Serum paraoxonase-1 activity is inversely related to free thyroxine in euthyroid subjects: The PREVEND Cohort Study.

Abstract

Low-normal thyroid function within the euthyroid range has been suggested to enhance atherosclerosis susceptibility. Paraoxonase-1 (PON-1) may protect against atherosclerotic cardiovascular disease development by attenuating oxidative stress. We evaluated relationships of PON-1 with thyroid stimulating hormone (TSH), free T4 , free T3 , lipids and apolipoprotein (apo)A-I in euthyroid subjects, and assessed whether such relationships are modified in the context of the metabolic syndrome (MetS). Serum PON-1 activity (arylesterase activity), TSH, free T4 , free T3 , lipids and apoA-I was measured in 2206 euthyroid subjects (aged 28-75years; 1138 men (age 49±13years) and 1068 women (age 46±12years), recruited from the general population (PREVEND cohort). In age- and sex-adjusted analysis, PON-1 activity (divided into tertiles) was positively related to TSH (β=-0.045, P=.036) and inversely to free T4 (β=-0.042, P=.050) but not to free T3 (β=-0.027, P=.20). PON-1 activity was positively related to total cholesterol, non-HDL cholesterol and triglycerides, as well as to HDL cholesterol and apoA-I (P<.01 to <.001). The inverse relationship of PON-1 activity with free T4 remained present after adjustment for lipids and other potential confounders (β=-0.066, P=.002), but the positive relationship with TSH lost significance (β=0.034, P=.11). The inverse relationship of PON-1 activity with free T4 was not different in subjects with vs without MetS (P=.94), nor modified by the presence of its individual components (P≥.22 for each). Serum PON-1 activity is inversely associated with free T4 in euthyroid subjects, suggesting that low-normal thyroid function may affect PON-1 regulation.