{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:55:44Z","timestamp":1790315744031,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.pmed.1003513","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T00:00:00Z","timestamp":1611100800000}}],"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T00:00:00Z","timestamp":1610496000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001729","name":"Stiftelsen f\u00f6r\u00a0Strategisk Forskning","doi-asserted-by":"publisher","award":["RB13-0197"],"award-info":[{"award-number":["RB13-0197"]}],"id":[{"id":"10.13039\/501100001729","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009252","name":"Science for Life Laboratory","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009252","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"}]},{"name":"OLINK Proteomics"},{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007601","name":"Horizon 2020","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01EA1801A"],"award-info":[{"award-number":["01EA1801A"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01EA1411A"],"award-info":[{"award-number":["01EA1411A"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007051","name":"Uppsala Universitet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007051","name":"Uppsala Universitet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001729","name":"Stiftelsen f\u00f6r\u00a0Strategisk Forskning","doi-asserted-by":"publisher","award":["RB13-0197"],"award-info":[{"award-number":["RB13-0197"]}],"id":[{"id":"10.13039\/501100001729","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Circulating biomarkers are associated with the development of coronary heart disease (CHD) and its complications by reflecting pathophysiological pathways and\/or organ dysfunction. We explored the associations between 157 cardiovascular (CV) and inflammatory biomarkers and CV death using proximity extension assays (PEA) in patients with chronic CHD.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods and findings<\/jats:title>\n<jats:p>The derivation cohort consisted of 605 cases with CV death and 2,788 randomly selected non-cases during 3\u20135 years follow-up included in the STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY (STABILITY) trial between 2008 and 2010. The replication cohort consisted of 245 cases and 1,042 non-cases during 12 years follow-up included in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study between 1997 and 2000. Biomarker levels were measured with conventional immunoassays and\/or with the OLINK PEA panels CVD I and Inflammation. Associations with CV death were evaluated by Random Survival Forest (RF) and Cox regression analyses.<\/jats:p>\n<jats:p>Both cohorts had the same median age (65 years) and 20% smokers, while there were slight differences in male sex (82% and 76%), hypertension (70% and 78%), and diabetes (39% and 30%) in the respective STABILITY and LURIC cohorts. The analyses identified 18 biomarkers with confirmed independent association with CV death by Boruta analyses and statistical significance (all <jats:italic>p<\/jats:italic> &lt; 0.0001) by Cox regression when adjusted for clinical characteristics in both cohorts. Most prognostic information was carried by N-terminal prohormone of brain natriuretic peptide (NTproBNP), hazard ratio (HR for 1 standard deviation [SD] increase of the log scale of the distribution of the biomarker in the replication cohort) 2.079 (95% confidence interval [CI] 1.799\u20132.402), and high-sensitivity troponin T (cTnT-hs) HR 1.715 (95% CI 1.491\u20131.973). The other proteins with independent associations were growth differentiation factor 15 (GDF-15) HR 1.728 (95% CI 1.527\u20131.955), transmembrane immunoglobulin and mucin domain protein (TIM-1) HR 1.555 (95% CI 1.362\u20131.775), renin HR 1.501 (95% CI 1.305\u20131.727), osteoprotegerin (OPG) HR 1.488 (95% CI 1.297\u20131.708), soluble suppression of tumorigenesis 2 protein (sST2) HR 1.478 (95% CI 1.307\u20131.672), cystatin-C (Cys-C) HR 1.370 (95% CI 1.243\u20131.510), tumor necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2) HR 1.205 (95% CI 1.131\u20131.285), carbohydrate antigen 125 (CA-125) HR 1.347 (95% CI 1.226\u20131.479), brain natriuretic peptide (BNP) HR 1.399 (95% CI 1.255\u20131.561), interleukin 6 (IL-6) HR 1.478 (95% CI 1.316\u20131.659), hepatocyte growth factor (HGF) HR 1.259 (95% CI 1.134\u20131.396), spondin-1 HR 1.295 (95% CI 1.156\u20131.450), fibroblast growth factor 23 (FGF-23) HR 1.349 (95% CI 1.237\u20131.472), chitinase-3 like protein 1 (CHI3L1) HR 1.284 (95% CI 1.129\u20131.461), tumor necrosis factor receptor 1 (TNF-R1) HR 1.486 (95% CI 1.307\u20131.689), and adrenomedullin (AM) HR 1.750 (95% CI 1.490\u20132.056).