Lipoprotein(a) and risk of subsequent Stanford type A aortic dissection in patients with acute coronary syndrome: a multicenter case-control study with Mendelian randomization analysis.

BACKGROUND AND AIMS: Lipoprotein(a) [Lp(a)] is associated with cardiovascular risk, but its role in Stanford type A aortic dissection (AD) following acute coronary syndrome (ACS) remains unclear. We evaluated whether Lp(a) at ACS presentation predicts subsequent type A AD, its incremental value, and to assess potential causal effects using a complementary two-sample Mendelian randomization (MR) analysis.

METHODS AND

RESULTS

In this bi-center retrospective case-control study, 222 patients with type A AD after ACS and 751 ACS controls were included. Overlap weighting balanced eight covariates. Lp(a) was analyzed as log-transformed values, tertiles, and >125 nmol/L. Dose-response was assessed with restricted cubic splines, and discrimination by AUC. Sensitivity analyses included matching and a time-restricted cohort. MR used 45 instruments with adjustment for low-density lipoprotein cholesterol (LDL-C) and systolic blood pressure. Lp(a) was higher in cases (P < 0.001). Each log-unit increase was associated with greater type A AD risk (OR 5.14, 95% CI 3.39-8.19). The highest tertile (OR 8.35, 95% CI 5.84-12.11) and >125 nmol/L (OR 1.82, 95% CI 1.06-3.16) also showed increased risk. Findings were consistent across analyses. Adding Lp(a) improved discrimination (AUC 0.820 vs 0.697). MR supported associations with aortic aneurysm and the composite outcome (IVW OR 1.196, 95% CI 1.083-1.320), independent of LDL-C and blood pressure.

CONCLUSIONS

Higher Lp(a) at ACS presentation predicts type A AD and improves risk stratification. Genetic analyses suggest links with aortic aneurysm and the composite outcome, but not thoracic aneurysm; evidence for dissection was limited by low power.