{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:22:21Z","timestamp":1790702541587,"version":"4.1.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2017,12,18]],"date-time":"2017-12-18T00:00:00Z","timestamp":1513555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["FP7-242209-BIOSTAT-CHF; EudraCT 2010-020808-29"],"award-info":[{"award-number":["FP7-242209-BIOSTAT-CHF; EudraCT 2010-020808-29"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Previously, low high-density lipoprotein (HDL) cholesterol was found to be one of the strongest predictors of mortality and\/or heart failure (HF) hospitalisation in patients with HF. We therefore performed in-depth investigation of the multifunctional HDL proteome to reveal underlying pathophysiological mechanisms explaining the association between HDL and clinical outcome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We selected a cohort of 90 HF patients with 1:1 cardiovascular death\/survivor ratio from BIOSTAT-CHF. A novel optimised protocol for selective enrichment of lipoproteins was used to prepare plasma. Enriched lipoprotein content of samples was analysed using high resolution nanoscale liquid chromatography-mass spectrometry-based proteomics, utilising a label free approach. Within the HDL proteome, 49 proteins significantly differed between deaths and survivors. An optimised model of 12 proteins predicted death with 76% accuracy (Nagelkerke R2=0.37, P &amp;lt;\u20090.001). The strongest contributors to this model were filamin-A (related to crosslinking of actin filaments) [odds ratio (OR) 0.31, 95% confidence interval (CI) 0.15\u20130.61, P =\u20090.001] and pulmonary surfactant-associated protein B (related to alveolar capillary membrane function) (OR 2.50, 95% CI 1.57\u20133.98, P &amp;lt;\u20090.001). The model predicted mortality with an area under the curve of 0.82 (95% CI 0.77\u20130.87, P &amp;lt;\u20090.001). Internal cross validation resulted in 73.3\u2009\u00b1\u20097.2% accuracy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study shows marked differences in composition of the HDL proteome between HF survivors and deaths. The strongest differences were seen in proteins reflecting crosslinking of actin filaments and alveolar capillary membrane function, posing potential pathophysiological mechanisms underlying the association between HDL and clinical outcome in HF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.1101","type":"journal-article","created":{"date-parts":[[2017,12,18]],"date-time":"2017-12-18T08:32:53Z","timestamp":1513585973000},"page":"260-267","source":"Crossref","is-referenced-by-count":35,"title":["Proteomic Diversity of High-Density Lipoprotein Explains its Association with Clinical Outcome in Patients with Heart Failure"],"prefix":"10.1093","volume":"20","author":[{"given":"Johanna Elisabeth","family":"Emmens","sequence":"first","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald J.L.","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Cancer Studies, University of Leicester, Leicester Royal Infirmary , Leicester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thong H.","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, University of Leicester, NIHR Leicester Biomedical Research Centre, Glenfield Hospital , Leicester ,","place":["UK"]},{"name":"Department of General Internal Medicine, University of Medicine and Pharmacy , Ho Chi Minh City ,","place":["Vietnam"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel C.S.","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, University of Leicester, NIHR Leicester Biomedical Research Centre, Glenfield Hospital , Leicester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon P.R.","family":"Romaine","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, University of Leicester, NIHR Leicester Biomedical Research Centre, Glenfield Hospital , Leicester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulene A.","family":"Quinn","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, University of Leicester, NIHR Leicester Biomedical Research Centre, Glenfield Hospital , Leicester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan D.","family":"Anker","sequence":"additional","affiliation":[{"name":"Division of Cardiology and Metabolism \u2013 Heart Failure, Cachexia and Sarcopenia, Department of Cardiology (CVK); and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Deutsches Zentrum f\u00fcr Herz-Kreislauf-Forschung (DZHK) Berlin , Charit\u00e9 Universit\u00e4tsmedizin Berlin ,","place":["Germany"]},{"name":"Department of Cardiology and Pneumology, University Medical Center G\u00f6ttingen (UMG) , G\u00f6ttingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G.","family":"Cleland","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Royal Brompton and Harefield Hospitals, Imperial College , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Dickstein","sequence":"additional","affiliation":[{"name":"University of Bergen , Bergen ,","place":["Norway"]},{"name":"Stavanger University Hospital , Stavanger ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerasimos","family":"Filippatos","sequence":"additional","affiliation":[{"name":"National and Kapodistrian University of Athens, School of Medicine, Heart Failure Unit, Department of Cardiology, Athens University Hospital Attikon , Athens ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans L.","family":"Hillege","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chim C.","family":"Lang","sequence":"additional","affiliation":[{"name":"School of Medicine Centre for Cardiovascular and Lung Biology, Division of Medical Sciences, University of Dundee, Ninewells Hospital & Medical School , Dundee ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Ponikowski","sequence":"additional","affiliation":[{"name":"Department of Heart Diseases, Wroclaw Medical University, and Cardiology Department, Military Hospital , Wroclaw ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilesh J.","family":"Samani","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, University of Leicester, NIHR Leicester Biomedical Research Centre, Glenfield Hospital , Leicester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk J.","family":"van Veldhuisen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faiz","family":"Zannad","sequence":"additional","affiliation":[{"name":"Inserm CIC 1433, Universit\u00e9 de Lorrain , CHU de Nancy, Nancy ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aeilko H.","family":"Zwinderman","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Metra","sequence":"additional","affiliation":[{"name":"Institute of Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia , Brescia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf A.","family":"de Boer","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriaan A.","family":"Voors","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leong L.","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, University of Leicester, NIHR Leicester Biomedical Research Centre, Glenfield Hospital , Leicester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,12,18]]},"reference":[{"key":"2026011721220012500_ejhf1101-bib-0001","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.1161\/CIRCULATIONAHA.109.830984","article-title":"Relations of lipid concentrations to heart failure incidence: the Framingham Heart Study","volume":"120","author":"Velagaleti","year":"2009","journal-title":"Circulation"},{"key":"2026011721220012500_ejhf1101-bib-0002","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/j.healun.2009.04.026","article-title":"High-density lipoprotein cholesterol levels and prognosis in advanced heart failure","volume":"28","author":"Mehra","year":"2009","journal-title":"J Heart Lung Transplant"},{"key":"2026011721220012500_ejhf1101-bib-0003","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.cardfail.2007.01.007","article-title":"Association of low serum levels of apolipoprotein A-I with adverse outcomes in patients with nonischemic heart failure","volume":"13","author":"Iwaoka","year":"2007","journal-title":"J Card Fail"},{"key":"2026011721220012500_ejhf1101-bib-0004","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1093\/eurjhf\/hfn046","article-title":"Predictors of fatal and non-fatal outcomes in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA): incremental value of apolipoprotein A-1, high-sensitivity C-reactive peptide and N-terminal pro B-type natriuretic peptide","volume":"11","author":"Wedel","year":"2009","journal-title":"Eur J Heart Fail"},{"key":"2026011721220012500_ejhf1101-bib-0005","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/978-3-319-09665-0_17","article-title":"Therapeutic potential of HDL in cardioprotection and tissue repair","volume":"224","author":"Van Linthout","year":"2015","journal-title":"Handb Exp Pharmacol"},{"key":"2026011721220012500_ejhf1101-bib-0006","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1002\/ejhf.785","article-title":"Development and validation of multivariable models to predict mortality and hospitalization in patients with heart failure","volume":"19","author":"Voors","year":"2017","journal-title":"Eur J Heart Fail"},{"key":"2026011721220012500_ejhf1101-bib-0007","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-3-319-09665-0_1","article-title":"Structure of HDL: particle subclasses and molecular components","volume":"224","author":"Kontush","year":"2015","journal-title":"Handb Exp Pharmacol"},{"key":"2026011721220012500_ejhf1101-bib-0008","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1002\/ejhf.531","article-title":"A systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure: rationale, design, and baseline characteristics of BIOSTAT-CHF","volume":"18","author":"Voors","year":"2016","journal-title":"Eur J Heart Fail"},{"key":"2026011721220012500_ejhf1101-bib-0009","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1074\/mcp.M500230-MCP200","article-title":"Absolute quantification of proteins by LCMSE: a virtue of parallel MS acquisition","volume":"5","author":"Silva","year":"2005","journal-title":"Mol Cell Proteomics"},{"key":"2026011721220012500_ejhf1101-bib-0010","doi-asserted-by":"crossref","first-page":"D183","DOI":"10.1093\/nar\/gkw1138","article-title":"PANTHER version 11: expanded annotation data from Gene Ontology and Reactome pathways, and data analysis tool enhancements","volume":"45","author":"Mi","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"2026011721220012500_ejhf1101-bib-0011","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.cca.2015.12.005","article-title":"Proteome profiles of HDL particles of patients with chronic heart failure are associated with immune response and also include bacteria proteins","volume":"453","author":"Oberbach","year":"2016","journal-title":"Clin Chim Acta"},{"key":"2026011721220012500_ejhf1101-bib-0012","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1161\/CIRCRESAHA.113.301684","article-title":"Exercise training in patients with chronic heart failure promotes restoration of high-density lipoprotein functional properties","volume":"113","author":"Adams","year":"2013","journal-title":"Circ Res"},{"key":"2026011721220012500_ejhf1101-bib-0013","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1016\/j.amjcard.2013.07.045","article-title":"Heart failure