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 subject s by using an oral retinyl palmitate (RP) fat-loading test. The chylom icron remnant clearance (S(f)<1,000 fraction), expressed as the area u nder 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 i n the S(f)>1,000 fraction were different between FCH and control subje cts as analyzed by molecular-sieve chromatography. Fasting high densit y 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 simi lar between FCH patients (94+/-25 and 427+/-57 milliunits/mL, respecti vely) and control subjects (126+/-16 and 362+/-33 milliunits/mL, respe ctively). 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 th erapy were significantly associated with the changes in chylomicron re mnant AUC-RP (r=0.87; p=0.02). Delayed elimination of atherogenic chyl omicron remnants may contribute to the increased risk of premature ath erosclerosis in FCH.