Prospective and randomized study of the antihypertensive effect and tolerability of three antihypertensive agents,losartan, amlodipine,and lisinopril,in hypertensive patients

We prospectively evaluated the antihypertensive effect and tolerability of three different antihypertensive agents, losartan (angiotensin II receptor blocker), amlodipine (calcium channel blocker), and lisinopril (angiotensin-coverting enzyme inhibitor), in patients with mild-to-moderate hypertension. After a 2-week washout period, 121 patients were randomly allocated to three different groups for 12 weeks. Medications were titrated upward as necessary to achieve the goal office-recorded sitting diastolic blood pressure (SiDBP) (defined as SiDBP 90mmHg or SiDBP 900mmHg but with a 10mmHg drop from baseline). Efficacy and tolerability were assessed after 4, 8, and 12 weeks of therapy with each regimen. At 12 weeks, significant differences in SiDBP compared with data of baseline were noted in all three groups (P 0.001 in all comparisons). Similarly, significant differences in the sitting systolic blood pressure compared with baseline data were also seen for all three groups (P 0.001 in all comparisons). The number of patients reaching goal SiDBP were comparable for the three groups: 25 patients (62.5%) in the losartan group, 27 patients (67.5%) in the amlodipine group, and 22 patients (59.5%) in the lisinopril group (not significant). Amlodipine produced a more pronounced reduction in SiDBP than the other two medications, although without statistical significance. Patients receiving lisinopril showed a high incidence of coughing (31.7%). Low leg edema was noted only in the amlodipine group (7.5%). Compared with the amlodipine and lisinopril groups, the losartan group seemed to have relatively fewer episodes (7.5%), and fewer patients (three cases) experienced adverse effects. In conclusion, this study demonstrates that losartan has the same antihypertensive effect, but has superior tolerability compared with the other two drugs. Coughing was a common side effect of lisinopril therapy in our population.     

Influence of T-calcium channel blocker treatment on deterioration of renal function in chronic kidney disease

Some calcium channel blockers (CCBs) have renoprotective effects. Our aim was to compare the effects of different subclasses of CCBs on the deterioration of renal function in chronic kidney disease (CKD). This is a prospective, observational cohort study in a single center. The subjects were 107 nondiabetic CKD patients. The rate of deterioration of estimated glomerular filtration rate (ΔeGFR) was calculated by [last visit eGFR — baseline eGFR/follow-up duration]. Multivariate analysis was performed using the change in urinary protein (ΔUP) and ΔeGFR during follow-up as response variables. CCB subclasses were L-type in 76 patients, T- and L-type in 28 patients, and nondihydropyridines in 6 patients. Multiregression analysis indicated that higher baseline proteinuria (UP) and the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers were associated with the decrease of UP, while the use of L-type CCBs, prednisolone, and probucol was associated with the increase of UP. The use of T- and L-type CCBs, ACEIs and diuretics was associated with a good outcome in terms of ΔeGFR, whereas chronic glomerulonephritis, polycystic kidney disease, and higher baseline eGFR and UP were associated with a poor outcome. It is suggested that the use of T- and L-type CCB among other subclasses may improve the outcome of patients with nondiabetic CKD in terms of renal function.     

血管紧张素转换酶抑制剂联合钙离子通道阻滞剂在高血压治疗中的应用进展

高血压是一种临床常见的心血管综合征,由于其发病机制复杂,单药治疗血压控制达标率低,而联合治疗通过干预多种升压机制,不仅使血压控制达标率明显增高,而且具有良好的靶器官保护作用。研究表明在众多联合治疗方案中血管紧张素转换酶抑制剂联合钙离子通道阻滞剂可能是最优化的一种,现将对此进行综述。     

