Objective: The association of thyroid peroxidase antibodies (TPOAb) status with cardiovascular disease (CVD) risk, independent of thyroid function, remains unclear. We aimed to determine whether positive TPOAb is associated with increased CVD risk, overall and among individuals with subclinical hypothyroidism.

Methods: We conducted a two-stage individual participant data analysis including cohort studies identified through the Thyroid Studies Collaboration and systematic database searches (MEDLINE, EMBASE, Cochrane Library) through November 2024. Primary outcomes were coronary heart disease (CHD) events, CHD mortality, stroke events, and stroke mortality. We used Cox proportional hazards models, adjusted for age, sex, and thyroid-stimulating hormone (TSH) within each cohort, followed by a random-effects meta-analysis to assess cardiovascular outcomes by TPOAb status, overall and in the subclinical hypothyroidism subgroup.

Results: Among 100 250 adults from 14 cohort studies (median age 55 years, 56.7% women), 11.9% were TPOAb-positive, and 5.4% had subclinical hypothyroidism. In the overall population, we found no evidence of increased CVD risk in TPOAb-positive compared to TPOAb-negative individuals: Hazard Ratio (HR) 1.00 (95% CI 0.90-1.11) for CHD events; HR 0.95 (95% CI 0.78-1.16) for CHD mortality; HR 0.98 (95% CI 0.87-1.11) for stroke events; and HR 1.06 (95% CI 0.81-1.40) for stroke mortality. In subclinical hypothyroidism, positive TPOAb was similarly not associated with increased risk for any of the CVD outcomes.

Conclusion: Positive TPOAb status was not associated with increased risk of CHD or stroke. These findings do not support the use of TPOAb testing for cardiovascular risk assessment in the overall population or among individuals with subclinical hypothyroidism.