Differential effects of extended-release carvedilol and extended-release metoprolol on lipid profiles in patients with hypertension: results of the Extended-Release Carvedilol Lipid Trial

Some β-blockers, although they are effective antihypertensive agents, may adversely effect dyslipidemia and decrease insulin sensitivity. β-blockers without adverse metabolic effects may provide an improvement in long-term hypertension therapy. Hypertensive patients (n = 568) without diabetes, not requiring lipid-lowering therapy, were randomized to once-daily extended-release carvedilol or extended-release metoprolol and titrated to target blood pressure (BP). Co-primary endpoints were comparison between groups in high-density lipoprotein (HDL) or triglycerides at 24 weeks. Extended-release carvedilol was superior to extended-release metoprolol in meeting the primary endpoint of a difference in triglycerides; the median % change in triglycerides being ?8.026% (P = .0141; 97.5% confidence interval [CI], ?15.35, ?0.67)] from baseline to 24 weeks. Triglycerides were unchanged with carvedilol and increased with metoprolol. There was no significant difference in effect on HDL. BP was similar between treatment groups. There was a significant decrease with extended-release carvedilol vs. extended-release metoprolol in insulin (?2.56 μU/mL [P = .0213; 95% CI, ?4.74 to ?0.38]) and c-peptide [(?0.43 ng/mL [P = .0007; 95% CI, ?0.68 to ?0.18]). In hypertension, extended-release carvedilol resulted in lower triglycerides, insulin, and C-peptide levels compared with extended-release metoprolol. Similar effects were observed in high-risk subgroups. Both treatments were well tolerated. This differential metabolic profile could be useful in determining antihypertensive treatment options.     

赖诺普利对高血压病患者内源性血压调节系统和左室重塑的影响

目的 探讨赖诺普利对高血压患者内源性血管活性因子及左室肥厚的影响.方法 分别用口服赖诺普利与卡托普利方法治疗高血压伴左室肥厚患者8周,应用超声心动图监测治疗前、后左室重量指数(LVMI),同时采用放射免疫法和(或)化学发光法检测血浆血管紧张素Ⅱ(AT-Ⅱ)、醛固酮(AID)、血浆内皮素(ET)、转化生长因子β1(TGF-β1)、心钠素(ANP)及血清胰岛素样生长因子-1(IGF-1)的浓度.结果 ①高血压组患者血浆AT-Ⅱ、ALD、ET、ANP、TGF-β1,及血清IGF-1浓度明显高于对照组(P值分别为0.042、0.039、0.041、0.045、0.038、0.047,P均<0.05),LVH组高于无LVH组(P均<0.01).②治疗后与治疗前比较,两组AT-Ⅱ、ALD、ET、ANP、TGF-β1、IGF-1和LVMI水平均显著降低(P值分别为0.037、0.041、0.046、0.048、0.038、0.044,P均<0.05),但赖诺普利组降低幅度明显高于卡托普利组,差异有统计学意义(P均<0.01).结论 赖诺普利与卡托普利均有降压及逆转左室肥厚的作用,但赖诺普利逆转LVH的强度更强.且不良反应少,依从性强,值得临床推广使用.     

国产卡维地洛的降压疗效及对高血压患者血浆一氧化氮和内皮素的影响

目的:观察国产卡维地洛的降压疗效及其对高血压患者血浆一氧化氮(NO)、内皮素(ET)含量的影响。方法:入选80例高血压患者按随机配对原则分入卡维地洛组(卡组)及络德对照组(络组)。病人在用药前及总疗程结束后采血,用亚硝酸还原法测定血浆NO,用放射免疫技术测定血浆ET。另10例正常对照组测定血浆NO、ET。结果:降压总有效率卡组为85%,络组为84.6%,两组用药后心率均下降,两组患者降压疗效及心率下降均无显著差异(P>0.05)。用药前血NO浓度:卡组、络组的均显著低于正常对照组(P<0.05),经治疗后卡组、络组的均显著上升(P均<0.05),用药前血ET浓度:卡组、络组的均高于正常对照组(P<0.01),用药后卡组、络组的均显著下降(P均<0.05)。两药对NO、ET影响无显著差异,两药的不良反应较轻,亦无显著差异(P>0.05)。结论:两种国产卡维地洛均有较好的降压疗效。高血压病人经卡维地洛治疗后血管内皮功能有改善。     

