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Diagnostic and therapeutic options of atherosclerotic injuries in dyslipidemic patients


Author: Victoria Ivanov
Degree:doctor habilitat of medicine
Speciality: 14.00.06 - Cardiology and Rheumatology
Year:2006
Scientific consultants: Mihai Popovici
doctor habilitat, professor, Public Medico-Sanitary Institution Moldavian Institute of Cardiology
Savelie Costin
doctor habilitat, associate professor (docent)
Institution:
Scientific council:

Status

The thesis was presented on the 14 September, 2006
Approved by NCAA on the 26 October, 2006

Abstract

Adobe PDF document0.87 Mb / in romanian

Keywords

dyslipidaemia, atherosclerosis, low-density lipoproteins cholesterol,goal, statins, BioR, endothelial disfunction, endothelial progenitor cells,apoptosis, metalloproteinases, oxidation

Summary

This study focused on the analysis of 299 patients with primary hypercholesterolemia having a purpose to study the lipid-lowering effects of the autochthonous remedy extract of Spirulina, BioR, in comparison with the effects of Lova- or Pravastatin. In addition, in patients with coronary heart disease (CAD), the diagnostic utility of identification of quantitative and functional indices of circulating endothelial progenitor cells (EPC) and of apoptotic endothelial cells (EC), as well as the action of the tested drugs on the key mechanisms of endothelial alterations, such as EC apoptosis, re-phenotypization of vascular smooth muscle cells and metalloproteinases expression have been tested.

The results of the present study showed that Lova- or Pravastatin, administered in standard doses (40 mg), achieve the LDL-C goal, e.g. ≤2,6 mmol/l in 48.2% of patients. Lipid-lowering action of this therapy was reached just wthin 1 month of treatment and remained sustained for the entire duration of medication. In order to strengthen the lipid-lowering effects of a 3-month standard-dose statin therapy, two therapeutic formulas have been tested, namely, doubling the doses of statin and co-administration of BioR (5mg/day) with statins in a standard dose. In both cases, an increased number of patients who reached the therapeutic goal was identified: by 26.1% - in the therapy with high doses of statins, and by 16.1% - in the combined therapy. In this context, it should be mentioned that the monotherapy with BioR has led to significant benefits that became more conspicuous in the combined therapy group.

This study has also identified that besides lipid-lowering effects, the statins, BioR, as well as the combinations of these, lead to notable antioxidative effects reflected by diminished lipidic peroxidation and modulation of antioxidative protection, during the whole period of therapy. Additionally, both the therapy with statins in the tested doses, as well as the combinations of these with the BioR, in conformity with the laboratory monitoring samples of anzimatic activity in serum, do not affect the cellular membranes and do not modify liver excretory and proteosynthetic functions.

In patients with angiographically verified CAD, a reduction of circulating EPC and an increase in the number of apoptotic EC in blood have been demonstrated. Both indices highly correlated with the number of alterated coronary arteries, as well as with the major risk factors, such as smoking and diabetes. The present study has also identified diminished adhesion properties and proliferative rates of EPC in patients with CAD as compared with controls. Taken together, estimation of the number and function of circulating EPC and the rate of apoptotic EC are valuable markers of endothelial cell dysfunction and may provide means of risk stratifying patients with likelihood of CAD progression and of developing plaque disruption and acute coronary events.

The effect of statins and that of the autochthonous BioR were also tested on EC human cultures. Both, Fluvastatin and BioR reduced significantly and to the same extent the rate of intracellular LDLoxi accumulation in the EC culture exposed to H2O2, and prevented apoptosis in 90% of EC. In addition, Fluvastatin and BioR significantly reduced the number of cultured vascular smooth muscle cells with synthetic phenotype which was induced by several proatherogenic cytokines. Moreover, Fluvastatin and BioR were found to significantly decrease expression leves of metalloproteinases - 2 and 9.

Thus, this study has developed new diagnostic and prognostic assays of the severity of atherosclerosis in patients with dyslipidemia, as well as new formulas of lipid-lowering therapy.