Effects of valsartan and perindopril combination therapy on left ventricular hypertrophy and aortic arterial stiffness in patients with essential hypertension

Objective To compare the effects of combined therapy of an angiotensin II receptor blocker (ARB; valsartan) and an angiotensin converting enzyme inhibitor (ACEI; perindopril) on blood pressure (BP), metabolic profiles, plasma brain natriuretic peptide (BNP) levels, echocardiographic findings, and aortic pulse wave velocity (PWV) with those of respective monotherapy in never-treated patients with essential hypertension.Methods This was a prospective randomized trial, in which there were 31 patients with essential hypertension and left ventricular hypertrophy (LVH) who visited the outpatient clinic of Oita Red Cross Hospital (14 women and 17 men; mean±SD age, 59±5 years). Each patient was randomly assigned to receive valsartan (160 mg/day, V group, n=10), perindopril (8 mg/day, P group, n=11), or a combination of valsartan (80 mg/day) and perindopril (4 mg/day, V+P group, n=10) for 40 weeks. Ambulatory BP monitoring (ABPM), echocardiographic findings, metabolic findings, plasma BNP levels, and brachial-ankle PWV (baPWV) were evaluated before and after the 40-week therapy.Results The baseline and post-therapeutic BP levels were similar among the three groups. At baseline ABPM, non-dipping was observed in 80, 82, and 80% in the V, P, and V+P groups, respectively. Each 40-week therapy regimen comparably reduced ABP. The plasma BNP levels (P<0.0001 for each), left ventricular mass index (LVMI) (P<0.01 for each), and PWV values (P<0.0001 for each) were also reduced. However, when compared with either V or P group, the percentage reduction in LVMI (P<0.05 and P<0.005, respectively), BNP (P<0.05 for each), and baPWV values (P<0.005 and P<0.001, respectively) was greater in the V+P group.Conclusions Our findings suggest that, when compared with each monotherapy, perindopril and valsartan combination therapy exerts greater beneficial effects regarding the regression of LVH, reduction in BNP, and improvement of PWV in a selected group of essential hypertensive patients with LVH and high prevalence of non-dipping patterns.     

Effect of nebivolol on renal nitric oxide availability and tubular function in patients with essential hypertension

Aims

Nebivolol is a selective β₁-receptor antagonist with vasodilating properties. In patients with essential hypertension, we tested the hypothesis that nebivolol increases systemic and renal nitric oxide (NO) availability using L-N^G-monomethyl arginine (L-NMMA) as an inhibitor of NO production.

Methods

In a randomized, placebo-controlled, crossover study, patients with essential hypertension were treated with nebivolol for five days, along with a standardized diet and fluid intake. We examined the acute effects of systemic NO synthase inhibition with L-NMMA on brachial blood pressure (bBP), pulse wave velocity (PWV) and central blood pressure (cBP) estimated by applanation tonometry, glomerular filtration rate (GFR), fractional excretion of sodium (FE_Na), urinary excretion of both aquaporin-2 (u-AQP2) and epithelial sodium channels (u-ENaC_γ), and plasma concentrations of nitrate/nitrite (p-NO_x) and vasoactive hormones after five days'' treatment with placebo and nebivolol.

Results

Nebivolol significantly reduced PWV, bBP, cBP and plasma renin, angiotensin II and aldosterone concentrations. The renal parameters, p-NO_x and plasma arginine vasopressin concentration were not changed by nebivolol. There was no difference between nebivolol and placebo in the response to L-NMMA, with LMMA inducing a similar increase in PWV, bBP and cBP and a similar decrease in GFR, uAQP2 and u-ENaC_γ and FE_Na [mean change −0.62% (95% confidence interval {CI} −0.40 to −0.84) during placebo vs. −0.57% (95% CI −0.46 to −0.68; P = 0.564) during nebivolol treatment]. Vasoactive hormones were changed to a similar extend by L-NMMA during administration of nebivolol and placebo.

Conclusions

Nebivolol did not change p-NO_x, and inhibition of NO synthesis induced the same response in blood pressure, GFR, renal tubular function and vasoactive hormones during nebivolol and placebo. Thus, the data did not support the hypothesis that nebivolol changes vascular and renal NO availability in patients with essential hypertension.     

