Discovery of new biomarkers for atrial fibrillation using a custom-made proteomics chip.
Apart from several established clinical risk factors for atrial fibrillation (AF), a number of biomarkers have also been identified as potential risk factors for AF. None of these have so far been adopted in clinical practice.



To use a novel custom-made proteomics chip to discover new prognostic biomarkers for AF risk.



In two independent community-based cohorts (Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (978 participants without AF, mean age 70.1 years, 50% women, median follow-up 10.0 years) and Uppsala Longitudinal Study of Adult Men (ULSAM) (n=725, mean age 77.5 years, median follow-up 7.9 years)), ninety-two plasma proteins were assessed at baseline by a proximity extension assay (PEA) chip. Of those, 85 proteins showed a call rate >70% in both cohorts.



Thirteen proteins were related to incident AF in PIVUS (148 events) using a false discovery rate of 5%. Of those, five were replicated in ULSAM at nominal multivariable p value (123 events, N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), fibroblast growth factor 23 (FGF-23), fatty acid-binding protein 4 (FABP4), growth differentiation factor 15 (GDF-15) and interleukin-6 (IL-6)). Of those, NT-pro-BNP and FGF-23 were also associated with AF after adjusting for established AF risk factors. In a prespecified secondary analysis pooling the two data sets, T-cell immunoglobulin and mucin domain 1 (TIM-1) and adrenomedullin (AM) were also significantly related to incident AF in addition to the aforementioned five proteins (Bonferroni-adjustment). The addition of NT-pro-BNP to a model with established risk factors increased the C-statistic from 0.605 to 0.676 (p<0.0001).



Using a novel proteomics approach, we confirmed the previously reported association between NT-pro-BNP, FGF-23, GDF-15 and incident AF, and also discovered four proteins (FABP4, IL-6, TIM-1 and AM) that could be of importance in the development of AF.
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Lars
L
Lind
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Johan
J
Sundström
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Markus
M
Stenemo
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Emil
E
Hagström
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.|Department of Health and Social Sciences, Dalarna University, Falun, Sweden.
Johan
J
Ärnlöv
D000367:Age Factors; D000368:Aged; D001281:Atrial Fibrillation / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000032:analysis*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D006801:Humans; D015994:Incidence; D056656:Lab-On-A-Chip Devices; D008297:Male; D046208:Microchip Analytical Procedures; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D011506:Proteins; D040901:Proteomics / Q000295:instrumentation* / Q000379:methods; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology
D015415:Biomarkers; D001798:Blood Proteins; C000717427:FGF23 protein, human; D011506:Proteins; D000089703:Fibroblast Growth Factor-23