福辛普利和缓释维拉帕米对原发性高血压患者纤溶系统的影响

目的 :比较福辛普利和缓释维拉帕米对原发性高血压患者纤溶系统的影响。方法 :将 40例轻、中度原发性高血压患者随机分为福辛普利组和缓释维拉帕米组 ,每组 2 0例 ,分别给予福辛普利(10～ 15mg ,每日 1次 )或缓释维拉帕米 (2 40～ 360mg ,每日 1次 )治疗 8周。治疗前后测定血组织型纤溶酶原激活剂(tPA)、组织型纤溶酶原激活物抑制剂 1(PAI 1)和纤维蛋白原浓度。同时测定血管紧张素 (Ang)Ⅱ ,血管紧张素转换酶(ACE)及去甲肾上腺素浓度。结果 :两组基线tPA和PAI 1浓度相似 (P >0 0 5 )。福辛普利组治疗后较治疗前血PAI 1浓度下降 ,有显著差异(P <0 0 5 ) ,而tPA浓度无显著变化 (P >0 0 5 )。缓释维拉帕米组治疗后较治疗前血PAI 1浓度增加 ,而tPA浓度下降 ,有显著差异 (P均 <0 0 5 )。此外 ,福辛普利组治疗后血ACE及AngⅡ浓度显著低于治疗前 ,有非常显著性差异 (P <0 0 1) ;而缓释维拉帕米组治疗后较治疗前血去甲肾上腺素水平显著降低 (P <0 0 5 )。结论 :福辛普利能显著降低原发性高血压患者PAI 1,增加纤溶活性 ;而缓释维拉帕米则抑制纤溶活性。对于有血栓倾向的高危患者 ,需注意降压药物对纤溶系统的影响     

不同时间服用阿司匹林联合不同种类降压药物对轻度高血压的影响

目的探讨不同时间服用阿司匹林且分别予钙离子拮抗剂(CCB)及血管紧张素转换酶抑制剂(ACEI)降压药联合对轻度高血压患者血压的影响。方法 120例轻度高血压患者经积极改良生活方式2个月后,血压仍未达标者,在继续生活方式改良的基础上,随机分为6组,每组20例。组1:晨服氨氯地平5 mg;组2:晨服氨氯地平5 mg+晨服拜阿司匹林100 mg;组3:晨服氨氯地平5 mg+睡前服拜阿司匹林100 mg;组4:晨服贝那普利10 mg;组5:晨服贝那普利10 mg+晨服拜阿司匹林100 mg;组6:晨服贝那普利10 mg+睡前服拜阿司匹林100 mg,观察3个月。治疗前后分别进行血压监测和血生化指标的测定。结果治疗后6组血压均明显下降(P<0.01);组3的降压幅度明显高于其他组(P<0.05或P<0.01);组6降压幅度较组1、组2、组4、组5有所增大,但差异无统计学意义(P>0.05);阿司匹林睡前服用组的降压幅度较晨服组和不服组增高(P<0.05或P<0.01),而晨服组与不服组间比较无统计学意义(P>0.05)。结论睡前服用阿司匹林比晨服有利于降低血压,与CCB合用效果更明显。     

Combination Therapy Versus Monotherapy in Reducing Blood Pressure: Meta-analysis on 11,000 Participants from 42 Trials

Objective

To quantify the incremental effect of combining blood pressure-lowering drugs from any 2 classes of thiazides, beta-blockers, angiotensin-converting enzyme inhibitors, and calcium channel blockers over 1 drug alone and to compare the effects of combining drugs with doubling dose.

Methods

Meta-analysis of factorial trials in which participants were randomly allocated to 1 drug alone, another drug alone, both drugs together, or a placebo.

