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 l ipoprotein (TRL) remnants of intestinal origin. Chylomicron remnants are ca usally related to atherosclerosis. We have shown previously that fasting pl asma apoB-48 may predict postprandial lipaemia. Remnant-like particle-chole sterol (RLP-C) may also reflect TRL remnants. We aimed to determine whether subjects with heterozygous familial hypercholesterolaemia (FH) had an accu mulation of remnants of intestinal origin, as reflected by fasting plasma a poB-48 and RLP-C levels. Methods The fasting plasma concentrations of apoB-48 and RLP-C were measure d in 15 subjects with heterozygous FH and 15 age- and sex-matched, normolip idaemic subjects. ApoB-48 was determined using SDS-PAGE and a western blott ing/enhanced chemiluminescence technique. RLP-C was measured using an immun e-separation assay. Serum apolipoprotein B-100 (apoB-100) levels were measu red using immmunonephelometry; lipids were assayed enzymatically. Results Compared with controls, FH subjects had significantly elevated plas ma 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 ele vated 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.