**1. Introduction**

In the last few decades, lipoprotein research has focused on the phenomenon of atherogenic and non-atherogenic lipoproteins, specifically, atherogenic and non-atherogenic lipoprotein profiles phenotype A and phenotype B [7, 18, 60] after it was reported that more than 75% of patients with an acute coronary syndrome or myocardial infarction had normal plasma values of cholesterol, Low Density Lipoprotein cholesterol (LDL cholesterol) and High Density Lipoprotein cholesterol (HDL cholesterol) [15 - 17].

Thus, it was necessary to look for other risks factors in plasma, the presence of which in relevant quantities could cause damage to endothelial cells and resultant endothelial dysfunction [59]. This called into question whether an increased total cholesterol level, or increased LDLcholesterol, as a criterion for the degree of atherogenic risk, provided a universal explanation for the origin of atherogenesis. A reasonable explanation was found in atherogenic lipoprotein subpopulations, the presence of which in plasma, even in very low concentrations, could impair the integrity of the vessel wall and lead to endothelial dysfunction with its fatal consequences [Table 1]: formation of atherothrombotic plaques, acute myocardial infarction, ischemic stroke, or sudden death [39, 59, 64].

The predominance of atherogenic lipoproteins in plasma is characteristic for the atherogenic lipoprotein spectrum, phenotype B. When present in plasma in high concentrations, these lipoproteins contribute to ischemic vascular impairment [6, 8, 57, 60]. The process of degen‐ erative changes in vessels results in the formation of atheromatous vascular plaques. These later play an important role in the formation of stable or unstable angina (pectoris), and critical ischemia of peripheral and/or cerebral arteries as well [39,56]. When atherogenic lipoproteins in plasma are present in small quantities, we obtain a picture of a non-atherogenic lipoprotein profile, phenotype A.

Various methods have been developed (gradient gel electrophoresis, ultracentrifugation, magnetic resonance spectroscopy, endothelial models for testing lipoprotein cytotoxicity) to identify atherogenic lipoproteins [2, 26, 45, 48], but because of technical and financial issues, long-term analyses and high operating costs, the previously mentioned methods were used primarily in basic research. Simple analytical procedures for routine distribution were lacking and the possibility of their implementation in every day laboratory practice remained limited.

An electrophoretic method by which to separate lipoproteins on polyacrylamide gel (PAG) with the use of Lipoprint LDL System [29, 41] has become a milestone in routine laboratory analysis and in diagnosing metabolism disorders of lipoproteins. It enables the analysis of 12 lipoprotein subfractions: VLDL, IDL 1-3, LDL 1-7, and HDL.

	- **a.** Atherogenic lipoproteins (VLDL, IDL1, IDL2, and LDL3-7, so-called small dense LDL)
	- **b.** Non-atherogenic lipoprotein entities (IDL3, HDL)
	- **c.** Lipoproteins with uncertain atherogenicity (LDL1, LDL2)

of cardiovascular disease, would be established as a new term used in the

**Keywords:** atherogenic lipoproteins, atherogenic lipoprotein profile, small dense

In the last few decades, lipoprotein research has focused on the phenomenon of atherogenic and non-atherogenic lipoproteins, specifically, atherogenic and non-atherogenic lipoprotein profiles phenotype A and phenotype B [7, 18, 60] after it was reported that more than 75% of patients with an acute coronary syndrome or myocardial infarction had normal plasma values of cholesterol, Low Density Lipoprotein cholesterol (LDL cholesterol) and High Density

Thus, it was necessary to look for other risks factors in plasma, the presence of which in relevant quantities could cause damage to endothelial cells and resultant endothelial dysfunction [59]. This called into question whether an increased total cholesterol level, or increased LDLcholesterol, as a criterion for the degree of atherogenic risk, provided a universal explanation for the origin of atherogenesis. A reasonable explanation was found in atherogenic lipoprotein subpopulations, the presence of which in plasma, even in very low concentrations, could impair the integrity of the vessel wall and lead to endothelial dysfunction with its fatal consequences [Table 1]: formation of atherothrombotic plaques, acute myocardial infarction,

The predominance of atherogenic lipoproteins in plasma is characteristic for the atherogenic lipoprotein spectrum, phenotype B. When present in plasma in high concentrations, these lipoproteins contribute to ischemic vascular impairment [6, 8, 57, 60]. The process of degen‐ erative changes in vessels results in the formation of atheromatous vascular plaques. These later play an important role in the formation of stable or unstable angina (pectoris), and critical ischemia of peripheral and/or cerebral arteries as well [39,56]. When atherogenic lipoproteins in plasma are present in small quantities, we obtain a picture of a non-atherogenic lipoprotein

Various methods have been developed (gradient gel electrophoresis, ultracentrifugation, magnetic resonance spectroscopy, endothelial models for testing lipoprotein cytotoxicity) to identify atherogenic lipoproteins [2, 26, 45, 48], but because of technical and financial issues, long-term analyses and high operating costs, the previously mentioned methods were used primarily in basic research. Simple analytical procedures for routine distribution were lacking and the possibility of their implementation in every day laboratory practice remained limited.

An electrophoretic method by which to separate lipoproteins on polyacrylamide gel (PAG) with the use of Lipoprint LDL System [29, 41] has become a milestone in routine laboratory

diagnostics of dyslipoproteinemias

Lipoprotein cholesterol (HDL cholesterol) [15 - 17].

ischemic stroke, or sudden death [39, 59, 64].

profile, phenotype A.

LDL, cardiovascular diseases

**1. Introduction**

88 Lipoproteins - From Bench to Bedside

**a.** The atherogenic vs. non-atherogenic lipoprotein spectrum, phenotype B vs. pheno‐ type A

Atherogenic lipoprotein spectrums are characterized according to the predominance of atherogenic lipoproteins: very low density (VLDL); intermediate density IDL1 and IDL2; and by the presence of small dense-low density lipoproteins (sd-LDL). The last represented small dense LDL are highly atherogenic LDL subfractions that form fractions LDL3-7. As the name implies, they are smaller than the other types of LDL with a diameter < 26.5 nm (265 Angströms) and they float within the density range of 1.048–1.065 g/ml, that is, higher than LDL1 and LDL2. On the separating polyacrylamide gel (PAG) sd-LDL are detected as subtle bands on the anodic end of the gel, right behind HDL, that migrate to the head of separated lipoproteins.


**Table 1.** Atherogenicity of small dense LDL

In our studies were analyzed serum lipoprotein spectrums in patients with newly recognized a) arterial hypertension, b) coronary heart disease, c) lower extremity arterial disease, and d) in patients who survived a stroke. As mentioned earlier, an analytical method for a quantitative evaluation of lipoprotein fractions was used, and the incidence of an atherogenic lipoprotein spectrum phenotype B (vs. phenotype A) in these four representatives of cardiovascular diseases was identified. At the same time, a lipoprotein spectrum of a control group of healthy individuals was examined and tested for the incidence of phenotype B.
