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Phenotypic Age Acceleration as a Mediator in Thyroid Hormone-Related Cardiovascular Risk Among the Elderly
Minmin Wen1, Yanjun Hou1,2, Kaijia Shi1
1Key Laboratory of Tropical Translational Medicine of Ministry of Education & Hainan Provincial Key Laboratory for Tropical Cardiovascular Diseases Research, School of Public Health, Hainan Medical University, Haikou, 571199, China, hainmc.edu.cn.
Cardiology Research and Practice
|June 30, 2026
Summary
Thyroid hormones free triiodothyronine (FT3) and total triiodothyronine (TT3) are linked to reduced cardiovascular disease (CVD) risk in older adults. Biological aging, measured by phenotypic age acceleration (PhenoAgeAccel), partially mediates this protective association.
Area of Science:
- Endocrinology
- Cardiology
- Gerontology
Background:
- The relationship between thyroid hormones and cardiovascular disease (CVD) is established, but the influence of biological aging is not well understood.
- Phenotypic age acceleration (PhenoAgeAccel) is a novel biomarker of aging that may mediate the effects of thyroid hormones on CVD risk.
Purpose of the Study:
- To investigate the mediating role of PhenoAgeAccel in the association between thyroid hormones (FT3 and TT3) and CVD.
- To examine the age-dependent relationship between thyroid hormones and CVD.
Main Methods:
- Utilized data from the National Health and Nutrition Examination Survey (NHANES) 2007-2010.
- Employed logistic regression, linear regression, restricted cubic splines, subgroup analyses, and mediation analysis to assess PhenoAgeAccel's role.
Main Results:
- Elevated FT3 and TT3 levels were associated with reduced CVD risk in individuals aged 60 years and older.
- PhenoAgeAccel mediated 21.13% of the FT3-CVD association and 23.41% of the TT3-CVD association in older adults.
Conclusions:
- An age-dependent relationship exists between FT3, TT3, and CVD.
- PhenoAgeAccel partially mediates the association between thyroid hormones and CVD in older adults, suggesting potential therapeutic targets for CVD prevention.
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