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

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 28-75 years; 1138 men (age 49 ± 13 years) and 1068 women (age 46 ± 12 years), 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.