<\/jats:p>\n<jats:p>The study is limited by the differences in design, size, and length of follow-up of the 2 studies and the lack of results from coronary angiograms and follow-up of nonfatal events.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Profiles of levels of multiple plasma proteins might be useful for the identification of different pathophysiological pathways associated with an increased risk of CV death in patients with chronic CHD.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Trial registration<\/jats:title>\n<jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/clinicaltrials.gov\/\" xlink:type=\"simple\">ClinicalTrials.gov<\/jats:ext-link> <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT00799903\" xlink:type=\"simple\">NCT00799903<\/jats:ext-link>.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pmed.1003513","type":"journal-article","created":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T19:35:25Z","timestamp":1610566525000},"page":"e1003513","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":114,"title":["Plasma proteins associated with cardiovascular death in patients with chronic coronary heart disease: A retrospective study"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0378-6531","authenticated-orcid":true,"given":"Lars","family":"Wallentin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2152-4343","authenticated-orcid":true,"given":"Niclas","family":"Eriksson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6013-4519","authenticated-orcid":true,"given":"Maciej","family":"Olszowka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja B.","family":"Grammer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3221-0144","authenticated-orcid":true,"given":"Emil","family":"Hagstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9402-7404","authenticated-orcid":true,"given":"Claes","family":"Held","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0663-7275","authenticated-orcid":true,"given":"Marcus E.","family":"Kleber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2064-9603","authenticated-orcid":true,"given":"Wolfgang","family":"Koenig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6083-8946","authenticated-orcid":true,"given":"Winfried","family":"M\u00e4rz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6167-1225","authenticated-orcid":true,"given":"Ralph A. H.","family":"Stewart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harvey D.","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7858-8233","authenticated-orcid":true,"given":"Mikael","family":"\u00c5berg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3955-5671","authenticated-orcid":true,"given":"Agneta","family":"Siegbahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,1,13]]},"reference":[{"key":"pmed.1003513.ref001","doi-asserted-by":"crossref","first-page":"2564","DOI":"10.1016\/j.jacc.2012.07.012","article-title":"2012 ACCF\/AHA\/ACP\/AATS\/PCNA\/SCAI\/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease: Executive Summary: A Report of the American College of Cardiology Foundation\/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons","volume":"60","author":"SD Fihn","year":"2012","journal-title":"J Am Coll Cardiol"},{"key":"pmed.1003513.ref002","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1093\/eurheartj\/ehz425","article-title":"2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes","volume":"41","author":"J Knuuti","year":"2020","journal-title":"Eur Heart J"},{"key":"pmed.1003513.ref003","article-title":"Initial Invasive or Conservative Strategy for Stable Coronary Disease","author":"DJ Maron","year":"2020","journal-title":"N Engl J Med"},{"key":"pmed.1003513.ref004","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1093\/eurheartj\/ehv320","article-title":"2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC)","volume":"37","author":"M Roffi","year":"2016","journal-title":"Eur Heart J"},{"key":"pmed.1003513.ref005","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1373\/clinchem.2016.255174","article-title":"Growth Differentiation Factor 15 as a Biomarker in Cardiovascular Disease","volume":"63","author":"KC Wollert","year":"2017","journal-title":"Clin Chem"},{"key":"pmed.1003513.ref006","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1373\/clinchem.2016.255190","article-title":"State