Efficacy of once-daily lisinopril monotherapy in systemic hypertension

Lisinopril is a new, long-acting angiotensin-converting enzyme inhibitor formulated for once-daily treatment of hypertension. This study assessed the 24-h efficacy and tolerability of lisinopril in Chinese patients with mild to moderate hypertension of World Health Organization Stages I to II. A total of 30 patients aged 30 to 60 years (mean 47 ± 9) entered a 2-week washout period. All patients had ambulatory diastolic blood pressure (BP) > 90 mmHg and were given active treatment with lisinopril for 4 to 7 weeks. The dose of lisinopril was titrated from 10 to 40 mg daily (at 8-9 A. M.). In each patient, 24-h ambulatory blood pressure (BP) monitoring (SpaceLabs 90202) was performed twice, once before and once following treatment. Mean 24-hour systolic/diastolic BPs after lisinopril were significantly decreased compared with baseline values (132 ± 12/86 ± 7 vs. 150 ± 11/98 ± 7 mmHg; p < 0.0005/ 0.0005). The average dose of lisinopril was 14.5 ± 5 mg daily after a titration period of 5 weeks of treatment. Mean daytime (6 A. M. to 6 P. M.) BP decreased from 152 ± 11/100 ± 8 to 134 ± 12/87 ± 8 mmHg (p < 0.0005/0.0005) and nighttime (6 P.M. to 6 A. M.) BP from 147 ± 14/95 ± 9 to 128 ± 14/83 ± 8 mmHg ( p < 0.0005/0.0005). BP reduction was more pronounced during the night. Before treatment, the circadian variation showed a peak BP at 11 A. M. and nadir at 3 P. M. After treatment, significant BP reduction (p < 0.0005/0.0005) was seen throughout the 24-h period. The circadian rhythm of BP was preserved as indicated by similar BP standard deviations (14 ± 3/11 ± 2 vs. 13 ± 3/10 ± 2 mmHg). Mean heart rate increased from 76 to 80 beats/min (p < 0.05). Four patients reported having a nonproductive cough. Thus, lisinopril administered as once-daily monotherapy provided effective BP control over a 24-h period with preserved circadian rhythm.     

卡维地洛治疗老年轻中度原发性高血压疗效观察

目的本研究以高选择性β受体阻滞剂比索洛尔为对照药，研究了卡维地洛治疗轻中度原发性高血压的临床疗效及安全性。方法选择轻中度原发性高血压患者60例，分别随机给予卡维地洛和比索洛尔口服治疗。结果2组在治疗2周时诊室血压均有所下降，在治疗6～8周末下降最明显，并维持至24周。卡维地洛组和比索洛尔组降压总有效率分别为93．3％和90％，总显效率分别为70％和56．7％。卡维地洛主要的不良反应有头晕（13％）、乏力（2％）、嗜睡（2％）。在服药过程中逐渐减轻，无因药物不良反应而终止者。结论本研究中的原发性高血压患者每日口服1次卡维地洛12．5～50mg，降压疗效明显，耐受性及安全性好。     

赖诺普利逆转高血压患者左室肥厚的相关性研究

目的探讨赖诺普利对高血压患者左室肥厚的逆转作用。方法分别口服赖诺普利与卡托普利治疗高血压伴左室肥厚患者8周,应用超声心动图监测治疗前、后左室重量指数（LVMI）,同时采用放射免疫法和（或）化学发光法检测血浆血管紧张素Ⅱ（AT-Ⅱ）醛固酮（ALD）,血清胰岛素样生长因子-1（IGF-1）的浓度。结果①高血压组患者血浆AT-Ⅱ、ALD,血清IGF-1浓度明显高于正常对照组（P值分别为0.023,0.018,0.032）,LVH组高于无LVH组（P值为0.0083）。②治疗后与治疗前比较,两组患者AT-Ⅱ、ALD、IGF-1和LVMI水平均显著降低（P值分别为0.036,0.028,0.031）,但赖诺普利组降低幅度明显高于卡托普利组,差异有统计学意义（P〈0.01）。结论赖诺普利与卡托普利均有降压及逆转左室肥厚的作用,但赖诺普利逆转LVH的强度更强,且不良反应少,依从性强,值得临床推广使用。     

Effect of indomethacin on the antihypertensive efficacy of valsartan and lisinopril: a multicentre study

