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Causal relationship between apolipoprotein B and risk of atherosclerotic cardiovascular disease: a mendelian

Xiangyong Kong1, Yanchen Cai1, Yuwei Li1

  • 1School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093 China.

Health Information Science and Systems
|January 6, 2025
PubMed

Insights

Apolipoprotein B (ApoB) has a causal link with coronary heart disease, large-artery, and small-vessel stroke. This finding supports ApoB as a key risk factor for atherosclerotic cardiovascular disease (ASCVD) and may improve its management.

Area of Science:

  • Cardiovascular Genetics
  • Epidemiology
  • Biochemistry

Background:

  • Atherosclerotic cardiovascular disease (ASCVD) poses a significant global health risk.
  • Elevated low-density lipoprotein cholesterol (LDL-C) is a primary risk factor for ASCVD.
  • Apolipoprotein B (ApoB) offers superior predictive value for ASCVD risk compared to LDL-C in optimal lipid scenarios.

Purpose of the Study:

  • To investigate the causal relationship between apolipoprotein B (ApoB) and various atherosclerotic cardiovascular diseases (ASCVDs).
  • To leverage genome-wide association study (GWAS) data and Mendelian randomization (MR) to assess genetic associations.
  • To enhance understanding of ApoB's genetic impact on ASCVD risk.

Main Methods:

  • Utilized a large-scale, European-based genome-wide association study (GWAS) dataset.
  • Performed univariate two-sample Mendelian randomization (MR) analyses.
  • Employed the inverse variance weighted (IVW) method, supplemented by MR-Egger, weighted model, and weighted median (WM) analyses.

Main Results:

  • A significant causal relationship was identified between ApoB and coronary heart disease (CHD) (OR=1.710, P=0.010).
  • Causal links were also found between ApoB and large-artery atherosclerotic stroke (ISL) (OR=1.430, P=2.714E-06) and small-vessel stroke (ISS) (OR=1.221, P=0.005).
  • No significant causal association was observed between ApoB and ischemic stroke (IS) or myocardial infarction (MI).

Conclusions:

  • The study confirms a causal role for ApoB in CHD, ISL, and ISS.
  • These findings reinforce ApoB's significance in ASCVD pathogenesis.
  • Understanding the genetic influence of ApoB can potentially improve ASCVD risk management and reduce disease prevalence.
Abstract

Keywords:
Apolipoprotein BAtherosclerotic cardiovascular diseaseMendelian randomizationRisk factors

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