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 in 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 study evaluated potential differences in the distribution and chemical composition of LDL species in patients with FCHL and normolipidemic control subjects. LDL from FCHL patients was characterized by a relative abundance of a discrete LDL species with a mean peak analytic ultracentrifuge 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 assessed by gradient gel electrophoresis. The major LDL species in the control 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 Angstrom). In addition, in a series of six LDL fractions separated by equilibrium density gradient ultracentrifugation, particle diameters were significantly smaller in all fractions from FCHL patients compared with those from control subjects. LDL particles from patients contained less free cholesterol, cholesteryl ester, and phospholipid than LDL from control subjects. The amount of triglyceride per LDL particle, however, did not differ between FCHL patients and control subjects. Differences in flotation rate and mass of the major LDL species between patients and control subjects could not be fully accounted for by differences in plasma triglyceride levels. Thus, LDL particles from FCHL patients are smaller and more dense with less cholesterol and phospholipid. Many of these differences appear to be independent of plasma triglyceride. Differences in LDL physical and chemical properties may contribute to the increase in premature coronary disease in FCHL.