Exploration of pathophysiological pathways for incident atrial fibrillation using a multiplex proteomic chip

Area of Science:

• Cardiology
• Biomarker Discovery
• Proteomics

Background:

• Atrial fibrillation (AF) is a prevalent arrhythmia linked to significant morbidity and mortality.
• The increasing incidence of AF necessitates the identification of novel biomarkers for risk stratification and understanding pathophysiological mechanisms.

Purpose of the Study:

• To identify novel protein biomarkers associated with the incidence of atrial fibrillation (AF) in a general population.
• To validate previously known risk markers and discover new ones independently of traditional risk factors.

Main Methods:

• Analysis of plasma samples from 1694 individuals using the Olink proximity extension assay CVD III panel (92 proteins).
• Incident AF cases (n=278) were identified through national registers over a mean follow-up of 9.7 years.
• Bonferroni-corrected multivariable Cox regression models were employed to assess protein associations with incident AF.

Main Results:

• N-terminal pro-B-type natriuretic peptide (NT-proBNP) was confirmed as a significant risk marker for incident AF (HR 1.80).
• Matrix metalloproteinase-2 (MMP-2) and osteopontin were identified as novel risk markers for incident AF.
• These novel markers (MMP-2 and osteopontin) showed associations independent of traditional risk factors and NT-proBNP.

Conclusions:

• The study confirmed NT-proBNP as a key risk marker for incident AF in a Swedish population.
• Matrix metalloproteinase-2 and osteopontin represent novel, independent risk markers for incident AF.
• These findings contribute to identifying individuals at higher risk for AF and understanding its underlying biology.