Association between low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and Lipoprotein(a) [Lp(a)] with aortic aneurysm: Univariable and Multivariable Mendelian Randomization Analysis

Abstract

To determine the relationship between blood lipids and the risk of aortic aneurysm (AA), including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and Lipoprotein(a) [Lp(a)], we performed univariable and multivariable Mendelian randomization (MR) analysis.Methods: The UK Biobank study of European ancestry provided data for single nucleotide polymorphisms (SNPs) associated with LDL-C(n=440546), and HDL-C(n=403943). SNPs for Lp(a) (n=377590) was a Neale Lab genome-wide association study (GWAS) based on European populations. And the data on AA were obtained from the latest analysis of genome-wide association studies (GWASs) with 209,366 subjects of European ancestry. Univariate and multivariate MR analyses were performed.Results: The Inverse variance weighted(IVW1) estimate showed that the HDL-C(odds ratio [OR]:0.728, 95%confidence interval [CI]:0.629-0.842, P = 1.87E-05) was negatively correlated with AA. The causal association between LDL-C(OR:1.467, 95%CI:1.184-1.816, P=4.49E-4), Lp(a)(OR:1.005, 95%CI:1.001-1.010, P=0.009) and AA were observed in the IVW1 method. The multivariable MR(MVMR) analysis indicated that HDL(OR:0.685, 95%CI: 0.581-0.807, P=6.77E-06) remained negatively associated with AA after adjusting for the LDL-C and Lp(a).Conclusion: Genetic evidence supported the role of greater LDL-C, Lp(a), and lower HDL-C as risk factors for AA. our MVMR study revealed a negative correlation between HDL and AA. Furthermore, additional research is required to confirm the probable relationship between lipid traits and AA risk. Moreover, therapies to reduce LDL-C and Lp(a) may be advantageous for AA.