Prediction of acute coronary syndromes by urinary proteome analysis
Identifieur interne : 002819 ( Pmc/Curation ); précédent : 002818; suivant : 002820Prediction of acute coronary syndromes by urinary proteome analysis
Auteurs : Nay M. Htun [Australie] ; Dianna J. Magliano [Australie] ; Zhen-Yu Zhang [Belgique] ; Jasmine Lyons [Australie] ; Thibault Petit [Belgique] ; Esther Nkuipou-Kenfack [Allemagne] ; Adela Ramirez-Torres [Allemagne, États-Unis] ; Constantin Von Zur Muhlen [Allemagne] ; David Maahs [États-Unis] ; Joost P. Schanstra [France] ; Claudia Pontillo [Allemagne] ; Martin Pejchinovski [Allemagne] ; Janet K. Snell-Bergeon [États-Unis] ; Christian Delles [Royaume-Uni] ; Harald Mischak [Allemagne, Royaume-Uni] ; Jan A. Staessen [Belgique, Pays-Bas] ; Jonathan E. Shaw [Australie] ; Thomas Koeck [Allemagne] ; Karlheinz Peter [Australie]Source :
- PLoS ONE [ 1932-6203 ] ; 2017.
Abstract
Identification of individuals who are at risk of suffering from acute coronary syndromes (ACS) may allow to introduce preventative measures. We aimed to identify ACS-related urinary peptides, that combined as a pattern can be used as prognostic biomarker. Proteomic data of 252 individuals enrolled in four prospective studies from Australia, Europe and North America were analyzed. 126 of these had suffered from ACS within a period of up to 5 years post urine sampling (cases). Proteomic analysis of 84 cases and 84 matched controls resulted in the discovery of 75 ACS-related urinary peptides. Combining these to a peptide pattern, we established a prognostic biomarker named Acute Coronary Syndrome Predictor 75 (ACSP75). ACSP75 demonstrated reasonable prognostic discrimination (c-statistic = 0.664), which was similar to Framingham risk scoring (c-statistics = 0.644) in a validation cohort of 42 cases and 42 controls. However, generating by a composite algorithm named Acute Coronary Syndrome Composite Predictor (ACSCP), combining the biomarker pattern ACSP75 with the previously established urinary proteomic biomarker CAD238 characterizing coronary artery disease as the underlying aetiology, and age as a risk factor, further improved discrimination (c-statistic = 0.751) resulting in an added prognostic value over Framingham risk scoring expressed by an integrated discrimination improvement of 0.273 ± 0.048 (
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DOI: 10.1371/journal.pone.0172036
PubMed: 28273075
PubMed Central: 5342174
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Htun</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Atherothrombosis and Vascular Biology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Atherothrombosis and Vascular Biology, Baker IDI Heart and Diabetes Institute, Melbourne</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>Department of Medicine, Monash University, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medicine, Monash University, Melbourne</wicri:regionArea></affiliation></author><author><name sortKey="Magliano, Dianna J" sort="Magliano, Dianna J" uniqKey="Magliano D" first="Dianna J." last="Magliano">Dianna J. 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Schanstra</name><affiliation wicri:level="1"><nlm:aff id="aff010"><addr-line>Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut of Cardiovascular and Metabolic Disease, Toulouse, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut of Cardiovascular and Metabolic Disease, Toulouse</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff011"><addr-line>Université Toulouse III Paul-Sabatier, Toulouse, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université Toulouse III Paul-Sabatier, Toulouse</wicri:regionArea></affiliation></author><author><name sortKey="Pontillo, Claudia" sort="Pontillo, Claudia" uniqKey="Pontillo C" first="Claudia" last="Pontillo">Claudia Pontillo</name><affiliation wicri:level="1"><nlm:aff id="aff005"><addr-line>Mosaiques Diagnostics GmbH, Hanover, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Mosaiques Diagnostics GmbH, Hanover</wicri:regionArea></affiliation></author><author><name sortKey="Pejchinovski, Martin" sort="Pejchinovski, Martin" uniqKey="Pejchinovski M" first="Martin" last="Pejchinovski">Martin Pejchinovski</name><affiliation wicri:level="1"><nlm:aff id="aff005"><addr-line>Mosaiques Diagnostics GmbH, Hanover, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Mosaiques Diagnostics GmbH, Hanover</wicri:regionArea></affiliation></author><author><name sortKey="Snell Bergeon, Janet K" sort="Snell Bergeon, Janet K" uniqKey="Snell Bergeon J" first="Janet K." last="Snell-Bergeon">Janet K. 