Comparison of nebivolol and atenolol on blood pressure, blood sugar, and lipid profile in patients of essential hypertension

Background:

Nebivolol is a third-generation β-blocker, with highest β₁ selectivity and nitric-oxide-derived vasodilatation. It also exhibits antiproliferative and antioxidant property that has beneficial metabolic profile compared to second-generation β blockers like atenolol. This study was planned to study the comparative effects of nebivolol and atenolol on metabolic parameters in patients with essential hypertension.

Materials and Methods:

A prospective, randomized, parallel, open-label clinical study was carried out on patients with essential hypertension. The patients were randomly assigned to receive tablet atenolol (Group A) and nebivolol (Group B) for a period of 24 weeks. Investigations were carried out at baseline and at the end of study period, that is, 24 weeks. Out of 69 patients, 60 completed the study and the data was analyzed using student''s t-test. P < 0.05 was considered statistically significant.

Results:

Atenolol and nebivolol both showed significant (P < 0.001) antihypertensive action after 24 weeks. Mean blood sugar and lipid profile were found to be significantly (P < 0.001) elevated after 24 weeks of treatment with atenolol but not with nebivolol. Heart rate was significantly (P < 0.001) decreased in both groups at 24 weeks.

Conclusion:

In view of metabolic adverse effects of atenolol, nebivolol is the better choice whenever β-blockers have to be used in essential hypertension.     

奈必洛尔联合缬沙坦治疗原发性高血压有效性和安全性分析

目的观察奈必洛尔联合缬沙坦治疗原发性高血压的有效性和安全性。方法选取98例原发性高血压患者随机分为观察组和对照组,对照组采用缬沙坦进行治疗,观察组采用奈必洛尔联合缬沙坦治疗,2个月后查看疗效和不良反应。结果 8周后观察组治疗总有效率为95.9%,对照组为79.6%,差异比较具有统计学意义(P<0.05);治疗4周和8周后,观察组收缩压、舒张压及静息心率均明显低于对照组,差异比较具有统计学意义(P<0.05);治疗4周及8周后观察组血压达标率均明显高于对照组,差异比较有统计学意义(P<0.05);对照组与缬沙坦有关的不良反应2例,发生率为4.1%。观察组与2种药品有关的不良发应3例,发生率6.1%,2组不良反应率比较差异无统计学意义(P>0.05)。结论奈必洛尔联合缬沙坦治疗原发性高血压疗效显著,安全性高,可在临床上进一步推广。     

培哚普利、氨氯地平降压治疗对原发性高血压患者大动脉弹性的影响

目的 比较培哚普利、氨氯地平改善原发性高血压患者动脉弹性的作用.方法 78例轻中度原发性高血压患者随机均分成培哚普利组和氨氯地平组,以血压＜140/90 mm Hg为降压达标,检测用药前和降压达标后4、12周的颈股脉搏波传导速度(cfPWV).结果 与治疗前比较,培哚普利组和氨氯地平组治疗后4、12周的cfPWV均明显下降[(12.9±2.3)m/s vs.(11.1±2.1) m/s、(9.6±1.7) m/s和(13.3±2.6)m/s vs.(11.4±2.2)m/s、(9.4±1.6)m/s](P＜0.01).结论 运用培哚普利、氨氯地平降压达标,均能改善原发性高血压患者大动脉弹性.     

替米沙坦对高血压患者颈总动脉内膜中层厚度的影响

目的 观察替米沙坦对高血压患者颈总动脉内膜中层厚度的影响.方法 选择104例轻、中度高血压病患者,随机分为替米沙坦组35例（服用替米沙坦80 mg/d）、雷米普利组35例（服用雷米普利5 mg/d）和对照组34例（使用其它降压药物）.治疗过程中监测血压,入选患者开始时和治疗12个月后测定颈总动脉内膜中层厚度（CIMT）.结果 完成12个月治疗者共91例：替米沙坦组33例,雷米普利组28例,对照组30例.替米沙坦组和雷米普利组在有效降低血压同时,CIMT明显减低（均P〈0.05）,与对照组CIMT差异无统计学意义;雷米普利引起干咳需要停用药物者5例.结论 替米沙坦能够有效降低血压并减低CIMT,雷米普利具有相似作用,但替米沙坦不良反应较少.     

