INTRODUCTION Statins inhibit hepatic 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase with conse- quent suppression of cholesterol biosynthesis. The advent of these drugs has signi fcantly impacted the treatment of cardiovascular disease with well documented beneft in primary and secondary prevention 1-3 . However, several clinical and basic science investigations suggested that the benefcial efects of statins may extend beyond their choles- terol lowering efects, the so-called “pleiotropic efects”; these include improving endothelial func- tion, inhibiting vascular infammation and oxida- tion 4-7 . CORRESPONDENCE Prof. Germano Di Sciascio, MD, Department of Cardiovascular Sciences, Campus Bio-Medico University, Via Alvaro del Portillo, 200, 00128 Rome, Italy Tel.+39-06-225411612 Fax.+39-06-225411638 E-mail: g.disciascio@unicampus.it CONFLICTS OF INTEREST The authors who contributed to this manuscript have no confict of interest to declare. None of these persons received compensation for their work. ISSN 2042-4884 ABSTRACT Statins exert benefcial efects on the endothelium, infammation and the coagulation cascade that are independent of cholesterol lowering. The main mechanism underlying these efects is inhibi- tion of isoprenoid synthesis, modulating the infammatory cascade and the endothelial activation reliable of atherosclerosis. Diferent studies demonstrated that statins improve endothelial function in patients with stable atherosclerotic plaque and that this efect is dose-dependent. Statins may modulate endothelial expression of adhesion molecules, as demonstrated in the ARMYDA-CAMS, and may enhance mobilisation of endothelial progenitor cells. Elevated C-reactive protein levels, an infammatory marker that also plays a direct pathogenetic role in the atherosclerotic process, have been correlated with worse outcome in patients with cardio- vascular disease. Multiple studies demonstrated that statin attenuates the rise of infammatory markers and improves clinical outcome in patients with stable angina, unstable angina and non-Q wave acute myocardial infarction. During percutaneous coronary intervention randomised trials showed a benefcal efect of statin pre-treatment in reducing peri-procedural myocardial damage probably by plaque stabilisation and inhibition of microembolisation phenomena during stent implantation. The ARMYDA study and the NAPLES II trial demonstrated this benefcial efect in patients undergoing coronary revascularisation for stable angina. Also in patients with ACS, receiving invasive strategy, the role of statins in preventing peri-procedural damage was demonstrated in the ARMYDA-ACS study by the administration of an acute high loading-dose with atorvastatin. In patients already on chronic statin therapy at the time of the procedure, an acute drug reload before stenting would have cardio- protective efects, like demonstrated in the ARMYDA RECAPTURE study. LDL-lowering Independent Efects of Early Pre-treatment with High-dose Statins in Patients Undergoing Percutaneous Coronary Interventions CARDIOVASCULAR RISK PREVENTION | REVIEW Annunziata Nusca, MD, Rosetta Melf, MD, Giuseppe Patti, MD, FACC & Germano Di Sciascio, MD, FACC, FESC Department of Cardiovascular Sciences, Campus Bio-Medico, University of Rome Received 14/1/2011, Reviewed 21/1/2011, Accepted 25/1/2011 DOI: 10.5083/ejcm.20424884.30 Anti-infammatory properties of statins: mechanisms of action The main mechanism underlying the pleio- tropic efects of statins is the inhibition of iso- prenoid synthesis (farnesil pyrophosphate and geranyl-geranyl pyrophosphate), which leads to the blockage of small G proteins (i.e. Rho and Ras) and subsequent suppression of nuclear transcription factors activation involved in pro- infammatory mechanisms 8,9 . In particular, in- hibition of Rho and its downstream target Rho kinase (ROCKs) may mediate the positive efects of statins on the vascular wall. 13 EUROPEAN JOURNAL OF CARDIOVASCULAR MEDICINE VOL I ISSUE III