Kinetic bases of the primar hperlipidaemias: studies of apolipoprotein B turnover in geneticall defined subjects

Abstract

Autologous 131I-labeled very low density lipoprotein (VLDL) and 125I-labeled low density lipoprotein (LDL) were injected into 7 normal subjects, and 43 hyperlipidemic patients. The patients were 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 per day, mean LDL-B peptide synthetic rate 7.7 mg/kg per day, and mean LDL-B fractional catabolic rate (FCR) 0.31/day. In heterozygous familial hypercholesterolemia (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 per day), and LDL-B peptide FCR values were markedly reduced (0.14-0.28 day), confirming the presence of a defect in LDL catabolism but indicating overproduction as well. In familial combined hyperlipidemia (n = 11) VLDL-B peptide production ranged from normal to elevated (13.9-44.4 mg/kg per day, mean 23.8 mg/kg per day), 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 per day, mean 12.2 mg/kg per day), and correlated with LDL cholesterol levels (i.e., the phenotype), (r = +0.66, P < 0.05). Three patients with unclassified hypercholesterolemia had increased LDL-B peptide synthetic rates. One patient with remnant hyperlipoproteinemia (type III) had a high normal VLDL-B peptide synthetic rate, 17.3 mg/kg per day, and a strikingly low FCR of VLDL-B. In familial hypertriglyceridemia (3 patients) there was a low VLDL-B peptide FCR. In unclassified hypertriglyceridemia VLDL overproduction was the finding in 7 patients but 4 patients appeared to have catabolic defects only. Overall, there were significant hyperbolic relationships between VLDL-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).