PCSK9 inhibitors increase CD34+ but not other endothelial progenitor cells in patients with chronic coronary disease and increased Lp(a) values

Background: Endothelial dysfunction is an independent predictor of cardiovascular events in patients with established atherosclerosis, while the circulating levels of endothelial progenitor cells (EPCs) reflects active endothelial function in heart failure patients. Although protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (PCSK9i) 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 levels of EPCs in peripheral blood of the patients with chronic coronary disease and significantly elevated lipoprotein (a) (Lp(a)) concentrations. Methods: In this randomized, double-blind, placebo-controlled trial we included 100 statin-treated patients at least 6 months post-myocardial infarction with elevated Lp(a) values. The patients received PCSK9i or placebo every two weeks for 6 months. Biochemical and flow cytometric analysis of peripheral blood mononuclear cells (PBMCs) were performed at baseline and after 6 months. Results: Treatment with PCSK9i increased the levels of mature EPCs (CD34+) compared to placebo (p=0.003). In contrast, no significant effects were observed 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 mature EPCs (CD34+) levels did not correlate with changes in PCSK9 concentration. No associations were detected between changes in PCSK9 concentration and changes in levels of EPC subtypes predominantly expressing CD309, nor between changes in levels of any EPCs and lipoprotein concentration variations at baseline or at the end of the study. Conclusion: In patients with chronic coronary disease, treatment with PCSK9i increases circulating levels of mature CD34+ EPCs, without affecting other EPC subtypes.