Improving the Diagnostic Accuracy of N-Terminal B-Type Natriuretic Peptide in Human Systolic Heart Failure by Plasma Profiling Using Mass Spectrometry

We have combined the measurement of N-terminal pro-B type natriuretic peptide (NTproBNP) with plasma peptide profiling to evaluate the effect on sensitivity and specificity of systolic heart failure (SHF) diagnosis. Plasma NTproBNP levels were measured from 100 SHF patients and 100 age/gender matche...

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Bibliographic Details
Published in:Journal of proteome research 2007-08, Vol.6 (8), p.3329-3334
Main Authors: Jones, Donald J. L, Willingale, Richard, Quinn, Paulene A, Lamb, John H, Farmer, Peter B, Davies, Joan E, Ng, Leong L
Format: Article
Language:English
Subjects:
Aged
Biomarkers - metabolism
Blood Proteins - analysis
Female
Heart Failure, Systolic - blood
Humans
Male
Middle Aged
Natriuretic Peptide, Brain - metabolism
ROC Curve
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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Summary:We have combined the measurement of N-terminal pro-B type natriuretic peptide (NTproBNP) with plasma peptide profiling to evaluate the effect on sensitivity and specificity of systolic heart failure (SHF) diagnosis. Plasma NTproBNP levels were measured from 100 SHF patients and 100 age/gender matched controls and plasma protein profiles obtained using MALDI-MS. Sixty-seven m/z peaks were significantly different between SHF and normals, and following logistic regression analysis with NTproBNP values, 6 peaks retained independent predictive value. Receiver operating characteristic (ROC) curves for SHF diagnosis had areas of 0.91 for NTproBNP, improving to 0.99 with the model. In a separate validation test set (32 SHF, 20 normals), the model remained highly accurate (ROC area 0.995). An artificial neural network with these 6 peak intensities and NTproBNP produced ROC areas of 0.99 in both training and test sets. The sensitivity and specificity of SHF diagnosis using NTproBNP in training (85, 85%) and test (93, 75%) sets was improved in the model for both training (96, 96%) and test (100, 95%) sets. The accuracy of SHF diagnosis using NTproBNP is improved by the use of a plasma profile of 6 peptide peaks, reducing the uncertainty in the diagnostic gray zone of using NTproBNP alone. Keywords: systolic heart failure • natriuretic peptides • mass spectrometry • sensitivity • specificity
ISSN:1535-3893
1535-3907
DOI:10.1021/pr070023d