RAS blockade and cardioprotection double-dummy, so each group received two tablets (one pharmacologically active plus placebo, except the group that received two pharmacologically active drugs). Both placebo and active drug tablets were in- distinguishable but for a letter label. Severe adverse re- actions were monitored to enable the study to be stopped early if they emerged. The patient code was re- vealed to the clinical researchers once recruitment, da- ta collection, laboratory analyses and statistical analy- sis were completed. No patient dropped out of the study, so all data of all patients were collected and analysed. An independent biostatistics expert analysed data and performed inferential analysis. All data analy- sis was carried out according to a pre-established analysis plan. The patients attended the clinic for a total of eight study visits: at 4 and 2 weeks before randomization, at randomization (week 0), and at 1, 6, 12, 18 and 24 weeks after randomization. At each visit blood pressure was measured in the morning after 5 min of rest, about 24 hours after the previous drug administration. Sitting blood pressure was measured three times with an inter- val of about 2 min, and the mean was calculated. Mean blood pressure (MBP) was calculated by the formula DBP plus 1/3 of pulse pressure. At 0 and 24 weeks after randomization, both biochemical and echocardiograph- ic measurements, circulating TGFβ1, PIP and PIIIP were determined. Measurements Patients underwent a general analytical laboratory parameters profile including BUN, creatinine and clear- ance, glycemia, electrolytes (serum sodium, potassium, chloride), by routine laboratory methods. Echocardiographic measurements All patients underwent an echocardiography exami- nation M and B-mode, by a computerized echocardiog- raphy (ESAOTE, Italy) for the determination of following parameters: left ventricular telediastolic internal diame- ter (LVIDd), interventricular septum (IVSTd), and poste- rior wall thickness (PWTd). The Penn convention was used to calculate left ventricular mass (LVM). LVM was normalized for height to the 2.7 power (23). According- ly, all the hypertensives with LVM/h2.7 50 g/m2.7 for men 42 and 47 g/m2.7 for women were considered to have left ventricular hypertrophy (LVH). The prevalence of hyper- tensives with LVH into three treatment groups was not sig- nificantly different (Losartan group n. 10/19; Ramipril group n.10/19; Combined treatment group n.11/19). The relative wall thickness (RWT) by formula [(PWTd/LVIDd)x2] was also calculated. Ejection fraction from left ventricular end-diastolic and end-systolic volumes was measured from the apical four chamber view, using the ellipsoidal single-plane algorithm. Mean ejection fraction was auto- matically calculated by the echocardiographic processing system. In our laboratory the ejection fraction calculated over five consecutive beats permitted optimal repro- ducibility and accuracy (24). LV relaxation and filling were evaluated by pulsed- wave Doppler interrogation of the LV inflow tract from the apical four-chamber view, with the sample volume placed at the tips of the mitral valve. After a stable sig- nal of the transmitral flow velocity was obtained, the Doppler cursor was moved toward the LV outflow tract in the apical five-chamber view for recording both mitral and aortic signals, including the closing click of the aor- tic valve and the opening click of the mitral valve. Doppler signals were recorded at high speed (80- 120mm/s) with the subjects in held expiration. An aver- age of five beats was used for analysis. Isovolumic relaxation time (IVRT) was calculated as the time from the closure click of the aortic valve to the opening click of the mitral valve. When either the clos- ing or opening click was not identified, the time from the end of the aortic flow to the onset of mitral flow from the continuous wave interrogation of the LV inflow-outflow tract was used. Peak early transmitral flow velocity (E), peak late transmitral flow velocity (A), and the decelera- tion time of E velocity (DTE) were measured at the tips of mitral leaflets at the maximum amplitude of E velocity. DTE was measured as the time from peak E velocity to the time when E wave descent intercepts the zero line. Statistical analysis Data are expressed as mean value ± standard devia- tion. Non parametric tests were performed to test hypothesis and two-sided value of p < 0.05 indicated a statistical significant difference. The Wilcoxon signed ranks test was performed to compare data at baseline and after treatment within groups. Groups’ data both at