title: Prediction of acute coronary syndromes by urinary proteome analysis.
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 (P < 0.0001) and net reclassification improvement of 0.405 ± 0.113 (P = 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.
authors.affiliation: Atherothrombosis and Vascular Biology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia.|Department of Medicine, Monash University, Melbourne, Australia.
authors.forename: Nay M
authors.initials: NM
authors.lastname: Htun
authors.affiliation: Clinical Diabetes and Epidemiology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: Dianna J
authors.initials: DJ
authors.lastname: Magliano
authors.affiliation: Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Zhang
authors.affiliation: Clinical Diabetes and Epidemiology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: Jasmine
authors.initials: J
authors.lastname: Lyons
authors.affiliation: Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
authors.forename: Thibault
authors.initials: T
authors.lastname: Petit
authors.affiliation: Mosaiques Diagnostics GmbH, Hanover, Germany.
authors.forename: Esther
authors.initials: E
authors.lastname: Nkuipou-Kenfack
authors.affiliation: Mosaiques Diagnostics GmbH, Hanover, Germany.|Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, United States of America.
authors.forename: Adela
authors.initials: A
authors.lastname: Ramirez-Torres
authors.affiliation: Department of Cardiology, University Heart Centre Freiburg, Germany.
authors.forename: Constantin
authors.initials: C
authors.lastname: von Zur Muhlen
authors.affiliation: Department of Paediatrics, Stanford School of Medicine, Stanford, California, United States of America.|Barbara Davis Centre for Diabetes, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Maahs
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut of Cardiovascular and Metabolic Disease, Toulouse, France.|Université Toulouse III Paul-Sabatier, Toulouse, France.
authors.forename: Joost P
authors.initials: JP
authors.lastname: Schanstra
authors.affiliation: Mosaiques Diagnostics GmbH, Hanover, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pontillo
authors.affiliation: Mosaiques Diagnostics GmbH, Hanover, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Pejchinovski
authors.affiliation: Barbara Davis Centre for Diabetes, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
authors.forename: Janet K
authors.initials: JK
authors.lastname: Snell-Bergeon
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Christian
authors.initials: C
authors.lastname: Delles
authors.affiliation: Mosaiques Diagnostics GmbH, Hanover, Germany.|Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Harald
authors.initials: H
authors.lastname: Mischak
authors.affiliation: Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.|R&D VitaK Group, Maastricht University, Maastricht, Netherlands.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Staessen
authors.affiliation: Clinical Diabetes and Epidemiology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Shaw
authors.affiliation: Mosaiques Diagnostics GmbH, Hanover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Koeck
authors.affiliation: Atherothrombosis and Vascular Biology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia.|Department of Medicine, Monash University, Melbourne, Australia.
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Peter
mesh_terms: D054058:Acute Coronary Syndrome / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000652:urine; D000367:Age Factors; D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D019075:Electrophoresis, Capillary; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D010455:Peptides / Q000652:urine*; D011379:Prognosis; D020543:Proteome / Q000032:analysis*; D040901:Proteomics; D012372:ROC Curve; D012307:Risk Factors; D060388:Support Vector Machine; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; D010455:Peptides; D020543:Proteome