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Published on: July 20, 2022
Large-Scale Plasma Proteomics Profiles for Predicting Atrial Fibrillation Associated Stroke Risk : Type of
Shengkang Huang1, Xin Feng2, Huilin Wu3
1Department of Cardiovascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, National Clinical Research Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
A new five-protein score improves stroke risk prediction in atrial fibrillation (AF) patients beyond the standard CHA₂DS₂-VASc score. This protein score offers valuable insights for assessing post-AF stroke risk.
Area of Science:
- Cardiovascular Medicine
- Proteomics
- Biomarker Discovery
Background:
- Atrial fibrillation (AF) significantly increases stroke risk.
- Current risk scores like CHA₂DS₂-VASc have limitations in predicting stroke heterogeneity.
- Identifying novel biomarkers is crucial for refining stroke risk assessment in AF patients.
Purpose of the Study:
- To identify plasma proteins associated with stroke in AF patients.
- To develop and validate a protein-based score for stroke risk prediction.
- To evaluate if a protein score offers incremental predictive value over the CHA₂DS₂-VASc score.
Main Methods:
- Analysis of 709 AF participants from the UK Biobank Pharma Proteomics Project.
- Identification of stroke-related proteins using Cox regression and machine learning.
- Construction and validation of a five-protein score, assessing its incremental predictive value using discrimination, calibration, and reclassification metrics.
- Supportive genetic evidence from Mendelian randomization.
Main Results:
- Five core proteins (EGFR, ATP6V1D, NTF4, AMN, DCBLD2) were identified.
- The five-protein score significantly improved stroke prediction discrimination (concordance index from 0.681 to 0.768).
- The combined model demonstrated favorable predictive accuracy and calibration across multiple time points, with improved net reclassification.
Conclusions:
- A five-protein score provides significant incremental predictive information for post-AF stroke risk.
- This protein score enhances the accuracy of stroke risk assessment beyond established clinical scores.
- The findings support the utility of proteomic biomarkers in cardiovascular risk stratification.