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Staessen</name><affiliation wicri:level="1"><nlm:aff id="aff004"><addr-line>Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium</addr-line></nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff013"><addr-line>R&D VitaK Group, Maastricht University, Maastricht, Netherlands</addr-line></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>R&D VitaK Group, Maastricht University, Maastricht</wicri:regionArea></affiliation></author><author><name sortKey="Shaw, Jonathan E" sort="Shaw, Jonathan E" uniqKey="Shaw J" first="Jonathan E." last="Shaw">Jonathan E. Shaw</name><affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Clinical Diabetes and Epidemiology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Clinical Diabetes and Epidemiology, Baker IDI Heart and Diabetes Institute, Melbourne</wicri:regionArea></affiliation></author><author><name sortKey="Koeck, Thomas" sort="Koeck, Thomas" uniqKey="Koeck T" first="Thomas" last="Koeck">Thomas Koeck</name><affiliation wicri:level="1"><nlm:aff id="aff005"><addr-line>Mosaiques Diagnostics GmbH, Hanover, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Mosaiques Diagnostics GmbH, Hanover</wicri:regionArea></affiliation></author><author><name sortKey="Peter, Karlheinz" sort="Peter, Karlheinz" uniqKey="Peter K" first="Karlheinz" last="Peter">Karlheinz Peter</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Atherothrombosis and Vascular Biology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Atherothrombosis and Vascular Biology, Baker IDI Heart and Diabetes Institute, Melbourne</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>Department of Medicine, Monash University, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medicine, Monash University, Melbourne</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">28273075</idno><idno type="pmc">5342174</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342174</idno><idno type="RBID">PMC:5342174</idno><idno type="doi">10.1371/journal.pone.0172036</idno><date when="2017">2017</date><idno type="wicri:Area/Pmc/Corpus">002969</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002969</idno><idno type="wicri:Area/Pmc/Curation">002819</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">002819</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Prediction of acute coronary syndromes by urinary proteome analysis</title><author><name sortKey="Htun, Nay M" sort="Htun, Nay M" uniqKey="Htun N" first="Nay M." last="Htun">Nay M. Htun</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Atherothrombosis and Vascular Biology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Atherothrombosis and Vascular Biology, Baker IDI Heart and Diabetes Institute, Melbourne</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>Department of Medicine, Monash University, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medicine, Monash University, Melbourne</wicri:regionArea></affiliation></author><author><name sortKey="Magliano, Dianna J" sort="Magliano, Dianna J" uniqKey="Magliano D" first="Dianna J." last="Magliano">Dianna J. Magliano</name><affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Clinical Diabetes and Epidemiology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Clinical Diabetes and Epidemiology, Baker IDI Heart and Diabetes Institute, Melbourne</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Zhen Yu" sort="Zhang, Zhen Yu" uniqKey="Zhang Z" first="Zhen-Yu" last="Zhang">Zhen-Yu Zhang</name><affiliation wicri:level="1"><nlm:aff id="aff004"><addr-line>Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium</addr-line></nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven</wicri:regionArea></affiliation></author><author><name sortKey="Lyons, Jasmine" sort="Lyons, Jasmine" uniqKey="Lyons J" first="Jasmine" last="Lyons">Jasmine Lyons</name><affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Clinical Diabetes and Epidemiology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Clinical Diabetes and Epidemiology, Baker IDI Heart and Diabetes Institute, Melbourne</wicri:regionArea></affiliation></author><author><name sortKey="Petit, Thibault" sort="Petit, Thibault" uniqKey="Petit T" first="Thibault" last="Petit">Thibault Petit</name><affiliation wicri:level="1"><nlm:aff