| Title: | Proteomic Signatures for Risk Prediction of Atrial Fibrillation |
| Journal: | Circulation |
| Published: | 22 May 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40401370/ |
| DOI: | https://doi.org/10.1161/circulationaha.124.073457 |
Publication 15253
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
BACKGROUND: Proteomic signatures might improve disease prediction and enable targeted disease prevention and management. We explored whether a protein risk score derived from large-scale proteomics data improves risk prediction of atrial fibrillation (AF).</p>
METHODS: A total of 51 680 individuals with 1459 unique plasma protein measurements and without a history of AF were included from the UKB-PPP (UK Biobank Pharma Proteomics Project). A protein risk score was developed with lasso-penalized Cox regression from a random subset of 70% (36 176 individuals, 54.4% women, 2155 events) and was tested on the remaining 30% (15 504 individuals, 54.4% women, 910 events). The protein risk score was externally replicated with the ARIC study (Atherosclerosis Risk in Communities; 11 012 individuals, 54.8% women, 1260 events).</p>
RESULTS: The protein risk score formula developed from the UKB-PPP derivation set was composed of 165 unique plasma proteins, and 15 of them were associated with atrial remodeling. In the UKB-PPP test set, a 1-SD increase in protein risk score was associated with a hazard ratio of 2.20 (95% CI, 2.05-2.41) for incident AF. The C index for a model including CHARGE-AF (Cohorts for Heart and Aging Research in Genomic Epidemiology Atrial Fibrillation), NT-proBNP (N-terminal B-type natriuretic peptide), polygenic risk score, and protein risk score was 0.816 (95% CI, 0.802-0.829) compared with 0.771 (95% CI, 0.755-0.787) for a model including CHARGE-AF, NT-proBNP, and polygenic risk score (C-index change, 0.044 [95% CI, 0.039-0.055]). Protein risk score added to CHARGE-AF, NT-proBNP, and polygenic risk score resulted in a risk reclassification of 5.4% (95% CI, 2.9%-7.9%) with a 5-year risk threshold of 5%. In the decision curve, the predicted net benefit before and after the addition of protein risk score to a model including CHARGE-AF, NT-proBNP, and polygenic risk score was 3.8 and 5.4 per 1000 people, respectively, at a 5-year risk threshold of 5%. External replication of a protein risk score in the ARIC study showed consistent improvement in risk stratification of AF.</p>
CONCLUSIONS: Protein risk score derived from a single plasma sample improved risk prediction of AF. Further research using proteomic signatures in AF screening and prevention is needed.</p>
13 Keywords
- Aged
- Atrial Fibrillation
- Biomarkers
- Blood Proteins
- Female
- Humans
- Male
- Middle Aged
- Predictive Value of Tests
- Proteomics
- Risk Assessment
- Risk Factors
- United Kingdom
12 Authors
- Hanjin Park
- Faye L. Norby
- Daehoon Kim
- Eunsun Jang
- Hee Tae Yu
- Tae-Hoon Kim
- Jae-Sun Uhm
- Jung-Hoon Sung
- Hui-Nam Pak
- Moon-Hyoung Lee
- Pil-Sung Yang
- Boyoung Joung
1 Application
| Application ID | Title |
|---|---|
| 77793 | The causal inference study to determine the association of genetically predicted biological, behavioral, ethnic factors with risk of atrial fibrillation and its associated complications. |
Enabling scientific discoveries that improve human health