Improvement of endothelial damage and regeneration indexes in patients with coronary artery disease after 4 weeks of statin therapy

Abstract 

Background

In patients with coronary artery disease (CAD), higher numbers of circulating endothelial progenitor cells (EPC) favourably influence clinical outcome. Controversially, increased apoptosis of endothelial cells (EC) may reflect vascular damage. Statins have been shown to improve vascular damage and enhance EPC function and numbers. The availability of ezetimibe, a potent novel cholesterol absorption inhibitor, allows to distinguish between lipid-lowering and pleiotropic properties of statins.

Methods and findings

43 patients with CAD were assigned to receive either: de novo atorvastatin (group A; n=17), ezetimibe as add-on to chronic statin therapy (group B; n=14), or dose escalation of atorvastatin (groupC; n=12) over 4 weeks. Circulating apoptotic EC (CD45⁻CD146⁺vWF⁺Annexin-V⁺) and EPC (CD34⁺KDR⁺) were quantified using flow cytometry.

LDL cholesterol levels were significantly reduced in all treatment arms. Both statin groups, group A and group C, showed significantly reduced circulating apoptotic EC by 50% each (p<0.01). On the other hand, there was a significant doubling in the numbers of circulating EPC in group A and group C (p<0.005, each). Consequently, the endothelial damage-index calculated from numbers of circulating apoptotic mature EC related to EPC numbers, was improved in group A by 79% (p<0.01) and in group C by 70% (p<0.05). In contrast, sole LDL reduction by ezetimibe exerted no effect on any of the different circulating endothelial cell types.

Conclusion

Thus, the improvement in numbers of EPC and reduction of mature apoptotic EC after 4 weeks of statin therapy, document a novel pleiotropic effect of statin therapy in patients with CAD.

Keywords: Pleiotropic, Circulating progenitor cells, Endothelial apoptosis, Lipid-lowering, Coronary artery disease