Phenotypic Age Acceleration as a Mediator in Thyroid Hormone-Related Cardiovascular Risk Among the Elderly

The association between thyroid hormones and cardiovascular disease (CVD) has been widely examined; however, the role of biological aging in this relationship remains unclear. This study systematically investigates the mediating role of phenotypic age acceleration (PhenoAgeAccel) in the relationship between thyroid hormones and CVD.

The data were sourced from the 2007-2010 cycles of the National Health and Nutrition Examination Survey (NHANES). Analyses included logistic regression, linear regression, restricted cubic splines, subgroup analyses, and mediation analysis to assess the role of PhenoAgeAccel.

Among participants aged ≥ 60 years, elevated free triiodothyronine (FT3) concentrations were linked to a reduced risk of CVD (adjusted odds ratio [aOR] = 0.483; 95% CI: 0.273-0.856; p = 0.013). Similarly, total triiodothyronine (TT3) levels were associated with a decreased CVD risk in those aged 60 and above (aOR = 0.988; 95% CI: 0.980-0.995; p = 0.013). Mediation analysis showed that PhenoAgeAccel mediated 21.13% of the FT3-CVD association and 23.41% of the TT3-CVD association in older adults.

This study identifies an age-dependent relationship between FT3, TT3, and CVD and reveals that PhenoAgeAccel partially mediates this association. These findings suggest that interventions targeting thyroid function and biological aging may offer novel strategies for CVD prevention and management in older populations.