Effects of telmisartan and losartan on cardiovascular protection in Japanese hypertensive patients.

The Telmisartan and Losartan Cardiac Evaluation Trial, a multicenter, prospective, randomized, open-labeled, blinded-endpoint trial, was designed to compare the effects of two angiotensin II receptor blockers (ARBs), telmisartan and losartan, on cardiovascular protection in Japanese patients with mild to moderate essential hypertension. We compared the effects of telmisartan and losartan on left ventricular (LV) hypertrophy, cardiac function, atherosclerosis of carotid arteries and surrogate markers related to the actions of peroxisome proliferator-activated receptor-γ. A total of 58 patients were enrolled in the present trial and the follow-up period was 1 year. There were no significant differences in blood pressure (BP) levels between the telmisartan group and the losartan group throughout the trial. The percentage of the patients treated with ARB monotherapy was significantly higher in the telmisartan group compared with the losartan group. In addition, the progression of intima-media thickness of common carotid artery was significantly inhibited in the telmisartan group compared with the losartan group. Neither group experienced significant changes in cardiac function and LV mass index. There were no differences between the groups with respect to changes in surrogate markers such as serum adiponectin, creatinine, homeostasis model assessment index, plasminogen activator inhibitor-1 and high sensitivity C-reactive protein. Although BP levels were equal and well controlled in both groups, telmisartan showed more protective vascular effects than losartan.

Effects of valsartan and amlodipine on cardiorenal protection in Japanese hypertensive patients: the Valsartan Amlodipine Randomized Trial.

The Valsartan Amlodipine Randomized Trial, a multicenter, prospective, randomized, open-labeled, blinded-end point trial, was designed to compare the beneficial effects of the angiotensin II receptor blocker valsartan and the calcium channel blocker amlodipine on cardiovascular events in Japanese essential hypertensive patients. The primary end point was a composite of all-cause death, sudden death, cerebrovascular death, cardiac events, vascular events and renal events. The secondary endpoints were effects on left ventricular hypertrophy, cardiac sympathetic nerve activity and renal function. A total of 1021 patients were enrolled in the present trial. The mean follow-up period was 3.4 years. There were no significant differences in blood pressure (BP) levels between the valsartan group and the amlodipine group throughout the trial. There was no significant difference in the primary endpoint between the two groups (hazard ratio: 1.0, P = 0.843). No difference in any event category of the primary endpoint was noted for either group. However, we observed a significant reduction of left ventricular mass index, as determined by echocardiography, in the valsartan group compared with the amlodipine group. We also observed a significant decrease in cardiac sympathetic nerve activity in the valsartan group but not in the amlodipine group. Moreover, there was a significant reduction in the urinary albumin to creatinine ratio in the valsartan group but not in the amlodipine group. Therefore, although BP levels were well controlled and remained equal in the two groups, valsartan had more protective effects on the heart and kidney than amlodipine in Japanese hypertensive patients.

Increased subcutaneous fat accumulation has a protective role against subclinical atherosclerosis in asymptomatic subjects undergoing general health screening.

PURPOSE: To evaluate the clinical role of subcutaneous fat accumulation in subclinical arteriosclerosis, using computed tomography (CT), we measured the subcutaneous fat area (SFA), the visceral fat area (VFA) and the VFA/SFA ratio and compared these with the calcium score of the whole aorta (CSWA) in asymptomatic subjects who were undergoing general health screening. METHODS: 122 consecutive asymptomatic subjects (40 female, mean age 56.2+/-8.4 years) were analyzed. Whole-body low-dose CT scan (mAs=50, slice thickness=5 mm) was performed. The SFA and VFA were measured at the umbilical level. Calcification of whole aorta was defined as an area with >90 HU and 1 mm(2), and CSWA was calculated using the modified Agatston method. RESULTS: Mean+/-SD of SFA, VFA and log CSWA were 158+/-67.1 cm(2), 94.0+/-44.8 cm(2), and 7.93+/-1.08, respectively. SFA was significantly and inversely correlated with log CSWA (r=-0.219, P=0.015) but VFA was not (r=0.105, P=0.250) and as a result, the VFA/SFA ratio was significantly and positively correlated with log CSWA (r=0.221, P=0.015). Subsequently, all predictor variables were used in a stepwise multiple regression model with log CSWA as dependent variable, and age, SFA and fasting plasma glucose significantly influenced log CSWA (P<0.001) by the multiple regression formula Y=0.046X1***-0.005X2**+0.015X3*+4.426, (***P<0.001, **P<0.01, and *P<0.05) where Y=log CSWA, X1=age, X2=SFA, and X3=fasting plasma glucose). CONCLUSIONS: SFA was significantly and inversely associated with log CSWA, in an independent fashion. These results suggest that subcutaneous fat accumulation might have a protective role against atherosclerosis in asymptomatic subjects.

[Blood pressure goal and choice of antihypertensive treatment in patients with mild hypertensive cardiovascular disease].

Guidelines for the management of hypertension are established to reduce hypertension-related morbidity and mortality. Fundamental aims of interventions are designed to prevent and/or slow the development of cardiovascular diseases such as myocardial ischemia, heart failure and left ventricular hypertrophy by effecting favorably the natural history. In clinical trials, antihypertensive therapy has been associated with reductions in cardiovascular events even in patients with mild hypertension. Several classes of medications are recommended to achieve target blood pressure in patients with mild hypertensive cardiovascular diseases.

Valsartan Amlodipine Randomized Trial (VART): design, methods, and preliminary results.

Antihypertensive therapy has been well established to reduce hypertension related morbidity and mortality, but the optimal therapy for Japanese patients remains unknown. The Valsartan Amlodipine Randomized Trial (VART), a prospective randomized open-label trial, was designed to determine whether treatment with an angiotensin II type 1 receptor blocker (valsartan) or a calcium channel blocker (amlodipine) lowers cardiovascular disease events in essential hypertensives in Japan. Registration, randomization and data entry were performed over the Internet. The minimization method (to control for age, gender, blood pressure level and history) was used at random assignment to ensure that the background factors were equivalent between the groups at baseline. After the registration, patients were followed-up for cardiovascular events (primary endpoints), echocardiography, (123)I-metaiodobenzylguanidine (MIBG) imaging, laboratory tests and blood pressure for 3 years. Currently, 797 patients have been enrolled and assigned to two groups: a valsartan (n=399) and an amlodipine (n=398) group. At baseline, controlled factors (age, gender, blood pressure level, and left ventricular hypertrophy) and the proportions of patients with diabetes and hyperlipidemia were equally allocated. At 12 months, both drugs evenly and significantly lowered blood pressure to the target level (valsartan: 133/79 mmHg; amlodipine: 132/79 mmHg). In conclusion, by combining the data on cardiovascular events with the results of echocardiographic, radionuclide imaging, and blood/urine studies, the VART study will provide mechanistic insights into the clinical outcomes and treatment effects of the trial.

Remarkable thickening of right atrial wall in subjects with cardiac amyloidosis complicated with sick sinus syndrome.

We observed a 63-year old male with cardiac amyloidosis who presented with the clinical symptoms of sick sinus syndrome and dyspnea and abnormal thickening of the right atrial wall, which extended to the junction of the superior vena cava. This may explain the relationship of abnormal thickening of the right atrium which extends to the junction of the superior vena cava and right atrium with amyloid deposits in the sinus node and occurrence of sick sinus syndrome.