| Title: | Lipoprotein(a) and Aortic Diseases: Epidemiological Evidence from Observation to Causation |
| Journal: | Journal of Clinical Lipidology |
| Published: | 1 Jul 2026 |
| DOI: | https://doi.org/10.1016/j.jacl.2026.07.014 |
Publication 20813
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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 16.5-year median follow-up, 3,122 AA/AD events occurred. Elevated Lp(a) independently predicted AA/AD with a dose-response relationship (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 (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.</p>
9 Authors
- Dexiang Xia
- Lei Zhang
- Junjie Fang
- Wentao Hu
- MaoHua Li
- YunFan Chen
- Chang Shu
- JieHua Li
- Xin Li
1 Application
| Application ID | Title |
|---|---|
| 917657 | UKB - Enabled Investigation of Blood and Cardiovascular Disease Risk, Diagnosis and Their Correlation |
Enabling scientific discoveries that improve human health