id="aff004"><addr-line>Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium</addr-line></nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven</wicri:regionArea></affiliation></author><author><name sortKey="Nkuipou Kenfack, Esther" sort="Nkuipou Kenfack, Esther" uniqKey="Nkuipou Kenfack E" first="Esther" last="Nkuipou-Kenfack">Esther Nkuipou-Kenfack</name><affiliation wicri:level="1"><nlm:aff id="aff005"><addr-line>Mosaiques Diagnostics GmbH, Hanover, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Mosaiques Diagnostics GmbH, Hanover</wicri:regionArea></affiliation></author><author><name sortKey="Ramirez Torres, Adela" sort="Ramirez Torres, Adela" uniqKey="Ramirez Torres A" first="Adela" last="Ramirez-Torres">Adela Ramirez-Torres</name><affiliation wicri:level="1"><nlm:aff id="aff005"><addr-line>Mosaiques Diagnostics GmbH, Hanover, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Mosaiques Diagnostics GmbH, Hanover</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff006"><addr-line>Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California</wicri:regionArea></affiliation></author><author><name sortKey="Von Zur Muhlen, Constantin" sort="Von Zur Muhlen, Constantin" uniqKey="Von Zur Muhlen C" first="Constantin" last="Von Zur Muhlen">Constantin Von Zur Muhlen</name><affiliation wicri:level="1"><nlm:aff id="aff007"><addr-line>Department of Cardiology, University Heart Centre Freiburg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Cardiology, University Heart Centre Freiburg</wicri:regionArea></affiliation></author><author><name sortKey="Maahs, David" sort="Maahs, David" uniqKey="Maahs D" first="David" last="Maahs">David Maahs</name><affiliation wicri:level="1"><nlm:aff id="aff008"><addr-line>Department of Paediatrics, Stanford School of Medicine, Stanford, California, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Paediatrics, Stanford School of Medicine, Stanford, California</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff009"><addr-line>Barbara Davis Centre for Diabetes, University of Colorado School of Medicine, Aurora, Colorado, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Barbara Davis Centre for Diabetes, University of Colorado School of Medicine, Aurora, Colorado</wicri:regionArea></affiliation></author><author><name sortKey="Schanstra, Joost P" sort="Schanstra, Joost P" uniqKey="Schanstra J" first="Joost P." last="Schanstra">Joost P. Schanstra</name><affiliation wicri:level="1"><nlm:aff id="aff010"><addr-line>Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut of Cardiovascular and Metabolic Disease, Toulouse, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut of Cardiovascular and Metabolic Disease, Toulouse</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff011"><addr-line>Université Toulouse III Paul-Sabatier, Toulouse, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université Toulouse III Paul-Sabatier, Toulouse</wicri:regionArea></affiliation></author><author><name sortKey="Pontillo, Claudia" sort="Pontillo, Claudia" uniqKey="Pontillo C" first="Claudia" last="Pontillo">Claudia Pontillo</name><affiliation wicri:level="1"><nlm:aff id="aff005"><addr-line>Mosaiques Diagnostics GmbH, Hanover, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Mosaiques Diagnostics GmbH, Hanover</wicri:regionArea></affiliation></author><author><name sortKey="Pejchinovski, Martin" sort="Pejchinovski, Martin" uniqKey="Pejchinovski M" first="Martin" last="Pejchinovski">Martin Pejchinovski</name><affiliation wicri:level="1"><nlm:aff id="aff005"><addr-line>Mosaiques Diagnostics GmbH, Hanover, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Mosaiques Diagnostics GmbH, Hanover</wicri:regionArea></affiliation></author><author><name sortKey="Snell Bergeon, Janet K" sort="Snell Bergeon, Janet K" uniqKey="Snell Bergeon J" first="Janet K." last="Snell-Bergeon">Janet K. Snell-Bergeon</name><affiliation wicri:level="1"><nlm:aff id="aff009"><addr-line>Barbara Davis Centre for Diabetes, University of Colorado School of Medicine, Aurora, Colorado, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Barbara Davis Centre for Diabetes, University of Colorado School of Medicine, Aurora, Colorado</wicri:regionArea></affiliation></author><author><name sortKey="Delles, Christian" sort="Delles, Christian" uniqKey="Delles C" first="Christian" last="Delles">Christian Delles</name><affiliation wicri:level="1"><nlm:aff id="aff012"><addr-line>Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow</wicri:regionArea></affiliation></author><author><name