Non-steady-state kinetics of low density lipoproteins in man: Studies after plasma exchange in healthy subjects and patients with familial hypercholesterolaemia

Five patients with heterozygous familial hypercholesterolaemia (EH), one patient with nonfamilial hypercholesterolaemia, and four healthy normals were treated with plasma exchange (PE). In order to achieve a non-steady-state situation with low plasma cholesterol levels, PE was performed twice in each subject at an interval of 1-3 days. At each time, 1500 ml of plasma were removed and replaced with colloids and albumin. Lipoprotein analyses were performed daily in all subjects for a period of 14 days following PE. Kinetic calculation of LDL cholesterol data using a two-compartment open model was performed, and rate constants, synthetic rate and apparent clearance of LDL were determined. A lower clearance and a tendency towards a higher synthesis of LDL were observed in the FH patients. In four of the subjects, LDL kinetics was also studied with the conventional ¹²⁵I-LDL turnover technique. The synthetic rates of LDL were compared using data derived from PE and ¹²⁵I-LDL kinetics. The two techniques showed a good correlation (r = +0.93) although synthetic rates in general were higher when calculated from the ¹²⁵I-LDL procedure (3.98 vs. 2.64 mmol d^-1 for LDL cholesterol synthesis). The results indicate that non-steady-state kinetics of LDL, as measured using the PE technique, is a useful method for analysis of LDL metabolism.