# Lipoprotein(a) Is Associated With Increased Risk of Abdominal Aortic Aneurysm

## TL;DR

High levels of Lp(a) are linked to a higher risk of abdominal aortic aneurysm, even after accounting for other heart disease risk factors.

## Contribution

This study shows a causal link between Lp(a) and AAA risk, independent of ApoB, suggesting Lp(a) could be a new therapeutic target.

## Key findings

- Lp(a) levels above 125 nmol/L and 150 nmol/L are linked to nearly double the risk of AAA.
- Genetic analysis confirms a causal relationship between Lp(a) and AAA, independent of ApoB.
- Lowering Lp(a) may offer therapeutic benefits for AAA management beyond conventional risk factors.

## Abstract

•Elevated Lp(a) levels were associated with increased risk of AAA, independent of traditional cardiovascular risk factors, including ApoB.•Using both observational and genetic analyses, we demonstrate an ApoB-independent association between Lp(a) and AAA risk.•Elevated Lp(a) levels above guideline (≥125 nmol/L) and trial-based (≥150 nmol/L) thresholds were associated with nearly 2-fold higher risk of AAA (OR: 1.82 and 1.93, respectively; both P < 0.001), compared with individuals below these thresholds.•These findings suggest that Lp(a) lowering may offer therapeutic benefit for AAA management, independent of conventional risk factor modification, including ApoB reduction.

Elevated Lp(a) levels were associated with increased risk of AAA, independent of traditional cardiovascular risk factors, including ApoB.

Using both observational and genetic analyses, we demonstrate an ApoB-independent association between Lp(a) and AAA risk.

Elevated Lp(a) levels above guideline (≥125 nmol/L) and trial-based (≥150 nmol/L) thresholds were associated with nearly 2-fold higher risk of AAA (OR: 1.82 and 1.93, respectively; both P < 0.001), compared with individuals below these thresholds.

These findings suggest that Lp(a) lowering may offer therapeutic benefit for AAA management, independent of conventional risk factor modification, including ApoB reduction.

Lp(a) is a genetically determined lipoprotein targeted by emerging therapies. In a UK Biobank analysis (1,026 abdominal aortic aneurysm [AAA] cases, 469,989 controls), elevated Lp(a) was associated with increased risk of AAA, including at clinically relevant thresholds while controlling for traditional risk factors, including ApoB. Multivariable Mendelian randomization confirmed a causal relationship between lipoprotein(a) [Lp(a)] and AAA independent of apolipoprotein B. These findings support Lp(a) as a modifiable risk factor and potential therapeutic target for AAA, a condition with limited medical treatment options. AAA should be considered as an outcome in future clinical trials of Lp(a)-lowering therapies.