Hyperlipoproteinemia as a risk factor for ischemic heart disease.

We analyzed serum lipoproteins and apolipoprotein E (apo E) from 199 patients in CCU, having ischemic heart disease, and from 211 healthy subjects. It was suggested that serum lipoprotein abnormalities, especially elevated low density lipoprotein (LDL) levels, are closely related to atherogenesis in relatively young patients and subjects with severe coronary lesions. The frequency of apo E-4 was higher and that of E-2 was lower in the CCU group than in the control group. Apo E mutants, E-7 (Glu244----Lys, Glu245----Lys) and E-5 (Glu3 (Glu3----Lys), were also frequent in the CCU group. Apo E isoproteins have higher pI in the order E-2, E-3, E-4, and we observed that LDL-cholesterol levels increased in the same order. The apo E mutants, E-5 and E-7, are also more basic than E-4. These findings suggest that basic apo Es were associated with the development of atherosclerosis. The prevalence of familial hypercholesterolemia (FH) in the CCU group was more than 10 times higher than the reported frequency of FH heterozygotes in normal population. The persistence of marked hypercholesterolemia from infancy probably makes FH patients susceptible to atherosclerosis. Based on the analysis of LDL-receptor protein synthesis, various types of mutations were observed even in phenotypically homozygous FH patients. FH homozygotes were divided into 2 groups, a receptor-negative group and a receptor-defective group. We found a great difference in the frequency of coronary heart disease depending on whether even a small number of receptors were present or not.