Low density lipoprotein apolipoprotein B metabolism: comparison of two methods to establish kinetic parameters

Elevated plasma cholesterol concentrations represent a major risk factor fo r coronary artery disease (CAD). Low density lipoprotein (LDL)-apolipoprote in (apo) B plays a key role in this process. Metabolic parameters of LDL-ap oB such as fractional catabolic rate (FCR) and production rate help to unde rstand the underlying pathomechanisms of elevated LDL-apoB and are usually determined with tracer studies (gold-standard). However, these parameters c an also be calculated from the rebound of plasma LDL-apoB concentration fol lowing a perturbation such as apheresis, if it is assumed that the perturba tion itself does not affect metabolic parameters. LDL-apoB metabolism was d etermined using two methods in eight hyperlipoproteinemic patients (47 +/- 15 years, body mass index (BMI) 27.5 +/- 4.1 kg/m): (a) by endogenous label ing using D-3-leucine (bolus 5 mg/kg) as tracer and multicompartmental mode ling; and (b) by fitting a monoexponential equation to LDL-apoB rebound con centration data following apheresis. LDL-apoB metabolic parameters determin ed using the two methods (mean +/- S.D.; FCR-tracer: 0.18 +/- 0.07 per day, FCR-rebound: 0.27 +/- 0.25 per day; production-tracer: 12.0 +/- 3.9 mg/kg per day; production-rebound: 15.2 +/- 8.0 mg/kg per day) were not correlate d, were not concordant (intraclass correlation coefficient), and were not s ignificantly different. Furthermore, only in five of the eight patients the rebound analysis predicted LDL-apoB steady-state concentrations that were within 20% of observed steady-state concentrations. These results indicate that parameters derived from LDL-apoB mass rebound following apheresis cann ot be used as a surrogate for parameters established with tracer methodolog y probably because the assumption that apheresis does not affect metabolic parameters of LDL-apoB may not be true in all patients. (C) 1999 Elsevier S cience Ireland Ltd. All rights reserved.