Impact of prior chronic statin therapy and high-intensity statin therapy at discharge on circulating endothelial progenitor cell levels in patients with acute myocardial infarction: a prospective observational study
Endothelial progenitor stem cells (EPCs) are mobilized to the peripheral circulation in response to myocardial ischemia, playing a crucial role in vascular repair. Statins have been shown to stimulate EPCs. However, neither the impact of previous statin therapy on EPC response of acute myocardial infarction (AMI) patients nor the effect of post-AMI high-intensity statin therapy on the evolution of circulating EPC levels has yet been addressed. Therefore, we aimed to compare circulating EPC levels between patients receiving long-term statin therapy before the AMI and statin-naive patients and to assess the impact of high-intensity statin therapy at discharge on the evolution of circulating EPCs post-AMI. This is a prospective observational study of 100 AMI patients. Circulating EPCs (CD45dimCD34 + KDR + cells) and their subpopulation coexpressing the homing marker CXCR4 were quantified by the high-performance flow cytometer FACSCanto II in whole blood, in two different moments: within the first 24 h of admission and 3 months post-AMI. Patients were followed up clinically for 2 years. Patients previously treated with statins had significantly higher levels of EPCs coexpressing CXCR4 (1.9 ± 1.4 vs. 1.3 ± 1.0 cells/1,000,000 events, p = 0.031) than statin-naive patients. In addition, the subanalysis of diabetics (N = 38) also revealed that patients previously on statins had significantly greater numbers of both CD45dimCD34 + KDR + CXCR4+ cells (p = 0.024) and CD45dimCD34 + KDR + CD133+ cells (p = 0.022) than statin-naive patients. Regarding the evolution of EPC levels after the AMI, patients not on a high-intensity statin therapy at discharge had a significant reduction of CD45dimCD34 + KDR + and CD45dimCD34 + KDR + CXCR4+ cells from baseline to 3 months follow-up (p = 0.031 and p = 0.005, respectively). However, patients discharged on a high-intensity statin therapy maintained circulating levels of all EPC populations, presenting at 3 months of follow-up significantly higher EPC levels than patients not on an intensive statin therapy. Moreover, the high-intensity statin treatment group had significantly better clinical outcomes during the 2-year follow-up period than patients not discharged on a high-intensity statin therapy. Chronic statin therapy prior to an AMI strongly enhances the response of EPCs to myocardial ischemia, even in diabetic patients. Furthermore, high-intensity statin therapy after an AMI prevents the expected decrease of circulating EPC levels during follow-up. These results reinforce the importance of an early and intensive statin therapy in AMI patients.