Genetics
UK Biobank observational and Mendelian randomisation analyses find Lp(a) raises abdominal aortic aneurysm risk independent of ApoB (medRxiv 2024)
Original title: Lipoprotein (a) is associated with increased risk of Abdominal Aortic Aneurysm
This study triangulated observational and genetic evidence for Lp(a)'s role in abdominal aortic aneurysm (AAA), analysing 795 UK Biobank participants with clinically diagnosed AAA against 374,772 without, controlling for traditional AAA risk factors and ApoB. Elevated Lp(a) was observationally associated with increased AAA risk (odds ratio 1.04 per 10 nmol/L, 95% CI 1.02-1.05, P < 0.01), and clinically elevated Lp(a) (above 150 nmol/L) carried higher AAA risk than levels below that threshold (odds ratio 1.47, 95% CI 1.15-1.88, P < 0.01). Multivariable Mendelian randomisation, using genetic instruments from GWAS of 335,796 (Lp(a)) and 418,505 (ApoB) UK Biobank participants tested against an AAA GWAS of 39,221 cases and 1,086,107 controls, confirmed a significant, ApoB-independent association between higher genetically predicted Lp(a) and AAA risk (odds ratio 1.13 per SD increase, 95% CI 1.02-1.24, P < 0.02). Both observational and genetic evidence support Lp(a) as an ApoB-independent contributor to AAA risk, suggesting it as both a therapeutic target and a candidate outcome for future Lp(a)-lowering drug trials.
Original abstract
Introduction: Lipoprotein(a) (Lp(a)) is a circulating apolipoprotein B (ApoB) containing particle that has been observationally linked to atherosclerotic cardiovascular disease and is the target of emerging therapeutics. Recent work has highlighted the role of circulating lipoproteins in abdominal aortic aneurysm (AAA). We sought to triangulate human observational and genetic evidence to evaluate the role of Lp(a) in AAA.
Methods: We tested the association between circulating levels of Lp(a) and clinically diagnosed abdominal aortic aneurysms while controlling for traditional AAA risk factors and levels of ApoB using logistic regression among 795 individuals with and 374,772 individuals without AAA in the UK Biobank (UKB). Multivariable Mendelian randomization (MVMR) was used to test for putatively causal associations between Lp(a) and AAA controlling for ApoB. Genetic instruments for Lp(a) and ApoB were created from genome-wide association studies (GWAS) of Lp(a) and ApoB comprising 335,796 and 418,505 UKB participants, respectively. The instruments were tested for association with AAA using data from a GWAS of 39,221 individuals with and 1,086,107 without AAA.
Results: Elevated Lp(a) levels were observationally associated with an increased risk of AAA (OR 1.04 per 10 nmol/L Lp(a); 95%CI 1.02-1.05; P<0.01). Clinically elevated Lp(a) levels (>150nmol/L) were likewise associated with an increased risk of AAA (OR 1.47; 95% CI 1.15-1.88; P < 0.01) when compared to individuals with Lp(a) levels <150nmol/L. MVMR confirmed a significant, ApoB-independent association between increased Lp(a) and increased risk of AAA (OR 1.13 per SD increase in Lp(a); 95%CI 1.02-1.24; P<0.02).
Conclusion: Both observational and genetic analyses support an association between increased Lp(a) and AAA risk that is independent of ApoB. These findings suggest that Lp(a) may be a therapeutic target for AAA and drive the inclusion of AAA as an outcome in clinical trials of Lp(a) antagonists.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.