Revisiting an old relationship: the causal associations of the ApoB/ApoA1 ratio with cardiometabolic diseases and relative risk factors-a mendelian randomization analysis

Cardiovasc Diabetol. 2024 Feb 3;23(1):51. doi: 10.1186/s12933-024-02140-2.

Abstract

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. The final verification confirmed whether the ApoB/ApoA1 ratio exhibits a mediating effect in CMD and related risk factors.

Results: In terms of CMD, a noteworthy correlation was observed between the increase in the ApoB/ApoA1 ratio and various CMD, including ischemic heart disease, major adverse cardiovascular events, aortic aneurysm, cerebral ischemic disease and so on (all PFDR<0.05). Meanwhile, the ApoB/ApoA1 ratio was significantly associated with CMD risk factors, such as hemoglobin A1c, fasting insulin levels, waist-to-hip ratio, sedentary behavior, and various others, demonstrating a notable causal relationship (all PFDR<0.05). Additionally, the ApoB/ApoA1 ratio played a mediating role in CMD and relative risk factors.

Conclusions: This MR study provides evidence supporting the significant causal relationship between the ApoB/ApoA1 ratio and CMD and its risk factors. Moreover, it demonstrates the mediating effect of the ApoB/ApoA1 ratio in 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.

Keywords: Cardiometabolic diseases and risk factors; Mendelian randomization; The ApoB/ApoA1 ratio.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Genome-Wide Association Study
  • Humans
  • Mendelian Randomization Analysis*
  • Myocardial Ischemia*
  • Risk Factors

Substances

  • Biomarkers