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Query: UMLS:C0085580 (essential hypertension)
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This study was designed to compare the clinical efficacy of two calcium channel blocker-based combination therapies with an angiotensin receptor blocker in Japanese patients with essential hypertension. A 16-week, double-blind, parallel-arm, randomized clinical trial was performed to compare the efficacy and safety of the combination therapy of controlled release nifedipine (nifedipine CR) plus valsartan vs. that of amlodipine plus valsartan. The primary endpoint was the target blood pressure achievement rate. Eligible patients were randomly allocated to nifedipine CR-based or amlodipine-based treatment groups. Patients were examined every 4 weeks to determine whether the blood pressure had reached the target level. When the target level was not achieved, the drug regimen was changed; when the target blood pressure was achieved, the same study medication was continued. A total of 505 patients were enrolled in the study (nifedipine CR group: 245 cases; amlodipine group: 260 cases). After 16 weeks of treatment, blood pressure was significantly reduced in both groups, but to a larger extent in the nifedipine CR group than in the amlodipine group (p < 0.01). The target blood pressure achievement rate was also significantly higher in the nifedipine CR group (p < 0.001). There was no significant difference in the incidence of drug-related adverse events between the groups. These results indicate that the nifedipine CR-based combination therapy was superior to the amlodipine-based therapy for decreasing blood pressure and achieving the target blood pressure in patients with essential hypertension.
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PMID:Controlled release nifedipine and valsartan combination therapy in patients with essential hypertension: the adalat CR and valsartan cost-effectiveness combination (ADVANCE-combi) study. 1728 66

Microalbuminuria (MA) is associated with increased cardiovascular risk in adult hypertensive patients, but no study has specifically examined the effects of MA lowering on regression of left ventricular hypertrophy (LVH) among pediatric patients with hypertension. Fifty-five patients with essential hypertension, 11-19 years old, were prospectively studied. All patients received concomitant therapy of hydrochlorothiazide and angiotensin-converting enzyme inhibitor. Five patients also required angiotensin receptor blocker to achieve the blood pressure goal. Baseline and 12-month follow-up measures of left ventricular mass index (LVMI), determined by echocardiography and urine microalbumin/creatinine ratio (MA/Cr), were collected. MA was defined as MA/Cr >30 microg/mg. LVH was defined as LVMI >38.6 g/m(2.7). The primary end points were reductions in MA and LVMI of 25% or more. Weight (r = 0.83), body surface area (r = 0.85), body mass index (BMI) (r = 0.86), systolic blood pressure (SBP) (r = 0.57), diastolic blood pressure (DBF) (r = 0.49), mean arterial pressure (r = 0.53) and MA (r= 0.87) were all univariate correlates of LVMI. In a multiple regression analysis, MA, BMI and SBP were significant correlates of LVMI. MA alone explained 76% of the variance of LVMI, whereas BMI and SBP explained only 1.6 and 0.4% of the variance, respectively. MA was the most significant correlate of follow-up LVMI after BMI and SBP were included in the overall multiple regression models. Thus, MA is a strong predictor of LVH in hypertensive children and adolescents. MA lowering halts the progression of LVH or induces its regression.
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PMID:Effect of microalbuminuria lowering on regression of left ventricular hypertrophy in children and adolescents with essential hypertension. 1730 44

Recent studies have shown that in response to vascular damage or ischemia, bone marrow-derived endothelial progenitor cells (EPCs) are recruited into the circulation. To investigate whether antihypertensive treatment has an influence on the number of circulating EPCs, patients with essential hypertension were treated either with the angiotensin receptor antagonist telmisartan, the calcium channel blocker nisoldipine, or their combination for 6 weeks. At baseline and after 3 and 6 weeks of treatment, EPCs were identified and quantified by fluorescence-activated cell sorting (FACS) analysis and by their capacity to generate colony-forming units of the endothelial lineage (CFU-EC) in a methylcellulose-based assay. During treatment, patients in the nisoldipine groups, but not in the telmisartan group, showed a significant mobilization of EPCs, which in part had the capacity to generate large-sized colonies comprising more than 1,000 cells. Moreover, a remarkable correlation between the number of CFU-EC and the number of circulating CD133(+)/CD34(+)/CD146(+) cells was observed, thereby providing strong evidence that cells with this phenotype represent functional EPCs. No correlation was found between the numbers of CFU-EC and the blood pressure levels at any time point during the treatment. Hence, nisoldipine-induced mobilization of EPCs might represent a novel mechanism by which this antihypertensive compound independently of its blood pressure-lowering effect contributes to vasoprotection in patients with essential hypertension.
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PMID:Mobilization of putative high-proliferative-potential endothelial colony-forming cells during antihypertensive treatment in patients with essential hypertension. 1752 Dec 43

