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, Law, Jonathan P, Cardoso, Victor R, Purmah, Yanish, Neculau, Georgiana, Jawad-Ul-Qamar, Muhammad, Russell, Kalisha, Turner, Ashley, Tull, Samantha P, Nehaj, Frantisek, Brady, Paul, Kastner, Peter, Ziegler, André, Gkoutos, Georgios V, Pavlovic, Davor, Ferro, Charles J, Kirchhof, Paulus and Fabritz, Larissa (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. This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs

[img]
Preview
Text (PDF file format)
PLOS.pdf - Published Version
Available under License Creative Commons Attribution 4.0.

Download (2MB) | Preview
Official URL: https://journals.plos.org/plosmedicine/article?id=...

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
Additional Information: This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs
Subjects: WG Cardiovascular system. Cardiology
Divisions: Emergency Services > Cardiology
Emergency Services > Renal
Related URLs:
Depositing User: Mrs Yolande Brookes
Date Deposited: 25 Feb 2021 16:02
Last Modified: 25 Feb 2021 16:02
URI: http://www.repository.uhblibrary.co.uk/id/eprint/4027

Actions (login required)

View Item View Item