Causal effect of Lipoprotein-associated phospholipase A2 activity on coronary artery disease and myocardial Infarction: A Two-Sample Mendelian Randomization study

Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity has been reported to be associated with coronary artery disease (CAD) and myocardial infarction (MI). However, whether Lp-PLA2 is a causal risk factor for CAD and MI remains unclear. Herein, we performed a two-sample mendelian randomization (MR) study to assess the causal effect of Lp-PLA2 activity on CAD and MI.

Methods: We selected 7 single-nucleotide polymorphisms (SNPs) associated with Lp-PLA2 activity as instrumental variables based on the data from Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium with 13,664 European individuals. Summary data about CAD and MI were obtained from Coronary Artery Disease Genome-wide Replication and Meta-analysis plus the Coronary Artery Disease Genetics (CARDIOGRAMPLUSC4D) consortium with 60,801 CAD cases and 43,676 MI cases (mostly European). The inverse-variance weighted method was applied to assess the causal associations of Lp-PLA2 activity with CAD and MI in the main analysis.

Results: The main inverse-variance weighted (IVW) MR analysis showed that 1-SD increment in genetically determined LP-PLA2 activity was associated with increased risks of CAD (odds ratio, 5.93; 95% CI, 2.91-12.07; p value = 9.43 × 10^-7) and MI (odds ratio, 4.71; 95% CI, 2.49-8.90; p value = 1.86 × 10^-6). MR-Egger regression showed no evidence of pleiotropic bias. The causal associations were consistent in sensitivity analyses with multiple MR methods, in which showed Lp-PLA2 activity was causally associated with an increased risk of CAD and MI.

Conclusions: In this two-sample MR study, high Lp-PLA2 activity was a causal risk factor for CAD and MI, indicating that Lp-PLA2 activity may be a promising intervention target in reducing the risk of CAD and MI.