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A multimarker approach to diagnose and stratify heart failure
Yunxia Wan1, Xi Xhang1, John J Atherton2
1The University of Queensland Diamantina Institute, The University of Queensland, The Translational Research Institute, Woolloongabba, Australia.
International Journal of Cardiology
|January 3, 2015
Summary
Novel assays measuring specific fragments of N-terminal pro-brain natriuretic peptide (NT-proBNP) show improved heart failure diagnosis. Combining NT-proBNP assays with NT-proBNP28-76 offers the best diagnostic performance.
Area of Science:
- Biomarker discovery and validation for cardiovascular diseases.
- Immunoassay development and optimization.
- Clinical diagnostics and patient stratification.
Background:
- Circulating N-terminal pro-brain natriuretic peptide (NT-proBNP) exhibits N- and C-terminal truncation.
- Understanding NT-proBNP heterogeneity is crucial for accurate heart failure (HF) assessment.
Purpose of the Study:
- To correlate NT-proBNP levels with NYHA functional classes using different antibody pairs.
- To evaluate the diagnostic potential of proBNP assays.
- To investigate the diagnostic accuracy of combined NT-proBNP and proBNP assays.
Main Methods:
- Development and validation of customized AlphaLISA® immunoassays for proBNP and NT-proBNP.
- Measurement of plasma samples from healthy controls (n=52) and HF patients (n=46).
- Evaluation of diagnostic performance and predictive value of various NT-proBNP and proBNP assay combinations.
Main Results:
- Plasma proBNP assay demonstrated acceptable diagnostic performance.
- NT-proBNP13-76 assay proved effective for diagnosing and stratifying HF patients, outperforming commercial NT-proBNP tests.
- Combining NT-proBNP13-76 and NT-proBNP28-76 assays yielded the highest diagnostic accuracy.
Conclusions:
- Specific, stable epitopes within NT-proBNP provide targets for reliable diagnostic assays despite overall peptide heterogeneity.
- A multimarker approach, rather than a single marker, is recommended for future HF diagnostic trials.
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