of the Art: Blood Biomarkers for Risk Stratification in Patients with Stable Ischemic Heart Disease","volume":"63","author":"T Omland","year":"2017","journal-title":"Clin Chem"},{"key":"pmed.1003513.ref007","first-page":"e1054","article-title":"Role of Biomarkers for the Prevention, Assessment, and Management of Heart Failure: A Scientific Statement From the American Heart Association","volume":"135","author":"SL Chow","year":"2017","journal-title":"Circulation"},{"key":"pmed.1003513.ref008","doi-asserted-by":"crossref","first-page":"S49","DOI":"10.1161\/01.cir.0000437741.48606.98","article-title":"2013 ACC\/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology\/American Heart Association Task Force on Practice Guidelines","volume":"129","author":"DCJ Goff","year":"2014","journal-title":"Circulation"},{"key":"pmed.1003513.ref009","doi-asserted-by":"crossref","first-page":"e95192","DOI":"10.1371\/journal.pone.0095192","article-title":"Homogenous 96-plex PEA immunoassay exhibiting high sensitivity, specificity, and excellent scalability","volume":"9","author":"E Assarsson","year":"2014","journal-title":"PLoS ONE"},{"key":"pmed.1003513.ref010","doi-asserted-by":"crossref","first-page":"20 10 1","DOI":"10.1002\/0471142727.mb2010s109","article-title":"Parallel protein detection by solid-phase proximity ligation assay with real-time PCR or sequencing","volume":"109","author":"T Ebai","year":"2015","journal-title":"Curr Protoc Mol Biol"},{"key":"pmed.1003513.ref011","doi-asserted-by":"crossref","first-page":"e25583","DOI":"10.1371\/journal.pone.0025583","article-title":"ProteinSeq: high-performance proteomic analyses by proximity ligation and next generation sequencing","volume":"6","author":"S Darmanis","year":"2011","journal-title":"PLoS ONE"},{"key":"pmed.1003513.ref012","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.ahj.2010.07.006","article-title":"Study design and rationale for the clinical outcomes of the STABILITY Trial (STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY) comparing darapladib versus placebo in patients with coronary heart disease","volume":"160","author":"H White","year":"2010","journal-title":"Am Heart J"},{"key":"pmed.1003513.ref013","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1056\/NEJMoa1315878","article-title":"Darapladib for preventing ischemic events in stable coronary heart disease","volume":"370","author":"HD White","year":"2014","journal-title":"N Engl J Med"},{"key":"pmed.1003513.ref014","doi-asserted-by":"crossref","first-page":"e003407","DOI":"10.1161\/JAHA.116.003407","article-title":"Lipoprotein-Associated Phospholipase A2 Activity Is a Marker of Risk But Not a Useful Target for Treatment in Patients With Stable Coronary Heart Disease","volume":"5","author":"L Wallentin","year":"2016","journal-title":"J Am Heart Assoc"},{"key":"pmed.1003513.ref015","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1373\/clinchem.2016.260570","article-title":"Growth Differentiation Factor 15 Predicts All-Cause Morbidity and Mortality in Stable Coronary Heart Disease","volume":"63","author":"E Hagstr\u00f6m","year":"2017","journal-title":"Clin Chem"},{"key":"pmed.1003513.ref016","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.jacc.2017.06.030","article-title":"Biomarker-Based Risk Model to Predict Cardiovascular Mortality in Patients With Stable Coronary Disease","volume":"70","author":"D Lindholm","year":"2017","journal-title":"J Am Coll Cardiol"},{"key":"pmed.1003513.ref017","doi-asserted-by":"crossref","first-page":"e005077","DOI":"10.1161\/JAHA.116.005077","article-title":"Inflammatory biomarkers Interleukin-6 and C-reactive protein and outcomes in stable coronary heart disease\u2013experiences from the STABILITY trial","volume":"6","author":"C Held","year":"2017","journal-title":"J Am Heart Assoc"},{"key":"pmed.1003513.ref018","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1471-2105-15-8","article-title":"Robustness of Random Forest-based gene selection methods","volume":"15","author":"MB Kursa","year":"2014","journal-title":"BMC Bioinformatics"},{"key":"pmed.1003513.ref019","author":"R Development Core Team","year":"2016"},{"key":"pmed.1003513.ref020","first-page":"1","article-title":"mice: Multivariate Imputation by Chained Equations in R","volume":"45","author":"S van Buuren","year":"2011","journal-title":"J Stat Softw"},{"key":"pmed.1003513.ref021","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1056\/NEJMoa0707064","article-title":"Use of multiple biomarkers to improve