{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:55:09Z","timestamp":1787018109547,"version":"build-2736575974"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"21","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2024,11,5]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Protein biomarkers that reflect different pathophysiological pathways have been associated with the risk of adverse cardiovascular events. However, it is uncertain whether these associations are sustained with increasing years after the biomarkers are measured.<\/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                      In this cohort study, 7745 patients with coronary heart disease who participated in the LIPID (Long\u2010Term Intervention With Pravastatin in Ischemic Disease) trial, BNP (B\u2010type natriuretic peptide), troponin I, cystatin\u2010C, C\u2010reactive protein,\n                      <jats:sc>d<\/jats:sc>\n                      \u2010dimer and midregional proadrenomedullin were measured at baseline and after 1\u2009year. Discrimination of plasma biomarker concentrations for cardiovascular death were evaluated in landmark analyses from 1\u2009year for the next 5\u2009years of the randomized trial, and for 10 additional years after trial completion. All 6 biomarkers were associated with risk of cardiovascular death (n=1903) both during and after the clinical trial (each\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      &lt;0.001). C\u2010statistics for BNP were 0.706 and 0.704; cystatin\u2010C, 0.686 and 0.693; troponin I, 0.686 and 0.689; C\u2010reactive protein, 0.655 and 0.684;\n                      <jats:sc>d<\/jats:sc>\n                      \u2010dimer, 0.670 and 0.679, and midregional adrenomedullin, 0.686 and 0.688, respectively. In multivariable models, adding all 6 biomarkers to models with clinical risk factors increased the C\u2010statistic for cardiovascular death from 0.709 to 0.775 during the clinical trial, and from 0.713 to 0.751 during 10\u2010year follow\u2010up after the randomized trial (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      &lt;0.001 for both).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">In patients with chronic coronary heart disease, biomarkers that reflect different pathophysiological pathways are associated with the risk of cardiovascular death for at least the next 15\u2009years.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.123.034367","type":"journal-article","created":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T07:03:07Z","timestamp":1729839787000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Plasma Protein Biomarkers and Long\u2010Term Cardiovascular Mortality Risk in Patients With Chronic Coronary Heart Disease"],"prefix":"10.1161","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6167-1225","authenticated-orcid":false,"given":"Ralph A. H.","family":"Stewart","sequence":"first","affiliation":[{"name":"Green Lane Cardiovascular Service, Auckland City Hospital, Te Toka Tumai, Te Whatu Ora\u2014Health New Zealand","place":["Auckland, New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0213-7652","authenticated-orcid":false,"given":"Kristy P.","family":"Robledo","sequence":"additional","affiliation":[{"name":"University of Syndey and The Royal Prince Alfred Hospital","place":["Camperdown, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5291-0610","authenticated-orcid":false,"given":"Andrew M.","family":"Tonkin","sequence":"additional","affiliation":[{"name":"Monash University","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9426-9136","authenticated-orcid":false,"given":"Anthony","family":"Keech","sequence":"additional","affiliation":[{"name":"University of Syndey and The Royal Prince Alfred Hospital","place":["Camperdown, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5818-8024","authenticated-orcid":false,"given":"Leonard","family":"Kritharides","sequence":"additional","affiliation":[{"name":"The University of Sydney","place":["Concord, Australia"]},{"name":"ANZAC Medical Research Institute, Faculty of Medicine, University of Sydney","place":["Concord, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6225-1572","authenticated-orcid":false,"given":"Ian","family":"Marschner","sequence":"additional","affiliation":[{"name":"University of Syndey and The Royal Prince Alfred Hospital","place":["Camperdown, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0023-5710","authenticated-orcid":false,"given":"Edward","family":"Janus","sequence":"additional","affiliation":[{"name":"University of Melbourne","place":["Parkville, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter L.","family":"Thompson","sequence":"additional","affiliation":[{"name":"The University of Western Australia","place":["Perth, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2276-1524","authenticated-orcid":false,"given":"Gerald F.","family":"Watts","sequence":"additional","affiliation":[{"name":"The University of Western Australia","place":["Perth, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Zeller","sequence":"additional","affiliation":[{"name":"University Heart Centre Hamburg","place":["Hamburg, Germany"]},{"name":"Department of General and Interventional Cardiology, German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg\/Kiel\/L\u00fcbeck, Campus Research","place":["Hamburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7712-6750","authenticated-orcid":false,"given":"Harvey D.","family":"White","sequence":"additional","affiliation":[{"name":"Green Lane Cardiovascular Service, Auckland City Hospital, Te Toka Tumai, Te Whatu Ora\u2014Health New Zealand","place":["Auckland, New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3740-7563","authenticated-orcid":false,"given":"John","family":"Simes","sequence":"additional","affiliation":[{"name":"University of Syndey and The Royal Prince Alfred Hospital","place":["Camperdown, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/jaha.116.005077"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/s2213-8587(16)30196-6"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.05.062"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003513"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.104170"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.943"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.109.912568"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2013.3018"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2019-033720"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/jaha.121.021327"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2015.07.080"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2017.06.098"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(99)80133-7"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199811053391902"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(02)08351-4"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.06.030"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(01)01360-2"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.115.018580"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-842x.2003.tb00615.x"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/s41512-018-0037-2"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.09.931"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.294.22.2866"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab484"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1080\/10408363.2018.1529734"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1515\/CCLM.2008.223"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehaa083"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht533"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.123.034367","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T11:04:44Z","timestamp":1784113484000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.123.034367"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,5]]},"references-count":27,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2024,11,5]]}},"alternative-id":["10.1161\/JAHA.123.034367"],"URL":"https:\/\/doi.org\/10.1161\/jaha.123.034367","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,5]]},"assertion":[{"value":"2024-03-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e034367"}}