TOPLINE:

Thyroid peroxidase antibody (TPOAb) positivity was not independently associated with an increased risk for coronary heart disease (CHD) outcomes or stroke events, even in those with subclinical hypothyroidism.

METHODOLOGY:

• Researchers performed an individual participant data meta-analysis of 14 prospective cohorts to assess whether a positive test for TPOAbs is independently associated with an increased risk for cardiovascular events.
• The pooled dataset comprised 100,250 participants (median age, 55 years; 56.7% women), with a median follow-up duration of 12.1 years.
• Individual cohorts provided baseline data on thyroid function, TPOAb status, demographics, history of cardiovascular disease and risk factors, medication use, and CHD outcomes.
• Euthyroidism was defined as thyroid‑stimulating hormone levels of 0.45-4.49 mIU/L; subclinical hypothyroidism was defined as thyroid-stimulating hormone levels of 4.50-19.99 mIU/L with normal free thyroxine or an elevated thyroid-stimulating hormone levels when free thyroxine was not measured.
• Outcomes were CHD events (non-fatal myocardial infarction, coronary artery revascularisation, incident angina pectoris, and hospital diagnosis of CHD), CHD mortality, and stroke events (fatal and non-fatal ischaemic or haemorrhagic stroke).

TAKEAWAY:

• At baseline, 11.9% of participants were positive for TPOAbs and 5.4% had subclinical hypothyroidism; among those with subclinical hypothyroidism, 41% were positive for TPOAbs.
• Compared with TPOAb-negative status, TPOAb-positive status was not associated with an increased risk for CHD events (hazard ratio [HR], 1.00; 95% CI, 0.90-1.11) in 68,671 participants across 10 cohorts or CHD mortality (HR, 0.95; 95% CI, 0.78-1.16) in 99,287 participants across 13 cohorts.
• Similarly, TPOAb-positive status was not linked to an increased risk for stroke events (HR, 0.98; 95% CI, 0.87-1.11) in 38,485 participants across eight cohorts or stroke mortality (HR, 1.06; 95% CI, 0.81-1.40) in 65,343 participants across 10 cohorts.
• Neither TPOAb‑positive nor TPOAb-negative status was associated with a higher risk for CHD events, CHD mortality, or stroke events among participants with subclinical hypothyroidism vs euthyroidism.

IN PRACTICE:

"Our results reinforce the importance of the degree of thyroid dysfunction rather than a positive antibody alone in cardiovascular risk assessment and management strategies to optimize patient care for individuals with thyroid dysfunction," the authors of the study wrote.

SOURCE:

This study was led by Ola Hysaj, Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland. It was published online on October 24, 2025, in the European Journal of Endocrinology.

LIMITATIONS:

Most cohorts comprised predominantly White participants from Europe and the US, which limited the generalisability of the findings to other populations. Most studies measured thyroid function and TPOAbs only at baseline, which may have prevented the analysis of changes in thyroid status over time. In addition, data on stroke subtypes and C‑reactive protein levels were not available.

DISCLOSURES:

This study was funded by a grant from the Swiss National Science Foundation. The individual cohorts were funded by the National Heart, Lung, and Blood Institute; National Institute of Neurological Disorders and Stroke; National Institute on Aging; Fundação de Amparo à Pesquisa do Estado de São Paulo; and other sources. The authors reported having no financial relationships with organisations that might have interest in the submitted work and declared having no support from any organisation for this research.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.