Effects of pitavastatin versus atorvastatin on the peripheral endothelial progenitor cells and vascular endothelial growth factor in high-risk patients: a pilot prospective, double-blind, randomized study

Abstract

BackgroundCirculating endothelial progenitor cells (EPCs) reflect endothelial repair capacity and may be a significant marker for the clinical outcomes of cardiovascular disease. While some high-dose statin treatments may improve endothelial function, it is not known whether different statins may have similar effects on EPCs.This study aimed to investigate the potential class effects of different statin treatment including pitavastatin and atorvastatin on circulating EPCs in clinical setting.MethodsA pilot prospective, double-blind, randomized study was conducted to evaluate the ordinary dose of pitavastatin (2 mg daily) or atorvastatin (10 mg daily) treatment for 12 weeks on circulating EPCs in patients with cardiovascular risk such as hypercholesterolemia and type 2 diabetes mellitus (T2DM). Additional in vitro study was conducted to clarify the direct effects of both statins on EPCs from the patients.ResultsA total of 26 patients (19 with T2DM) completed the study. While the lipid-lowering effects were similar in both treatments, the counts of circulating CD34+KDR+EPCs were significantly increased (from 0.021 ± 0.015 to 0.054 ± 0.044% of gated mononuclear cells, P < 0.05) only by pitavastatin treatment. Besides, plasma asymmetric dimethylarginine level was reduced (from 0.68 ± 0.10 to 0.53 ± 0.12 μmol/L, P < 0.05) by atorvastatin, and plasma vascular endothelial growth factor (VEGF) level was increased (from 74.33 ± 32.26 to 98.65 ± 46.64 pg/mL, P < 0.05) by pitavastatin. In the in vitro study, while both statins increased endothelial nitric oxide synthase (eNOS) expression, only pitavastatin increased the phosphorylation of eNOS in EPCs. Pitavastatin but not atorvastatin ameliorated the adhesion ability of early EPCs and the migration and tube formation capacities of late EPCs.ConclusionsWhile both statins similarly reduced plasma lipids, only pitavastatin increased plasma VEGF level and circulating EPCs in high-risk patients, which is probably related to the differential pleiotropic effects of different statins.Trial registrationThis trial is registered at ClinicalTrials.gov, NCT01386853.

Effect of statins on fasting glucose in non-diabetic individuals: nationwide population-based health examination in Korea

“…In patients who were prescribed statins, discontinuation and poor adherence were common in clinical practice, which limits assessing the diabetogenic effect of statins [ 72 ]. The effect of statins on glucose metabolism are complex and interconnected by multiple pathways; individual statins may have a heterogenous impact on the multiple processes [ 11 ]. To obtain further knowledge of individual statins on glucose metabolism, there is need for further extensive studies.…”

“…However, there are still insufficient data for the longitudinal changes in fasting glucose with the use of statins. In addition, there are multiple types of statin, each with a different chemical structure and pharmacokinetic profile [ 11 , 12 ]. The individual statin types may have different effects on glucose metabolism [ 13 , 14 ].…”

Vildagliptin, but not glibenclamide, increases circulating endothelial progenitor cell number: a 12-month randomized controlled trial in patients with type 2 diabetes

“…Based on the previous considerations, anti-diabetic drugs effective in enhancing EPC number may convey an added value, beyond glucose control, to reduce CV risk and to prevent CV disease in patients with type 2 diabetes. A number of anti-diabetic drugs, namely pioglitazone [ 6 ] and insulin [ 7 ], and statins [ 8 ] have been shown to improve EPC biology in ex vivo studies. Recent evidence points to a potential role of dipeptidyl peptidase-4 inhibitors (DPP-4i) in increasing circulating EPC number.…”

Endothelial progenitor cells: Exploring the pleiotropic effects of statins

“…A double blinded randomised pilot study found greater number of circulating CD34 + VEGFR-2 + EPCs after 12 wk of therapy with pravastatin 20 mg when compared to atorvastatin 10 mg[97]. Similarly, in ACS patients’ intensive statin therapy with atorvastatin 80 mg after primary or rescue PCI was associated with greater EPC count at 4-mo follow up as compared to 20 mg atorvastatin.…”