Cardiovascular Health, Genetic Susceptibility, and the Risk of Incident Autoimmune Disorders in the UK Biobank: A Prospective Cohort Study

Background Autoimmune diseases are closely linked to cardiovascular diseases. This study aimed to assess the relationship between cardiovascular health (CVH) defined by Life's Essential 8 (LE8), genetic predisposition, and the risk of 19 autoimmune disorders. Methods and Results A total of 247 660 participants without prior autoimmune diseases from the UK Biobank were included. CVH was assessed using LE8 scores, categorized into low, moderate, and high. Cox proportional hazards models estimated the association between CVH, genetic susceptibility, and autoimmune disorder risk. Over 13.2 years of follow‐up, 11 422 incident autoimmune disorders occurred. Higher CVH levels were associated with reduced risks of overall autoimmune disorders (hazard ratio, 0.68 [95% CI, 0.62–0.74]) and specific conditions, including Graves disease, inflammatory bowel disease, polymyalgia rheumatica, psoriasis, rheumatoid arthritis, and type 1 diabetes. Dose–response analyses revealed a linear negative relationship between continuous LE8 scores and the risks of Graves disease, inflammatory bowel disease, polymyalgia rheumatica, psoriasis, rheumatoid arthritis, and type 1 diabetes ( P nonlinear >0.05). Genetic predisposition to autoimmune disorders (including ankylosing spondylitis, celiac disease, Graves disease, inflammatory bowel disease, polymyalgia rheumatica, psoriasis, rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, systemic sclerosis, and type 1 diabetes) significantly modified these associations ( P interaction <0.05), with protective effects more pronounced in women, participants aged <65 years, and those with low genetic risk. Conclusions LE8 scores inversely and linearly predicted autoimmune disease incidence. Prioritizing CVH optimization through LE8 adherence may reduce the global autoimmune disease burden.