DELAYED CHYLOMICRON REMNANT CLEARANCE IN SUBJECTS WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA

Objectives. To study the role of the LDL receptor in the clearance of chylomicron remnants in humans. Design. Chylomicron remnant clearance was studied in five untreated subjects with heterozygous familial hype rcholesterolaemia (FH) and nine normolipidaemic controls, by oral reti nyl palmitate-fat loading tests. Fasting plasma triglycerides (TG), wh ich are important determinators of chylomicron and remnant clearance, were not significantly different between FH (1.76 +/- 0.32 mmol L-1, m ean +/- SEM) and controls (1.26 +/- 0.18 mmol L-1). Chylomicrons (Sf > 1000) and their remnants (Sf < 1000) were separated by flotation and their clearance was estimated by calculating the area under the 24 h-r etinyl palmitate curve (AUC-RP). The factors determining chylomicron a nd remnant clearance were studied by univariate and multiple regressio n analysis. Results. Triglyceride clearance in plasma, Sf > 1000 fract ions and Sf < 1000 fractions was not significantly different between F H subjects and controls. In subjects with heterozygous FH, chylomicron remnant clearance was two-fold delayed (AUC-RP, 49.39 +/- 11.61 h.mg L-1) compared to controls (27.45 +/- 3.95 h.mg L-1; P = 0.048). Moreov er, 28.4% higher fasting plasma TG in FH resulted in 44.4% higher area s under the remnant-curves compared to controls. The clearance of chyl omicron RP was associated to plasma apo E (P = 0.73, P = 0.011), plasm a LDL cholesterol (P = 0.62, P = 0.018) and plasma TG (beta = 0.58, P = 0.029). The clearance of remnant RP was associated to the diagnosis (FH vs, non-FH), but not to the well-known determinants of remnant cle arance like plasma TG.Conclusions. The clearance of chylomicrons and l arge remnants isolated in the Sf > fraction depends primarily on the a po B, E (LDL) receptor and to a lesser extent on plasma triglycerides. The clearance of smaller chylomicron remnants isolated in the Sf < 10 00 depends to a large extent on the apo B, E (LDL) receptor.