IMPAIRED CHYLOMICRON REMNANT CLEARANCE IN FAMILIAL COMBINED HYPERLIPIDEMIA

Postprandial chylomicron remnant clearance was studied in six patients with familial combined hyperlipidemia (FCH) and seven control subjects by using an oral retinyl palmitate (RP) fat-loading test. The chylomicron remnant clearance (S(f)<1,000 fraction), expressed as the area under the RP curve (AUC-RP), was delayed in FCH subjects (65.05+/-12.84 hours x [mg/L]) compared with control subjects (25.1+/-5.4 hours x[mg/L]; p=0.01). Postprandial lipoprotein particle size and composition in the S(f)>1,000 fraction were different between FCH and control subjects as analyzed by molecular-sieve chromatography. Fasting high density lipoprotein cholesterol was lower in FCH patients (0.54+/-0.09 mmol/L) than in control subjects (0.89+/-0.05 mmol/L; p<0.01). Mean plasma postheparin lipoprotein lipase and hepatic lipase activities were similar between FCH patients (94+/-25 and 427+/-57 milliunits/mL, respectively) and control subjects (126+/-16 and 362+/-33 milliunits/mL, respectively). In FCH, a 54% reduction (p<0.05) of plasma triglycerides to 2.63+/-0.41 mmol/L by drug treatment resulted in an enhanced, but not normalized, clearance of chylomicron remnants (39.4+/-6.0 hours x [mg/L]). Univariate regression analysis revealed that in FCH subjects the changes in fasting plasma apolipoprotein C-III concentrations after therapy were significantly associated with the changes in chylomicron remnant AUC-RP (r=0.87; p=0.02). Delayed elimination of atherogenic chylomicron remnants may contribute to the increased risk of premature atherosclerosis in FCH.