Autoimmune disease and new-onset atrial fibrillation: A UK Biobank study

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Senior Scientist Grant from the Dutch Heart Foundation. Background and Aims The underlying mechanisms of atrial fibrillation (AF) are largely unknown. Inflammation may underlie atrial remodeling. Autoimmune diseases, and their accompanying increased (systemic) inflammation, may therefore be associated with new-onset AF. Purpose To assess the association of various autoimmune diseases with new-onset AF in the general population. Additionally, we aimed to investigate the causal relationship between the aforementioned conditions. Methods 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 analyses were conducted to calculate hazard ratios (HR) and 95% confidence intervals (CI) to quantify the associations. Moreover, using large publicly available summary data of genome-wide association studies, two-sample Mendelian randomization (MR) analyses, inverse variance weighted method, were performed to assess the potential causality between the genetic predisposition to various autoimmune diseases and AF. Further sensitivity analyses in the form of weighted median estimator, MR-Egger, and MR-PRESSO were performed. Results 494,072 participants free from AF at baseline 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. Two-sample MR analyses showed no significant associations between any of the included autoimmune diseases and AF. Conclusions Various autoimmune diseases are associated with new-onset AF, more distinct in women. Lack of causal associations between autoimmune diseases and AF could suggest that inflammation itself, rather than the autoimmune disease, is the major risk marker for incident AF. Our findings further elaborate on the pathophysiological differences in autoimmunity and AF risk between men and women.