Kinetic bases of the primary hyperlipidaemias: studies of apolipoprotein B turnover in genetically defined subjects.

Autologous 131I-labelled very low density lipoprotein (VLDL) and 125I-labelled low density lipoprotein (LDL) were injected into seven normal subjects and into forty-three hyperlipidaemic patients, classified into groups on the basis of family studies and clinical findings, to quantitate VLDL and LDL apolipoprotein B kinetics. In normal subjects, mean VLDL-B peptide synthetic rate was 15 . 1 mg kg-1 day-1, mean LDL-B peptide synthetic rate 7 . 7 mg kg-1 day-1 and mean LDL-B fractional catabolic rate (FCR) 0 . 31 day-1. In heterozygous familial hypercholesterolaemia (n = 14) VLDL-B peptide production was normal in patients with normal triglyceride levels; in those with high triglyceride levels there was either VLDL overproduction or a catabolic defect. LDL-B peptide synthetic rates ranged from high normal to increased (8 . 5--18 . 0 mg kg-1 day-1) and LDL-B peptide FCR values were markedly reduced (0 . 14--0 . 28 day-1) confirming the presence of a defect in LDL catabolism but indicating over-production as well. In familial combined hyperlipidaemia (n = 11) VLDL-B peptide production ranged from normal to elevated (13 . 9--44 . 4 mg kg-1 day-1, mean 23 . 8 mg kg-1 day-1) correlating with the VLDl triglyceride level (i.e. with the phenotypic expression of the disorder). LDL-B peptide production ranged from high normal to markedly increased (8 . 9--19 . 5 mg kg-1 day-1, mean 12 . 2 mg kg-1 day-1) and correlated with LDL cholesterol levels (i.e. the phenotype), (r = +0 . 66, P < 0 . 05). Three patients with unclassified hypercholesterolaemia had increased LDL-B peptide synthetic rates. One patient with remnant hyperlipoproteinaemia (type III) had a high normal VLDL-B peptide synthetic rate, 17 . 3 mg kg-1 day-1, and a strikingly low FCR of VLDL-B. In familial hypertriglyceridaemia (three patients) there was a low VLDL-B peptide FCR. In unclassified hypertriglyceridaemia VLDL over-production was the finding in seven patients but four patients appeared to have catabolic defects only. Overall there were significant hyperbolic relationships between VLCL-B peptide FCR and VLDL-B peptide concentration (r = -0 . 78, P < 0 . 001, for the log/log relationship) and between LDL-B peptide FCR and LDL cholesterol (r = -0 . 88, P < 0 . 001 for the log/log relationship.)