Abstract
BACKGROUND: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a chronic inflammatory condition of the gastrointestinal tract. The "Life's Critical 9" (LC9) health score, proposed by the American Heart Association (AHA), incorporates nine modifiable factors including psychological health. This study aims to evaluate the association between the LC9 score and the risk of IBD, particularly UC and CD. METHODS: This prospective cohort study utilized UK Biobank data from 370,645 participants. Cox proportional hazards models assessed associations between LC9 score and IBD, UC, and CD risk. Subgroup analyses examined interactions with age, sex, ethnicity, education, smoking, alcohol consumption, and body mass index (BMI). Mediation analyses evaluated the role of triglycerides, neutrophils, albumin, and C-reactive protein (CRP). Sensitivity analyses replaced the overall LC9 score with the mental-psychological subscale to evaluate robustness. RESULTS: Higher LC9 scores were significantly associated with reduced UC risk (hazard ratio [HR] 0.909, 95% confidence interval [CI] 0.863-0.958) and overall IBD risk (HR 0.976, 95% CI 0.953-1.001). No significant association was observed for CD (HR 0.928, 95% CI 0.858-1.003, P = 0.059). Subgroup analyses revealed stronger inverse associations for UC among individuals aged ≥ 60 years, females, European descent, lower education levels, current drinkers, and BMI 18.5-25. Mediation analyses showed triglycerides, neutrophils, albumin, and CRP accounted for 10.78%, 26.74%, 4.77%, and 22.95% of the LC9-UC association, respectively. Sensitivity analyses using the mental-psychological subscale demonstrated consistent protective associations across all models for IBD (HR 0.991, 95% CI 0.990-0.992), UC (HR 0.995, 95% CI 0.993-0.997), and CD (HR 0.996, 95% CI 0.994-0.998), all P < 0.001. CONCLUSION: Higher LC9 scores were significantly associated with reduced UC risk, with notable interactions across demographic and behavioral characteristics. The comprehensive LC9 framework, incorporating cardiovascular, metabolic, and psychological factors, may provide a holistic approach to IBD risk assessment and prevention strategies.