CHANGES IN LIPOPROTEIN(A), LDL-CHOLESTEROL AND APOLIPOPROTEIN-B IN HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIC PATIENTS TREATED WITH DEXTRAN SULFATE LDL-APHERESIS

We evaluated the effect of periodical treatment with LDL-apheresis by adsorption to dextran sulfate (Liposorber LA-15) on several aspects related to LDL and Lipoprotein(a) metabolisms, in three homozygous familial hypercholesterolaemic patients with LDL receptor deficiency. The dextran sulfate columns retained apolipoprotein B-containing particles with high affinity and capacity, in such a way that the treatment of a volume of plasma equivalent to three times the patient plasma volume resulted in an 85% decrease of circulating LDL-cholesterol and Lipoprotein(a). The continuous treatment with LDL-apheresis was highly beneficial for these patients since an average plasma concentration lower than 200 mg dl(-1) for LDL-choresterol, and lower than 25 mg dl(-1) for Lipoprotein(a) could be achieved by treating the patients once a week. After each apheresis treatment, plasma concentrations of these metabolites progressively returned to the pretreatment, steady-state, levels. The analysis of the rates of return allowed us to estimate the fractional catabolic rates. FCRs of LDL-cholesterol were 0.052, 0.049 and 0.047 pools day(-1), and those of apolipoprotein B, 0.065, 0.045 and 0.050 pools day(-1) in the three subjects, respectively. These values are much lower than those in normolipidaemic individuals as observed by others, and are in accordance with the LDL-receptor deficiency condition of our patients. Two of them had highly elevated Lipoprotein(a) plasma concentrations, and their FCRs of Lipoprotein(a) were calculated to be 0.112 and 0.066 pools day(-1). These values were significantly higher than the respective FCR of LDL-cholesterol and apolipoprotein B, which demonstrates that Lipoprotein(a) and LDL were not metabolically homogeneous in these patients. Values of -kt for Lipoprotein(a), LDL-cholesterol and apolipoprotein B correlated during the first days immediately after each apheresis session, suggesting that production of Lipoprotein(a) in these individuals was associated to that of apolipoprotein B. It is proposed that elevated Lipoprotein(a) plasma levels in familial hypercholesterolaemia are mainly a consequence of a high production rate rather than decreased fractional catabolic rate.