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

Chua, Winnie and Law, Jonathan P. and Cardoso, Victor R. and Purmah, Yanish and Neculau, Georgiana and Jawad-Ul-Qamar, Muhammad and Russell, Kalisha and Turner, Ashley and Tull, Samantha P. and Nehaj, Frantisek and Brady, Paul and Kastner, Peter and Ziegler, André and Gkoutos, Georgios V. and Pavlovic, Davor and Ferro, Charles J. and Kirchhof, Paulus and Fabritz, Larissa and Sulzgruber, Patrick (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. PLOS Medicine, 18 (2). e1003405. ISSN 1549-1676

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Abstract

Background
Large-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 findings
For 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 < 0.001) and FGF23 (median [Q1, Q3] per 100 pg/ml: with AF 1.93 [1.30, 4.16], without AF 1.55 [1.04, 2.62]; p < 0.001). Univariate associations remained after adjusting for heart failure and estimated glomerular filtration rate, known confounders of NT-proBNP and FGF23. The fitted model yielded a C-statistic of 0.688 (95% CI 0.656, 0.719), almost identical to that of the derived model (C-statistic 0.691; 95% CI 0.638, 0.744). The key limitation is that this validation was performed in a cohort that is very similar demographically to the one used in model development, calling for further external validation.

Conclusions
Age, sex, and BMI combined with elevated NT-proBNP and elevated FGF23, quantified on a high-throughput platform, reliably identify patients with AF.

Trial registration
Registry IRAS ID 97753 Health Research Authority (HRA), United Kingdom

Item Type: Article
Subjects: Journal Eprints > Medical Science
Depositing User: Managing Editor
Date Deposited: 15 Dec 2022 11:09
Last Modified: 13 Mar 2024 04:21
URI: http://repository.journal4submission.com/id/eprint/332

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