sortKey="Mischak, Harald" sort="Mischak, Harald" uniqKey="Mischak H" first="Harald" last="Mischak">Harald Mischak</name><affiliation wicri:level="1"><nlm:aff id="aff005"><addr-line>Mosaiques Diagnostics GmbH, Hanover, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Mosaiques Diagnostics GmbH, Hanover</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff012"><addr-line>Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow</wicri:regionArea></affiliation></author><author><name sortKey="Staessen, Jan A" sort="Staessen, Jan A" uniqKey="Staessen J" first="Jan A." last="Staessen">Jan A. Staessen</name><affiliation wicri:level="1"><nlm:aff id="aff004"><addr-line>Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium</addr-line></nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff013"><addr-line>R&D VitaK Group, Maastricht University, Maastricht, Netherlands</addr-line></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>R&D VitaK Group, Maastricht University, Maastricht</wicri:regionArea></affiliation></author><author><name sortKey="Shaw, Jonathan E" sort="Shaw, Jonathan E" uniqKey="Shaw J" first="Jonathan E." last="Shaw">Jonathan E. Shaw</name><affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Clinical Diabetes and Epidemiology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Clinical Diabetes and Epidemiology, Baker IDI Heart and Diabetes Institute, Melbourne</wicri:regionArea></affiliation></author><author><name sortKey="Koeck, Thomas" sort="Koeck, Thomas" uniqKey="Koeck T" first="Thomas" last="Koeck">Thomas Koeck</name><affiliation wicri:level="1"><nlm:aff id="aff005"><addr-line>Mosaiques Diagnostics GmbH, Hanover, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Mosaiques Diagnostics GmbH, Hanover</wicri:regionArea></affiliation></author><author><name sortKey="Peter, Karlheinz" sort="Peter, Karlheinz" uniqKey="Peter K" first="Karlheinz" last="Peter">Karlheinz Peter</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Atherothrombosis and Vascular Biology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Atherothrombosis and Vascular Biology, Baker IDI Heart and Diabetes Institute, Melbourne</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>Department of Medicine, Monash University, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medicine, Monash University, Melbourne</wicri:regionArea></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Identification of individuals who are at risk of suffering from acute coronary syndromes (ACS) may allow to introduce preventative measures. We aimed to identify ACS-related urinary peptides, that combined as a pattern can be used as prognostic biomarker. Proteomic data of 252 individuals enrolled in four prospective studies from Australia, Europe and North America were analyzed. 126 of these had suffered from ACS within a period of up to 5 years post urine sampling (cases). Proteomic analysis of 84 cases and 84 matched controls resulted in the discovery of 75 ACS-related urinary peptides. Combining these to a peptide pattern, we established a prognostic biomarker named Acute Coronary Syndrome Predictor 75 (ACSP75). ACSP75 demonstrated reasonable prognostic discrimination (c-statistic = 0.664), which was similar to Framingham risk scoring (c-statistics = 0.644) in a validation cohort of 42 cases and 42 controls. However, generating by a composite algorithm named Acute Coronary Syndrome Composite Predictor (ACSCP), combining the biomarker pattern ACSP75 with the previously established urinary proteomic biomarker CAD238 characterizing coronary artery disease as the underlying aetiology, and age as a risk factor, further improved discrimination (c-statistic = 0.751) resulting in an added prognostic value over Framingham risk scoring expressed by an integrated discrimination improvement of 0.273 ± 0.048 (<italic>P</italic> < 0.0001) and net reclassification improvement of 0.405 ± 0.113 (<italic>P</italic> = 0.0007). In conclusion, we demonstrate that urinary peptide biomarkers have the potential to predict future ACS events in asymptomatic patients. