Elevated apolipoprotein B-48 and remnant-like particle-cholesterol in heterozygous familial hypercholesterolaemia

Background Apolipoprotein B-48 (apoB-48) is a marker of triglyceride-rich lipoprotein (TRL) remnants of intestinal origin. Chylomicron remnants are causally related to atherosclerosis. We have shown previously that fasting plasma apoB-48 may predict postprandial lipaemia. Remnant-like particle-cholesterol (RLP-C) may also reflect TRL remnants. We aimed to determine whether subjects with heterozygous familial hypercholesterolaemia (FH) had an accumulation of remnants of intestinal origin, as reflected by fasting plasma apoB-48 and RLP-C levels. Methods The fasting plasma concentrations of apoB-48 and RLP-C were measured in 15 subjects with heterozygous FH and 15 age- and sex-matched, normolipidaemic subjects. ApoB-48 was determined using SDS-PAGE and a western blotting/enhanced chemiluminescence technique. RLP-C was measured using an immune-separation assay. Serum apolipoprotein B-100 (apoB-100) levels were measured using immmunonephelometry; lipids were assayed enzymatically. Results Compared with controls, FH subjects had significantly elevated plasma concentrations of apoB-48 (29.3 median, 16.7-45.1 mg L-1 range vs. 12.8, 7.3-28.6; P < 0.001) and RLP-C (16.2, 1.5-114.3 mg dL(-1) vs. 8.5, 5.0-13.5; P = 0.003), as well as serum total apoB-100 (1.9, 1.3-2.6 g L-1 vs. 1.0, 0.3-1.3; P < 0.001), LDL-cholesterol (8.1, 4.6-10.4 mmol L-1 vs. 3.5, 2.4-4.4; P < 0.001) and trigIyceride (1.5, 0.6-5.6 mmol L-1 vs. 1.0, 0.4-1.8; P = 0.018). There was no significant difference in HDL cholesterol. Conclusion The findings suggest that patients with heterozygous FH have elevated plasma concentrations of TRL remnants, including those of intestinal origin. This may be a consequence of decreased clearance of these particles by the LDL-receptor.