Results

We identified 42 trials (10,968 participants). With a thiazide used alone, the mean placebo-subtracted reduction in systolic blood pressure was 7.3 mm Hg and 14.6 mm Hg combined with a drug from another class. The corresponding reductions were 9.3 mm Hg and 18.9 mm Hg with a beta-blocker, 6.8 mm Hg and 13.9 mm Hg with an angiotensin-converting enzyme, and 8.4 mm Hg and 14.3 mm Hg with a calcium channel blocker. The expected blood pressure reduction from 2 drugs together, assuming an additive effect, closely predicted the observed blood pressure reductions. The ratios of the observed to expected incremental blood pressure reductions from combining each class of drug with any other over that from 1 drug were, respectively, for thiazides, beta-blockers, angiotensin-converting enzyme inhibitors, and calcium channel blockers: 1.04 (95% confidence interval [CI], 0.88-1.20), 1.00 (95% CI, 0.76-1.24), 1.16 (95% CI, 0.93-1.39), and 0.89 (95% CI, 0.69-1.09); the overall average was 1.01 (95% CI, 0.90-1.12). Comparison of our results with those of a published meta-analysis of different doses of the same drug showed that doubling the dose of 1 drug had approximately one fifth of the equivalent incremental effect (0.22 [95% CI, 0.19-0.25]).

Conclusion

Blood pressure reduction from combining drugs from these 4 classes can be predicted on the basis of additive effects. The extra blood pressure reduction from combining drugs from 2 different classes is approximately 5 times greater than doubling the dose of 1 drug.     

依那普利与吲哒帕胺对高血压患者中心和外周动脉压的影响

目的比较依那普利和吲哒帕胺对中心动脉压和外周动脉压的影响。方法采用随机双盲方法,经2周的安慰剂洗脱后,年龄30—75岁的轻、中度原发性高血压患者被随机分为依那普利组（10mg,1次／d）或吲哒帕胺组（2．5mg,1次／d）,共治疗8周。所有患者在开始服药前及研究结束时均做脉搏波检查。只有完成8周治疗的患者列入最终分析。结果共有101例患者（依那普利组51例,吲哒帕胺组50例）完成该研究,治疗前两组间的各参数基线水平差异均无统计学意义（P值均〉0,05）。经8周治疗后,与基线值比较,除心率和吲哒帕胺组的反射波增压指数无显著变化外,脉搏波所有观察指标均显著下降;两组间比较,除依那普利组中心动脉收缩压、反射波增压、反射波增压指数显著低于吲哒帕胺组外,其他指标差异均无统计学意义（P值均〉0．05）;依那普利组中心动脉收缩压和脉压下降值显著大于肱动脉,而吲哒帕胺组未见显著性差异。结论依那普利和吲哒帕胺降低外周动脉压效果相似,但依那普利降低中心动脉收缩压和反射波增压指数更显著,这可能与该药使波反射降低有关。     

多普勒肾血流测定对不同降压药肾脏保护作用的随访

高血压作为一项心血管病危险因素,是造成心脑血管病、肾功能衰竭和周围血管病的主要原因。众多的临床试验表明,血压是独立的肾损害预后决定因素。因而在应用抗高血压药物时,其是否具有肾脏保护作用已得到国内外学者的广泛关注。目前对血管紧张素转换酶抑制剂(ACEI)及钙通道阻滞     

卒中预防中的抗高血压药选择

控制高血压对于卒中预防至关重要.对于大多数患者来说,单药治疗往往不能使血压降至正常水平,而联合用药可提高降压效应,但并非所有降压药均效果良好.中国高血压干预效果研究的早期数据分析以及缬沙坦对血压未控制的心血管高危日本患者发病率和病死率影响研究的亚组分析显示,二氢吡啶类钙通道阻滞药氨氯地平和血管紧张素转换酶抑制药缬沙坦是...     

