SUSCEPTIBILITY OF SMALL, DENSE, LOW-DENSITY LIPOPROTEINS TO OXIDATIVE MODIFICATION IN SUBJECTS WITH THE ATHEROGENIC LIPOPROTEIN PHENOTYPE, PATTERN-B

PURPOSE: To test whether low-density lipoprotein (LDL) from subjects with an atherogenic lipoprotein phenotype characterized by small, dense LDL (pattern B) demonstrates greater susceptibility to oxidative modification than LDL from subjects exhibiting primarily larger, more buoyant LDL particles (pattern A). PATIENTS AND METHODS: Measures of susceptibility to oxidative modification were compared in six density subfractions of LDL isolated from pattern A and pattern B subjects. Seven male and three female pattern A subjects and five male and two female pattern B subjects, classified on the basis of peak LDL particle size, were studied. Plasma lipid and lipoprotein levels, apolipoprotein B, mean LDL particle diameter, lag phase, and rate of oxidation after initiation of oxidation by copper sulfate were measured. RESULTS: The lag time, a measure of resistance to oxidative modification, was inversely related (p < 0.001) to LDL density in both groups of subjects, without an independent effect of phenotype. The fraction that had the major LDL peak had a shorter lag time (p < 0.05) in pattern B than in pattern A. Pattern B subjects also demonstrated an increased rate of oxidation (p < 0.005) in fraction 1, which includes remnants of triglyceride-rich lipoproteins. CONCLUSIONS: The increased atherogenic risk associated with the pattern B phenotype may result in part from increased concentrations of lipoprotein subpopulations that are relatively susceptible to oxidative modification.