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Discovery of new biomarkers for atrial fibrillation using a custom-made proteomics chip
  1. Lars Lind1,
  2. Johan Sundström1,
  3. Markus Stenemo1,
  4. Emil Hagström1,
  5. Johan Ärnlöv1,2
  1. 1Department of Medical Sciences, Uppsala University, Uppsala, Sweden
  2. 2Department of Health and Social Sciences, Dalarna University, Falun, Sweden
  1. Correspondence to Professor Lars Lind, Department of Medical Sciences, University Hospital, Uppsala 751 85, Sweden; lars.lind{at}medsci.uu.se

Abstract

Background 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.

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

Methods 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.

Results 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).

Conclusions 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.

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