Protein Mediators Linking Autoimmune Diseases and Incident Atrial Fibrillation: Insights from the UK Biobank.

Authors

Jingwen Huang, Chang Liu, Faisal M Merchant, Alvaro Alonso, Yan V Sun

Published in

Heart rhythm. Jul 31, 2026. Epub Jul 31, 2026.

Abstract

Emerging evidence suggests autoimmune diseases (AIDs) are associated with atrial fibrillation (AF) through systemic inflammation. However, causal mechanisms and potential protein mediators remain unexplored.
To identify proteins mediating the link between AIDs and incident AF using high-dimensional mediation analysis.
This study used UK Biobank data with proteomic profiling (Olink platform). Participants without prevalent AF were grouped into musculoskeletal (MSK), vasculitis, gastrointestinal (GI), neurologic, and rheumatic fever subsets. Fine-Gray models identified AID-AF associations, treating non-cardiovascular death as a competing risk. Two separate Proteome-wide association studies (PWAS) identified proteins linked to AIDs and incident AF, respectively. All models adjusted for age, sex, lipids, BMI, smoking, hypertension, diabetes, coronary artery disease, peripheral vascular disease, stroke, and heart failure. Proteins associated with both AIDs and AF were selected for high-dimensional mediation analysis (HIMA).
Among 419,888 participants (median age 58 years, 45.7% male) followed for a median 14.4 years, MSK, vasculitis, GI, and rheumatic fever AIDs significantly increased incident AF risk (HR 1.17, 1.39, 1.17, and 1.46, respectively; P<0.001), but not neurologic AID (P=0.13). In 44,872 participants with proteomic data, HIMA of 232 proteins identified 60 unique mediators, with adrenomedullin, soluble urokinase plasminogen activator receptor, and insulin-like growth factor binding protein 2 shared across multiple AID groups.
The identification of protein biomarkers that may help elucidate potential pathways between AID and AF provides mechanistic insights into immune-related atrial remodeling and suggests possible therapeutic targets for AF prevention and risk stratification in AID patients.

PMID:
42537973
Bibliographic data and abstract were imported from PubMed on 01 Aug 2026.

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