脉君安片联合卡托普利对高血压病患者降压疗效观察

目的观察中西药结合制剂脉君安片联合卡托普利对高血压病患者的降压疗效。方法将60例高血压病患者随机单盲分为观察组和对照组，观察组30例用脉君安片＋卡托普利，对照组30例用安慰剂＋卡托普利，疗程均为4周，分别在治疗前、后测量血压。结果观察组和对照组治疗后血压均显著下降（P〈0．01），与对照组相比观察组降低幅度更大（P〈0．05），两组均未见药物不良反应。结论脉君安片具有一定的降压作用，无药物不良反应，与卡托普利联用的疗效更好。     

Add-on therapy with doxazosin in patients with hypertension influences arterial stiffness and albuterol-mediated arterial vasodilation

What is already known about this subject

• Hypertension is associated with increased arterial stiffness and impaired endothelial function.
• Arterial vasodilation depends on endothelial function and can be regulated by β₂-adrenergic stimulation.
• Doxazosin is a known and potent antihypertensive agent. However, its effects on arterial stiffness and vasodilation have not been fully established.

What this study adds

Sixteen-week add-on antihypertensive therapy with 4 mg of doxazosin extended release daily:

• Reduces arterial stiffness.
• Improves albuterol-mediated, i.e. endothelium-dependent, arterial vasodilation.
• Does not influence nitroglycerin-mediated, i.e. endothelium-independent, arterial vasodilation.

Aims

Doxazosin is an antihypertensive agent with largely unknown effects on arterial stiffness and vasodilation. The aim of this study was to determine the effect of the addition of doxazosin extended-release (ER) to the standard management of hypertension in patients with inadequately controlled blood pressure (BP) on arterial stiffness and arterial vasodilation.

Methods

Twenty patients with inadequately controlled hypertension were treated with 4 mg doxazosin ER daily for 16 weeks as an adjunct to their existing antihypertensive regimen.

Results

Doxazosin ER add-on therapy was associated with significantly reduced systolic (P < 0.0001) and diastolic (P = 0.0003) BP, improved arterial stiffness (determined by digital volume pulse analysis (P = 0.048) and albuterol-mediated arterial vasodilation (P = 0.030).

Conclusions

Add-on therapy with 4 mg of doxazosin ER daily reduces BP and arterial stiffness and improves arterial vasodilation in response to adrenergic stimulation.     

针刺治疗对原发性高血压患者血压变异性和心率变异性的影响

目的：探讨针刺治疗对原发性高血压患者血压变异性和心率变异性的影响。方法选择符合条件的60例原发性高血压患者进行针刺治疗,疗程为30 d,采用自身前后对照,分别于治疗前后完善24 h动态血压及24 h动态心电图检查。结果针刺治疗后血压变异性各指标（24 h平均收缩压、24 h平均舒张压、24 h收缩压标准差、24 h舒张压标准差、白昼收缩压标准差、白昼舒张压标准差、夜间收缩压标准差、夜间舒张压标准差）均较治疗前降低,差异具有统计学意义（ P＜0．05）;心率变异性各指标（连续RR间期标准差、平均5 min RR间期标准差、平均5 min RR间期标准差的平均值、连续RR间期差值的均方根值、相邻RR间期大于50 ms的百分数）均较治疗前有所改善,差异具有统计学意义（ P＜0．05）。结论针刺治疗能显著降低原发性高血压患者的血压变异性,改善心率变异性,从而可能改善高血压患者的靶器官损害。     

