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


Delles, C; Schiffer, E; von Zur Muhlen, C; Peter, K; Rossing, P; Parving, H H; Dymott, J A; Neisius, U; Zimmerli, L U; Snell-Bergeon, J K; Maahs, D M; Schmieder, R E; Mischak, H; Dominiczak, A F (2010). Urinary proteomic diagnosis of coronary artery disease: identification and clinical validation in 623 individuals. Journal of Hypertension, 28(11):2316-2322.

Abstract

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.

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.

Citations

55 citations in Web of Science®
61 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic and Policlinic for Internal Medicine
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2010
Deposited On:07 Feb 2011 15:44
Last Modified:05 Apr 2016 14:41
Publisher:Lippincott Wiliams & Wilkins
ISSN:0263-6352
Publisher DOI:10.1097/HJH.0b013e32833d81b7
PubMed ID:20811296

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