Alterations in the concentration of an apolipoprotein E-containing subfraction of plasma high density lipoprotein in coronary heart disease

Abstract

The concentrations of high density lipoprotein (HDL) subfractions in 100 healthy male subjects were compared with 100 newly presenting patients with myocardial infarction (MI) within 12 h of the onset of chest pain. A subfraction of HDL enriched in apolipoprotein E (apo E), separated by heparin-Sepharose affinity chromatography, was present in lower concentrations (P < 0.001) in the plasma of the coronary patients than in the control subjects. This finding was confirmed by a lower content (P < 0.02) of apo E, measured by ELISA, in the total HDL fraction isolated from the coronary patients. Gradient gel electrophoresis of the total HDL demonstrated that the coronary patients had a significantly decreased concentration of the large HDL particles, HDL2b, of mean diameter 10.57 nm and a higher concentration of the smaller-sized HDL3, especially HDL3c, of mean diameter 7.62 nm. The coronary patients had a lower concentration of HDL cholesterol than the control subjects, attributable to the HDL2 fraction, with no difference in HDL2a between the two groups. There was no difference in the concentration of plasma cholesterol or triglyceride. The distribution of apo E phenotypes was similar in the two groups. HDL2b produced the highest discriminant power between the two groups, followed by apo E-rich HDL, HDL2 and HDL3c Plasma cholesterol correlated strongly with apo E-rich HDL for control subjects but not for MI survivors. This study demonstrates that the inverse relationship between HDL cholesterol and coronary risk shown in epidemiological studies is attributable to the large, apo E-containing HDL subspecies which under some circumstances are implicated in cholesterol removal by reverse cholesterol transport. This study also suggests that the concentration of the large, apo E-containing HDL may provide a sensitive predictor for subjects at risk of developing coronary heart disease.