苯那普利、缬沙坦对自发性高血压大鼠肾脏血管紧张素转换酶2表达的影响

目的观察苯那普利与缬沙坦对自发性高血压大鼠(SHR)血浆血管紧张素Ⅱ(AngⅡ)和肾脏血管紧张素转换酶2(ACE2)表达水平的影响,探讨ACE2在高血压发病机制和药物治疗中的意义。方法12周龄雄性SHR28只,分为空白对照组(Sc)、苯那普利组(10mg/kg.d)(Sb)、小剂量缬沙坦组(10mg/kg.d)(Sl)、大剂量缬沙坦组(30mg/kg.d)(Sh),每组7只,7只雄性WKY大鼠为正常对照。药物治疗3月后,用放射免疫法测定血浆AngⅡ含量,RT-PCR法测定肾脏中ACE和ACE2mRNA的表达水平,免疫组化法比较肾脏中ACE2蛋白的表达。结果与WKY大鼠相比,SHR肾脏中ACE2mRNA及其蛋白的表达均明显降低,而ACEmRNA的表达和血浆AngⅡ水平则明显升高(P<0.05)。缬沙坦治疗后SHR血压显著下降而血浆AngⅡ水平则进一步升高,肾脏中ACE2的表达水平明显升高,且呈剂量依赖性(P<0.05)。苯那普利治疗对SHR血浆AngⅡ水平及肾脏ACE2的表达则无明显影响。结论SHR体内ACE和ACE2的表达失衡可能在高血压的发病机制中有重要意义。血管紧张素受体拮抗剂(ARB)可能通过升高SHR血浆AngⅡ的水平而增加肾脏中ACE2的表达,ACE2表达的增加可能是ARB抗高血压治疗的一个新药理机制。     

Treatment and prevention of atrial fibrillation with nonantiarrhythmic pharmacologic therapy

Atrial fibrillation is one of the most frequent heart rhythm disturbances found in clinical practice. Anticoagulation, rate control, cardioversion, and ablative procedures have been the mainstay of treatment. The frequent recurrence of atrial fibrillation and the side effects when antiarrhythmic drugs are used have led to dissatisfaction with available treatment of this arrhythmia. Pharmacologic therapy with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, statins, and perhaps aldosterone and calcium channel blockers may have a role in the prevention of atrial fibrillation onset and recurrence. We summarize the possible biologic mechanisms and the clinical observations supporting the use of non-antiarrhythmic medications in the prevention of atrial fibrillation.     

Update on the drug treatment of hypertension in patients with cardiovascular disease

The management of the high-risk patient with hypertension has become more challenging in recent years. Drug therapy should be initiated earlier and at lower blood pressure levels in patients with coexisting cardiovascular or kidney diseases. The blood pressure goals of drug therapy are substantially lower when patients have concomitant heart or kidney disease or diabetes mellitus. Numerous clinical trials in tens of thousands of hypertensive patients with increased cardiovascular risk have demonstrated that the calcium antagonists are as effective and safe as diuretics, beta-adrenergic blockers, and renin-angiotensin blocking agents to prevent heart attack and stroke but not heart failure. Several recent studies also demonstrate that angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers are effective in preventing stroke, progressive renal insufficiency, and heart failure in higher risk patients with hypertension. To achieve the aggressive blood pressure goals in patients with cardiovascular disease, thoughtful combinations of additive or synergistic agents improve efficacy and tolerability and have become an integral part of the modern management of hypertensive patients with coexisting cardiovascular disease.     

Treatment of Isolated Systolic Hypertension in the Elderly: The Syst-Eur Trial

The Syst-Eur study investigated whether active antihypertensive treatment could reduce cardiovascular complications in elderly patients with isolated systolic hypertension. Patients ≥ 60 years) were randomly assigned to active treatment (n = 2398), i.e. nitrendipine, with the possible addition of enalapril and hydrochlorothiazide, or matching placebos (n = 2297). In the intention-to-treat analysis, the beween-group difference in blood pressure amounted to 10.1/4.5 mm Hg (P < 0.001). Active treatment reduced the total incidence of stroke (primary endpoint) by 42% (P = 0.003), of all cardiac endpoints by 26% (P = 0.03), and of all cardiovascular endpoints combined by 31% (P < 0.001). Cardiovascular mortality was slightly lower on active treatment (-27%; P = 0.07), but all-cause mortality was not influenced (-14%; P = 0.22). For total (P = 0.009) and cardiovascular mortality (P = 0.09), the benefit of antihypertensive treatment weakened with advancing age and for total mortality it decreased with higher systolic blood pressure at entry (P = 0.05). The benefits of active treatment were not independently related to gender or to the presence of cardiovascular complications at entry. Further analyses also suggested benefit in patients who were taking nitrendipine as the sole therapy. The per-protocol analysis largely confirmed the intention-to-treat results. It can be concluded that stepwise antihypertensive drug treatment, starting with the dihydropyridine calcium channel blocker nitrendipine, improves prognosis in elderly patients with isolated systolic hypertension.     

