HDL cholesterol as a mediator of the relationship between breastfeeding and coronary atherosclerosis from a two-step

Baoquan Zhang1, Bin Yang2, Wenlong Xiu2

  • 1Department of Neonatology, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350000, China. zbq2701@fjmu.edu.cn.

Scientific Reports
|August 6, 2025
PubMed

Insights

Breastfeeding is linked to a lower risk of coronary atherosclerosis (CA). This protective effect may be partly mediated by increased high-density lipoprotein cholesterol (HDL-C) levels.

Area of Science:

  • Cardiovascular Epidemiology
  • Genetics
  • Public Health

Background:

  • The relationship between breastfeeding and coronary atherosclerosis (CA) remains debated.
  • Investigating early-life factors like breastfeeding is crucial for understanding cardiovascular disease (CVD) etiology.
  • Mendelian randomization (MR) offers a robust method to explore causal links between exposures and outcomes.

Purpose of the Study:

  • To investigate the causal association between breastfeeding and coronary atherosclerosis (CA) using Mendelian randomization (MR).
  • To identify potential mediating factors, such as lipid profiles, that explain the link between breastfeeding and CA.
  • To evaluate the role of high-density lipoprotein cholesterol (HDL-C) as a mediator in this association.

Main Methods:

  • Utilized two independent European adult cohorts for discovery and replication analyses.
  • Employed summary statistics from large genome-wide association studies (GWAS) for CA and breastfeeding phenotypes.
  • Conducted two-step MR analysis to assess the mediating effect of candidate variables, including HDL-C.

Main Results:

  • MR analysis revealed a significant protective association between breastfeeding and reduced risk of CA in both discovery (OR: 0.826) and replication (OR: 0.439) datasets.
  • High-density lipoprotein cholesterol (HDL-C) was identified as a significant mediator, explaining 10.26% of the total effect.
  • The findings suggest that breastfeeding confers a protective effect against CA, partly through elevated HDL-C levels.

Conclusions:

  • Breastfeeding demonstrates a causal protective effect against coronary atherosclerosis.
  • Increased HDL-C levels represent a key mediating pathway for the cardioprotective benefits of breastfeeding.
  • Promoting breastfeeding could be a valuable early-life intervention strategy for long-term cardiovascular health.

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