Association Between Low Serum Free Thyroxine Concentrations and Coronary Artery Calcification in Healthy Euthyroid Subjects

Abstract

Considerable evidence suggests that hypothyroidism could promote atherosclerotic vascular changes. We planned this study to investigate whether serum free thyroxine (FT4) or thyroid-stimulating hormone (TSH) levels are associated with coronary artery calcification measured in healthy euthyroid subjects. A cross-sectional analysis was performed among subjects who visited our hospital for a health checkup. Among 1849 subjects, 669 (mean age 55.3±8.8 years; 392 men) with FT4 and TSH in the normal ranges were included after excluding those with diabetes, a history of current smoking and cardiovascular disease (CVD), or the use of drugs for hypertension, antithyroid drugs, or thyroid hormone preparations. Coronary artery calcium scores (CACS) were measured by multi-detector computed tomography. Subjects with a CACS >100 had lower FT4 levels than those with a lower CACS (p=0.017), whereas no difference was observed in the TSH levels among CACS categories. FT4 levels had an odds ratio of 0.06 for high CACS (95% confidence interval=0.01-0.74; p=0.028) after the adjustment for CVD risk factors. In multivariate regression analysis, CACS was negatively correlated with FT4 levels (β=-0.823, p=0.032), and the inverse association between FT4 and CACS remained significant only in men (p=0.011). FT4 levels were inversely associated with coronary artery calcification in euthyroid healthy subjects, especially in men independent of conventional CVD risk factors. Further studies are needed to validate whether subjects with decreased FT4 levels within the normal reference range are at a high CVD risk and have poor cardiovascular outcomes.