Deciphering thyroid function and CIMT: a Mendelian randomization study of the U-shaped influence mediated by apolipoproteins

Front Endocrinol (Lausanne). 2024 Mar 22:15:1345267. doi: 10.3389/fendo.2024.1345267. eCollection 2024.

Abstract

Background: Carotid Intima-Media Thickness (CIMT) is a key marker for atherosclerosis, with its modulation being crucial for cardiovascular disease (CVD) risk assessment. While thyroid function's impact on cardiovascular health is recognized, the causal relationship and underlying mechanisms influencing CIMT remain to be elucidated.

Methods: In this study, Mendelian Randomization (MR) was employed to assess the causal relationship between thyroid function and CIMT. Thyroid hormone data were sourced from the Thyroidomics Consortium, while lipid traits and CIMT measurements were obtained from the UK Biobank. The primary analysis method was a two-sample MR using multiplicative random effects inverse variance weighting (IVW-MRE). Additionally, the study explored the influence of thyroid hormones on lipid profiles and assessed their potential mediating role in the thyroid function-CIMT relationship through multivariate MR analysis.

Results: The study revealed that lower levels of Free Thyroxine (FT4) within the normal range are significantly associated with increased CIMT. This association was not observed with free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), or TPOAb. Additionally, mediation analysis suggested that apolipoprotein A-I and B are involved in the relationship between thyroid function and CIMT. The findings indicate a potential U-shaped curve relationship between FT4 levels and CIMT, with thyroid hormone supplementation in hypothyroid patients showing benefits in reducing CIMT.

Conclusion: This research establishes a causal link between thyroid function and CIMT using MR methods, underscoring the importance of monitoring thyroid function for early cardiovascular risk assessment. The results advocate for the consideration of thyroid hormone supplementation in hypothyroid patients as a strategy to mitigate the risk of carotid atherosclerosis. These insights pave the way for more targeted approaches in managing patients with thyroid dysfunction to prevent cardiovascular complications.

Keywords: Mendelian randomization; apolipoprotein A-I; apolipoprotein B; carotid intima-media thickness; thyroid hormones.

MeSH terms

  • Apolipoproteins
  • Carotid Intima-Media Thickness*
  • Humans
  • Hypothyroidism* / complications
  • Hypothyroidism* / genetics
  • Mendelian Randomization Analysis
  • Thyroid Hormones

Substances

  • Thyroid Hormones
  • Apolipoproteins

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by Beijing University of Traditional Chinese Medicine Leader Youth Project (2023-JYB-JBQN-020) and Chinese Society of Traditional Chinese Medicine Joint Key Project Basic Research (2023DYPLHGG-11). The corresponding author JL obtained the fundings. The funders had no role in this work. The views expressed in the paper are those of the authors and not necessarily of the listed funders.