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Urinary proteomic diagnosis of coronary artery disease: identification and clinical validation in 623 individuals

Delles, Christiana,*; Schiffer, Ericb,*; von zur Muhlen, Constantinc; Peter, Karlheinzd; Rossing, Petere; Parving, Hans-Henrikf; Dymott, Jane Aa; Neisius, Ulfa; Zimmerli, Lukas Ua,†; Snell-Bergeon, Janet Kg; Maahs, David Mg; Schmieder, Roland Eh; Mischak, Haraldb; Dominiczak, Anna Fa

doi: 10.1097/HJH.0b013e32833d81b7
Original papers: Heart

Objectives We studied the urinary proteome in a total of 623 individuals with and without coronary artery disease (CAD) in order to characterize multiple biomarkers that enable prediction of the presence of CAD.

Methods Urine samples were analyzed by capillary electrophoresis coupled online to micro time-of-flight mass spectrometry.

Results We defined a pattern of 238 CAD-specific polypeptides from comparison of 586 spot urine samples from 408 individuals. This pattern identified patients with CAD in a blinded cohort of 138 urine samples (71 patients with CAD and 67 healthy individuals) with high sensitivity and specificity (area under the receiver operator characteristic curve 87%, 95% confidence interval 81–92) and was superior to previously developed 15-marker (area under the receiver operator characteristic curve 68%, P < 0.0001) and 17-marker panels (area under the receiver operator characteristic curve 77%, P < 0.0001). The sequences of the discriminatory polypeptides include fragments of alpha-1-antitrypsin, collagen types 1 and 3, granin-like neuroendocrine peptide precursor, membrane-associated progesterone receptor component 1, sodium/potassium-transporting ATPase gamma chain and fibrinogen-alpha chain. Several biomarkers changed significantly toward the healthy signature following 2-year treatment with irbesartan, whereas short-term treatment with irbesartan did not significantly affect the polypeptide pattern.

Conclusion Urinary proteomics identifies CAD with high confidence and might also be useful for monitoring the effects of therapeutic interventions.

aBHF Glasgow Cardiovascular Research Centre, Faculty of Medicine, University of Glasgow, Glasgow, UK

bmosaiques diagnostics GmbH, Hannover, Germany

cDepartment of Cardiology and Angiology, University Hospital, Freiburg, Germany

dBaker Heart Research Institute, Melbourne, Victoria, Australia

eSteno Diabetes Center, Gentofte, Denmark

fDepartment of Endocrinology, Rigshospitalet University Hospital of Copenhagen, Copenhagen, Denmark

gBarbara Davis Center for Childhood Diabetes, Aurora, Colorado, USA

hDepartment of Medicine IV, Nephrology and Hypertension, University of Erlangen-Nürnberg, Bavaria, Germany

*C.D. and E.S. contributed equally to the writing of this article.

Present address: Division of Internal Medicine, University Hospital Zürich, Zürich, Switzerland.

Received 9 April, 2010

Revised 16 June, 2010

Accepted 22 June, 2010

Correspondence to Professor Anna F. Dominiczak, BHF, Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK Tel: +44 141 330 5420; fax: +44 141 330 6997; e-mail: ad7e@clinmed.gla.ac.uk

© 2010 Lippincott Williams & Wilkins, Inc.