![]() ![]() Cardiovascular disease mediated 14.3% and 5.9% of the associations of subclinical hypothyroidism and high-normal TSH with all-cause mortality, respectively, with the CVD mediation being most pronounced in women (7.5%-13.7% of the association) and participants aged 60 years and older (6.0%-14.8% of the association).Ĭonclusions and Relevance In this study, CVD mediated the associations of subclinical hypothyroidism and high-normal TSH concentrations with all-cause mortality in the US general population. Throughout follow-up (median, 7.3 years), serum thyroid function test results consistent with subclinical hypothyroidism and high-normal TSH concentrations were both associated with increased all-cause mortality (subclinical hypothyroidism: hazard ratio, 1.90 95% CI, 1.14-3.19 high-normal TSH: hazard ratio, 1.36 95% CI, 1.07-1.73) compared with the middle-normal TSH group. ![]() ![]() Mediation analysis was used within the counterfactual framework to estimate natural direct associations (not through CVD) and indirect associations (through CVD). Main Outcomes and Measures Cox proportional hazards regression models were used to investigate associations between the TSH concentration category (subclinical hypothyroidism or tertiles of serum TSH concentrations within the reference range low-normal TSH, 0.34-1.19 mIU/L middle-normal TSH, 1.20-1.95 mIU/L and high-normal TSH, 1.96-5.60 mIU/L) and all-cause mortality. Data were analyzed from January to August 2019. Objective To elucidate the extent to which subclinical hypothyroidism, elevated serum TSH and normal serum free thyroxine, or high-normal TSH concentrations (ie, upper normative–range TSH concentrations) are associated with mortality through CVD among US adults.ĭesign, Setting, and Participants This cohort study relied on representative samples of US adults enrolled in the National Health and Nutrition Examination Survey in 2001 to 2002, 2007 to 2008, 2009 to 2010, and 2011 to 2012 and their mortality data through 2015. However, the extent to which CVD mediates the association between elevated serum thyrotropin (TSH) and mortality has not yet been well established or sufficiently quantified. Importance Subclinical hypothyroidism is a common clinical entity among US adults associated in some studies with an increase in the risk of cardiovascular disease (CVD) and mortality. Shared Decision Making and Communication.Scientific Discovery and the Future of Medicine.Health Care Economics, Insurance, Payment.Clinical Implications of Basic Neuroscience.Challenges in Clinical Electrocardiography.Direct and Indirect Associations (Hazard Ratio Scale ) of Serum TSH Concentrations on All-Cause Mortality Through Cardiovascular Disease Stratified by Age in NHANES 12 Followed Through 2015 Direct and Indirect Associations (Hazard Ratio Scale ) of Serum TSH Concentrations on All-Cause Mortality Through Cardiovascular Disease Using Different Cut-off for TSH (0.4-4.3 mIU/L as Normal Range) in NHANES 2001-2002 and NHANES 2007-2012 Followed Through 2015ĮTable 4. Direct and Indirect Effects (Hazard Ratio Scale ) of Serum TSH Concentrations on All-Cause Mortality Through Cardiovascular Disease Additionally Adjusted for Comorbidities in NHANES 2001-2002 and NHANES 2007-2012 Followed Through 2015ĮTable 3. Associations Between Serum TSH Concentrations and All-Cause Mortality Additionally Adjusted for Comorbidities in NHANES 12 Followed Through 2015ĮTable 2. Association Between Serum TSH Concentrations and All-Cause Mortality Additionally Adjusted for Comorbidities Using a Restricted Cubic Spline Regression Model in NHANES 12 Followed Through 2015ĮTable 1. Causal Diagram Under InvestigationĮFigure 2. ![]()
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