两种不同联合降压方案对轻中度原发性高血压患者血压变异性及肌酸激酶的影响

目的比较硝苯地平控释片联合美托洛尔缓释片和厄贝沙坦片联合美托洛尔缓释片对轻中度原发性高血压患者血压变异性(BPV)和肌酸激酶(CK)的影响。方法①入选2017年6月—2018年5月门诊和住院年龄在18～65岁且静息心率≥80次·min~(-1)的初诊为轻中度原发性高血压患者52例为高血压组,选择同期体检的正常人60例为正常血压组,比较两组一般资料的差异;②将52例高血压患者随机分为两组:硝苯地平组(27例,硝苯地平控释片联合美托洛尔缓释片)及厄贝沙坦组(25例,厄贝沙坦片联合美托洛尔缓释片),比较两组治疗前及治疗12周后常规生化和部分24 h动态血压监测指标。结果①高血压组CK、尿酸(UA)与体质量指数(BMI)明显高于正常血压组(P <0.05,P <0.01);②治疗12周后,硝苯地平组及厄贝沙坦组较治疗前平均血压均明显降低(P <0.01),硝苯地平组24 h收缩压标准差(24 h SBPSD)、白昼收缩压标准差(d SBPSD)、夜间收缩压标准差(n SBPSD)较治疗前明显降低(P<0.05);③治疗12周后硝苯地平组及厄贝沙坦组CK、UA等较治疗前均无明显差异(P> 0.05),但硝苯地平组CK有下降趋势。结论①硝苯地平组及厄贝沙坦组对轻中度原发性高血压患者降压疗效相当,但硝苯地平组在降低轻中度原发性高血压患者收缩压变异性方面优于厄贝沙坦组;②硝苯地平组与厄贝沙坦组对CK均无明显影响。     

血脂康对血脂正常的高血压患者血压及动脉弹性的影响

目的观察应用血脂康对血脂正常高血压患者血压及动脉弹性的影响。方法共纳入血脂正常的高血压患者60例,随机分为治疗组(血脂康+硝苯地平缓释片)30例,对照组(硝苯地平缓释片)30例。观察治疗前后血压、上臂-脚踝脉搏波传导速度(baPWV)及动脉内膜中层厚度(CIMT)的变化,疗程均为12周。结果治疗后,治疗组baPWV及CIMT较对照组明显下降,差异有统计学意义(P<0.05)。结论血脂康胶囊显著改善血脂正常的高血压患者动脉弹性,体现了中药多位点、多靶点作用的优势。     

Effects of salbutamol and glyceryl trinitrate on large arterial stiffness are similar between patients with hypertension and adults with normal blood pressure

AIMS: Endothelial function is characteristically impaired in patients with hypertension. Endothelial function was assessed in men and women with hypertension using a recently described, non-invasive method. METHODS: Twenty patients and 20 controls received salbutamol 400 microg and glyceryl trinitrate (GTN) 500 microg in a two-way randomized, single-blind study. Effects on augmentation index (AIx) were assessed using pulse wave analysis (PWA). RESULTS: Responses (absolute AIx reduction and 95% confidence interval) to salbutamol were 8.4% (6.2, 10.6) and 8.3% (7.0, 9.6) in patients and controls, respectively, and those to GTN were 13.6% (10.8, 16.4) and 15.5% (13.0, 17.0), respectively. CONCLUSIONS: Systemic arterial responses to endothelium-dependent and -independent vasodilators are preserved in patients with mild, uncomplicated hypertension, indicating normal large arterial endothelial function.     

Effect of guanfacine on ambulatory blood pressure and its variability in elderly patients with essential hypertension.

The effect of guanfacine (2 mg once daily) on ambulatory blood pressure was studied with the Remler M 2000 recorder in 16 elderly hypertensive patients during a randomized, double-blind, placebo-controlled, balanced, cross-over study. Guanfacine significantly reduced heart rate and systolic and diastolic ambulatory blood pressure. The antihypertensive effect was maintained over the whole recording period. Systolic and diastolic blood pressure variability was not changed by guanfacine, neither when defined as standard deviation or variation coefficient of the mean, nor when defined as the range between the highest and lowest ambulatory blood pressure, suggesting that blood pressure variability is unrelated to sympathetic nervous system activity.     

