6<\/jats:sub> catabolism. These findings lend a support to the hypothesis that Hcy\u2010thiolactone is mechanistically involved in cardiovascular disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/joim.12834","type":"journal-article","created":{"date-parts":[[2018,9,7]],"date-time":"2018-09-07T22:27:26Z","timestamp":1536359246000},"page":"232-244","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Urinary excretion of homocysteine thiolactone and the risk of acute myocardial infarction in coronary artery disease patients: the <scp>WENBIT<\/scp> trial"],"prefix":"10.1111","volume":"285","author":[{"given":"K.","family":"Borowczyk","sequence":"first","affiliation":[{"name":"Department of Microbiology, Biochemistry and Molecular Genetics Rutgers\u2010New Jersey Medical School International Center for Public Health Newark NJ USA"},{"name":"Department of Environmental Chemistry Faculty of Chemistry University of \u0141\u00f3d\u017a \u0141\u00f3d\u017a Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Piechocka","sequence":"additional","affiliation":[{"name":"Department of Environmental Chemistry Faculty of Chemistry University of \u0141\u00f3d\u017a \u0141\u00f3d\u017a Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"G\u0142owacki","sequence":"additional","affiliation":[{"name":"Department of Environmental Chemistry Faculty of Chemistry University of \u0141\u00f3d\u017a \u0141\u00f3d\u017a Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Dhar","sequence":"additional","affiliation":[{"name":"Department of Clinical Science University of Bergen Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d8.","family":"Midtun","sequence":"additional","affiliation":[{"name":"Bevital AS Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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