通过脉搏波分析比较咪达普利对中心和外周动脉压的影响

目的:比较咪达普利对中心动脉压和外周动脉压的影响.方法:经2周的安慰剂洗脱后,年龄18～79岁的53例轻、中度原发性高血压患者每日服用咪达普利5～10 mg共治疗6周.所有患者在开始服药前及研究结束时均做脉搏波检查.只有完成6周治疗的患者列入最终分析.结果:共有48例患者完成该研究.经6周治疗后,脉搏波所有观察指标显著下降(P均＜0.05～0.001),且中心动脉收缩压和脉压下降幅度显著大于肱动脉收缩压和脉压下降(P值分别为0.002和0.003).结论:咪达普利降低外周动脉压和中心动脉压均有效,且降低收缩压和脉压在中心动脉比外周动脉显著,其差异可能系波反射降低所致.     

苯那普利、缬沙坦对糖尿病大鼠肾脏紧张素转换酶2表达的影响

目的 观察糖尿病大鼠肾脏血管紧张素转换酶2(ACE2)的表达及苯那普利、缬沙坦对糖尿病大鼠肾脏ACE2表达水平的影响,初步探讨ACE2在糖尿病肾病发病机制中的作用.方法 3月龄的SD雄性大鼠,腹腔内注射链脲佐菌素建立糖尿病大鼠模型,随机分为3组,每组7只,分别为糖尿病模型组、苯那普利治疗组[10 mg/(kg·d)]、缬沙坦治疗组[10 mg/(kg·d)],SD雄鼠7只作为正常对照组.给药3月后,处死动物、留取标本,反转录-聚合酶链式反应(RT-PCR)法测定肾脏中ACE和ACE2 mRNA的表达水平,免疫组化法比较肾脏中ACE2蛋白的表达水平.结果 与正常对照组相比,糖尿病模型组大鼠ACE、ACE2 mRNA表达分别下降30.7%、50.1%(P＜0.05).与糖尿病模型组比较,苯那普利组ACE mRNA的表达明显增加(P＜0.01),ACE2 mRNA的表达无明显差异;缬沙坦组ACE mRNA的表达治疗后没有明显变化,而ACE2 mRNA和蛋白的表达均有明显增加,分别增加68.7%和69.8%(P＜0.01).结论 1)肾脏局部ACE2表达水平的降低可能是糖尿病大鼠肾损害的发病机制之一;2)ARB可能是通过增加肾脏局部ACE2的表达而发挥肾脏保护作用.     

苯那普利、缬沙坦对糖尿病大鼠肾脏血管紧张素转换酶2表达的影响

目的观察糖尿病大鼠肾脏血管紧张素转换酶2(ACE2)的表达及苯那普利、缬沙坦对糖尿病大鼠肾脏ACE2表达水平的影响,初步探讨ACE2在糖尿病肾病发病机制中的作用。方法3月龄的SD雄性大鼠,腹腔内注射链脲佐菌素建立糖尿病大鼠模型,随机分为3组,每组7只,分别为糖尿病模型组、苯那普利治疗组[10mg/(kg.d)]、缬沙坦治疗组[10mg/(kg.d)],SD雄鼠7只作为正常对照组。给药3月后,处死动物、留取标本,反转录-聚合酶链式反应(RT-PCR)法测定肾脏中ACE和ACE2 mRNA的表达水平,免疫组化法比较肾脏中ACE2蛋白的表达水平。结果与正常对照组相比,糖尿病模型组大鼠ACE、ACE2 mRNA表达分别下降30.7%、50.1%(P<0.05)。与糖尿病模型组比较,苯那普利组ACE mRNA的表达明显增加(P<0.01),ACE2 mRNA的表达无明显差异;缬沙坦组ACE mRNA的表达治疗后没有明显变化,而ACE2 mRNA和蛋白的表达均有明显增加,分别增加68.7%和69.8%(P<0.01)。结论1)肾脏局部ACE2表达水平的降低可能是糖尿病大鼠肾损害的发病机制之一;2)ARB可能是通过增加肾脏局部ACE2的表达而发挥肾脏保护作用。     

