Impaired thyroid hormone sensitivity is associated with cardiovascular disease risk and mortality in euthyroid...

Fluctuations in thyroid function among euthyroid individuals have been linked to cardiovascular disease (CVD). We investigated whether central thyroid hormone sensitivity correlates with CVD risk, CVD-related death, and overall mortality in subjects with normal thyroid function, particularly examining how age modifies these associations.

We analyzed data from 6,374 euthyroid adults enrolled in NHANES 2007-2012. Central thyroid hormone sensitivity was quantified using three indices: the thyroid feedback quantile-based index (TFQI), the thyrotropin-thyroxine resistance index (TT4RI) and the TSH index (TSHI). The Framingham Risk Score (FRS) estimated each participant's 10-year probability of developing CVD. CVD mortality and all-cause mortality were ascertained by linkage to the National Death Index through December 31, 2015. Associations were evaluated using logistic regression (10-year CVD risk) and Cox proportional hazards models (mortality), adjusted for sex and race, with analyses stratified by age (< 40 and ≥ 40 years).

Of the 6,374 participants (mean age 48.24 ± 17.59 years; 52.0% male), 18.5% had a 10-year CVD risk > 10%; during follow-up. In sex- and race-adjusted models, all three indices were positively associated with an elevated 10-year CVD risk (> 10%): TFQI (OR 1.40, 95% CI 1.15-1.71), TSHI (OR 1.27, 95% CI 1.11-1.45), and TT4RI (OR 1.01, 95% CI 1.01-1.02). Each index was also significantly associated with higher CVD mortality and all-cause mortality, with TFQI showing the strongest associations (CVD mortality: HR 3.30, 95% CI 2.24-4.85; all-cause mortality: HR 2.19, 95% CI 1.83-2.62). These associations remained significant in participants aged ≥ 40 years (p < 0.001) but not in those aged < 40 years.

Impaired central thyroid hormone sensitivity shows association with elevated CVD risk, CVD mortality, and all-cause mortality in euthyroid individuals aged 40 years and older.