Age-dependent association of thyroid peroxidase antibodies with incident cardiovascular disease events: Insights from a longitudinal cohort study.

Authors

Farhad Shaker, Safdar Masoumi, Ladan Mehran, Mohamadamin Tarighat-Payma, Atieh Amouzegar, Fereidoun Azizi, Salman Razvi

Published in

Journal of translational autoimmunity. Volume 13. Pages 100403. Epub Sep 22, 2026.

Abstract

The relationship between thyroid autoimmunity and cardiovascular disease (CVD) is controversial, and age-specific effects are not well characterized. We examined associations between thyroid peroxidase antibodies (TPOAb) status and incident CVD.
In this prospective population-based cohort, 4825 adults aged ≥20 years without baseline CVD were identified. Survival analyses were conducted using a 1.5-year landmark approach. Mean follow-up after the landmark was 14.8 ± 3.3 years. TPOAb was analyzed as a log-transformed continuous variable, dichotomous status, and categorical levels. Cox proportional hazards models were used to estimate hazard ratios (HRs) with progressive adjustment for demographic, lifestyle, cardiometabolic, and thyroid-related factors. Effect modification by age was assessed using interaction and spline analyses.
A total of 4825 participants (56.5% female and mean age of 39.7 ± 14.0 years) were included. During follow-up, 576 incident CVD events occurred. In the overall population, TPOAb was not associated with CVD risk (adjusted HR per 1-SD increase: 1.04, 95%CI 0.95-1.13). The primary continuous-age spline analysis demonstrated significant effect modification by age (global interaction P = 0.024). In exploratory age-stratified analyses, higher TPOAb levels were associated with increased CVD risk among participants aged <40 years (adjusted HR: 1.35, 95%CI 1.10-1.66), but not among those aged ≥40 years (HR, 1.00; 95% CI, 0.92-1.10). The association among younger participants remained significant in the euthyroid subgroup and in sensitivity analyses using Firth penalized regression and hard cardiovascular outcomes. Dose-response analyses further suggested increased risk at higher TPOAb levels among younger participants.
Thyroid autoimmunity was not associated with incident CVD in the overall cohort but demonstrated a significant age-dependent association. Exploratory analyses suggested increased risk among participants aged <40 years. These hypothesis-generating findings identify age as a potentially important modifier of the thyroid autoimmunity-CVD association and warrant validation in independent cohorts.

PMID:
42835607
Bibliographic data and abstract were imported from PubMed on 25 Oct 2026.

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