the prediction of death from cardiovascular causes","volume":"358","author":"B Zethelius","year":"2008","journal-title":"N Engl J Med"},{"key":"pmed.1003513.ref022","doi-asserted-by":"crossref","first-page":"355","DOI":"10.3109\/1354750X.2015.1093546","article-title":"Effect of genetic and environmental factors on protein biomarkers for common non-communicable disease and use of personally normalized plasma protein profiles (PNPPP)","volume":"20","author":"S Enroth","year":"2015","journal-title":"Biomarkers"},{"key":"pmed.1003513.ref023","doi-asserted-by":"crossref","first-page":"17282","DOI":"10.1038\/srep17282","article-title":"Protein profiling reveals consequences of lifestyle choices on predicted biological aging","volume":"5","author":"S Enroth","year":"2015","journal-title":"Sci Rep"},{"key":"pmed.1003513.ref024","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.atherosclerosis.2015.07.023","article-title":"Use of a proximity extension assay proteomics chip to discover new biomarkers for human atherosclerosis","volume":"242","author":"L Lind","year":"2015","journal-title":"Atherosclerosis"},{"key":"pmed.1003513.ref025","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1002\/ejhf.980","article-title":"Circulating proteins as predictors of incident heart failure in the elderly","volume":"20","author":"M Stenemo","year":"2018","journal-title":"Eur J Heart Fail"},{"key":"pmed.1003513.ref026","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1177\/2047487317725017","article-title":"GDF-15 and TRAIL-R2 are powerful predictors of long-term mortality in patients with acute myocardial infarction","volume":"24","author":"E Skau","year":"2017","journal-title":"Eur J Prev Cardiol"},{"key":"pmed.1003513.ref027","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.1001\/jama.2016.5951","article-title":"Development and Validation of a Protein-Based Risk Score for Cardiovascular Outcomes Among Patients With Stable Coronary Heart Disease","volume":"315","author":"P Ganz","year":"2016","journal-title":"JAMA"},{"key":"pmed.1003513.ref028","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.amjcard.2017.03.265","article-title":"Usefulness of Multiple Biomarkers for Predicting Incident Major Adverse Cardiac Events in Patients Who Underwent Diagnostic Coronary Angiography (from the Catheter Sampled Blood Archive in Cardiovascular Diseases [CASABLANCA] Study)","volume":"120","author":"CP McCarthy","year":"2017","journal-title":"Am J Cardiol"},{"key":"pmed.1003513.ref029","doi-asserted-by":"crossref","first-page":"e78797","DOI":"10.1371\/journal.pone.0078797","article-title":"GDF-15 for prognostication of cardiovascular and cancer morbidity and mortality in men","volume":"8","author":"L Wallentin","year":"2013","journal-title":"PLoS ONE"},{"key":"pmed.1003513.ref030","doi-asserted-by":"crossref","first-page":"e014634","DOI":"10.1161\/JAHA.119.014634","article-title":"Prognosis and Reclassification by YKL-40 in Stable Coronary Artery Disease","volume":"9","author":"J Schroder","year":"2020","journal-title":"J Am Heart Assoc"},{"key":"pmed.1003513.ref031","doi-asserted-by":"crossref","first-page":"e008447","DOI":"10.1161\/JAHA.117.008447","article-title":"Anti-TIM-1 Monoclonal Antibody (RMT1-10) Attenuates Atherosclerosis By Expanding IgM-producing B1a Cells","volume":"7","author":"H Hosseini","year":"2018","journal-title":"J Am Heart Assoc"},{"issue":"9","key":"pmed.1003513.ref032","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1186\/ar2165","article-title":"Biology of RANK, RANKL, and osteoprotegerin","volume":"1","author":"BF Boyce","year":"2007","journal-title":"Arthritis Res Ther"},{"key":"pmed.1003513.ref033","doi-asserted-by":"crossref","first-page":"e007009","DOI":"10.1161\/JAHA.117.007009","article-title":"Osteoprotegerin Is Associated With Major Bleeding But Not With Cardiovascular Outcomes in Patients With Acute Coronary Syndromes: Insights From the PLATO (Platelet Inhibition and Patient Outcomes) Trial","volume":"7","author":"T Ueland","year":"2018","journal-title":"J Am Heart Assoc"},{"key":"pmed.1003513.ref034","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1136\/heartjnl-2011-301260","article-title":"Osteoprotegerin and cardiovascular mortality in patients with non-ST elevation acute coronary syndromes","volume":"98","author":"R R\u00f8ysland","year":"2012","journal-title":"Heart"},{"key":"pmed.1003513.ref035","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.jacc.2007.09.058","article-title":"Circulating osteoprotegerin levels and long-term