Lipid and lipoprotein factors associated with variation in Lp(a) density

To determine the facets of lipoprotein metabolism associated with variation in lipoprotein(a) [Lp(a)] density, we examined by density gradient ultracentrifugation 246 plasma samples exhibiting single apo(a) isoform band phenotypes. Estimated molecular weights of apo(a) isoforms ranged from 488 to 874 kD, and they accounted for approximately 80% of variation in Lp(a) density. After adjustment for variation in the protein composition, we found in univariate analyses that variation in residual Lp(a) density was associated with 10 different measures of lipoprotein size and concentration. Residual Lp(a) density was positively correlated with measures of apoB-containing lipoproteins and negatively correlated with measures of HDL. HDL size phenotypes were based on nondenaturing gradient gel electrophoresis fractions after staining for esterified cholesterol with Sudan black B and for apoA-I with immunoblotting methods. The HDL size variables in each case had higher correlations with residual Lp(a) density than did the HDL concentration measures. Stepwise regression analyses selected two lipoprotein variables (LDL density and HDL size) that were significantly correlated with residual Lp(a) density, and they accounted for approximately 35% of variation in density. The densities of LDL and Lp(a) were highly correlated, and additional stepwise regression analyses showed that they were similarly correlated with triglyceride concentration and with a measure of HDL size. Thus, with respect to residual Lp(a) density, the results show that small, dense Lp(a) particles are found under conditions leading also to small, dense LDL particles and to small, dense HDLs.