Dose-dependent impact of statin therapy intensity on circulating progenitor cells in patients undergoing percutaneous coronary intervention for the treatment of acute versus chronic coronary syndrome

Abstract

Background: By low-density lipoprotein (LDL) reduction, statins play an important role in cardiovascular risk modification. Incompletely understood pleiotropic statin effects include vasoprotection that might originate from mobilisation and differentiation of vascular progenitor cells. Data on the potentially differential impact of statin treatment intensity on circulating progenitor cells in patients undergoing percutaneous coronary intervention (PCI) are scarce. This study examines the potential association of different permanent statin treatment regimens on circulating progenitor cells in patients with coronary syndrome.

Methods and results: In a monocentric prospective all-comers study, 105 consecutive cases scheduled for coronary angiography due to either (A) non-invasive proof of ischemia and chronic coronary syndrome (CCS) or (B) troponin-positive acute coronary syndrome (ACS) were included. According to the 2018 American College of Cardiology Guidelines on Blood Cholesterol, patients were clustered depending on their respective permanent statin treatment regimen in either a high- to moderate-intensity statin treatment (HIST) or a low-intensity statin treatment (LIST) group. Baseline characteristics including LDL levels were comparable. From blood drawn at the time of PCI, peripheral blood mononuclear cells were isolated, cultivated and counted and, by density gradient centrifugation, levels of circulating progenitor cells were determined using fluorescence-activated cell sorting (FACS) analysis. In ACS patients both absolute and relative numbers of circulating early-outgrowth endothelial progenitor cells (EPCs) concurrently were significantly lower in the HIST group as compared to the LIST group. This effect was more pronounced in ACS patients than in CCS patients. Both in ACS and CCS patients, HIST caused a significant reduction of the number of circulating SMPCs.

Conclusions: In patients undergoing PCI, a dose intensity-dependent and LDL level-independent pro-differentiating vasoprotective pleiotropic capacity of statins for EPC and SMPC is demonstrated.

Fig 1. Similar whole blood PBMC counts.

PBMC counts were similar in all ACS versus CCS patients (left); also, PBMC counts were similar in ACS versus CCS patients stratified by permanent statin treatment intensity (HIST: high- to moderate-intensity statin treatment; LIST: low-intensity statin treatment) (right).

Fig 2. Reduced relative and absolute EPC counts under HIST.

EPC counts per cm² (relative numbers) (left) and per mL whole blood (absolute numbers) (right) in each group depending on the clinical status and statin potency.

Fig 3. Reduced percentage of CD34+/KDR+ cells under HIST.

FACS analysis with double fluorescence with PE-labelled KDR and FITC-labelled CD34 antibodies. Double positive cells are indicated in the upper right quadrant (left).

Fig 4. Pronounced EPC adhesion capacity in ACS patients under LIST.

EPC adhesion capacity/20000 cells (fluorescence intensity at 485 and 535nm) (left) and normalised EPC adhesion capacity/mL whole blood (right) reveal markedly higher adhesion capacity in LIST ACS patients.

Fig 5. Suppressed SMPC counts in patients under HIST.

Relative (left) and absolute (right) SMPC counts revealed significantly lower SMPC levels in patients treated with HIST.

Fig 6. Depleted percentages of CD34+/PDGFR+ cells under HIST.

Statin intensity impact on CD34⁺/PDGFR⁺ cells detected by FACS demonstrated lower percentages in patients under HIST (right). Double fluorescence with PE-labelled PDGFR and FITC-labelled CD34 antibodies; double positive cells are indicated in the upper right quadrant (left).