Lower free triiodothyronine levels within the reference range are associated with higher cardiovascular mortality: An analysis of the NHANES

Background: Thyroid hormones play a central role in cardiovascular homeostasis. Lower free triiodothyronine (FT3) levels have been associated with worse prognosis in several conditions. However, contrary to thyrotropin (TSH) and free thyroxine (FT4), the role of FT3 in morbidity and mortality in the general population remains uncertain. Our objective was to evaluate the association between within the normal range FT3 levels and mortality in the general population. Methods: We evaluated 7116 adults in the National Health and Nutrition Examination Survey (NHANES) 2001–2002, 2007–2008, and 2009–2010 cycles with mortality evaluated as of December 2011. Exclusion criteria were: pregnancy; history of thyroid disease; use of thyroid-related drugs; and TSH, FT4, or FT3 level outside the reference range. Results: During a median follow-up of 45 months, 357 participants died. In unadjusted analysis, lower FT3 levels were associated with higher all-cause (HR per 0.1 pg/mL increase in FT3: 0.82 [95% confidence interval, 0.78–0.87]), cardiovascular (HR 0.74 [0.66–0.83]), cancer-related (HR 0.88 [0.80–0.97]) and other cause-related mortality (HR 0.83 [0.77–0.90]). After adjustment with Cox proportional hazard models, lower FT3 levels remained significantly associated with higher cardiovascular mortality (HR 0.83 [0.75–0.93]), but not with all-cause (HR 0.97 [0.92–1.02]), cancer-related (HR 1.02 [0.89–1.17]), or other cause-related mortality (HR 1.00 [0.92–1.10]). Conclusions: Lower levels of FT3 within the reference range may independently predict higher cardiovascular mortality in the general population.