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Abstract
Background Proteomic biomarkers have shown promise in predicting various cardiovascular conditions, but their utility in assessing the risk of atrial fibrillation (AF) remains unclear. This study aimed to develop and validate a protein-based risk score for predicting incident AF and to compare its predictive performance with traditional clinical risk factors and polygenic risk scores in a large cohort from the UK Biobank.
Methods We analysed data from 36 129 white British individuals without prior AF, assessing 2923 plasma proteins using the Olink Explore 3072 assay. The cohort was divided into a training set (70%) and a test set (30%) to develop and validate a protein risk score for AF. We compared the predictive performance of this score with the HARMS2-AF risk model and a polygenic risk score.
Results Over an average follow-up of 11.8 years, 2450 incident AF cases were identified. A 47-protein risk score was developed, with N-terminal prohormone of brain natriuretic peptide (NT-proBNP) being the most significant predictor. In the test set, the protein risk score (per SD increment, HR 1.94; 95% CI 1.83 to 2.05) and NT-proBNP alone (HR 1.80; 95% CI 1.70 to 1.91) demonstrated superior predictive performance (C-statistic: 0.802 and 0.785, respectively) compared with HARMS2-AF and polygenic risk scores (C-statistic: 0.751 and 0.748, respectively).
Conclusions A protein-based risk score, particularly incorporating NT-proBNP, offers superior predictive value for AF risk over traditional clinical and polygenic risk scores, highlighting the potential for proteomic data in AF risk stratification.
- Atrial Fibrillation
Data availability statement
Data may be obtained from a third party and are not publicly available. The UK Biobank data are available on application to the UK Biobank, and the analytical methods and study materials that support the findings of this study will be available from the corresponding author on request.
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Data availability statement
Data may be obtained from a third party and are not publicly available. The UK Biobank data are available on application to the UK Biobank, and the analytical methods and study materials that support the findings of this study will be available from the corresponding author on request.
Footnotes
Contributors ML and XQ designed and conducted the research. ML, YZ and ZY performed the data management and statistical analyses. ML and XQ wrote the manuscript. All authors reviewed/edited the manuscript for important intellectual content. All authors read and approved the final manuscript. Guarantor: XQ accepted full responsibility for the finished work and/or the conduct of the study, had access to the data and controlled the decision to publish.
Funding The study was supported by the National Key Research and Development Program (2022YFC2009600, 2022YFC2009605 to XQ) and the National Natural Science Foundation of China (81973133 to XQ).
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
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