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Determinants and clinical implications of thyroid peroxidase antibodies in middle-aged and elderly individuals: the Rotterdam Study.

BACKGROUND
Thyroid peroxidase antibodies (TPO-Abs) play an important role in autoimmune thyroid disease, but are also prevalent in healthy individuals. However, it is unclear what determinants may influence occurrence of TPO-Abs in healthy individuals and how TPO-Abs may affect health outcomes in these individuals. We aimed to identify determinants of TPO-Abs in a large, prospective population-based cohort of middle-aged and elderly individuals and to subsequently assess the association between TPO-Abs and risk of overall and cause-specific mortality.


METHODS
We performed binomial and multinomial logistic regression analyses to obtain odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association of potential determinants based on previous literature with TPO-Ab positivity (>35 kU/L), TPO-Ab detectability (>5 kU/L), and TPO-Ab categories. Cox proportional hazards regression analyses were performed to obtain hazard ratios (HRs) and 95% CIs for the association of TPO-Abs and mortality risk.


RESULTS
In 9,685 participants (57% women, median baseline age 63.3 years, median follow-up time 10.1 years), we identified female sex (OR: 2.47; 95% CI: 2.13-2.86) and current smoking (OR: 3.10; 95% CI: 2.66-3.62) as determinants of TPO-Ab positivity and TPO-Ab detectability respectively. Higher age (OR: 0.98; 95% CI: 0.97-0.98) and all categories of alcohol consumption (ORs ranging from 0.71-0.78) were associated with a lower odds of TPO-Ab detectability. TPO-Ab detectability was associated with a higher risk of overall (HR: 1.09; 95% CI: 1.01-1.17), cancer related (HR: 1.18; 95% CI: 1.01-1.38), and cardiovascular mortality (HR: 1.21; 95% CI: 1.01-1.45). Interestingly, this was more prominent in men compared to women (HR for cardiovascular mortality 1.50 versus 0.99 respectively).


CONCLUSIONS
In community-dwelling middle-aged and elderly individuals, female sex and current smoking are the most important determinants associated with TPO-Ab levels in the detectable and positive range, whereas alcohol consumption is associated with a lower odds of TPO-Abs. The clinical importance of detectable TPO-Ab levels is illustrated by the association with an increased mortality risk, mainly in men. Our results warrant further exploration of the clinical applicability of detectable TPO-Ab levels, potentially as marker for low-grade inflammation.