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.

Keywords: Atrial fibrillation; Autoimmune disease; Inflammation; Risk factors; Sex differences.

Graphical Abstract

Figure 1

Prevalence of (the combination of) various autoimmune diseases. Depicted are the prevalences of single autoimmune diseases (one dot) as well as combinations of those autoimmune diseases (multiple dots) in individuals for women (upper part of the bar) and men (lower part of the bar). The left Y-axis depicts the number of individuals for MSK, GI, neurological, RF, and the combination of MSK and GI. On the right Y-axis, the numbers are depicted for the other combinations of diseases. Rheumatic fever included rheumatic fever without heart involvement. Neurological disorders included multiple sclerosis and myasthenia gravis. Gastrointestinal disorders included Crohn’s disease and ulcerative colitis. MSK disorders included rheumatoid arthritis, psoriatic and enteropathic arthropathies, systemic lupus erythematosus, dermatopolymyositis, systemic sclerosis, ankylosing spondylitis, and Paget’s disease. GI, gastrointestinal disordes; MSK, musculoskeletal and connective tissue disorders; RF, rheumatic fever.

Figure 2

The survival time free of atrial fibrillation per autoimmune disorder. Depicted is the probability of survival free of AF over time per autoimmune disorder group, adjusted for age, sex, ethnicity, BMI, total cholesterol, HDL-cholesterol, use of cholesterol-lowering medication, use of blood pressure lowering medication, smoking status, prevalent hypertension, prevalent type 2 diabetes, prevalent heart failure, and prevalent acute myocardial infarction. AF, atrial fibrillation; BMI, body mass index; HDL, high-density lipoprotein; MSK, musculoskeletal and connective tissue disorders.

Figure 3

Association of various autoimmune diseases with new-onset atrial fibrillation, stratified by sex. Depicted are hazard ratios with their corresponding 95% confidence intervals from model 2. Neurological disorders included multiple sclerosis and myasthenia gravis. Gastrointestinal disorders included Crohn’s disease, and ulcerative colitis. MSK disorders included rheumatoid arthritis, psoriatic and enteropathic arthropathies, systemic lupus erythematosus, dermatopolymyositis, systemic sclerosis, ankylosing spondylitis, and Paget’s disease. CI, confidence interval; HR, hazard ratio; MSK; musculoskeletal and connective tissue disorders.