Metabolism of plasma low density lipoproteins in familial combined hyperlipidaemia: effect of acipimox therapy

Ten male patients with familial combined hyperlipidaemia (FCHL) were studied with regard to LDL metabolism and composition. The FCHL patients had higher LDL levels than healthy controls (5.4 +/- 1.4 vs. 3.7 +/- 0.7 mmol l-1; P0.005) and a higher rate of production of the lipoprotein (15.8 +/- 3.1 mg kg-1 d-1 in FCHL vs. 13.1 +/- 1.8 mg kg-1 d-1 in the normals; P0.005). The fractional catabolic rate of LDL was low-normal in the FCHL patients, with a high level of interindividual variation. The actual individual LDL cholesterol level within the FCHL patient group appeared to be more closely associated with the LDL apoB FCR value than the rate of production of the particle. Analysis of the LDL particles from FCHL patients revealed a relative enrichment in triglycerides, while the cholesterol content of the lipoprotein was normal. Institution of acipimox therapy in 8 patients reversed the high rate of synthesis of LDL (15.2 +/- 3.5 mg kg-1 d-1) to a more normal level (13.9 +/- 4.0 mg kg-1 d-1; P = 0.08), while the FCR did not change significantly. In conclusion, patients with FCHL show an apparent overproduction of LDL apoB, while the actual degree of LDL elevation appears to be dependent on the clearance capacity of the lipoprotein, measured as LDL apoB FCR. The overproduction defect of LDL apoB can, at least in part, be managed by treatment with the nicotinic acid analogue acipimox.