European Journal of Clinical Investigation (2007) 37, 454–462 © 2007 The Authors. Journal Compilation © 2007 Blackwell Publishing Ltd Blackwell Publishing Ltd Atorvastatin therapy improves exercise oxygen uptake kinetics in post-myocardial infarction patients M. Guazzi * , G. Tumminello * , G. Reina † , M. Vicenzi * and M. D. Guazzi † *† University of Milan, Italy Abstract Background Statins represent a modern mainstay of the drug treatment of coronary artery disease and acute coronary syndromes. Reduced aerobic work performance and slowed VO 2 kinetics are established features of the clinical picture of post-myocardial infarction (MI) patients. We tested the hypothesis that statin therapy improves VO 2 exercise performance in normocholesterolaemic post-MI patients. Materials and methods According to a double-blinded, randomized, crossover and placebo- controlled study design, in 18 patients with uncomplicated recent (3 days) MI we investigated the effects of atorvastatin (20 mg day -1 ) on gas exchange kinetics by calculating VO 2 effective time constant (tau) during a 50-watt constant workload exercise, brachial artery flow- mediated dilatation (FMD) as an index of endothelial function, left ventricular function (echocardiography) and C-reactive protein (CRP, as an index of inflammation). Atorvastatin or placebo was given for 3 months each. Results Atorvastatin therapy significantly improved exercise VO 2 tau and FMD, and reduced CRP levels. We did not observe changes in cardiac contractile function and relaxation properties during all study periods in either group. Conclusions In post-MI patients exercise performance is a potential additional target of benefits related to statin therapy. Endothelial function improvement is very likely implicated in this newly described therapeutic property. Keywords Endothelium, exercise, oxygen kinetics, statin. Eur J Clin Invest 2007; 37 (6): 454–462 Introduction Statin therapy forms the mainstay basis of contemporary drug treatment of coronary artery diseases [1]. Most large- scale trials have underscored the effectiveness of statins on morbidity and mortality in both primary and secondary prevention of cardiovascular events [2–7]. Evidence is accumulating that pleiotropic effects account for several therapeutic properties of these compounds [1,8,9]. This is strengthened by studies suggesting that statin treatment reduces cardiovascular events even in normocholesterolaemic patients and especially in those having normal low-density lipoprotein (LDL) cholesterol [10,11]. Exercise intolerance and reduced oxygen uptake (VO 2 ) are established features of the clinical picture of post-myocardial infarction (MI) patients [12,13]. Measuring the gas exchange response to exercise, Koike and co-workers [14] have reported that VO 2 kinetics during submaximal exercise is decreased in these patients. The basic haemodynamic factors involved in the post-MI reduction of exercise performance are a limited increase in cardiac output and/or an impaired blood flow redistribution to working muscles. At least theoretically, both lipid-lowering and pleiotropic effects of statin therapy may affect exercise pathophysiology of post-MI patients by improving both vascular and/or cardiac function. Specifically, statins may improve blood flow distribution to working muscles through a systemic endothelial effect [15]. Moreover, pleiotropic anti-inflammatory effects may be at work at cardiac level improving the myocardial con- traction and relaxation processes [16] Accordingly, we tested the hypothesis that statin therapy improves VO 2 exercise performance in normocholesterolaemic post-MI patients. Cardiopulmonary Unit, Cardiology Division, University of Milan, S. Paolo Hospital, Milan, Italy (M. Guazzi, G. Tumminello, M. Vicenzi); Institute of Statistics and Biometry, University of Milan, Italy (G. Reina); Institute of Cardiology, University of Milan, Italy (M. D. Guazzi). Correspondence to: Marco Guazzi, MD, PhD, FACC, Cardiopulmonary Unit, Cardiology, Division, University of Milan, San Paolo Hospital, Via A. di Rudinì, 8, 20142 Milan, Italy. Tel./fax: +39 02 50323144; e-mail: marco.guazzi@unimi.it Received 23 October 2006; Accepted 12 February 2007