Revisiting an old relationship：The causal associations of the ApoB/ApoA1 ratio with cardiometabolic diseases and relative risk factors——A Mendelian randomization analysis

Background It has been confirmed that the ApoB/ApoA1 ratio is closely associated with the incidence of cardiometabolic diseases (CMD). However, due to uncontrolled confounding factors in observational studies, the causal relationship of this association remains unclear. Methods In this study, we extracted the ApoB/ApoA1 ratio and data on CMD and its associated risk factors from the largest European genome-wide association study. The purpose was to conduct Mendelian Randomization (MR) analysis. The causal relationship between the ApoB/ApoA1 ratio and CMD was evaluated using both univariable and multivariable MR analyses. Furthermore, bidirectional MR analysis was performed to estimate the causal relationship between the ApoB/ApoA1 ratio and risk factors for CMD. Results In terms of CMD, the increase in the ApoB/ApoA1 ratio was significantly related to ischemic diseases such as ischemic heart disease, major adverse cardiovascular events, ischemic stroke, transient ischemic attack, aortic aneurysm (all p༜0.05), and so on. In multivariate MR analysis, the above results were still valid. Regarding CMD risk factors, a significant bidirectional causality existed between the ApoB/ApoA1 ratio and waist circumference, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol. Meanwhile, the ApoB/ApoA1 ratio also had a strong causality with glucose metabolism indicators, obesity-related indicators, and behaviorally relevant indicators. Conclusions This MR study provides evidence supporting the significant causal relationship between the ApoB/ApoA1 ratio and CMD and its risk factors. These findings suggest that the ApoB/ApoA1 ratio may serve as a potential indicator for identifying the risk of developing CMD in participants.