Chronic conditions and aortic disease risk: a prospective cohort study with predictive and etiological analyses

Abstract Aortic diseases are often clinically silent until advanced stages, and risk determinants beyond traditional cardiovascular factors remain incompletely characterised. Here, we investigate associations of 42 chronic conditions and multimorbidity with incident aortic disease in UK Biobank (UKB), with external validation in China Kadoorie Biobank (CKB). In UKB, 21 chronic conditions are associated with overall aortic disease after false discovery rate correction, including coronary heart disease, hypertension, atrial fibrillation, peripheral vascular disease, heart failure, and COPD; similar patterns are observed in CKB. Aortic atherosclerosis shows the broadest comorbidity profile, whereas dissection and aneurysm subtypes show narrower profiles. Higher multimorbidity burden is associated with higher incidence in both cohorts. In UKB, hypertension shows the largest estimated population-attributable fraction, with additional contributions from COPD and chronic kidney disease. Mendelian randomization supports selected associations, and machine-learning models show internal discriminatory performance. These findings support consideration of multimorbidity in aortic disease risk assessment.