**6. Discussion**

In the last few decades, lipoprotein research has focused on the phenomenon of atherogen‐ ic and non-atherogenic lipoproteins, and on the phenotype A vs. phenotype B characteriza‐ tion, as a consequence of the published evidence that the majority of the patients with an acute coronary syndrome or patients who survive a myocardial infarction had normal plasma values of cholesterol, LDL-cholesterol, and HDL-cholesterol [15-17]. A reasonable explanation for this fact was to posit a new, active atherogenic substance in plasma, an atherogenic lipoprotein subfraction, 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. Several clinical studies reported observations that in the plasma of patients with coronary heart disease there are subfractions of lipopro‐ teins, which could play a crucial role in atherodegenerative processes and form the atherothrombotic plaques [5, 33, 34, 37, 39,49]. The Quebec Cardiovascular Study, a prospective study of 2,103 men [33,34] concluded that " a significant proportion of the risk for heart disease associated with small, dense LDL particles may be independent of variations in plasma lipid concentrations. Small LDL particles and elevated apo B levels were found to be the most predictive indications for ischemic heart disease ".

For this reason, patients who were suffering from cardiovascular diseases were examined in order to quantify the atherogenic lipoproteins in serum and to determine the incidence of an atherogenic lipoprotein profile in patients who had a diagnosis of cardiovascular diseases.

The clinical studies included 366 patients with a diagnosis of arterial hypertension (n=107), coronary heart disease (n= 104), lower extremity arterial disease (n= 100), and ischemic stroke (n= 55). Patients were tested with the diagnostic method Lipoprint LDL System, which quantifies atherogenic lipoproteins and identifies an atherogenic and a non-atherogenic lipoprotein profile [29]. This was a fundamental methodological contribution of this new analytical and diagnostic method.

Our study confirmed that more than 80% of tested patents with cardiovascular diseases have an atherogenic lipoprotein profile, with a high level of strongly atherogenic small dense LDL. The atherogenic lipoprotein profile was found to be the overwhelming lipoprotein profile in tested cardiovascular diseases. Such a profile was found in arterial hypertension in 78.5%, in coronary heart disease in 81.7%, in lower extremity arterial disease in 80%, and in patients who survived an ischemic stroke in 85%. The average atherogenic lipoprotein profile in all these tested diagnoses in the study was found to be of 81.3%.

This study also highlights the observation that, in the atherogenic lipoprotein profiles, in all diagnoses, compared to the non-atherogenic profiles, the concentration of total cholesterol is lower (n.s.) and the concentration of triglycerides is higher (even statistically significant; in AH, CHD, LEAD, as well as in the control group, up to p<0.002). Hypertriglyceridemia accompanied the hypercholesterolemia in all tested diagnoses, that is, in AH, CHD, LEAD, and stroke). The concentration of triglycerides, compared to the control group, was signifi‐ cantly increased (p<0.0001) and proportionally even higher than cholesterol. From this result, it can be assumed that triglycerides/hypertriglyceridemia can play a much more important role than was generally accepted, as until now the most important role in the pathogenesis of vascular degenerative atherosclerotic injury was attributed to cholesterol and hypercholester‐ olemia. Our present results are in agreement with other authors, who have called attention to hypertriglyceridemia as a risk factor for cardiovascular diseases [8,12,19, 36,58], as triglyceriderich lipoproteins can generate small dense LDL in high quantities [46].

The strong atherogenic lipoproteins – small dense LDL – have been found in the lipoprotein profile of all diagnostic groups [25,52,55,56]. Their presence is decisive for an atherogenic profile declaration. This is a rule that is valid not only for a hyperlipidemia, but also for a normolipidemia.

In the case of normolipidemia (see the atherogenic lipoprotein profile in the control group), a new phenomenon could be established – atherogenic normolipidemia [44] – as a risk factor for the development of cardiovascular disease. A special form of normolipidemia can also be atherogenic. This is new knowledge, and this new knowledge could help in the prevention and treatment of cardiovascular disease.
