Hyperthyroidism linked to lower recurrent VTE risk among elderly patients

Older patients with subclinical hyperthyroidism appeared at lower risk for recurrent venous thromboembolism, according to the results of a prospective cohort study conducted in Switzerland.

Although hypothyroidism appeared associated with recurrent VTE, the association did not reach statistical significance and it did not demonstrate differences in thrombophilic biomarkers, results showed.

Older patients frequently experience VTE and subclinical thyroid dysfunction. Although subclinical thyroid dysfunction has been linked to an increased thromboembolic risk, prospective data in this area are lacking.

Nicolas Rodondi, MD, MAS, head of the ambulatory care unit at University Hospital of Bern in Switzerland, and colleagues conducted a prospective cohort study to observe the relationship between subclinical thyroid dysfunction and recurrent VTE, all-cause mortality and thrombophilic biomarkers in an elderly patient population.

The researchers defined subclinical hypothyroidism as elevated thyroid-stimulating hormone (TSH) levels (4.5-19.99 mIU L^-1) and subclinical hyperthyroidism as TSH levels less than 0.45 mIU L^-1, both with normal free thyroxine levels.

Researchers measured thyroid hormones and thrombophilic biomarkers 1 year after acute VTE.

The incidence of recurrent VTE and overall mortality during follow-up — beginning after the 1-year blood sampling — served as the primary endpoints.

Mean follow-up was 20.8 ± 9.1 months.

The study included data from 561 participants (median age, 74 years; interquartile range, 69-80; 41% women), 89% (n = 500) of whom had normal thyroid function. Six percent of participants (n = 35) had subclinical hypothyroidism and 5% (n = 26) had subclinical hyperthyroidism.

Fifty-two participants (9.2%) experienced a recurrent VTE during follow-up, 87% of whom were off anticoagulation.

No events occurred among participants with subclinical hyperthyroidism. The recurrent VTE incidence rates among participants with subclinical hypothyroidism was 7.2 (95% CI, 2.7-19.9) per 100 person-years, compared with 5.85 (95% CI, 4.41-7.77) per 100 person-years among euthyroid controls.

A multivariate analysis showed that compared with euthyroid controls, participants with subclinical hyperthyroidism had a sub-HR for recurrent VTE of 0.00 (95% CI, 0.00-0.58), whereas participants with subclinical hypothyroidism had a sub-HR of 1.5 (95% CI, 0.52-4.34).

However, participants with subclinical hypothyroidism did not exhibit increased levels of thrombophilic biomarkers compared with euthyroid participants.

During follow-up, 10% of the participants died; however, mortality did not differ by thyroid status. Neither subclinical hyperthyroidism (HR = 0.8; 95% CI, 0.23-2.81) nor subclinical hypothyroidism (HR = 0.99; 95% CI, 0.3-3.29) appeared associated with increased mortality.

The researchers acknowledged limitations of their study, including the relatively small number of patients with recurrent VTE, leading to the possibility that associations between VTE and thyroid dysfunction may not be causal.

They also noted that because they took samples beginning 1 year after VTE, they could not determine the short-term risk for recurrent VTE among patients with subclinical thyroid disorders.

“Future research projects should verify our results, particularly in younger populations (requiring larger study samples or longer observation times), and additionally assess a possible dose-dependent effect of TSH on coagulation parameters and clinical outcomes, which would need larger cohort studies with a higher prevalence of subclinical hypothyroidism,” Rodondi and colleagues wrote. “Finally, to definitively prove a causal relationship between thyroid replacement therapy and recurrent VTE, randomized controlled trials would be needed.” – by Cameron Kelsall

Disclosure: Rodondi reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.