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id><journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosone</journal-id><journal-title-group><journal-title>PLoS ONE</journal-title></journal-title-group><issn pub-type="epub">1932-6203</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, CA USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">28273075</article-id><article-id pub-id-type="pmc">5342174</article-id><article-id pub-id-type="doi">10.1371/journal.pone.0172036</article-id><article-id pub-id-type="publisher-id">PONE-D-16-45061</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Biochemistry</subject><subj-group><subject>Biomarkers</subject></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Biochemistry</subject><subj-group><subject>Proteins</subject><subj-group><subject>Collagens</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Vascular Medicine</subject><subj-group><subject>Coronary Heart Disease</subject></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Cardiology</subject><subj-group><subject>Coronary Heart Disease</subject></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Biochemistry</subject><subj-group><subject>Peptides</subject></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Anatomy</subject><subj-group><subject>Body Fluids</subject><subj-group><subject>Urine</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Anatomy</subject><subj-group><subject>Body Fluids</subject><subj-group><subject>Urine</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Physiology</subject><subj-group><subject>Body Fluids</subject><subj-group><subject>Urine</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Physiology</subject><subj-group><subject>Body Fluids</subject><subj-group><subject>Urine</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Biochemistry</subject><subj-group><subject>Proteins</subject><subj-group><subject>Proteomes</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Biochemistry</subject><subj-group><subject>Proteomics</subject></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Endocrinology</subject><subj-group><subject>Endocrine Disorders</subject><subj-group><subject>Diabetes Mellitus</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Metabolic Disorders</subject><subj-group><subject>Diabetes Mellitus</subject></subj-group></subj-group></subj-group></article-categories><title-group><article-title>Prediction of acute coronary syndromes by urinary proteome analysis</article-title><alt-title alt-title-type="running-head">Urine proteomics to predict ACS</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Htun</surname><given-names>Nay M.</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref ref-type="aff" rid="aff002"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Magliano</surname><given-names>Dianna J.</given-names></name><xref ref-type="aff" rid="aff003"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Zhen-Yu</given-names></name><xref ref-type="aff" rid="aff004"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lyons</surname><given-names>Jasmine</given-names></name><xref ref-type="aff" rid="aff003"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Petit</surname><given-names>Thibault</given-names></name><xref ref-type="aff" rid="aff004"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Nkuipou-Kenfack</surname><given-names>Esther</given-names></name><xref ref-type="aff" rid="aff005"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ramirez-Torres</surname><given-names>Adela</given-names></name><xref ref-type="aff" rid="aff005"><sup>5</sup></xref><xref ref-type="aff" rid="aff006"><sup>6</sup></xref></contrib><contrib contrib-type="author"><name><surname>von zur Muhlen</surname><given-names>Constantin</given-names></name><xref ref-type="aff" rid="aff007"><sup>7</sup></xref></contrib><contrib contrib-type="author"><name><surname>Maahs</surname><given-names>David</given-names></name><xref ref-type="aff" rid="aff008"><sup>8</sup></xref><xref ref-type="aff" rid="aff009"><sup>9</sup></xref></contrib><contrib contrib-type="author"><name><surname>Schanstra</surname><given-names>Joost P.</given-names></name><xref ref-type="aff" rid="aff010"><sup>10</sup></xref><xref ref-type="aff" rid="aff011"><sup>11</sup></xref></contrib><contrib contrib-type="author"><name><surname>Pontillo</surname><given-names>Claudia</given-names></name><xref ref-type="aff" rid="aff005"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Pejchinovski</surname><given-names>Martin</given-names></name><xref ref-type="aff" rid="aff005"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Snell-Bergeon</surname><given-names>Janet K.