Research Paper Volume 15, Issue 19 pp 10117—10132

Causal association between placental growth factor and coronary heart disease: a Mendelian randomization study

Bo Zuo1, *, , Sha Zhu2, *, , Guoting Zhong2, , Haoyang Bu3, , Hui Chen1, ,

  • 1 Department of Cardiology, Cardiovascular Centre, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
  • 2 Department of Neurology, Peking University International Hospital, Beijing 102206, China
  • 3 Department of Neurology, The First Hospital of Handan, Handan, China
* Equal contribution

Received: February 20, 2023       Accepted: August 28, 2023       Published: October 2, 2023
How to Cite

Copyright: © 2023 Zuo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Objective: Placental growth factor (PlGF), an important polypeptide hormone, plays an important regulatory role in various physiological processes. Observational studies have shown that PlGF is associated with the risk of coronary heart disease (CHD). However, the causal association between PlGF and CHD is unclear at present. This study aimed to investigate the causal association between genetically predicted PlGF levels and CHD.

Methods: Single nucleotide polymorphisms (SNPs) associated with PlGF were selected as instrumental variables (IVs) to evaluate the causal association between genetically predicted circulating PlGF levels and CHD risk by two-sample Mendelian randomization (MR).

Results: Inverse variance weighted (IVW) analysis showed that there was a suggestive causal association between genetically predicted PlGF level and the risk of CHD (OR = 0.79, 95% CI: 0.66–0.95, P = 0.011) overall. In addition, PlGF levels had a significant negative causal association with the risk of myocardial infarction (OR = 0.83, 95% CI: 0.72–0.95, P = 0.007). A negative correlation trend was found between PlGF level and the risk of angina pectoris (OR = 0.89, 95% CI: 0.79–1.01, P = 0.067). In addition, PlGF levels had a significant negative association with the risk of unstable angina pectoris (OR = 0.78, 95% CI: 0.64–0.94, P = 0.008). PlGF levels were negatively correlated with CHD events with suggestive significance (OR = 0.89, 95% CI: 0.80–0.99, P = 0.046).

Conclusion: Genetically predicted circulating PlGF levels are causally associated with the risk of CHD, especially acute coronary syndrome, and PlGF is a potential therapeutic target for CHD.


PlGF: placental growth factor; CHD: coronary heart disease; SNPs: single nucleotide polymorphisms; IVs: instrument variables; MR: Mendelian randomization; IVW: inverse variance weighted; AP: persistent angina pectoris; MI: myocardial infarction; PCI: percutaneous coronary intervention; ACS: acute coronary syndrome; GWAS: genome-wide association study; WM: weighted median; VEGFR1: vascular endothelial growth factor receptor 1; EA: effect _ allele; EAF: effect allele frequency; Chr: chromosome; SE: standard error.