The vasodilator action of nebivolol in forearm vasculature of subjects with essential hypertension

AIMS: Brachial artery administration of nebivolol increases forearm blood flow in normotensive subjects through activation of the L-arginine/NO pathway. The aim of the present study was to investigate the effect of brachial artery administration of nebivolol in subjects with essential hypertension. METHODS: We studied eight patients with uncomplicated essential hypertension and serum cholesterol less than 6.9 mmol l-1. Antihypertensive medication was discontinued 2 weeks before the study in previously treated patients. Following cannulation of the left brachial artery, saline was infused to establish baseline blood flow, followed by increasing doses of nebivolol (88.5, 177 and 354 microg min-1, each dose for 6 min), followed by saline for 12 min, followed by a 30 min infusion of L-NMMA (2 mg min-1 ). During the final 18 min of the L-NMMA infusion, nebivolol was coinfused using the same doses as before. Forearm blood flow was measured in both arms using venous occlusion plethysmography. RESULTS: Blood flow in the noninfused arm did not change significantly throughout the study. In the infused arm blood flow increased significantly in a dose-related manner during the first series of nebivolol infusions from 2.76+/-0.39 ml min-1-1 100 ml forearm-1 during the baseline period to 4.40+/-0.60 ml min-1-1 100 ml forearm-1 (mean+/-s.e. mean, n=8, P=0.0003 by anova ). L-NMMA antagonized the vasodilator effect of nebivolol: baseline blood flow in the infused arm was 2.41+/-0.53 ml min-1 100 ml forearm-1 and 2.94+/-0.42 ml min-1 100 ml forearm-1 during coinfusion of the top dose of nebivolol with L-NMMA (P=0.0006 for an effect of L-NMMA on nebivolol response). There were no serious adverse events. CONCLUSIONS: Nebivolol causes vasodilation in the forearm vascular bed in subjects with essential hypertension. Since this response is antagonized by L-NMMA, the vasodilatation is probably caused by activation of the L-arg/NO pathway.     

The influence of CYP2D6 phenotype on the clinical response of nebivolol in patients with essential hypertension

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * The variability in drug metabolism has been recognized as an important factor in the occurrence of adverse effects or lack of therapeutic efficacy. * The metabolism of the third-generation beta(1)-receptor antagonist nebivolol has been shown to be highly dependent on cytochrome P450 2D6 enzymatic activity in preclinical studies. WHAT THIS STUDY ADDS: * This paper assesses the role of a cytochrome P450 2D6 gene defect on the antihypertensive response to nebivolol in a clinical setting. * Despite significant differences in drug disposition, the chronic administration of nebivolol produced similar efficacy and tolerability in hypertensive patients either characterized as poor or extensive metabolizers of the drug. * The study offers insight into the relative contribution of nebivolol enantiomers in systemic blood pressure control. AIMS: Nebivolol is a beta(1)-adrenergic receptor antagonist with vasodilating properties used in the treatment of hypertension. It is administered as a racemic mixture (D- and L-nebivolol) and is highly metabolized by the cytochrome P-450 2D6 (CYP2D6). The purpose of this study was to determine the role of CYP2D6 phenotypes on the efficacy and tolerability of nebivolol during chronic administration to patients with essential hypertension. METHODS: Two hundred and eighteen patients were genotyped and phenotyped for CYP2D6 activity, allowing to find and match 14 poor metabolizers (PMs) with 23 extensive metabolizers (EMs). Patients took rac-nebivolol 5 mg daily for 12 weeks. Blood pressure (BP), heart rate, adverse events, plasma levels of the two enantiomers D- and L-nebivolol and their corresponding hydroxymetabolites were assessed. RESULTS: The metabolic disposition of nebivolol was enantioselective and highly influenced by CYP2D6 phenotypes. Mean steady-state plasma concentrations of D- and L-nebivolol were 10- and 15-fold greater in PMs than in EMs, respectively (P < 0.0001). Despite these differences in the pharmacokinetics of nebivolol, EMs and PMs displayed similar BP responses. Mean reductions in sitting systolic and diastolic BPs were -11/-10 +/- 9/4 mmHg in EMs and -11/-9 +/- 10/5 mmHg in PMs. Side-effects were mild to moderate and not different between groups. CONCLUSION: Polymorphisms in the gene encoding CYP2D6 significantly influenced the metabolism of nebivolol, but not its antihypertensive efficacy and tolerability. The similar clinical response between EMs and PMs could be explained by the contribution of active hydroxylated metabolites of nebivolol to its antihypertensive actions in EMs.     

