Autoimmunity-related atrial fibrillation incidence: an emerging conundrum meriting further investigation

This Letter to the Editor refers to the article ‘Autoimmune diseases and new-onset atrial fibrillation: a UK Biobank study’ by Tilly et al. https://doi.org/10.1093/europace/euac244. A response to this letter is available ‘Autoimmunity-related atrial fibrillation incidence: an emerging conundrum meriting further investigation—authors’ reply’ by Tilly et al. We perused with great interest the recently published population-based study by Tilly et al. The authors investigated the relationship between autoimmune disease and incident atrial fibrillation (AF).1 The authors report for the first time sex-specific risk factors for AF incidence within a large population followed-up for a long period (i.e. a median of 12.8 years). Their adjusted analyses yielded that various autoimmune diseases such as rheumatic fever without heart involvement, Crohn’s disease, ulcerative colitis, rheumatoid arthritis (RA), polyarteritis nodosa, and systemic sclerosis were associated with new-onset AF. This association was stronger in women. These findings are in line with other studies, suggesting a potential link between underlying autoimmune diseases and AF. A study published by Lim SY et al. showed that patients with SLE had a higher incidence of AF compared to age- and sex-matched controls. Furthermore, a nationwide cohort study involving 18 247 patients with RA followed for a median of 4.8 years found a 40% increase in the risk of AF in patients with RA, compared with the general population.2 On the other hand, a USA nationwide cohort study of 20 852 RA and 104 260 non-RA patients found no difference in risk of AF after adjusting for parameters such as medications and comorbidities.3 The mechanisms underlying the discussed association between autoimmune diseases and AF are not yet fully understood. Some studies suggest that the underlying inflammatory process in autoimmune diseases may contribute to AF.4 Various inflammatory markers (C-reactive protein, tumour necrosis factor-α, interleukin-2, interleukin-6, and interleukin-8) have been associated with AF, and the proposed mechanisms linking inflammation with the prothrombotic AF state include endothelial activation/damage, production of tissue factor from monocytes, and increased expression of fibrinogen.5 Furthermore, treatment with glucocorticoids seems to reduce recurrence of AF.6 Part of this anti-arrhythmic effect may be through anti-inflammatory activity, which also suggests that the chronic inflammation in autoimmune diseases may contribute per se to the development of AF.7 It seems valuable to continue investigating the relationship between autoimmune disease and AF, with focus on underlying mechanisms and potential targets for intervention. The long-term associations of novel immunomodulatory drugs with incident AF merit further investigation. The role of specific autoimmune-related biomarkers and their association with risk of AF would be of clinical interest. An association between autoimmune disease activity and incident AF could have important therapeutic implications. In conclusion, the authors should be congratulated for shedding light on the potential link between autoimmune diseases and AF occurrence by utilizing the UK Biobank data. Further research is warranted to better understand the mechanisms underlying this association and to develop strategies to prevent and manage AF in individuals with autoimmune diseases.