Lipoprotein(a) and apolipoprotein B plasma concentrations in hypothyroid, euthyroid, and hyperthyroid subjects.

Abstract

Overt hypothyroidism is associated with premature coronary artery disease, and this is assumed to be due to a deteriorated metabolism of atherogenic lipoproteins. The effect of thyroid status on plasma concentrations of lipoprotein(a) [Lp(a)], a recently recognized highly atherogenic lipoprotein in man, is unknown. In a cross-sectional study, plasma Lp(a) concentrations were higher in overtly hypothyroid subjects [255 +/- 28 (+/- SD) mg/L; n = 19] and lower in hyperthyroid subjects (75 +/- 28 mg/L; n = 27) compared to those in 54 euthyroid subjects (150 +/- 36 mg/L) and a reference population of local blood bank donors (155 +/- 31 mg/L; n = 114). These findings were confirmed in a follow-up study of 19 hypothyroid and 8 hyperthyroid individuals. In the hypothyroid subjects, initial levo-T4 substitution therapy (25 micrograms daily) caused a 55% decrease in plasma Lp(a) concentrations and a 27% decrease in total plasma apolipoprotein B (apo B). Good agreement was found between the decrease in Lp(a) and apo B at a normal free T4 index. Follow-up of 8 hyperthyroid subjects revealed that their plasma Lp(a) and apo B concentrations significantly increased with return of euthyroidism. In conclusion, good agreement was found between the direction and magnitude of the responses of apo B and Lp(a) to changes in thyroid status. The following findings suggest that different thyroid hormone-dependent mechanisms modulate plasma Lp(a) concentrations in man, in part analogous to modulation of apo B: 1) impaired catabolism in the hypothyroid state, and 2) a combination of suppressed secretion of apoB and Lp(a) with increased catabolism in hyperthyroid subjects. Increased plasma Lp(a) concentrations may contribute to the increased risk of premature coronary artery disease in the hypothyroid state.