Apolipoprotein A-I kinetics in heterozygous familial hypercholesterolemia:a stable isotope study

Heterozygous familial hypercholesterolemia (FH) is associated with a modera te decrease of plasma apoA-I and HDL-cholesterol levels. The aim of the stu dy was to test the hypothesis that these abnormalities were related to an i ncrease of HDL-apoA-I fractional catabolic rate (FCR), We performed a 14-h infusion of [5,5,5-H-2(3)]leucine in seven control subjects and seven heter ozygous FH patients (plasma total cholesterol 422 +/- 27 vs. 186 +/- 42 mg/ dL, P < 0.001, respectively), Plasma apoA-I concentration was not changed i n FH compared to controls (respectively 115 +/- 18 vs. 122 +/- 15 mg-/dL, N S), and HDL-cholesterol level was decreased (37 +/- 7 vs. 46 +/- 19 mg/dL, NS), Kinetics of HDL metabolism were modeled as a single compartment as no differences were observed between HDL2 and HDL3 subclasses. Both mean apoA- I FCR and absolute production rate (APR) were increased in FH (respectively , 0.36 +/- 0.14 vs. 0.22 +/- 0.05 pool/d, P < 0.05, and 18.0 +/- 7.7 and 11 .2 +/- 2.3 mg/kg/d, P < 0.05), Higher HDL-triglyceride and HDL apoE levels were observed in patients with heterozygous FH, (Respectively 19 +/- 8 vs. 8 +/- 3 mg/dL, P < 0.05, and 5.3 +/- 0.8 vs. 3.7 +/- 0.9 mg/dL, P < 0.05). We conclude that the catabolism of HDL-apoA-I is increased in heterozygous FH patients, However, plasma apoA-I concentration was maintained because of an increased HDL-apoA-I production rate.