title: Improving the diagnostic accuracy of N-terminal B-type natriuretic peptide in human systolic heart failure by plasma profiling using mass spectrometry.
abstract: 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.
authors.affiliation: Cancer Biomarkers and Prevention Group, Biocentre, University of Leicester, UK. djlj1@le.ac.uk
authors.forename: Donald J L
authors.initials: DJ
authors.lastname: Jones
authors.forename: Richard
authors.initials: R
authors.lastname: Willingale
authors.forename: Paulene A
authors.initials: PA
authors.lastname: Quinn
authors.forename: John H
authors.initials: JH
authors.lastname: Lamb
authors.forename: Peter B
authors.initials: PB
authors.lastname: Farmer
authors.forename: Joan E
authors.initials: JE
authors.lastname: Davies
authors.forename: Leong L
authors.initials: LL
authors.lastname: Ng
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001798:Blood Proteins / Q000032:analysis*; D005260:Female; D054143:Heart Failure, Systolic / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000378:metabolism*; D012372:ROC Curve; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D020097:Natriuretic Peptide, Brain