Background Hypercholesterolemia is a well-established risk factor for the development of vascular events. Statins have pleiotropic effects beyond reducing the low-density lipoprotein-cholesterol (LDL-C) concentration. This study sought to determine whether treatment with pitavastatin affects latent regional left ventricular (LV) systolic and diastolic dysfunction and carotid arterial stiffness in patients with hypercholesterolemia and preserved LV ejection fraction (LVEF), using newly developed ultrasonic strain imaging and carotid ultrasonography. Methods and Results A total of 30 patients with hypercholesterolemia (≥220 mg/dl for serum total cholesterol, and/or ≥140 mg/dl for LDL-C) were randomized to either administration of pitavastatin (1 or 2 mg/day; n=15) or no statin therapy (n=15) for 12 months. LV systolic and diastolic functions were evaluated by measuring transmitral flow velocity, mitral annular motion velocity, and the myocardial strain and strain rate profiles using pulsed Doppler, tissue velocity, and ultrasonic strain imaging. Subclinical atherosclerosis also was determined by measuring the intima - media thickness (IMT) and stiffness β of the left and right common carotid arteries using B- and M-mode ultrasonography. During the follow-up period, the mean peak systolic strains of the LV posterior and inferior walls increased from 39.2±15.9% to 51.5±17.7% (p<0.01) and 46.0±12.2% to 57.5±10.3% (p<0.01), respectively, in the pitavastatin group compared with the no statin group. The mean peak early diastolic strain rates of the LV posterior and inferior walls also increased from -6.5±2.9 s^-1 to -9.5±2.8 s^-1 (p<0.01) and -6.5±2.5 s^-1 to -9.1±2.7 s^-1 (p<0.01), respectively, in the pitavastatin group. The stiffness β decreased from 5.6±2.5 to 4.1±0.8 (p<0.05) in the pitavastatin group, whereas there was no significant change in IMT. Conclusions One year of pitavastatin treatment improved not only carotid arterial stiffness but also regional LV systolic and diastolic function in patients with hypercholesterolemia and preserved LVEF. Ultrasonic strain imaging has the potential to become a sensitive tool for detecting the effects of early medical intervention on latent regional LV myocardial dysfunction in this patient population. (Circ J 2008; 72: 538 - 544)