prognosis in patients with acute coronary syndromes","volume":"51","author":"T Omland","year":"2008","journal-title":"J Am Coll Cardiol"},{"key":"pmed.1003513.ref036","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.1016\/j.jacc.2004.06.076","article-title":"Prognostic value of osteoprotegerin in heart failure after acute myocardial infarction","volume":"44","author":"T Ueland","year":"2004","journal-title":"J Am Coll Cardiol"},{"key":"pmed.1003513.ref037","doi-asserted-by":"crossref","first-page":"3499","DOI":"10.1093\/eurheartj\/ehy310","article-title":"Modulation of the interleukin-6 signalling pathway and incidence rates of atherosclerotic events and all-cause mortality: analyses from the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS)","volume":"39","author":"PM Ridker","year":"2018","journal-title":"Eur Heart J"},{"key":"pmed.1003513.ref038","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1056\/NEJMoa1912388","article-title":"Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction","volume":"381","author":"JC Tardif","year":"2019","journal-title":"N Engl J Med"},{"key":"pmed.1003513.ref039","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1056\/NEJMoa1707914","article-title":"Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease","volume":"377","author":"PM Ridker","year":"2017","journal-title":"N Engl J Med"},{"key":"pmed.1003513.ref040","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.ijcard.2015.07.080","article-title":"Biomarkers in stable coronary heart disease, their modulation and cardiovascular risk: The LIPID biomarker study","volume":"201","author":"AM Tonkin","year":"2015","journal-title":"Int J Cardiol"},{"key":"pmed.1003513.ref041","doi-asserted-by":"crossref","first-page":"367","DOI":"10.2217\/bmm-2017-0452","article-title":"Carbohydrate antigen 125: a promising tool for risk stratification in heart diseases","volume":"12","author":"F Falc\u00e3o","year":"2018","journal-title":"Biomark Med"},{"key":"pmed.1003513.ref042","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.atherosclerosis.2017.03.042","article-title":"Fibroblast growth factor 23 as a predictor of cardiovascular and all-cause mortality in prospective studies","volume":"261","author":"Z Qin","year":"2017","journal-title":"Atherosclerosis"},{"key":"pmed.1003513.ref043","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1161\/01.RES.0000261961.41889.9c","article-title":"Genetic dissection of a blood pressure quantitative trait locus on rat chromosome 1 and gene expression analysis identifies SPON1 as a novel candidate hypertension gene","volume":"100","author":"JR Clemitson","year":"2007","journal-title":"Circ Res"},{"key":"pmed.1003513.ref044","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.2215\/CJN.11901113","article-title":"Urinary kidney injury molecule-1 and the risk of cardiovascular mortality in elderly men","volume":"9","author":"AC Carlsson","year":"2014","journal-title":"Clin J Am Soc Nephrol"},{"key":"pmed.1003513.ref045","doi-asserted-by":"crossref","first-page":"761","DOI":"10.2215\/CJN.08560816","article-title":"Urine Kidney Injury Biomarkers and Risks of Cardiovascular Disease Events and All-Cause Death: The CRIC Study","volume":"12","author":"M Park","year":"2017","journal-title":"Clin J Am Soc Nephrol"},{"key":"pmed.1003513.ref046","doi-asserted-by":"crossref","first-page":"17113","DOI":"10.1073\/pnas.0508643102","article-title":"T cell Ig and mucin 1 (TIM-1) is expressed on in vivo-activated T cells and provides a costimulatory signal for T cell activation","volume":"102","author":"AJ de Souza","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pmed.1003513.ref047","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1159\/000348365","article-title":"Plasma renin and cardiovascular risk: what is the evidence for an association?","volume":"125","author":"M Volpe","year":"2013","journal-title":"Cardiology"},{"key":"pmed.1003513.ref048","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1002\/ejhf.749","article-title":"A multimarker multi-time point-based risk stratification strategy in acute heart failure: results from the RELAX-AHF trial","volume":"19","author":"BG Demissei","year":"2017","journal-title":"Eur J Heart Fail"},{"key":"pmed.1003513.ref049","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s10557-017-6718-1","article-title":"Increased Plasma Concentrations of Soluble ST2 Independently Predict Mortality but not Cardiovascular Events in Stable Coronary Heart Disease Patients: 13-Year Follow-up of the KAROLA