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Thyroid Function and the Risk of Atherosclerotic Cardiovascular Morbidity and Mortality: The Rotterdam Study
Arjola Bano1, Layal Chaker1, Francesco U S Mattace-Raso1
1From the Department of Internal Medicine (A.B., L.C., F.U.S.M.-R., R.P.P.), Academic Center for Thyroid Diseases (A.B., L.C., R.P.P.), Department of Epidemiology (A.B., L.C., M.A.I., O.H.F., R.P.P., M.K.), Section of Geriatric Medicine, Department of Internal Medicine (F.U.S.M.-R.), and Department of Radiology (A.v.d.L.), Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands; and Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (L.C.).
Rationale:
Thyroid hormones have been linked with various proatherogenic and antiatherogenic processes. However, the relationship of thyroid function with manifestations of atherosclerosis remains unclear.
Objective:
To investigate the association of thyroid function with atherosclerosis throughout its spectrum; that is, subclinical atherosclerosis, incident atherosclerotic cardiovascular (ASCV) events, and ASCV mortality.
Methods And Results:
This population-based study was embedded within the Rotterdam Study. The risk of atherosclerosis was evaluated by measuring (1) presence of subclinical atherosclerosis, assessed by coronary artery calcification score >100 AU; (2) ASCV events, defined as fatal and nonfatal myocardial infarction, other coronary heart disease mortality, or stroke; (3) ASCV mortality, defined as death because of coronary heart disease and cerebrovascular or other atherosclerotic diseases. Associations of thyroid-stimulating hormone and free thyroxine with the outcomes were assessed through logistic regression and Cox proportional hazard models, adjusted for potential confounders, including cardiovascular risk factors. A total of 9420 community-dwelling participants (mean age±SD, 64.8±9.7 years) were included. During a median follow-up of 8.8 years (interquartile range, 4.5-11.8 years), 934 incident ASCV events and 612 ASCV deaths occurred. Free thyroxine levels were positively associated with high coronary artery calcification score (odds ratio, 2.28; 95% confidence interval, 1.30-4.02) and incident ASCV events (hazard ratio, 1.87; confidence interval, 1.34-2.59). The risk of ASCV mortality increased in a linear manner with higher free thyroxine levels (hazard ratio, 2.41; confidence interval, 1.68-3.47 per 1 ng/dL) and lower thyroid-stimulating hormone levels (hazard ratio, 0.92; confidence interval, 0.84-1.00 per 1 logTSH). Results remained similar or became stronger among euthyroid participants.
Conclusions:
Free thyroxine levels in middle-aged and elderly subjects were positively associated with atherosclerosis throughout the whole disease spectrum, independent of cardiovascular risk factors.
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