Immunothrombosis and new-onset atrial fibrillation in the general population: the Rotterdam Study

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Background: Atrial fibrillation (AF) is the most common age-related cardiac arrhythmia. The etiology underlying AF is still largely unknown. At the intersection of the innate immune system and hemostasis, immunothrombosis may be a possible cause of atrial remodeling, and therefore be an underlying cause of AF. Methods: From 1990 to 2014, we followed participants aged 55 and over, free from AF at inclusion. Immunothrombosis factors fibrinogen, von Willebrand factor, ADAMTS13, and neutrophil extracellular traps (NETs) levels were measured at baseline. Participants were followed until either onset of AF, loss-to-follow-up, or reaching the end-date of 01-01-2014. Cox proportional hazard modelling was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for cardiovascular risk factors. Results: We followed 6174 participants (mean age 69.1 years, 57% women) for a median follow-up time of 12.8 years. 364 men (13.7%, incidence rate 13.0/1000 person-years) and 365 women (10.4%, incidence rate 8.9/1000 person-years) developed AF. We found no significant association between markers of immunothrombosis and new-onset AF after adjusting for cardiovascular risk factors [HR 1.00 (95% CI 0.93–1.08) for fibrinogen, 1.04 (0.97–1.12) for von Willebrand factor, 1.00 (1.00–1.01) for ADAMTS13, and 1.01 (0.94–1.09) for NETs]. In addition, we found no differences in associations between men and women. Conclusion: We found no associations between markers of immunothrombosis and new-onset AF in the general population. Inflammation and immunothrombosis may be associated with AF through other cardiovascular risk factors or predisposing conditions of AF. Our findings challenge the added value of biomarkers in AF risk prediction. Graphic abstract: [Figure not available: see fulltext.].

Original languageEnglish
Pages (from-to)96-104
Number of pages9
JournalClinical Research in Cardiology
Issue number1
Early online date24 Sept 2021
Publication statusPublished - Jan 2022

Bibliographical note

Funding Information:
The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. Further support was obtained from the Netherlands Consortium for Healthy Ageing and the Dutch Heart Foundation (2012T008) and the Dutch Cancer Society (NKI-20157737). This project is supported by an Erasmus MC (Mrace) grant. This project is further supported by the Gender and Prevention grant (555003017) from ZonMw. The measurement of MPO–DNA complex levels in participants of the Rotterdam study was supported by a research grant (Prof. Heimburger Award 2018, CSL Behring). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
© 2021, The Author(s).


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