</given-names></name><xref ref-type="aff" rid="aff009"><sup>9</sup></xref></contrib><contrib contrib-type="author"><name><surname>Delles</surname><given-names>Christian</given-names></name><xref ref-type="aff" rid="aff012"><sup>12</sup></xref></contrib><contrib contrib-type="author"><name><surname>Mischak</surname><given-names>Harald</given-names></name><xref ref-type="aff" rid="aff005"><sup>5</sup></xref><xref ref-type="aff" rid="aff012"><sup>12</sup></xref></contrib><contrib contrib-type="author"><name><surname>Staessen</surname><given-names>Jan A.</given-names></name><xref ref-type="aff" rid="aff004"><sup>4</sup></xref><xref ref-type="aff" rid="aff013"><sup>13</sup></xref></contrib><contrib contrib-type="author"><name><surname>Shaw</surname><given-names>Jonathan E.</given-names></name><xref ref-type="aff" rid="aff003"><sup>3</sup></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Koeck</surname><given-names>Thomas</given-names></name><xref ref-type="aff" rid="aff005"><sup>5</sup></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Peter</surname><given-names>Karlheinz</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref ref-type="aff" rid="aff002"><sup>2</sup></xref><xref ref-type="corresp" rid="cor001">*</xref></contrib></contrib-group><aff id="aff001"><label>1</label><addr-line>Atherothrombosis and Vascular Biology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia</addr-line></aff><aff id="aff002"><label>2</label><addr-line>Department of Medicine, Monash University, Melbourne, Australia</addr-line></aff><aff id="aff003"><label>3</label><addr-line>Clinical Diabetes and Epidemiology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia</addr-line></aff><aff id="aff004"><label>4</label><addr-line>Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium</addr-line></aff><aff id="aff005"><label>5</label><addr-line>Mosaiques Diagnostics GmbH, Hanover, Germany</addr-line></aff><aff id="aff006"><label>6</label><addr-line>Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, United States of America</addr-line></aff><aff id="aff007"><label>7</label><addr-line>Department of Cardiology, University Heart Centre Freiburg, Germany</addr-line></aff><aff id="aff008"><label>8</label><addr-line>Department of Paediatrics, Stanford School of Medicine, Stanford, California, United States of America</addr-line></aff><aff id="aff009"><label>9</label><addr-line>Barbara Davis Centre for Diabetes, University of Colorado School of Medicine, Aurora, Colorado, United States of America</addr-line></aff><aff id="aff010"><label>10</label><addr-line>Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut of Cardiovascular and Metabolic Disease, Toulouse, France</addr-line></aff><aff id="aff011"><label>11</label><addr-line>Université Toulouse III Paul-Sabatier, Toulouse, France</addr-line></aff><aff id="aff012"><label>12</label><addr-line>Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom</addr-line></aff><aff id="aff013"><label>13</label><addr-line>R&D VitaK Group, Maastricht University, Maastricht, Netherlands</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Ahrens</surname><given-names>Ingo</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>University Medical Center, GERMANY</addr-line></aff><author-notes><fn fn-type="COI-statement" id="coi001"><p><bold>Competing Interests: </bold>The authors have declared the following potential conflict of interest: H. Mischak is the founder and coowner of Mosaiques Diagnostics GmbH, who developed the CE-MS technology for clinical application. E. Nkuipou-Kenfack, A. Ramirez-Torres, C. Pontillo, M. Pejchinovski and T. Koeck are employees of Mosaiques Diagnostics GmbH. This does not alter our adherence to PLOS ONE policies on sharing data and materials.</p></fn><fn fn-type="con"><p><list list-type="simple"><list-item><p><bold>Conceptualization:</bold> NMH DJM TK KP.</p></list-item><list-item><p><bold>Data curation:</bold> NMH TK DJM.</p></list-item><list-item><p><bold>Formal analysis:</bold> NMH DJM CP ENK ART MP TK KP.</p></list-item><list-item><p><bold>Funding acquisition:</bold> HM KP JAS JPS.</p></list-item><list-item><p><bold>Investigation:</bold> NMH DJM CP ENK ZYZ JL TK TP CVZM DM JPS JKSB CD HM JAS JES KP.</p></list-item><list-item><p><bold>Methodology:</bold> NMH DJM TK HM KP.</p></list-item><list-item><p><bold>Project administration:</bold> HM KP.</p></list-item><list-item><p><bold>Resources:</bold> NMH JAS CD HM KP.</p></list-item><list-item><p><bold>Software:</bold> NMH DJM ENK TK HM KP.</p></list-item><list-item><p><bold>Supervision:</bold> HM KP.</p></list-item><list-item><p><bold>Validation:</bold> NMH DJM HM TK KP.