Increased apolipoprotein E level and reduced high-density lipoprotein mean particle size associate with low high-density lipoprotein cholesterol and features of metabolic syndrome

Abstract 

The metabolic syndrome (MetS) pandemic predisposes patients to low high-density lipoprotein cholesterol (HDL-C). To successfully treat low HDL-C, there is an urgent need for a better understanding of the changes in HDL particles in the low–HDL-C state. Especially, apolipoprotein (apo) E metabolism in HDL particles is an emerging and important issue. Therefore, we determined HDL subspecies, apo E distribution, and the impact of the MetS in subjects with low and high HDL-C. We studied 246 subjects derived from the Finnish Health 2000 Health Examination Survey. The 2 groups included 113 low–HDL-C (≤10th percentile) and 133 high–HDL-C (≥90th percentile) subjects. The low–HDL-C subjects had higher apo E concentration (39.4 ± 19.4 vs 25.6 ± 8.0 μg/mL, P < .001) and smaller HDL mean particle size (9.0 ± 0.2 vs 9.8 ± 0.3 nm, P < .001). The distribution of apo E genetic isoforms could not explain the difference. Apolipoprotein E content of very low-density lipoprotein particles was comparable between the study groups. In the low–HDL-C subjects, apo E level in large HDL particles was lower (P < .001) compared with that in the high–HDL-C subjects. The subjects with MetS had smaller HDL mean particle size and higher serum apo E concentration. Serum apo E concentration associated positively with different MetS markers (waist circumference, triglycerides, and glucose), whereas HDL mean particle size associated with those negatively. Our results highlight that, in the low–HDL-C state, there are changes in the size and composition of HDL particles associating with MetS. Apolipoprotein E, although generally considered antiatherogenic, associates with MetS and low HDL-C. Our results emphasize the need for a better understanding of apo E metabolism in HDL particles.