Abstract 678: Accurate Assessment of Very Low Density Lipoprotein-apoB100 Turnover Rates
Elevated levels of apolipoprotein B (apoB)-containing lipoproteins are associated with increased risk of cardiovascular disease. Tracer kinetics studies are used to determine rates of VLDL-apoB100 production and catabolism. Different methods are used to assess VLDL-apoB100 kinetics following a primed constant infusion of labeled amino acids:
the fractional synthetic rate (FSR) using the initial slope and plateau enrichment,
kinetics determined by fitting a monoexponential rise-to-plateau function, and
the fractional catabolic rate (FCR) derived using a compartmental model that incorporates the VLDL-apoB and plasma amino acid enrichment time courses.
Theoretically, the kinetic parameters determined by these methods should be identical. We determined VLDL-apoB kinetic parameters using the three methods in 101 normolipidemic subjects who received a 12-h primed continuous infusion of 2H3-leucine. Of the 2 methods that fit the full 12-h data set, the fit was significantly better using the compartmental model compared to the monoexponential function (p<0.001), establishing this as the reference method. The monoexponential method exhibited a large mean square error compared to the compartmental model (19%; range −41% to +65%). The difference between the two methods was correlated with the degree of over- or under-priming of the of the H3-leucine dose for individual studies (r2=0.65, p=10-24), resulting in an over- or under- estimate, respectively, of the apoB turnover rate using the monoexponential function compared with the compartmental model FCR. The compartmental model provided the best fit to the VLDL-apoB enrichment data because the modeling process accommodated variations in the priming dose for individual subjects. The FSR method significantly underestimated the compartmental model FCR (p<10-16), with the percentage error increasing with the turnover rate. We conclude that a compartmental model that accounts for the plasma amino acid enrichment time course should be used to assess VLDL-apoB kinetics, and that approaches that do not take into account all of the available tracer data, particularly the plasma amino acid enrichment data, do not provide accurate estimates of VLDL-apoB kinetics.