Study","volume":"31","author":"V Pfetsch","year":"2017","journal-title":"Cardiovasc Drugs Ther"},{"key":"pmed.1003513.ref050","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1016\/j.ahj.2010.02.022","article-title":"ST2 and mortality in non-ST-segment elevation acute coronary syndrome","volume":"159","author":"KM Eggers","year":"2010","journal-title":"Am Heart J"},{"key":"pmed.1003513.ref051","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1373\/clinchem.2012.191106","article-title":"Soluble ST2 is associated with all-cause and cardiovascular mortality in a population-based cohort: the Dallas Heart Study","volume":"59","author":"LQ Chen","year":"2013","journal-title":"Clin Chem"},{"key":"pmed.1003513.ref052","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1373\/clinchem.2013.209858","article-title":"Increased soluble ST2 predicts long-term mortality in patients with stable coronary artery disease: results from the Ludwigshafen risk and cardiovascular health study","volume":"60","author":"B Dieplinger","year":"2014","journal-title":"Clin Chem"},{"key":"pmed.1003513.ref053","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1160\/TH11-10-0711","article-title":"Hepatocyte growth factor: molecular biomarker and player in cardioprotection and cardiovascular regeneration","volume":"107","author":"R Madonna","year":"2012","journal-title":"Thromb Haemost"},{"key":"pmed.1003513.ref054","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1089\/hum.2017.217","article-title":"Hepatocyte Growth Factor Gene Therapy for Ischemic Diseases","volume":"29","author":"LS Wang","year":"2018","journal-title":"Hum Gene Ther"},{"key":"pmed.1003513.ref055","doi-asserted-by":"crossref","first-page":"2387","DOI":"10.1093\/eurheartj\/ehi436","article-title":"Serum hepatocyte growth factor levels predict long-term clinical outcome after percutaneous coronary revascularization","volume":"26","author":"S Susen","year":"2005","journal-title":"Eur Heart J"},{"key":"pmed.1003513.ref056","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1136\/hrt.2010.220228","article-title":"Hepatocyte growth factor is a strong predictor of mortality in patients with advanced heart failure","volume":"97","author":"K Rychli","year":"2011","journal-title":"Heart"},{"key":"pmed.1003513.ref057","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.atherosclerosis.2018.03.040","article-title":"Hepatocyte growth factor is associated with progression of atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA)","volume":"272","author":"EJ Bell","year":"2018","journal-title":"Atherosclerosis"},{"key":"pmed.1003513.ref058","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1111\/joim.12648","article-title":"Plasma levels of hepatocyte growth factor and placental growth factor predict mortality in a general population: a prospective cohort study","volume":"282","author":"K Santalahti","year":"2017","journal-title":"J Intern Med"},{"key":"pmed.1003513.ref059","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.amjcard.2016.05.048","article-title":"Usefulness of the Hepatocyte Growth Factor as a Predictor of Mortality in Patients Hospitalized With Acute Heart Failure Regardless of Ejection Fraction","volume":"118","author":"JI P\u00e9rez-Calvo","year":"2016","journal-title":"Am J Cardiol"},{"key":"pmed.1003513.ref060","doi-asserted-by":"crossref","first-page":"e008299","DOI":"10.1161\/JAHA.117.008299","article-title":"10-Year Associations Between Tumor Necrosis Factor Receptors 1 and 2 and Cardiovascular Events in Patients With Stable Coronary Heart Disease: A CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) Trial Substudy","volume":"7","author":"AC Carlsson","year":"2018","journal-title":"J Am Heart Assoc"}],"updated-by":[{"DOI":"10.1371\/journal.pmed.1003513","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T00:00:00Z","timestamp":1611100800000}}],"container-title":["PLOS Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1003513","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T19:43:23Z","timestamp":1611171803000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1003513"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,13]]},"references-count":60,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1,13]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pmed.1003513","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pmed.1003513","asserted-by":"object"}]},"ISSN":["1549-1676"],"issn-type":[{"value":"1549-1676","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,13]]}}}