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  • Title: Low density lipoprotein apolipoprotein B metabolism: comparison of two methods to establish kinetic parameters.
    Author: Parhofer KG, Barrett PH, Schwandt P.
    Journal: Atherosclerosis; 1999 May; 144(1):159-66. PubMed ID: 10381289.
    Abstract:
    Elevated plasma cholesterol concentrations represent a major risk factor for coronary artery disease (CAD). Low density lipoprotein (LDL)-apolipoprotein (apo) B plays a key role in this process. Metabolic parameters of LDL-apoB such as fractional catabolic rate (FCR) and production rate help to understand the underlying pathomechanisms of elevated LDL-apoB and are usually determined with tracer studies (gold-standard). However, these parameters can also be calculated from the rebound of plasma LDL-apoB concentration following a perturbation such as apheresis, if it is assumed that the perturbation itself does not affect metabolic parameters. LDL-apoB metabolism was determined using two methods in eight hyperlipoproteinemic patients (47 +/- 15 years, body mass index (BMI) 27.5 +/- 4.1 kg/m): (a) by endogenous labeling using D3-leucine (bolus 5 mg/kg) as tracer and multicompartmental modeling; and (b) by fitting a monoexponential equation to LDL-apoB rebound concentration data following apheresis. LDL-apoB metabolic parameters determined 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 correlated, were not concordant (intraclass correlation coefficient), and were not significantly 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 cannot be used as a surrogate for parameters established with tracer methodology probably because the assumption that apheresis does not affect metabolic parameters of LDL-apoB may not be true in all patients.
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