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

Abstract

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.

​Comprehensive mendelian randomization analysis of plasma proteomics to identify new therapeutic targets for the treatment of coronary heart disease and myocardial infarction

“…On the other hand, it enhances the risk of plaque rupture by recruiting monocytes, improving foam cell formation, and triggering inflammatory responses [ 59 , 60 ]. Consistent with our findings, an MR study conducted by Zuo et al [ 61 ] revealed an inverse relationship between PGF levels and the risk of coronary heart disease (CHD) and myocardial infarction (MI). Furthermore, clinical evidence suggests that a rapid elevation in serum PGF levels following MI correlates positively with subsequent improvement in left ventricular function [ 62 ].…”

Causal relationship between serum uric acid and cardiovascular disease: a Mendelian randomization study

“…Mendelian randomization (MR) is an analytical method employing single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) to assess causal relationships between exposures and outcomes (12). As genetic variants are assigned randomly at conception, MR circumvents confounding factors and reverse causality, common issues in traditional observational studies (13).…”