The Effect of Pravastatin on Renal Function and Lipid Metabolism in Patients with Renal Dysfunction with Hypertension and Hyperlipidemia

The effect of pravastatin on renal function in hypertensive patients with mild renal dysfunction and hyperlipidemia was examined. A total of 57 subjects given dihydropyridine calcium blockers were randomly assigned to placebo (n=25) and pravastatin groups (n=32). The period of study was 6 months. In the placebo group, lipid metabolism did not change throughout the study period, but the serum creatinine concentration (Scr) increased from a baseline of 1.6± 0.07 mg/dl to 2.1 ±0.2 mg/dl in the 6th month vof study and blood urea nitrogen     

Effects of Quinapril Hydrochloride in Patients with Essential Hypertension and Impaired Renal Function

The short-term effects of administration of an angiotensin-converting enzyme (ACE) inhibitor, quinapril hydrochloride (quinapril) (5–10mg/day), for 12 weeks on blood pressure and renal function were evaluated in 8 patients (60.5±7.3 years old, mean±SD) with mild to moderate essential hypertension and mild impairment of renal function due to nephrosclerosis. Systolic blood pressure and diastolic blood pressure were significantly reduced from 163.0± 4.0 to 132.3± 17.6 mmHg (p<0.01) and from 98.3± 4.6 to 81.5± 6.4 mmHg (p<0.001), respectively, before to after treatment. Both renal plasma flow (RPF) and glomerular filtration rate (GFR) were significantly increased in all patients, from 203.9 ± 33.3 to 245.4 ± 36.7 ml/min/1.73m² (p<0.01), and from 43.4± 6.4 to 53.5± 4.6 ml/min/1.73m² (p<0.05), respectively.

Short-term quinapril administration was beneficial to renal function in patients with essential hypertension and impaired renal function.     

Treatment of Hypertension in Metabolic Syndrome Subjects with Amlodipine and Olmesartan—Effects on Oxidized Non-Esterified Free Fatty Acids and Cytokine Production

Purpose  Angiotensin II increases activation of oxidative signaling and vascular inflammatory gene expression, and interruption of the renin-angiotensin system has been considered more vasculoprotective than use of calcium channel antagonists and other anti-hypertensive therapies. Despite these putative mechanisms, amlodipine is equally efficacious as other therapies in reducing cardiovascular events. Methods  Double-blind, controlled trial, designed to investigate the effects of 2-months treatment with amlodipine and olmesartan on oxidized non-esterified fatty acids (ox-NEFA), and lipopolysaccharide-stimulated cytokine production in whole blood among 23 hypertensive subjects with the metabolic syndrome. Results  Treatment with olmesartan was no different than amlodipine in changing concentrations of total oxidized fatty acids (p = 0.37), total ox-NEFA (p = 0.43) and 9, 10, 11, 12, 13, 14, 15 and 16 ox-NEFA concentrations. In contrast, 8 ox-NEFA increased (median [interquartile ranges] by 45.2% [5.3 to 50.0] in olmesartan-treated subjects) compared with a decrease of 18.4% (−45.1–13.9) in amlodipine-treated subjects (p = 0.03). Lipopolysaccharide-stimulated cytokine production and levels of soluble cellular adhesion molecules did not change with either treatment. Conclusion  Despite experimental data that demonstrates that angiotensin receptor antagonists reduce cellular oxidant stress and inflammation, olmesartan was not different than amlodipine in changing ox-NEFA and inflammatory markers in hypertensive subjects with the metabolic syndrome.