Genetics
Lp(a) is causally linked to aortic aneurysm risk by Mendelian randomisation, UK Biobank cohort of 312,332 (J Clin Lipidol 2026)
Original title: Lipoprotein(a) and aortic diseases: Epidemiological evidence from observation to causation
Prospective UK Biobank cohort of 312,332 participants, median follow-up 16.5 years (3122 aortic aneurysm/dissection events), combining observational and two-sample Mendelian randomisation (MR) analyses of Lp(a) and aortic disease. Elevated Lp(a) independently predicted incident aortic aneurysm/dissection with a dose-response relationship (hazard ratio 1.40 for Lp(a) above 180 versus below 50 nmol/L; hazard ratio 1.15 per 75 nmol/L increment), confirmed in competing-risk analyses. MR analyses supported a causal association between Lp(a) and aortic aneurysm overall (odds ratio 1.31, 95% CI 1.08-1.62) and abdominal aortic aneurysm specifically (odds ratio 1.80, 95% CI 1.37-2.37), but did not provide sufficient evidence for thoracic aortic aneurysm or dissection, likely reflecting low statistical power for those rarer subtypes. The authors propose Lp(a) as a promising biomarker for aortic disease risk stratification.
Original abstract
Background: Aortic aneurysm and dissection (AA/AD) are life-threatening vascular diseases with high mortality, yet no effective drugs to delay progression. Lipoprotein(a) [Lp(a)] is genetically determined and associated with atherosclerotic disease, but high-quality evidence on its causal role in AA/AD remains limited.
Objective: To investigate the association between Lp(a) and AA/AD and assess potential causal relationships with major aortic disease subtypes.
Methods: A prospective cohort of 312,332 UK Biobank participants was analyzed. Kaplan-Meier curves, Cox regression, and Fine-Gray competing-risk models assessed associations between Lp(a) and incident AA/AD. Two-sample Mendelian randomization (MR) analyses evaluated the potential causal effects of Lp(a) on AA, abdominal aortic aneurysm (AAA), thoracic aortic aneurysm (TAA), and AD.
Results: During a median follow-up of 16.5 years, 3122 AA/AD events occurred. Elevated Lp(a) independently predicted AA/AD with a dose-response relationship (hazard ratio [HR] = 1.40 for >180 vs <50 nmol/L; HR = 1.15 per 75 nmol/L increment). Competing-risk analyses yielded consistent results. MR analyses supported a causal association between Lp(a) and AA (odds ratio [OR] = 1.31, 95% CI: 1.08-1.62) and AAA (OR = 1.80, 95% CI: 1.37-2.37), whereas MR analyses did not provide sufficient evidence for causal associations with TAA or AD.
Conclusion: Lp(a) may serve as a promising biomarker for risk assessment and stratification in aortic disease. However, the MR analysis for AD was limited by low statistical power, and the clinical utility of Lp(a) measurement requires further investigation.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.