Interplay of Multipathway Dyslipidemia, Inflammation, and Cholesterol-Lowering Medication in Modifying Abdominal...

Abdominal aortic aneurysm (AAA) carries high rupture mortality, yet medical therapies remain limited. While dyslipidemia and inflammation are implicated in AAA pathogenesis, the individual and joint roles of key lipid fractions, LDL-C (low-density lipoprotein-cholesterol), Lp(a) (lipoprotein[a]), and remnant cholesterol (RC), with systemic inflammation, are not fully established, particularly in the context of widespread cholesterol-lowering medication use.

We performed a prospective analysis of 338 758 UK Biobank participants free of AAA at baseline. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for associations between biomarkers and incident AAA.

Over a median follow-up of 13.65 years, 1694 incident AAA cases occurred. Among participants not taking cholesterol-lowering medication, concurrent elevations of LDL-C, Lp(a), and RC (>75th percentile) conferred the highest risk (adjusted HR, 2.53 [95% CI, 1.97-3.24]). Coexisting elevated Hs-CRP (high-sensitivity C-reactive protein) with this triple-lipid elevation further increased the risk (adjusted HR, 4.19 [95% CI, 2.97-5.91]). Among cholesterol-lowering medication users, significant associations persisted for LDL-C (adjusted HR, 1.19 [95% CI, 1.09-1.29]) and RC (adjusted HR, 1.22 [95% CI, 1.14-1.31]) but not for Lp(a) (adjusted HR, 1.03 [95% CI, 0.97-1.10]). In this group, the combination of elevated LDL-C, RC, and Hs-CRP was associated with the greatest risk (adjusted HR, 2.46 [95% CI, 1.86-3.26]).

Combined elevations of multiple lipid fractions and systemic inflammation were associated with a substantially increased risk of AAA. Cholesterol-lowering medication was associated with an attenuated risk relationship for LDL-C and Lp(a) but not for RC or Hs-CRP. Comprehensive risk assessment integrating a full lipid profile and Hs-CRP can improve identification of high-risk phenotypes for targeted AAA prevention.