João Sérgio Neves1, Lia Leitão2, Rute Baeta Baptista3, Miguel Bigotte Vieira4, Rita Magriço5, Catarina Viegas Dias6, Ana Oliveira7, Inês Falcão-Pires8, André Lourenço8, Davide Carvalho9, Adelino Leite-Moreira10. 1. Departamento de Cirurgia e Fisiologia, Unidade de Investigação Cardiovascular, Faculdade de Medicina, Universidade do Porto, Porto, Portugal; Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário de São João, Faculdade de Medicina, Universidade do Porto, Porto, Portugal. 2. Neurology Department, Hospital Prof. Doutor Fernando Fonseca, Amadora, Portugal. 3. Pediatrics Department, Hospital de Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Portugal. 4. Nephrology and Renal Transplantation Department, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal. 5. Nephrology Department, Hospital Curry Cabral, Centro Hospitalar Universitário de Lisboa Central, Portugal. 6. NOVA Medical School, Lisbon, Portugal. 7. Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário de São João, Faculdade de Medicina, Universidade do Porto, Porto, Portugal. 8. Departamento de Cirurgia e Fisiologia, Unidade de Investigação Cardiovascular, Faculdade de Medicina, Universidade do Porto, Porto, Portugal. 9. Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário de São João, Faculdade de Medicina, Universidade do Porto, Porto, Portugal; Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal. 10. Departamento de Cirurgia e Fisiologia, Unidade de Investigação Cardiovascular, Faculdade de Medicina, Universidade do Porto, Porto, Portugal. Electronic address: amoreira@med.up.pt.
Abstract
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.
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.