is associated with impaired anti-inflammatory and antioxidant properties of high-density lipoproteins","volume":"112","author":"Kim","year":"2013","journal-title":"Am J Cardiol"},{"key":"2026011721220012500_ejhf1101-bib-0014","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1161\/CIRCHEARTFAILURE.110.958348","article-title":"Diminished antioxidant activity of high-density lipoprotein-associated proteins in systolic heart failure","volume":"4","author":"Tang","year":"2011","journal-title":"Circ Heart Fail"},{"key":"2026011721220012500_ejhf1101-bib-0015","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.116.004169","article-title":"Impaired high-density lipoprotein anti-oxidative function is associated with outcome in patients with chronic heart failure","volume":"5","author":"Schrutka","year":"2016","journal-title":"J Am Heart Assoc"},{"key":"2026011721220012500_ejhf1101-bib-0016","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0157507","article-title":"Metrics of high-density lipoprotein function and hospital mortality in acute heart failure patients","volume":"11","author":"Poto\u010dnjak","year":"2016","journal-title":"PLoS One"},{"key":"2026011721220012500_ejhf1101-bib-0017","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1080\/AC.69.4.3036656","article-title":"Serum fetuin-A levels in patients with systolic heart failure","volume":"69","author":"Ke\u00e7eba\u015f","year":"2014","journal-title":"Acta Cardiol"},{"key":"2026011721220012500_ejhf1101-bib-0018","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.jjcc.2009.10.003","article-title":"Serum beta2-microglobulin concentration as a novel marker to distinguish levels of risk in acute heart failure patients","volume":"55","author":"Kawai","year":"2010","journal-title":"J Cardiol"},{"key":"2026011721220012500_ejhf1101-bib-0019","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1002\/ejhf.777","article-title":"High-density lipoprotein-associated paraoxonase-1 activity for prediction of adverse outcomes in outpatients with chronic heart failure","volume":"19","author":"Hammadah","year":"2017","journal-title":"Eur J Heart Fail"},{"key":"2026011721220012500_ejhf1101-bib-0020","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.tcb.2009.12.001","article-title":"Filamins in cell signaling, transcription and organ development","volume":"20","author":"Zhou","year":"2010","journal-title":"Trends Cell Biol"},{"key":"2026011721220012500_ejhf1101-bib-0021","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1093\/cvr\/cvu226","article-title":"Deficiency of filamin A in endothelial cells impairs left ventricular remodelling after myocardial infarction","volume":"105","author":"Bandaru","year":"2015","journal-title":"Cardiovasc Res"},{"key":"2026011721220012500_ejhf1101-bib-0022","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1164\/ajrccm.159.2.9806064","article-title":"Lung epithelium-specific proteins: characteristics and potential applications as markers","volume":"159","author":"Hermans","year":"1999","journal-title":"Am J Respir Crit Care Med"},{"key":"2026011721220012500_ejhf1101-bib-0023","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1164\/ajrccm.164.4.2010111","article-title":"Elevated plasma surfactant protein-B predicts development of acute respiratory distress syndrome in patients with acute respiratory failure","volume":"164","author":"Bersten","year":"2001","journal-title":"Am J Respir Crit Care Med"},{"key":"2026011721220012500_ejhf1101-bib-0024","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1046\/j.1440-1681.1999.03015.x","article-title":"Partitioning lung and plasma proteins: circulating surfactant proteins as biomarkers of alveolocapillary permeability","volume":"26","author":"Doyle","year":"1999","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"2026011721220012500_ejhf1101-bib-0025","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.ijcard.2016.07.003","article-title":"Surfactant protein B: from biochemistry to its potential role as diagnostic and prognostic marker in heart failure","volume":"221","author":"Banfi","year":"2016","journal-title":"Int J Cardiol"},{"key":"2026011721220012500_ejhf1101-bib-0026","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1681\/ASN.2011070668","article-title":"Serum amyloid A in uremic HDL promotes inflammation","volume":"23","author":"Weichhart","year":"2012","journal-title":"J Am Soc Nephrol"},{"key":"2026011721220012500_ejhf1101-bib-0027","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.jacl.2015.05.002","article-title":"The risk of cardiovascular events with increased apolipoprotein CIII: a systematic review and meta-analysis","volume":"9","author":"Wyler von Ballmoos","year":"2015","journal-title":"J Clin Lipidol"}],"container-title":["European Journal of Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fejhf.1101","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/20\/2\/260\/66270838\/eurjhf_20_2_260.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/20\/2\/260\/66270838\/eurjhf_20_2_260.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T02:24:39Z","timestamp":1768703079000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurjhf\/article\/20\/2\/260\/8414972"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,18]]},"references-count":27,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2017,12,18]]},"published-print":{"date-parts":[[2018,2,1]]}},"URL":"https:\/\/doi.org\/10.1002\/ejhf.1101","relation":{},"ISSN":["1388-9842","1879-0844"],"issn-type":[{"value":"1388-9842","type":"print"},{"value":"1879-0844","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2018,2]]},"published":{"date-parts":[[2017,12,18]]}}}