Hyper-betalipoproteinemia LDL 1,2: a newly identified nonatherogenic hypercholesterolemia in a group of hypercholesterolemic subjects.

OBJECTIVE: The identification of a non-atherogenic and an atherogenic lipoprotein profile, non-athero phenotype A vs. athero phenotype B, in a group of hypercholesterolemic subjects reveals newly discovered non-atherogenic hypercholesterolemia. Individuals with this type of hypercholesterolemia, or hyper-betalipoproteinemia LDL1,2, are probably not at increased risk to develop a premature atherothrombosis or a sudden cardiovascular event. Examined individuals with hyper-betalipoproteinemia LDL1,2 were divided into two subgroups: individuals under 40 years of age, and older individuals between 46 and 71 years of age. Subjects in the under 40 years of age group did not have any apparent clinical or laboratory-proven impairment of the cardiovascular system. The older subjects with hyper-betalipoproteinemia and a non-atherogenic lipoprotein profile had only mild signs of clinically irrelevant aortic valve sclerosis.

METHODS: A quantitative analysis of the lipoprotein spectrum in plasma in a group of hypercholesterolemic subjects was performed. An innovative electrophoresis method on polyacrylamide gel (PAG) was used for the analysis of plasma lipoproteins and for the identification of atherogenic vs. non-atherogenic lipoproteins in plasma. With regard to lipids, total cholesterol and triglycerides in plasma were analyzed with an enzymatic CHOD PAP method (Roche Diagnostics, FRG). A new parameter, the score for anti-atherogenic Risk (SAAR), was calculated as the ratio between non-atherogenic to atherogenic plasma lipoproteins in the examined subjects.

RESULTS: There was a high concentration of LDL1, and LDL2 subfractions (p<0.0001), and an extremely low concentration of LDL3-7 (p<0.0001) in the non-atherogenic lipoprotein profile of hyper-betalipoproteinemia LDL1,2 compared to the control group. Higher concentrations (p<0.0001) of lipids and lipoproteins in the non-atherogenic hypercholesterolemia, compared to the control group, were also found. The hyper-betalipoproteinemia LDL1,2 was also characterized by high SAAR values. There was found a higher concentration of HDL large and HDL intermediate subfractions in hypercholesterolemic subjects.

CONCLUSIONS: The advantages of this new diagnostic method include: (i) identification of the existence of a non-atherogenic hyper-betalipoproteinemia LDL1,2 in examined hypercholesterolemic subjects with untreated hypercholesterolemia (ii) introduction of a new risk measure, the score for anti-atherogenic risk (SAAR), for the estimation of atherogenic/anti-atherogenic risk. (iii) the presence of small dense LDL in plasma is decisive for the declaration of an atherogenic lipoprotein profile. It is valid for hyperlipidemia and for normolipidemia as well.