Lipoprotein (a) metabolism estimated by nonsteady-state kinetics |
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Authors: | Klaus G Parhofer Thomas Demant Michael M Ritter H Christian Geiss Markus Donner Peter Schwandt |
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Affiliation: | (1) Department of Clinical Chemistry, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany;(2) Department of Internal Medicine II, Klinikum Grosshadern, Marchioninistr 15,81377, Munich, Germany |
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Abstract: | Lipoprotein (a) Lp(a)] is a low-density lipoprotein (LDL) particle with an additional apolipoprotein named apo(a). The concentration
of Lp(a) in plasma is determined to a large extent by the size of the apo(a) isoform. Because elevated Lp(a) concentrations
in plasma are associated with risk for premature coronary heart disease it is important to determine whether variations in
production or catabolism mediate differences in Lp(a) concentration. We determined metabolic parameters of Lp(a) in 17 patients
with heterozygous familial hypercholesterolemia or severe mixed hyperlipidemia by fitting a monoexponential function to the
rebound of Lp(a) plasma concentration following LDL-apheresis. In 8 of those 17 patients this was done twice following two
different aphereses. Although this approach allows one to estimate metabolic parameters without the use of a tracer, it requires
several major assumptions such as that apheresis itself does not change production or catabolism of Lp(a) and that Lp(a) metabolism
can be described by a single compartment. One apheresis decreased Lp(a) concentration by 59.1±8.3%. The fractional catabolic
rate (FCR) was 0.16±0.12 d−1 and production rate 6.27±5.26 mg·kg−1·d−1. However, observed (concentration before first apheresis) and predicted steady-state concentrations differed considerably
(more than 20%) in 9 of 17 patients, indicating that not all assumptions were fulfille in all patients. Production rate but
not FCR was correlated with Lp(a) plasma concentration (r
2=0.43. P=0.004) and molecular weight of apo(a) (r
2=0.48, P=0.011), which confirms radiotracer experiments showing that variations in Lp(a) plasma concentrations are due to differences
in production not catabolism. When parameters were estimated tiwce in a subgroup of eight patients, satisfactory reproducibility
was observed in six patients. Although parameters determined on two occasions correlated well, only FCR was concordant (intraclass
correiation coefficient). Thus, despite the limitations arising from the assumptions implicit to this method, metabolic parameters
of Lp(a) can be estimated from the rebound of plasma concentration following apheresis.
Parts of this study were presented at the meeting of the International Atherosclerosis Society, Paris, October 5–9, 1997. |
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