LDL PHYSICAL AND CHEMICAL-PROPERTIES IN FAMILIAL COMBINED HYPERLIPIDEMIA

Familial combined hyperlipidemia (FCHL) is characterized by elevations of triglyceride and/or cholesterol within families and an elevation i n apoB. Although small dense LDL has been consistently associated with hypertriglyceridemia, small dense LDL persists despite reductions in triglyceride after treatment with gemfibrozil in FCHL. The current stu dy evaluated potential differences in the distribution and chemical co mposition of LDL species in patients with FCHL and normolipidemic cont rol subjects. LDL from FCHL patients was characterized by a relative a bundance of a discrete LDL species with a mean peak analytic ultracent rifuge flotation rate (S-f(o)) of 4.7+/-0.5 (SEM), a density of 1.041/-0.001 g/mL, and a particle diameter of 250+/-1 Angstrom A as assesse d by gradient gel electrophoresis. The major LDL species in the contro l subjects had a higher mean S-f(o) rate (6.3+/-0.4), was more buoyant (density, 1.037+/-0.001 g/mL), and was larger (diameter, 262+/-2 Angs trom). In addition, in a series of six LDL fractions separated by equi librium density gradient ultracentrifugation, particle diameters were significantly smaller in all fractions from FCHL patients compared wit h those from control subjects. LDL particles from patients contained l ess free cholesterol, cholesteryl ester, and phospholipid than LDL fro m control subjects. The amount of triglyceride per LDL particle, howev er, did not differ between FCHL patients and control subjects. Differe nces in flotation rate and mass of the major LDL species between patie nts and control subjects could not be fully accounted for by differenc es in plasma triglyceride levels. Thus, LDL particles from FCHL patien ts are smaller and more dense with less cholesterol and phospholipid. Many of these differences appear to be independent of plasma triglycer ide. Differences in LDL physical and chemical properties may contribut e to the increase in premature coronary disease in FCHL.