Abstract 1639: Statin Therapy Restores Reduced Endothelial Progenitor Cell Levels in the Metabolic Syndrome
Rationale Endothelial Progenitor Cells (EPC) contribute to endothelial regeneration, protecting against atherosclerotic disease. EPC have previously been shown to be reduced in diabetic patients. The metabolic syndrome is associated with high cardiovascular risk and an increased risk of developing type 2 diabetes. We investigated EPC numbers in the metabolic syndrome and the effect of lipid-lowering therapy. In addition, we measured serum VEGF, which is a mobilizing factor for EPC, but may also stimulate intraplaque neovascularization, associated with an unstable plaque phenotype.
Methods EPC were quantified as CD34+KDR+ cells by flow cytometry in 20 male subjects with the metabolic syndrome (ATP III criteria), and 13 healthy controls. Subjects with the MS were subsequently enrolled in a randomized double-blind cross-over study comparing low dose (10mg) simvastatin / 10mg cholesterol-uptake inhibitor ezetimibe (LD-STAT/EZET) with high-dose (80mg) simvastatin (HD-STAT). Serum VEGF was measured using ELISA.
Results The metabolic syndrome was associated with lower levels of circulating EPC (331±44 vs 594±46 /ml, p<0.01). LD-STAT/EZET increased EPC numbers to 626±98 /ml (p<0.01); HD-STAT to 524±85 /ml (p<0.05). After the two treatments, EPC levels were not statistically different from each other and control values, LDL-reduction was equal and HDL levels had remained unchanged. At baseline, serum VEGF levels were slightly lower, but not statistically different from controls (55.1±11.9 vs 66.6±16.7 pg/ml; p=0.578), and correlated modestly with EPC numbers (r=0.433; p=0.019). VEGF levels decreased to 38.7±8.4 pg/ml after LD-STAT/EZET treatment and to 36.3±7.8 pg/ml after HD-STAT (both p<0.01 vs baseline).
Conclusions EPC levels are reduced in the metabolic syndrome, which may contribute to the increased risk of cardiovascular disease. Lipid-lowering therapy with either LD-STAT/EZET or HD-STAT normalized EPC levels while lowering VEGF. We did not observe a statin dose-reponse relationship when LDL was reduced equally by adding ezetimibe. This is consistent with an effect of LDL-reduction rather than lipid-lowering-independent pleiotropic statin effects.