</p></list-item><list-item><p><bold>Visualization:</bold> NMH DJM TK KP.</p></list-item><list-item><p><bold>Writing – original draft:</bold> NMH DJM CP ENK ZYZ JL TK TP CVZM DM JPS JKSB CD HM JAS JES KP.</p></list-item><list-item><p><bold>Writing – review & editing:</bold> NMH DJM ENK HM JES KP MP.</p></list-item></list></p></fn><corresp id="cor001">* E-mail: <email>Karlheinz.Peter@bakeridi.edu.au</email></corresp></author-notes><pub-date pub-type="epub"><day>8</day><month>3</month><year>2017</year></pub-date><pub-date pub-type="collection"><year>2017</year></pub-date><volume>12</volume><issue>3</issue><elocation-id>e0172036</elocation-id><history><date date-type="received"><day>13</day><month>11</month><year>2016</year></date><date date-type="accepted"><day>30</day><month>1</month><year>2017</year></date></history><permissions><copyright-statement>© 2017 Htun et al</copyright-statement><copyright-year>2017</copyright-year><copyright-holder>Htun et al</copyright-holder><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions><self-uri content-type="pdf" xlink:href="pone.0172036.pdf"></self-uri><abstract><p>Identification of individuals who are at risk of suffering from acute coronary syndromes (ACS) may allow to introduce preventative measures. We aimed to identify ACS-related urinary peptides, that combined as a pattern can be used as prognostic biomarker. Proteomic data of 252 individuals enrolled in four prospective studies from Australia, Europe and North America were analyzed. 126 of these had suffered from ACS within a period of up to 5 years post urine sampling (cases). Proteomic analysis of 84 cases and 84 matched controls resulted in the discovery of 75 ACS-related urinary peptides. Combining these to a peptide pattern, we established a prognostic biomarker named Acute Coronary Syndrome Predictor 75 (ACSP75). ACSP75 demonstrated reasonable prognostic discrimination (c-statistic = 0.664), which was similar to Framingham risk scoring (c-statistics = 0.644) in a validation cohort of 42 cases and 42 controls. However, generating by a composite algorithm named Acute Coronary Syndrome Composite Predictor (ACSCP), combining the biomarker pattern ACSP75 with the previously established urinary proteomic biomarker CAD238 characterizing coronary artery disease as the underlying aetiology, and age as a risk factor, further improved discrimination (c-statistic = 0.751) resulting in an added prognostic value over Framingham risk scoring expressed by an integrated discrimination improvement of 0.273 ± 0.048 (<italic>P</italic> < 0.0001) and net reclassification improvement of 0.405 ± 0.113 (<italic>P</italic> = 0.0007). In conclusion, we demonstrate that urinary peptide biomarkers have the potential to predict future ACS events in asymptomatic patients. Further large scale studies are warranted to determine the role of urinary biomarkers in clinical practice.</p></abstract><funding-group><funding-statement>The project was partly supported by the European Union grants EU-MASCARA (HEALTH-FP7-278249), HOMAGE (HEALTH-FP7-305507), SYSVASC (HEALTH-FP7-603288), the European Research Council Advanced Researcher Grant EXPLORE (2011-294713) and the National Health and Medical Research Council of Australia (NHMRC) - European Union Collaborative Research Grant GNT1102158. The Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium (G.0881.13 and G.0880.13) supported the FLEMENGHO study. N. M. Htun was supported by scholarships from the Cardiac Society of Australia and New Zealand (CSANZ) and NHMRC, Australia. D. J. Magliano, J. E. Shaw and K. Peter are supported by research fellowships from the NHMRC. The funders provided support in the form of salaries for authors [NMH, DJM, ENK, JPS, CD, HM, JAS, JES, TK, KP], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.</funding-statement></funding-group><counts><fig-count count="2"></fig-count><table-count count="4"></table-count><page-count count="18"></page-count></counts><custom-meta-group><custom-meta id="data-availability"><meta-name>Data Availability</meta-name><meta-value>All relevant data are within the paper and its Supporting Information files.</meta-value></custom-meta></custom-meta-group></article-meta><notes><title>Data Availability</title><p>All relevant data are within the paper and its Supporting Information files.</p></notes></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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