厄贝沙坦氢氯噻嗪对高血压患者血压变异性和左心室肥厚的影响

目的 观察厄贝沙坦氢氯噻嗪对原发性高血压患者血压变异性和左心室肥厚的影响.方法 选择2009年12月至2011年12月空军航空医学研究所附属医院门诊及住院治疗的92例原发性高血压患者,口服厄贝沙坦氢氯噻嗪（每片含厄贝沙坦150 mg及氢氯噻嗪12.5 mg）,1片/次,1次/d,共 8周,比较治疗前后血压、血压变异性,以收缩压、舒张压标准差（SD）表示血压变异性,24 h 收缩压、24 h 舒张压变异（24 h 收缩压变异、24 h 舒张压变异）及左心室质量的变化.结果治疗前、后24 h 收缩压变异分别为（14.8±3.6）、（9.7±2.8） mmHg（1 mmHg=0.133 kPa）,24 h 舒张压变异分别为（12.9±3.1）、（8.6±2.4）mmHg,治疗后24 h收缩压变异、24 h 舒张压变异较治疗前降低,差异有统计学意义（P〈0.05）;治疗前左心室质量为（242±40）g,治疗后为（223±20）g,左心室质量较治疗前下降,差异有统计学意义（P〈0.05）.结论 厄贝沙坦氢氯噻嗪在稳定降压的同时可降低血压变异性,改善心室重构.     

硝苯地平对原发性高血压患者血压变异性及内皮功能的影响

目的：探讨硝苯地平对原发性高血压患者血压变异性及内皮功能的影响。方法：68例高血压患者停药2周后口服硝苯地平控释片,每日30～60mg,共4周;患者用药前后均行24h动态血压监测,采静脉血用放射免疫法测定血浆内皮素。结果：口服硝苯地平后患者的24h平均收缩压、24h平均舒张压、24h收缩压变异性、白昼收缩压变异性、内皮素含量明显下降。结论：高血压患者血压增高与内皮功能受损有关,硝苯地平有较好的降压作用,可减少血压变异性,而且可改善高血压患者的内皮功能。     

高血压患者脉压指数与血浆内皮素-1的关系

目的：探讨原发性高血压病（EH）患者的脉压指数（PPI）与血浆内皮素一1（ET一1）的相互关系。方法：146例EH患者,行24h动态血压监测,计算PPI值,根据PPI值分为三组,PPI〈0．35为A组,PP10．35～0．45为B组,PPI〉0．45为C组。正常体检者64例为对照组（D组）。四组研究对象均抽血化验血浆ET一1。结果：与对照组相比高血压患者血浆ET一1明显增加（P〈0．05）。而EH患者随着PPI的增加,ET—1增加更明显（P〈0．05）,相关分析显示PPI与ET—1呈正相关（P〈0．01）。结论：EH患者PPI和血浆ET一1明显增加。     

糖尿病及糖尿病合并高血压对动脉僵硬度的影响

目的探讨糖尿病及糖尿病合并高血压患者动脉僵硬度的变化。方法将188例患者分为健康对照组(A组,30例),单纯糖尿病组(B组,33例),单纯高血压病组(C组,46例)及糖尿病合并高血压组(D组,79例)。测量臂-踝脉搏波速度(baPWV)、踝臂指数(ABI);检测血脂、糖化血红蛋白(HbA1c)、血糖及肾功能。结果 D组baPWV大于B组和C组,B组、C组及D组均大于A组(P<0.05)。多元逐步回归分析提示年龄、收缩压(SBP)和HbA1c是baPWV的独立影响因素。结论糖尿病合并高血压患者动脉僵硬度大于单纯糖尿病或单纯高血压患者;年龄、SBP和HbA1c是baPWV的独立影响因素。     

原发性高血压患者血压变异性的临床研究

目的 探讨原发性高血压病(EH)血压变异性(BPV)的临床意义.方法 对45例EH患者和40例健康者(对照组)进行24h动态血压监测(ABPM),以测得的各时间段血压标准差(SD)作为BPV指标.结果 EH组血压变异性明显大于对照组,Ⅱ、Ⅲ期EH患者血压变异性明显大于Ⅰ期EH患者;EH患者血压变异性随血压水平的增加而逐...