{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T03:12:39Z","timestamp":1768446759148,"version":"3.49.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Plasma total homocysteine (\n              <jats:styled-content style=\"fixed-case\">tH<\/jats:styled-content>\n              cy) is related to plasma neopterin, an indicator of interferon\u2010\u03b3\u2010mediated immune activation, and both biomarkers positively predict cardiovascular risk. We examined whether the association between\n              <jats:styled-content style=\"fixed-case\">tH<\/jats:styled-content>\n              cy and subsequent risk of acute myocardial infarction (\n              <jats:styled-content style=\"fixed-case\">AMI<\/jats:styled-content>\n              ) was modified by systemic concentrations of neopterin and C\u2010reactive protein among patients with coronary heart disease.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              By Cox modeling, we explored the association between\n              <jats:styled-content style=\"fixed-case\">tH<\/jats:styled-content>\n              cy and risk of\n              <jats:styled-content style=\"fixed-case\">AMI<\/jats:styled-content>\n              in 4164 patients with suspected stable angina pectoris. Subgroup analyses were performed according to median levels of neopterin and C\u2010reactive protein. A replication study was performed among 3749 patients with\n              <jats:styled-content style=\"fixed-case\">AMI<\/jats:styled-content>\n              at baseline. Median follow\u2010up was 7.3 and 8.3\u00a0years among patients with stable angina pectoris and\n              <jats:styled-content style=\"fixed-case\">AMI<\/jats:styled-content>\n              , respectively.\n              <jats:styled-content style=\"fixed-case\">tH<\/jats:styled-content>\n              cy and neopterin correlated in both cohorts (\n              <jats:italic>r<\/jats:italic>\n              <jats:sub>s<\/jats:sub>\n              =0.34 and\n              <jats:italic>r<\/jats:italic>\n              <jats:sub>s<\/jats:sub>\n              =0.30 among stable angina pectoris and\n              <jats:styled-content style=\"fixed-case\">AMI<\/jats:styled-content>\n              patients, respectively, both\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001).\n              <jats:styled-content style=\"fixed-case\">tH<\/jats:styled-content>\n              cy predicted\n              <jats:styled-content style=\"fixed-case\">AMI<\/jats:styled-content>\n              in both cohorts, independent of B\u2010vitamin treatment. However, significant risk associations were confined to patients with plasma neopterin above the median (hazard ratios [95% confidence interval] per 1\u2010\n              <jats:styled-content style=\"fixed-case\">SD<\/jats:styled-content>\n              increment of log\u2010transformed\n              <jats:styled-content style=\"fixed-case\">tH<\/jats:styled-content>\n              cy 1.38 [1.26\u20131.50] and 1.18 [1.10\u20131.26] among stable angina pectoris and\n              <jats:styled-content style=\"fixed-case\">AMI<\/jats:styled-content>\n              patients, respectively) (\n              <jats:italic>P<\/jats:italic>\n              <jats:sub>int<\/jats:sub>\n              &lt;0.005 in both cohorts). Further, adding information on the interaction between\n              <jats:styled-content style=\"fixed-case\">tH<\/jats:styled-content>\n              cy and neopterin improved model discrimination and reclassification.\n              <jats:styled-content style=\"fixed-case\">tH<\/jats:styled-content>\n              cy and C\u2010reactive protein were weakly related, and no effect modification was found by C\u2010reactive protein.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Among patients with coronary heart disease,\n              <jats:styled-content style=\"fixed-case\">tH<\/jats:styled-content>\n              cy predicted risk of\n              <jats:styled-content style=\"fixed-case\">AMI<\/jats:styled-content>\n              only in subjects with concomitantly elevated plasma neopterin. Our results motivate further research on the relationship between homocysteine metabolism, cellular immune activation, and atherothrombosis.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.117.006500","type":"journal-article","created":{"date-parts":[[2017,11,3]],"date-time":"2017-11-03T00:10:59Z","timestamp":1509667859000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["Neopterin as an Effect Modifier of the Cardiovascular Risk Predicted by Total Homocysteine: A Prospective 2\u2010Cohort Study"],"prefix":"10.1161","volume":"6","author":[{"given":"Espen \u00d8.","family":"Bj\u00f8rnestad","sequence":"first","affiliation":[{"name":"Faculty of Medicine, University of Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A.","family":"Borsholm","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gard F. T.","family":"Svingen","sequence":"additional","affiliation":[{"name":"Department of Heart Disease, Haukeland University Hospital, Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva R.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Heart Disease, Haukeland University Hospital, Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reinhard","family":"Seifert","sequence":"additional","affiliation":[{"name":"Department of Heart Disease, Haukeland University Hospital, Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00d8ivind","family":"Midttun","sequence":"additional","affiliation":[{"name":"Bevital AS, Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Per M.","family":"Ueland","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway"},{"name":"Department of 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