Relationship of Apolipoprotein B to Aortic Aneurysm: Frailty Index as a Partial Mediator – a Mendelian Randomization Study

• DOI: 10.18087/cardio.2025.2.n2796
• Publication Date: 2025-03-07T14:32:11Z
• Authors: Tongxue Zhang; Yajing Li; Xiaoyu Liu; Jinfeng Wang; Danlei Chen; Hanyu Lei; Yupeng Zhang; Huanhuan Lin; Yizhen Jia; Lin Xu; Keyang Duan

Aim Aortic aneurysm is characterized by localized expansion and damage to the vessel wall. While apolipoprotein B (ApoB) has been linked to atherosclerosis, its causal relationship with aortic aneurysm remains unclear. This study used a Mendelian randomization (MR) approach to explore the causal relationships between ApoB, aortic aneurysm, and potential mediators.Material and methods Single nucleotide polymorphism (SNP) data related to ApoB, apolipoprotein A1 (ApoA1), triglycerides, frailty index, and aortic aneurysm were obtained from large-scale genome-wide association studies. MR analysis was conducted to evaluate causal relationships, using inverse variance weighting (IVW) as the primary statistical method. Additionally, we assessed whether the frailty index mediates the relationship between ApoB and aortic aneurysm.Results Univariate MR analysis revealed that ApoB is significantly associated with aortic aneurysm (IVW odds ratio (OR) = 1.443, 95 % confidence interval (CI) = 1.273–1.637, p < 0.001). Multivariable MR (MVMR) analysis, adjusted for ApoA1 and triglycerides, confirmed these results. In mediation analysis, the frailty index was found to partially mediate the effect of ApoB on aortic aneurysm (mediation contribution: 20.1 %–23.1 %). The ORs for ApoB and the frailty index with respect to aortic aneurysm were 1.325 (95 % CI = 1.168–1.505) and 4.188 (95 % CI = 1.859–9.435), respectively.Conclusion ApoB has a causal relationship with aortic aneurysm, with the frailty index acting as a partial mediator in this pathway.