Elevated C-reactive protein (CRP) levels have been associated with increased cardiovascular risk in hypertensive adults. The aim of this study was to determine whether plasma CRP level is more predictive of left ventricular hypertrophy (LVH) than is ambulatory blood pressure (BP) in hypertensive children. Baseline and 12-month follow-up measures of BP, body mass index (BMI), low-density lipoprotein/high density lipoprotein cholesterol, left ventricular mass (LVM), and CRP data collected from 48 newly diagnosed, untreated hypertensive children were analyzed. CRP was measured by a highly sensitive nephelometric method. Left ventricular mass index (LVMI) was calculated as LVM/height2.7, and LVH was defined as LVMI>38.6 g/m2.7 being the cut-point for the 95th percentile found in healthy children. Average systolic BP (SBP), diastolic BP (DBP), SBP index, and DBP index were calculated. All patients received hydrochlorothiazide therapy in combination with angiotensin converting enzyme inhibitor treatment. Five patients also had angiotensin receptor blocker therapy to reach the target BP (<95th percentile corrected for age and gender). In a multiple regression analysis, LMVI was correlated with CRP, BMI, SBP, and SBP index. CRP alone explained 77% of the variance of LVMI, whereas BMI, SBP, and SBP index explained only 1.3, 0.3, and 0.4% of the variance, respectively. CRP was also the most significant correlate of follow-up LVH. In conclusion, elevated CRP level is significantly associated with LVH in children with essential hypertension. BP reduction with renin-angiotensin system blocker and hydrochlorothiazide therapy reduces LVH while lowering CRP level.
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PMID:C-reactive protein and incident left ventricular hypertrophy in essential hypertension. 1756 29

Valsartan administration at bedtime as opposed to on wakening improves the sleep time-relative blood pressure decline toward a more dipper pattern without loss in 24-hour efficacy. Yet to be determined is whether this administration time-dependent efficacy is a class-related feature, characteristic of all angiotensin receptor blockers or specific only to valsartan. Terminal half-life is a major difference between angiotensin receptor blockers, being largest ( approximately 24 hours) for telmisartan. This trial investigated the administration time-dependent antihypertensive efficacy of telmisartan. We studied 215 patients with hypertension (114 men and 101 women), 46.4+/-12.0 years of age, randomly assigned to receive telmisartan (80 mg/d) as a monotherapy either on awakening or at bedtime. Blood pressure was measured for 48 hours before and after 12 weeks of treatment. The significant blood pressure reduction after treatment was similar for both groups. Bedtime administration of telmisartan, however, was more efficient than morning dosing in reducing the nocturnal blood pressure mean. The sleep time-relative blood pressure decline was slightly reduced after telmisartan on awakening but significantly increased with bedtime dosing, thus reducing the prevalence of nondipping from baseline by 76%. Telmisartan administered at bedtime, as opposed to morning dosing, improved the sleep time-relative blood pressure decline toward a more dipper pattern without loss in 24-hour efficacy. Nocturnal BP regulation is significantly better achieved with bedtime dosing of telmisartan. Results from this prospective trial suggest that these beneficial features of bedtime dosing may be class related for angiotensin receptor blockers. These results should be taken into account when prescribing this class of antihypertensive medication for treatment of essential hypertension.
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PMID:Comparison of the efficacy of morning versus evening administration of telmisartan in essential hypertension. 1763 51

Both essential hypertension and diabetes mellitus affect the same major target organs. The common denominator of hypertensive/diabetic target organ-disease is the vascular tree. Left ventricular hypertrophy and coronary artery disease are much more common in diabetic hypertensive patients than in patients suffering from hypertension or diabetes alone. The combined presence of hypertension and diabetes concomitantly accelerates the decrease in renal function, the development of diabetic retinopathy and the development of cerebral diseases. Lowering blood pressure to less than 130/80 mm Hg is the primary goal in the management of the hypertensive diabetic patients. Beta-blockers have been reported to adversely affect the overall risk factor profile in the diabetic patient. In contrast, calcium antagonists, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have been reported to be either neutral or beneficial with regard to the overall metabolic risk factor profile. Combination therapy is usually required to achieve blood pressure goal in diabetic patients. The addition of aldosterone antagonists may be beneficial in patients with resistant hypertension and low levels of serum potassium. Aggressive control of blood pressure, cholesterol and glucose levels should be attempted to reduce the cardiovascular risk of diabetic hypertensive patients.
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PMID:Hypertension and diabetes. 1823 Sep 57

The purpose of the present study was to assess angiotensin receptor blocker (ARB) treatment on arterial stiffness in select hypertensive patients and define possible differences between smokers and nonsmokers. The authors evaluated 81 consecutive, nondiabetic patients (mean age, 52 years; 47 men) with uncomplicated essential hypertension with high plasma renin activity who were administered monotherapy with irbesartan, an ARB, at maximal dose. Patients were divided into smokers (n=24) and nonsmokers (n=57). Carotid-radial pulse wave velocity (PWVc-r), carotid-femoral pulse wave velocity (PWVc-f), and augmentation index (AIx) were measured before and 6 months after ARB antihypertensive treatment. All mean values of elastic effect indices were decreased after irbesartan monotherapy (AIx, from 26.3%to 21.2% [P<.01;] PWVc-f, from 7.7 m/s to 7.3 m/s [P<.05], and PWVc-r, from 8.9 m/s to 8.3 m/s [P<.001]). When comparing smokers vs nonsmokers, no difference was noted in AIx and PWVc-f change (P=not significant), while PWVc-r change was greater in smokers compared with nonsmokers (P<.05). Chronic ARB treatment may favorably affect arterial stiffness and wave reflections in hypertensive chronic smokers with elevated plasma renin levels.
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PMID:Beneficial effect of angiotensin II type 1 receptor blocker antihypertensive treatment on arterial stiffness: the role of smoking. 1832 60

