Effect of low-density lipoproteins on apolipoprotein AI kinetics in heterozygous familial hypercholesterolemia☆

Abstract In patients with heterozygous familial hypercholesterolemia (FH), both synthetic and clearance rates of high-density lipoproteins (HDL) are increased compared with control subjects. According to in vitro data on hepatocytes, the expanded pool size of low-density lipoproteins (LDL) in FH could partly explain the enhanced HDL production. Therefore, we have tested the hypothesis that a reduction of LDL pool size, achieved by LDL-apheresis, is associated with a downregulation of HDL synthesis. We studied the kinetics of HDL by infusing [5,5,5- 2 H 3 ]-leucine in 7 heterozygous FH patients before and after 3 biweekly LDL-apheresis using dextran sulfate columns. Both plasma and LDL-cholesterol levels were decreased after LDL-apheresis (169 [plusmn] 35 v 422 [plusmn] 27 mg/dL, P [lt ] .05, and 85 [plusmn] 19 v 327 [plusmn] 52 mg/dL, P [lt ] .05, respectively). Plasma triglyceride level was unaffected (162 [plusmn] 43 v 176 [plusmn] 35 mg/dL, not significant [NS]) and HDL composition remained stable (HDL-cholesterol 29 [plusmn] 6 v 37 [plusmn] 7 mg/dL, NS, and HDL-triglyceride 20 [plusmn] 6 v 19 [plusmn] 8 mg/dL, NS). Plasma apolipoprotein AI (apo AI) was also similar (122 [plusmn] 20 v 115 [plusmn] 18 mg/dL, NS). Mean HDL-apo AI fractional catabolic rate (FCR) was slightly higher (0.41 [plusmn] 0.07 v 0.36 [plusmn] 0.14 pool/d, NS), and absolute production rate (APR) was increased (22.1 [plusmn] 5.7 v 18.0 [plusmn] 5.7 mg/kg/d, P [lt ] .05) after LDL-apheresis. These human kinetic data suggest that LDL do not play a major role on HDL production in heterozygous FH patients.