Lipoprotein(a) and other lipoproteins in hypothyroid patients before and after thyroid replacement therapy

Aims: To analyse the influence of thyroid hormones on serum lipoprotein(a) (Lp(a)) concentration and other lipid parameters, and hence potentially on coronary artery disease (CAD) risk. Methods: Thirty-six patients with hypothyroidism and 165 age-matched control euthyroid subjects were evaluated in a cross- sectional study, determining thyroid function tests and fasting serum lipids and lipoproteins. In a follow-up study for those hypothyroid patients the same determinations were repeated after normalization of thyroid state by levothyroxine (L-T4) replacement therapy. Patients needing other treatments were excluded. At baseline, patients with hypothyroidism had significantly higher levels of Lp(a), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (apo) A-I and apo B, and a higher TC/high-density lipoprotein cholesterol (HDL-C) ratio than control subjects. Results: Severity of the hypothyroid state, expressed by serum thyroid-stimulating hormone, wascorrelated with serum levels of Lp(a), LDL-C, and TC (r = 0.64, 0.52, 0.49, P = 0.005, P = 0.033, P = 0.048, respectively). The pretreatment Lp(a) levels were also correlated with those of posttreatment Lp(a)(r = 0.68, P = 0.002). All patients, who presented basal Lp(a) levels higher than 30 mg/dl, showed a decrease in Lp(a) concentrations by L-T4 therapy, and these normalized in eight cases (22.2%). Euthyroid state gave rise to a significant reduction of serum Lp(a) by 32.3%, of LDL-C by 22.8%, of TC by 17%, of apo A-I by 9.6%, and of apo B by 9.3%. After L-T4 therapy, CAD risk, expressed as TC/HDL-C ratio, decreased by 19.9%. Conclusions: These results show that hypothyroidism is associated not only with elevated serum levelsof LDL-C but also with elevated serum Lp(a) concentrations. Lp(a) levels may be at least partially modulated by thyroid hormone-dependent mechanisms, thus increasing the risk of developing premature atherosclerosis in hypothyroid state, that might be reduced by L-T4 therapy.