Systemic inflammation, polygenic risk score, and risk of incident abdominal aortic aneurysm in the UK biobank

AIMS: There remains clinical uncertainty concerning the relationship between systemic inflammation and subsequent abdominal aortic aneurysm (AAA) risk. To investigate the association between chronic systematic inflammation markers (C-reactive protein (CRP), peripheral immune cell counts, and their derived ratios) and risk of AAA incidence, and identify potential effect modifiers. METHODS: We included 271,068 individuals from the UK Biobank, who were free of aortic aneurysm and other conditions impacting their inflammatory states at baseline. Cox proportional-hazards model was used to analyze associations between inflammatory biomarkers and AAA, adjusting for AAA polygenetic risk score (PRS) and major risk factors. Restricted cubic splines were plotted to visualize non-linear relationship. Subgroup analyses by age, sex, hypertension, smoking and PRS were performed to identify any interaction. RESULTS: Over a median follow-up of 13·9 years, 629 incident AAAs were recorded. For each 1-SD increase in baseline CRP, lymphocyte, monocyte, and neutrophil counts, the risk of AAA increased by 46%, 17%, 27% and 27%, respectively (all p < 0·001). The cubic splines showed the CRP-AAA association to be monotonic. The highest tertile of PRS was associated with an 80% increased AAA risk compared with the lowest tertile. The association between CRP and AAA was significant and comparable across PRS tertile groups. Sex and smoking status modified the CRP-AAA association, with the strongest association observed in males and current smokers. CONCLUSIONS: Our study found a significant association between chronic systemic inflammation and risk of AAA incidence. CRP compliments PRS and other AAA risk factors in better identifying high-risk populations.