A potentially underestimated predictor of coronary artery disease risk: The ApoB/ApoA1 ratio.

Background: Cardiovascular disease (CVD) is the leading cause of death worldwide, and statin therapy is the cornerstone of atherosclerotic cardiovascular disease. However, clinical practice is unsatisfactory, and there is significant interest in the risk of residual cardiovascular events. Traditional study methods make it difficult to exclude the crosstalk of confounding factors, and we investigated the impact of the ApoB/ApoA1 ratio on CVD using two-sample Mendelian randomization (MR) and multivariate Mendelian randomization (MVMR) methods. Methods: Two-sample MR and MVMR analyses were performed using pooled statistics from genome-wide association studies (GWAS) of ApoB/ApoA1 ratio (BAR), lipoprotein (a) (Lp(a)), and triglyceride (TG) in Europeans to assess the causal relationship between BAR, Lp(a), and TG with coronary artery disease (CAD). Results: The genetic prediction of BAR was significantly correlated with CAD (Inverse variance weighted (IVW) beta = 0.255; OR = 1.291; 95 % CI = 1.061-1.571; P = 0.011) in a two-sample MR analysis. MVMR studies showed that BAR (beta = 0.373; OR = 1.452; 95 % CI = 1.305-1.615; P = 7.217e-12), Lp (a) (beta = 0.238; OR = 1.269; 95 % CI = 1.216-1.323; P = 2.990e-28), and TG (beta = 0.155; OR = 1.168; 95 % CI = 1.074-1.270; P = 2.829e-04) were significantly associated with CAD. After further colinearity analyses of LASSO regressions, the results of multivariate analyses were similar for IVW, MR-Egger, MR-Lasso, and median methods. Conclusion: BAR is causally related to coronary artery disease. BAR is an independent predictor of CAD risk, independent of routine lipid measurements and other risk factors. TG and Lp(a) may be causally related to CAD, subject to verification in clinical practice.