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

In patients with heterozygous familial hypercholesterolemia (FH), both synt hetic 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 hypothe sis that a reduction of LDL pool size, achieved by LDL-apheresis, is associ ated with a downregulation of HDL synthesis. We studied the kinetics of HDL by infusing [5,5,5-H-2(3)]-leucine in 7 heterozygous FH patients before an d after 3 biweekly LDL-apheresis using dextran sulfate columns. Both plasma and LDL-cholesterol levels were decreased after LDL-apheresis (169 +/- 35 v 422 +/- 27 mg/dL, P < .05, and 85 <plus/minus> 19 v 327 +/- 52 mg/dL, P < .05, respectively). Plasma triglyceride level was unaffected (162 <plus/mi nus> 43 v 176 +/- 35 mg/dL, nor significant [NS]) and HDL composition remai ned stable (HDL-cholesterol 29 +/- 6 v 37 +/- 7 mg/dL, NS, and HDL-triglyce ride 20 +/- 6 v 19 +/- 8 mg/dL, NS). Plasma apolipoprotein Al(apo Al) was a lso similar (122 +/- 20 v 115 +/- 18 mg/dL, NS). Mean HDL-apo Al fractional catabolic rate (FCR) was slightly higher (0.41 +/- 0.07 v 0.36 +/- 0.14 po ol/d, NS), and absolute production rate (APR) was increased (22.1 +/- 5.7 v 18.0 +/- 5.7 mg/kg/d, P < .05) after LDL-apheresis. These human kinetic da ta suggest that LDL do not play a major role on HDL production in heterozyg ous FH patients, Copyright (C) 2001 by W.B. Saunders Company.