A multimarker approach to diagnose and stratify heart failure

Int J Cardiol. 2015 Feb 15:181:369-75. doi: 10.1016/j.ijcard.2014.12.052. Epub 2014 Dec 23.

Abstract

Background: We have previously demonstrated that circulating NT-proBNP is truncated at the N and C termini. Aims of this study are three-fold: firstly to determine whether the NT-proBNP levels correlate with NYHA functional classes when measuring with different antibody pairs; secondly to evaluate the diagnostic potential of ProBNP and; thirdly to investigate whether combining NT-proBNP assays with or without ProBNP would lead to better diagnostic accuracies.

Methods: Plasma samples were collected from healthy controls (n=52) and HF patients (n=46). Customized AlphaLISA® immunoassays were developed and validated to measure the concentrations of proBNP and NT-proBNP (with antibodies targeting 13-45, 13-76, 28-76). The diagnostic performance and predictive value of proBNP and NT-proBNP assays and their combinations were evaluated.

Results: Plasma proBNP assay showed acceptable diagnostic performance. NT-proBNP13-76 assay is useful in diagnosing and stratifying HF patients. The diagnostic performance of NT-proBNP13-76 demonstrated improvement over commercial NT-proBNP tests. The combination of NT-proBNP13-76 with NT-proBNP28-76 assays gave the best diagnostic assay performance.

Conclusion: Our results demonstrate that while there is major heterogeneity in circulating NT-proBNP, specific epitopes of the peptides are extraordinarily stable, providing ideal targets for clinically useful diagnostic assays. Future new clinical diagnostic clinical trials should include a multimarker approach rather than using a single marker to diagnose HF.

Keywords: Classify heart failure; NT-proBNP; proBNP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Female
  • Heart Failure / blood*
  • Heart Failure / diagnosis*
  • Humans
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood*
  • Peptide Fragments / blood*
  • Young Adult

Substances

  • Biomarkers
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain