PLoS Medicine (Feb 2021)

Quantification of fibroblast growth factor 23 and N-terminal pro-B-type natriuretic peptide to identify patients with atrial fibrillation using a high-throughput platform: A validation study.

  • Winnie Chua,
  • Jonathan P Law,
  • Victor R Cardoso,
  • Yanish Purmah,
  • Georgiana Neculau,
  • Muhammad Jawad-Ul-Qamar,
  • Kalisha Russell,
  • Ashley Turner,
  • Samantha P Tull,
  • Frantisek Nehaj,
  • Paul Brady,
  • Peter Kastner,
  • André Ziegler,
  • Georgios V Gkoutos,
  • Davor Pavlovic,
  • Charles J Ferro,
  • Paulus Kirchhof,
  • Larissa Fabritz

DOI
https://doi.org/10.1371/journal.pmed.1003405
Journal volume & issue
Vol. 18, no. 2
p. e1003405

Abstract

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BackgroundLarge-scale screening for atrial fibrillation (AF) requires reliable methods to identify at-risk populations. Using an experimental semi-quantitative biomarker assay, B-type natriuretic peptide (BNP) and fibroblast growth factor 23 (FGF23) were recently identified as the most suitable biomarkers for detecting AF in combination with simple morphometric parameters (age, sex, and body mass index [BMI]). In this study, we validated the AF model using standardised, high-throughput, high-sensitivity biomarker assays.Methods and findingsFor this study, 1,625 consecutive patients with either (1) diagnosed AF or (2) sinus rhythm with CHA2DS2-VASc score of 2 or more were recruited from a large teaching hospital in Birmingham, West Midlands, UK, between September 2014 and February 2018. Seven-day ambulatory ECG monitoring excluded silent AF. Patients with tachyarrhythmias apart from AF and incomplete cases were excluded. AF was diagnosed according to current clinical guidelines and confirmed by ECG. We developed a high-throughput, high-sensitivity assay for FGF23, quantified plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) and FGF23, and compared results to the previously used multibiomarker research assay. Data were fitted to the previously derived model, adjusting for differences in measurement platforms and known confounders (heart failure and chronic kidney disease). In 1,084 patients (46% with AF; median [Q1, Q3] age 70 [60, 78] years, median [Q1, Q3] BMI 28.8 [25.1, 32.8] kg/m2, 59% males), patients with AF had higher concentrations of NT-proBNP (median [Q1, Q3] per 100 pg/ml: with AF 12.00 [4.19, 30.15], without AF 4.25 [1.17, 15.70]; p ConclusionsAge, sex, and BMI combined with elevated NT-proBNP and elevated FGF23, quantified on a high-throughput platform, reliably identify patients with AF.Trial registrationRegistry IRAS ID 97753 Health Research Authority (HRA), United Kingdom.