RAS blockade and cardioprotection brosis in cardiac ventricles (5). The increased collagen and unchanged or insufficient degradation by collage- nase (6) has been reported to promote systolic dysfunc- tion, myocardial stiffness and abnormalities in diastolic ventricular filling and relaxation (7). Hemodynamic and non hemodynamic factors play a main role in the colla- gen turnover in hypertension (8, 9). Experimental data suggest that Angiotensin II stimulates fibroblast-medi- ated collagen synthesis (10, 11) independently of me- chanical load either directly or via specific growth fac- tors (12) and inhibits collagenase. Even if antihypertensive drugs reverse left ventricu- lar hypertrophy (LVH) by lowering blood pressure (13), meta-analyses of clinical trials have demonstrated that ACE-inhibitors (ACEi) and A-II type 1 receptor blockers (ARB) decrease left ventricular mass most effectively than other antihypertensive drugs (14). Moreover, some recent studies have reported that the combina- tion of two agents, ACEi and ARB, that inhibit two con- secutive renin-angiotensin-system (RAS) steps, pro- motes a decrease in myocardial fibrosis and left ven- tricular hypertrophy (15-18). This effect is due to a di- minished AT1 receptor activation by a decreased An- giotensin II production. Other data indicate that ad- ministration of ACEi may be able to reduce the colla- gen content with consequent improvement of diastolic filling (16). Clinical data, comparing ACEi and ARB therapy in hypertensive heart disease, indicate that ARB have equivalent effects to ACEi on blood pressure and left ventricular hypertrophy (19), and these actions seem partially independent of their hemodynamic ef- fects (8). In addition, experimental and clinical studies indicate that the combination of low doses of ACEi and ARB have a synergic and most effectiveness on left ventricular hypertrophy (20, 21). These effects might explain a better cardioprotection attributed to ACEi and ARB than other antihypertensive drugs. Although a combination of ACEi and ARB treatment seems actractive, thus far limited data have emerged to sup- port such as strategy. Accordingly, the main goal of the present study was to determine the effects of 24 weeks’ losartan and ramipril administration on measurements of left ven- tricular geometry and function in hypertensive pa- tients. For this reason hypertensive subjects were allo- cated randomly to 24 weeks of treatment with ACEi and ARB alone or in combination. 40 SUBJECTS AND METHODS Patients Subjects eligible for the study were screened for ar- terial hypertension at the antihypertensive center of the Department of Internal Medicine, University of Palermo, Italy. Subjects with a casual systolic blood pressure (SBP) 140 mmHg and < 180 mmHg and/or with casual diastolic blood pressure (DBP) 90 mmHg and < 110 mmHg obtained with a standard sphygmomanometer after 5 min of rest on three independent occasions, were invited to our day hospital for a detailed medical examination including history taking, physical, routine laboratory and echocardiographic examination. Exclu- sion criteria included the presence of any form of sec- ondary hypertension; stage III essential hypertension, any irreversible end organ damage due to arterial hy- pertension; metabolic bone disease, hyperthyroidism, cardiovascular disease, diabetes, dyslipidemia, hepatic disease, alcoholic liver disease, malignants. According- ly, from a large number of hypertensives, we established three groups of patients single matched for age, gender, body mass index (BMI) , SBP and DBP. Fifty-seven pa- tients fullfilled the selection criteria and baseline char- acteristics of the study participants are given in Table I. Study design and active treatment Each patient gave a written consent after having re- ceived a detailed description of the study procedure. The study was approved by the Ethics Committee of our Institution. Multiple comparisons power analysis was performed to determine sample size. The primary end- point was considered the level of TGF-β1 changes and sample size was computed basing on the following as- sumptions: α = 0.05, power of at least 0.80 (β error equal or below 0.20), a minimum detectable difference of 3.00 with a standard deviation of 2.00 (minimum de- tectable difference/standard deviation =1.5). The total sample size resulted in 57 subjects (19 subjects for each of the three arms); it achieved 83% power using the Hsu (With Best) multiple comparison test at 0.05000 significance level. This study was a randomized, double-blind, three- arm double-dummy independent trial. It was planned and conducted according to the revised recommenda-