Effect of different doses of atorvastatin therapy on endothelial progenitor cells and angiogenic factors in patients with ischemic heart disease

Abstract

Aim. Research and application of endothelial progenitor cells (EPC) is now considered as a promising trend in cardiology and angiology, since it is known that they are actively involved in the vascular endothelium reparation and angiogenesis. Reduction of EPC levels was demonstrated as an independent predictor of cardiovascular morbidity and mortality. The purpose of current research was to assess changes in EPC and angiogenic factors levels during atorvastatin therapy in ischemic heart disease (IHD) patients, and to compare them with lipid profile dynamics.
Materials and methods. The main group included 58 patients with IHD: 26 patients received 10 mg of atorvastatin and 32 patients received 40 mg of atorvastatin daily. Number of EPC (CD34+/CD133+/CD309+ phenotype) was measured by flow cytometry two times – before treatment and 3 months after. Vascular endothelial growth factor (VEGF), C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), endostatin levels and lipid profile were also measured twice. The control group consisted of 10 healthy volunteers with the same analyzes performed once.
Results. The results showed that EPC levels were 4 times lower, VEGF levels were 52% higher and endostatin levels were 13% lower in IHD patients compared to healthy volunteers (p<0.05). Atorvastatin therapy in IHD patients within three months of treatment caused a significant (on average 72%) increase of EPC levels (p<0.05). EPC gain did not depend on statin dose, but it was higher when initial EPC values were low (p=0.01). The therapy showed reliable levels reduction of VEGF – 11% (p<0.01), CRP – 26% (p<0.01), total cholesterol (TC) – 30% (p<0.01), low-density lipoprotein-cholesterol (LDL-C) – 35% (p<0.01), triglycerides – 18% (p<0.01), while endostatin, MCP-1 and high-density lipoprotein-cholesterol levels did not change. Correlations between EPC, TC and LDL-C changes during therapy were revealed: higher EPC levels gain was associated with higher TC
(p=0.37, r<0.01) and LDL-C (p=0.41, r<0.01) levels decrease.
Conclusion. We found a significant increase of EPC levels in IHD patients treated with atorvastatin for 3 month without any significant difference depending on dosage. The EPC increase was higher in patients with smaller initial EPC levels and when higher TC and LDL-C decrease was achieved.