{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T17:18:33Z","timestamp":1793726313502,"version":"4.6.1"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>We sought to identify protein biomarkers of new-onset heart failure (HF) in 3 independent cohorts (HOMAGE cohort [Heart Omics and Ageing], ARIC study [Atherosclerosis Risk in Communities], and FHS [Framingham Heart Study]) and assess if and to what extent they improve HF risk prediction compared to clinical risk factors alone.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>A nested case-control design was used with cases (incident HF) and controls (without HF) matched on age and sex within each cohort. Plasma concentrations of 276 proteins were measured at baseline in ARIC (250 cases\/250 controls), FHS (191\/191), and HOMAGE cohort (562\/871).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              In single protein analysis, after adjusting for matching variables and clinical risk factors (and correcting for multiple testing), 62 proteins were associated with incident HF in ARIC, 16 in FHS, and 116 in HOMAGE cohort. Proteins associated with incident HF in all cohorts were BNP (brain natriuretic peptide), NT-proBNP (N-terminal pro-B-type natriuretic peptide), eukaryotic translation initiation factor 4E-BP1 (4E-binding protein 1), hepatocyte growth factor (HGF), Gal-9 (galectin-9), TGF-alpha (transforming growth factor alpha), THBS2 (thrombospondin-2), and U-PAR (urokinase plasminogen activator surface receptor). The increment in\n              <jats:italic>C<\/jats:italic>\n              -index for incident HF based on a multiprotein biomarker approach, in addition to clinical risk factors and NT-proBNP, was 11.1% (7.5%\u201314.7%) in ARIC, 5.9% (2.6%\u20139.2%) in FHS, and 7.5% (5.4%\u20139.5%) in HOMAGE cohort, all\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001), each of which was a larger increase than that for NT-proBNP on top of clinical risk factors. Complex network analysis revealed a number of overrepresented pathways related to inflammation (eg, tumor necrosis factor and interleukin) and remodeling (eg, extracellular matrix and apoptosis).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>A multiprotein biomarker approach improves prediction of incident HF when added to natriuretic peptides and clinical risk factors.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circheartfailure.122.009694","type":"journal-article","created":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T18:00:40Z","timestamp":1684260040000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":40,"title":["Protein Biomarkers of New-Onset Heart Failure: Insights From the Heart Omics and Ageing Cohort, the Atherosclerosis Risk in Communities Study, and the Framingham Heart Study"],"prefix":"10.1161","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3278-2057","authenticated-orcid":true,"given":"Nicolas","family":"Girerd","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Lorraine, Inserm, Centre d\u2019Investigations Cliniques- Plurith\u00e9matique 14-33, and Inserm U1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France (N.G., K.D., J.P.F., A.P., A.-C.H., P.R., F.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1843-8724","authenticated-orcid":true,"given":"Daniel","family":"Levy","sequence":"additional","affiliation":[{"name":"National Heart, Lung, and Blood Institute\u2019s and Boston University\u2019s Framingham Heart Study, Framingham, MA (D.L., J.H., S.-J.H)."},{"name":"Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (D.L., J.H., S.-J.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0292-0498","authenticated-orcid":true,"given":"Kevin","family":"Duarte","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Inserm, Centre d\u2019Investigations Cliniques- Plurith\u00e9matique 14-33, and Inserm U1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France (N.G., K.D., J.P.F., A.P., A.-C.H., P.R., F.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2304-6138","authenticated-orcid":true,"given":"Joao Pedro","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Inserm, Centre d\u2019Investigations Cliniques- Plurith\u00e9matique 14-33, and Inserm U1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France (N.G., K.D., J.P.F., A.P., A.-C.H., P.R., F.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6432-1730","authenticated-orcid":true,"given":"Christie","family":"Ballantyne","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Houston, TX (C.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3095-277X","authenticated-orcid":true,"given":"Timothy","family":"Collier","sequence":"additional","affiliation":[{"name":"London School of Hygiene and Tropical Medicine, United Kingdom (T.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2705-6365","authenticated-orcid":true,"given":"Anne","family":"Pizard","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Inserm, Centre d\u2019Investigations Cliniques- Plurith\u00e9matique 14-33, and Inserm U1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France (N.G., K.D., J.P.F., A.P., A.-C.H., P.R., F.Z.)."},{"name":"Inserm 1024, Institut de Biologie de l\u2019\u00c9cole Normale Sup\u00e9rieure (IBENS), PSL University of Paris, France (A.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1856-0754","authenticated-orcid":true,"given":"Jens","family":"Bj\u00f6rkman","sequence":"additional","affiliation":[{"name":"TATAA Biocenter AB, Gothenburg, Sweden (J.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7683-4720","authenticated-orcid":true,"given":"Javed","family":"Butler","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Mississippi School of Medicine, Jackson (J.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8362-668X","authenticated-orcid":true,"given":"Andrew","family":"Clark","sequence":"additional","affiliation":[{"name":"Hull York Medical School, Castle Hill Hospital, Cottingham, United Kingdom (A.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G.","family":"Cleland","sequence":"additional","affiliation":[{"name":"Robertson Centre for Biostatistics and Clinical Trials, Institute of Health and Wellbeing, University of Glasgow, United Kingdom (J.G.C., P.P.)."},{"name":"National Heart and Lung Institute, Royal Brompton and Harefield Hospitals, Imperial College, London, United Kingdom (J.G.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2238-2612","authenticated-orcid":true,"given":"Christian","family":"Delles","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (C.D.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3414-6919","authenticated-orcid":true,"given":"Javier","family":"Diez","sequence":"additional","affiliation":[{"name":"Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (J.D.C., A.G.C.)."},{"name":"CIBERCV, Carlos III Institute of Health, Madrid, Spain (J.D.C., A.G.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5986-6528","authenticated-orcid":true,"given":"Arantxa","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"CIBERCV, Carlos III Institute of Health, Madrid, Spain (J.D.C., A.G.C.)."},{"name":"Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), Spain (J.D.C., A.G.C.)."},{"name":"Departments of Nephrology, and Cardiology and Cardiac Surgery, University of Navarra Clinic, Pamplona, Spain 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