Abstract 4365891: PCSK9 inhibitors increase CD34+ but not other endothelial progenitor cells in patients with stable coronary heart disease and increased Lp(a) values

Abstract

Background: Endothelial dysfunction is an independent predictor of cardiovascular events in patients with established atherosclerosis, while the concentration of endothelial progenitor cells (EPCs) reflects active endothelial function in heart failure patients. Although protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (PCSK9i) effectively lower lipid concentration and reduce cardiovascular events, their impact on endothelial function remains poorly understood. Purpose: We aimed to examine the effect of PCSK9i on the concentration of EPCs in peripheral blood in patients with stable coronary disease and significantly elevated lipoprotein (a) (Lp(a)) levels. Methods: In randomized, double-blind, placebo-controlled trial we included 100 statin-treated patients in stable phase after myocardial infarction elevated Lp(a) values. The patients received PCSK9i or placebo every two weeks for 6 months. Biochemical, genetic and cell analysis at baseline and after 6 months were performed. Results: Treatment with PCSK9i significantly increased the concentration of mature EPCs (CD34+) compared to placebo ( p =0.023), with no effect on early EPC subtypes (CD34 CD309+, CD34 CD133+, CD133 CD309+ and CD133+) ( p =0.611, p =0.451, p =0.739 and p =0.161, respectively). The increase in the concentration of mature EPCs (CD34+) correlated inversely with the changes in PCSK9 concentration (ρ=-0.262, p =0.045). No associations were detected between changes in PCSK9 concentration and changes in the concentration of EPCs, which predominantly express CD309 or vascular endothelial growth factor (VEGF), or between changes in the concentration of any EPCs and lipoprotein concentration variations at baseline or at the end of the study. Conclusion: In patients with stable coronary disease, treatment with PCSK9i significantly increases circulating CD34+ EPCs concentrations, but not other EPCs.