Autoimmune diseases and new-onset atrial fibrillation: a UK Biobank study

Abstract

Aims The underlying mechanisms of atrial fibrillation (AF) are largely unknown. Inflammation may underlie atrial remodelling. Autoimmune diseases, related to increased systemic inflammation, may therefore be associated with new-onset AF. Methods and results Participants from the population-based UK Biobank were screened for rheumatic fever, gastrointestinal autoimmune diseases, autoimmune diseases targeting the musculoskeletal system and connective tissues, and neurological autoimmune diseases. Between 2006 and 2022, participants were followed for incident AF. Cox proportional hazards regression analyses were performed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) to quantify associations. 494 072 participants free from AF were included (median age 58.0 years, 54.8% women). After a median of 12.8 years, 27 194 (5.5%) participants were diagnosed with new-onset AF. Rheumatic fever without heart involvement (HR, 95% CI: 1.47, 1.26–1.72), Crohn’s disease (1.23, 1.05–1.45), ulcerative colitis (1.17, 1.06–1.31), rheumatoid arthritis (1.39, 1.28–1.51), polyarteritis nodosa (1.82, 1.04–3.09), systemic lupus erythematosus (1.82, 1.41–2.35), and systemic sclerosis (2.32, 1.57–3.44) were associated with a larger AF risk. In sex-stratified analyses, rheumatic fever without heart involvement, multiple sclerosis, Crohn’s disease, seropositive rheumatoid arthritis, psoriatic and enteropathic arthropathies, systemic sclerosis and ankylosing spondylitis were associated with larger AF risk in women, whereas only men showed a larger AF risk associated with ulcerative colitis. Conclusions Various autoimmune diseases are associated with new-onset AF, more distinct in women. Our findings elaborate on the pathophysiological differences in autoimmunity and AF risk between men and women.

Integrative proteomic analyses across common cardiac diseases yield new mechanistic insights and enhanced prediction

“…Furthermore, some of the largest differences in protein-disease associations between sexes were observed for aortic stenosis. Prior histological work in aortic stenosis patients suggests distinct tissue composition differences between men and women, with women showing less valvular calcification but more fibrosis than men 40 . Building upon these findings, we identified several sex-specific senescence-associated biomarkers (e.g., IGFBP7 and TNF) associated with incident aortic stenosis in female, but not male, participants.…”

Inflammatory bowel disease and atrial fibrillation: a contemporary overview

“…Interestingly, Tilly et al examined the relationship between autoimmune diseases and new-onset atrial fibrillation in a large UK population [28]. Regarding IBD, it was shown that the incidence of atrial fibrillation was higher in women with Crohn's disease while in ulcerative colitis the incidence of atrial fibrillation was higher only in men [28]. It was hypothesized that the estrogen receptors may play an important role in this setting explaining why men suffered more from colitis, in contrast to women who suffered more from ileitis [28].…”

“…Moreover, they had a greater risk of requiring mechanical ventilation, developing cardiac arrest, and ICU admission [25]. Interestingly, Tilly et al examined the relationship between autoimmune diseases and new-onset atrial fibrillation in a large UK population [28]. Regarding IBD, it was shown that the incidence of atrial fibrillation was higher in women with Crohn's disease while in ulcerative colitis the incidence of atrial fibrillation was higher only in men [28].…”

Autoimmune Atrial Fibrillation or Atrial Fibrillation–Induced Autoimmunity? A New Atrial Fibrillation Begets Atrial Fibrillation Pathway?

“…The last decade has seen the emergence of autoimmunity as a potential contributing mechanism of cardiac arrhythmias, leading to the concept of “autoimmune cardiac channelopathies.” 5 Meanwhile, a recent cohort study based on the UK Biobank has shown that autoimmune diseases such as rheumatic fever, Crohn’s disease, ulcerative colitis, rheumatoid arthritis, polyarteritis nodosa, systemic lupus erythematosus, and systemic sclerosis were associated with a larger AF risk. 6…”

“…5 Meanwhile, a recent cohort study based on the UK Biobank has shown that autoimmune diseases such as rheumatic fever, Crohn's disease, ulcerative colitis, rheumatoid arthritis, polyarteritis nodosa, systemic lupus erythematosus, and systemic sclerosis were associated with a larger AF risk. 6 However, association is not causation. Inflammation by itself may promote or trigger cardiac arrhythmias, especially if an arrhythmogenic substrate preexists.…”