Increased levels of free thyroxine and risk of venous thrombosis in a large population-based prospective study.

Background: Recent studies have shown that high levels of free thyroxine (FT4), even without leading to hyperthyroidism, are associated with a procoagulant state.

Objectives: The aim of our study was to determine whether high levels of thyroid hormones are associated with an increased risk of venous thrombosis.

Patients/methods: From a prospective nested case-cohort design within the second Nord-Trøndelag Health Study (HUNT2) cohort (1995-1997; 66,140 subjects), all patients with venous thrombosis during follow-up (n=515) and 1476 randomly selected age-stratified and sex-stratified controls were included. Relative and absolute risks for venous thrombosis were calculated for different cut-off levels of thyroid hormones on the basis of percentiles in the controls and different times between blood sampling and thombosis.

Results: In subjects with an FT4 level above the 98th percentile (17.3 pmol L(-1)), the odds ratio (OR) was 2.5 (95% confidence interval [CI] 1.3-5.0) as compared with subjects with levels below this percentile. For venous thrombosis within 1 year from blood sampling, this relative risk was more pronounced, with an OR of 4.8 (95% CI 1.7-14.0). Within 0.5 years, the association was even stronger, with an OR of 9.9 (95% CI 2.9-34.0, adjusted for age, sex, and body mass index). For thyroid-stimulating hormone, the relationship was inverse and less pronounced. The absolute risk within 6 months in the population for FT4 levels above the 98th percentile was 6.1 per 1000 person-years (95% CI 1.7-15.7).

Conclusions: Levels of FT4 at the upper end of the normal range are a strong risk factor for venous thrombosis. The risk increased with higher levels of thyroxine and shorter time between blood sampling and thrombosis. Further studies on the effect of clinical hyperthyroidism are warranted.