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July 26, 2026Translational Stroke Research

A five-protein score added to CHA₂DS₂-VASc improves AF stroke risk discrimination, raising C-index to ~0.77.

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Why the study?

Does a five-protein score improve stroke risk prediction beyond the CHA₂DS₂-VASc score in patients with atrial fibrillation?

Population

709 participants with atrial fibrillation from the UK Biobank Pharma Proteomics Project, including 76 with…

Comparison

A five-protein score added to the CHA₂DS₂-VASc… vs CHA₂DS₂-VASc score alone

Design

Cohort

Key result

Adding a five-protein score to the CHA₂DS₂-VASc score improved discrimination for post-AF stroke risk, increasing the concordance index from 0.681 to 0.768.

Authors

SHShengkang HuangXFX H FengHWHuilin Wu

Discussion

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Overview

Hypothesis-generating for biomarker-enhanced AF stroke risk prediction; leaves open prospective validation before practice change.

Key Points

  • This research aims to identify plasma proteins linked to stroke risk following atrial fibrillation (AF) and to evaluate the effectiveness of a protein score in improving risk prediction compared to the CHA₂DS₂-VASc scoring system.
  • Analyzed 709 atrial fibrillation participants from the UK Biobank Pharma Proteomics Project, with 76 incident strokes.
  • Identified stroke-related proteins using Cox regression, LASSO Cox regression, and machine-learning approaches.
  • Constructed a five-protein score and assessed its predictive value beyond CHA₂DS₂-VASc through various statistical analyses.
  • Identified five proteins: EGFR, ATP6V1D, NTF4, AMN, and DCBLD2.
  • The five-protein score improved the concordance index from 0.681 to 0.768 when added to CHA₂DS₂-VASc.
  • Showed a continuous net reclassification improvement of 0.459 (P = 0.028).

Study Design

Type

Cohort (n=709)

Structured PICO

Does a five-protein score improve stroke risk prediction beyond the CHA₂DS₂-VASc score in patients with atrial fibrillation?

P
Population
709 participants with atrial fibrillation from the UK Biobank Pharma Proteomics Project, evaluated for incident stroke.
E
Exposure
A five-protein score (EGFR, ATP6V1D, NTF4, AMN, DCBLD2) added to the CHA₂DS₂-VASc score
C
Comparator
CHA₂DS₂-VASc score alone
O
Outcome
Incident strokehard clinical

Main Result

Effect estimate: NRI 0.459

p-value: p=0.028

A novel five-protein score provides incremental predictive value beyond the CHA₂DS₂-VASc score for assessing stroke risk in patients with atrial fibrillation.

Cite This Study

Huang et al. (2026) conducted a cohort in atrial fibrillation (n=709). Five-protein score vs. CHA₂DS₂-VASc score was evaluated on incident stroke (NRI 0.459, p=0.028). Adding a five-protein score to the CHA₂DS₂-VASc score improved discrimination for post-AF stroke risk, increasing the concordance index from 0.681 to 0.768.

synapsesocial.com/papers/6a65ab2dd3aea3239cd794e1https://doi.org/10.1007/s12975-026-01476-z
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