Switzerland: Researchers have reported that thyroid peroxidase antibody (TPOAb) positivity does not independently increase the risk of coronary heart disease (CHD) or stroke, even among individuals with subclinical hypothyroidism. The findings are based on a large individual participant data analysis published in the European Journal of Endocrinology, led by Ola Hysaj and colleagues from the University of Bern, Switzerland.
The team conducted an extensive evaluation to clarify whether the presence of TPO antibodies contributes to cardiovascular risk beyond abnormalities in thyroid hormone levels. While TPOAb testing is frequently used in clinical practice, its role in predicting cardiovascular events has remained uncertain. This study, pooling detailed data from 14 prospective cohorts, provides the most comprehensive evidence to date addressing this question.
The analysis included 100,250 adults with a median age of 55 years, of whom 56.7% were women. Participants were followed for a median duration of 12.1 years. Baseline information from the cohorts captured thyroid function, TPOAb status, demographic details, established cardiovascular risk factors, medication use, and the occurrence of cardiovascular events over time. Thyroid function categories were defined using thyroid-stimulating hormone (TSH) levels, with euthyroidism ranging from 0.45–4.49 mIU/L and subclinical hypothyroidism classified by elevated TSH paired with normal free thyroxine levels.
Key Findings:
- At baseline, 11.9% of participants were positive for thyroid peroxidase antibodies (TPOAbs), and 5.4% had subclinical hypothyroidism.
- Among those with subclinical hypothyroidism, about 41% tested positive for TPOAbs.
- TPOAb positivity did not correspond to an increased risk of cardiovascular events.
- In 68,671 participants across 10 cohorts, the risk of coronary heart disease (CHD) events was the same for TPOAb-positive and TPOAb-negative individuals (HR 1.00).
- No elevated risk was observed for CHD mortality (HR 0.95).
- Stroke events also showed no significant difference between the two groups (HR 0.98).
- Stroke mortality remained comparable as well (HR 1.06).
- Even when the analysis was limited to individuals with subclinical hypothyroidism, TPOAb positivity did not increase the likelihood of CHD events, cardiovascular mortality, or stroke.
- These findings indicate that TPOAb status does not offer additional predictive value for cardiovascular risk.
The authors emphasized the clinical relevance of these findings, noting that cardiovascular risk evaluation should prioritize the extent of thyroid dysfunction rather than the presence of TPO antibodies. “Our results reinforce the importance of the degree of thyroid dysfunction rather than a positive antibody alone in cardiovascular risk assessment and management strategies,” the researchers wrote.
Overall, the study challenges the routine use of TPOAb testing for cardiovascular risk stratification. The evidence suggests that in both the general population and those with subclinical hypothyroidism, TPOAb positivity does not warrant concern regarding CHD or stroke risk. Instead, clinicians are encouraged to focus on TSH levels and traditional cardiovascular risk factors when guiding patient care.
Reference:
Hysaj, O., Efthimiou, O., Collet, T., Cappola, A. R., Alwan, H., Gussekloo, J., Chaker, L., Kavousi, M., Azizi, F., Köttgen, A., Selvin, E., Trompet, S., Walsh, J. P., Brown, S. J., Iacoviello, M., Dullaart, R. P., Bakker, S. J., Sgarbi, J. A., Ittermann, T., . . . Collaboration, T. S. (2025). Thyroid antibody status, thyroid function, and the risk of coronary heart disease and stroke: An individual participant data analysis from 14 cohorts. European Journal of Endocrinology, 193(5), S71-S82. https://doi.org/10.1093/ejendo/lvaf209