POLYDISPERSE LOW-DENSITY LIPOPROTEINS IN HYPERALPHALIPOPROTEINEMIC CHRONIC ALCOHOL DRINKERS IN ASSOCIATION WITH MARKED REDUCTION OF CHOLESTERYL ESTER TRANSFER PROTEIN-ACTIVITY

Long-term heavy alcohol intake is well known to increase serum high-density lipoprotein (HDL) cholesterol concentrations. Epidemiologic studies have shown that the protective effect of alcohol intake against coronary heart disease (CHD) is observed in moderate alcohol drinkers, but not in heavy ones. To clarify whether heavy alcohol intake may cause abnormalities in lipoprotein metabolism, we analyzed the plasma lipoproteins in eight male chronic heavy alcohol drinkers with marked hyperalphalipoproteinemia. Although their serum HDL cholesterol levels were remarkably high, ranging from 2.67 to 3.58 mmol/L, three patients had CHD and corneal arcus was present in seven patients. Cholesteryl ester transfer protein (CETP) activity was reduced in all subjects (7.3% ± 4.2%/10 μL/18 h in alcohol drinkers v 20.5% ± 2.4%/10 μL/18 h in control; mean ± SD, P < .001). The CETP mass levels were also markedly reduced in these subjects. The analysis of low-density lipoprotein (LDL) on nondenaturing polyacrylamide gradient gel electrophoresis revealed that four subjects with severely low CETP activity (<25% of control) had polydisperse LDLs, similar to those observed in genetic CETP deficiency. The other four subjects with approximately half the normal CETP activity had homogeneous but smaller-sized LDLs, as compared with control subjects. Particle size of HDL was larger than that of normal control HDL in all subjects. After cessation of alcohol intake, plasma HDL cholesterol levels were decreased and LDLs became more homogeneous and normal in size, in parallel with elevation of CETP activity. The current study demonstrates for the first time that long-term heavy alcohol intake may reduce CETP activity, leading to marked hyperalphalipoproteinemia and changes in LDL subclass patterns. Our results strongly suggest that long-term heavy alcohol intake causes a marked hyperalphalipoproteinemia with some characteristics similar to those of patients with a genetic CETP deficiency. © 1992.