Sexual dysfunction is currently considered a serious quality-of-life-related health problem, exerting a major impact on patients' and their sexual partners' life. Available data indicate that essential hypertension is a risk factor for sexual dysfunction, as male and female sexual dysfunction is more prevalent in hypertensive patients than normotensive individuals. Several mechanisms have been implicated in the pathogenesis of sexual dysfunction in hypertensive patients, and major determinants include severity and duration of hypertension, age, and antihypertensive therapy. Female sexual dysfunction, although more frequent than its male counterpart, remains largely under-recognized. Older antihypertensive drugs (diuretics, beta-blockers, centrally acting) exert negative results, whereas newer drugs have either neutral (calcium antagonists, angiotensin-converting enzyme inhibitors) or beneficial effects (angiotensin receptor blockers). Erectile dysfunction is related to ischemic heart disease and might be an 'early therapeutic window' of asymptomatic coronary artery disease. It seems of utmost importance for every physician treating hypertensive patients to become familiar with sexual dysfunction (through better education and specific seminars) for the proper management of these patients.
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PMID:Sexual dysfunction: the 'prima ballerina' of hypertension-related quality-of-life complications. 1885 43

As recommended by the guidelines such as JSH 2004, combination therapy with multiple agents is now being applied to many patients with hypertension. However, a pharmacoeconomic analysis of each therapy has not been fully undertaken in Japan, despite increasing societal interest. In this study, the cost-effectiveness of two calcium channel blockers, each coadministered with an angiotensin receptor blockade, was compared using data from the ADVANCE-Combi study. The ADVANCE-Combi study was a 16-week double-blind, randomized clinical trial to compare the efficacy and safety of two combination therapies (controlled-release nifedipine [nifedipine CR] plus valsartan vs. amlodipine plus valsartan) on blood pressure (BP) control in patients with moderate to severe essential hypertension. The incremental cost effectiveness of each cohort was compared from the perspective of insurers. The average total cost per patient was Japanese yen (JPY) 31,615 for the nifedipine CR treatment group and JPY 35,399 for the amlodipine treatment group (p < 0.001). The achievement rate of the target BP (SBP/DBP < 130/85 mmHg for patients aged under 60 years; SBP/DBP < 140/90 mmHg for those aged 60 years and over) was significantly higher in the nifedipine CR treatment group (61.2%) than in the amlodipine treatment group (34.6%) (p < 0.001), with no difference in the incidence of drug-related adverse events. Accordingly, the base case economic analysis demonstrated that the nifedipine CR treatment group was dominant (more efficacious and less costly) to the amlodipine treatment group. This result was supported by univariate and probabilistic sensitivity analyses. These results indicate that nifedipine CR-based combination therapy is superior to amlodipine-based combination therapy for the management of essential hypertension in the Japanese population.
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PMID:Cost-effectiveness analysis: controlled-release nifedipine and valsartan combination therapy in patients with essential hypertension: the adalat CR and valsartan cost-effectiveness combination (ADVANCE-Combi) study. 1895 11

The combination of angiotensin I-converting enzyme inhibitors and angiotensin receptor blockers has been shown to be more effective than the individual drugs alone in the treatment of chronic kidney disease and chronic heart failure. In the present study, we evaluated the effect of treatment with the calcium channel blocker amlodipine or the angiotensin I-converting enzyme inhibitor perindopril on vascular endothelial function and arteriosclerosis in patients with essential hypertension who had already been receiving angiotensin receptor blocker monotherapy. Thirty-two patients with essential hypertension treated with angiotensin receptor blocker monotherapy were randomized to receive 5 mg of amlodipine (n=16) or 4 mg of perindopril (n=16) once daily in the morning for 24 weeks. The patients were evaluated before and after therapy to assess changes in blood pressure, flow-mediated vasodilation (a parameter of vascular endothelial function), and brachial-ankle pulse wave velocity (a parameter of arteriosclerosis). Before treatment, there were no significant differences in the above parameters between groups. After treatment, there was a similar significant decrease in blood pressure in both groups. Flow-mediated vasodilation increased significantly in the perindopril group compared with the amlodipine group; however, the decrease in brachial-ankle pulse wave velocity was not significantly different between groups. In conclusion, these results suggest that the angiotensin I-converting enzyme inhibitor perindopril is superior to the calcium channel blocker amlodipine for reducing vascular endothelial dysfunction when co-administered with angiotensin receptor blockers in patients with essential hypertension.
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PMID:Beneficial effects of combination therapy with angiotensin II receptor blocker and angiotensin-converting enzyme inhibitor on vascular endothelial function. 1897 36


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