OBJECTIVE : To compare the effect on antihypertensive efficacy produced by the addition of indomethacin to the angiotensin II (Ang II) antagonist, valsartan, or to the angiotensin-converting enzyme inhibitor, lisinopril, in hypertensive patients with chronic osteoarthritis. SUBJECTS AND METHODS : One hundred and twenty-eight patients (52 men and 76 women) aged 25-82 years (mean age 55.7 years), with diastolic blood pressure (DBP) > 100 mmHg at the end of a 2-week placebo washout period were allocated randomly to groups to receive valsartan (80-160 mg once daily) or lisinopril (10-20 mg once daily). At the end of 10 weeks of treatment, patients with DBP < 90 mmHg, while continuing to receive valsartan or lisinopril treatment, were allocated randomly to groups to receive either indomethacin (50 mg three times a day) or the corresponding placebo for 2 weeks, with a 1-week washout period between the two treatments, according to a double-blind, crossover design. After the initial washout period, patients were examined at the end of the 4th, 8th and 10th weeks of randomized treatment with valsartan and lisinopril, at the end of the first crossover period and then at the beginning and at the end of the second crossover period. At each visit, sitting and standing blood pressure were measured by standard mercury sphygmomanometer. RESULTS : The addition of indomethacin blunted the blood pressure-decreasing effect of both antihypertensive drugs. Although indomethacin produced greater increases in both systolic and DBP values in the lisinopril-treated patients (5.45/3.22 mmHg) than in the valsartan-treated ones (2.12/1.87 mmHg), no significant difference between the two drugs was found. CONCLUSIONS : From a theoretical standpoint, these findings suggest that prostaglandins may play a part in the antihypertensive action of Ang II antagonists. From a practical standpoint, hypertensive patients treated with valsartan or with lisinopril should be monitored to detect changes in blood pressure control while receiving indomethacin.     

卡维地洛治疗原发性高血压疗效观察

目的 :评价第三代 β-受体阻滞剂卡维地洛治疗原发性高血压 ( EH)的疗效和安全性 ,并与拉贝洛尔比较。方法 :68例轻中度 EH患者 ,其中 3 0例进入随机单盲试验 ;服用卡维地洛、拉贝洛尔各 15例。另外 3 8例采用开放试验 ,全部服用卡维地洛 ,起始剂量卡维洛尔 10 m g/ d,拉贝洛尔 10 0 m g/ d,前 6周每 2周随访并调整剂量 ,服药至 10周末。服药前后行有关实验室检查。结果 :服药后 2、4、6、10周血压与用药前比较差异有显著性意义 ,单盲对照试验和开放试验卡维地洛总有效率分别为 76.9%和 76.3 % ,拉贝洛尔总有效率 5 7.1% ,治疗后心率略下降。不良反应少。结论 :卡维地洛用于 EH是一安全、有效药物     

Treatment of isolated systolic hypertension: the SHELL study results

OBJECTIVE: Our aim was to compare the effect of lacidipine and chlorthalidone on cardiovascular outcome as a primary parameter and blood pressure as a secondary in elderly patients with isolated systolic hypertension in a prospective study with an open design. METHODS: 1882 males and females outpatients > or = 60 years were randomly assigned to the administration of chlorthalidone 12.5 mg o.d. or lacidipine 4 mg o.d. Patients were recruited if sitting systolic blood pressure was > or = 160 mmHg with a diastolic blood pressure equal or lower than 95 mmHg. Primary endpoint was a composite of cardiovascular and cerebrovascular events. RESULTS: At randomization mean systolic blood pressure was 178.1 mmHg in the lacidipine and 178.2 mmHg in the chlorthalidone group, the corresponding mean diastolic values being 86.9 and 86.8 mmHg. In both lacidipine and chlorthalidone groups treatment caused a significant (p < 0.001) and marked systolic blood pressure reduction which was maintained throughout the treatment period with a significant (p < 0.001) and steady although less marked reduction in diastolic blood pressure as well. At the end of treatment period (median 32 months), the reduction was 36.8/8.1 mmHg (systolic/diastolic) in the chlorthalidone and 38.4/7.9 mmHg in the lacidipine group, the final on treatment blood pressures being 142.0/79.2 and 143.2/79.5 mmHg, respectively. Treatments were similarly effective in males and females and in age groups between 60 and 69 years (n = 763), 70 and 79 years (n = 744) and > or = 80 years (n = 375). Similar reductions were obtained in a subgroup of patients (n = 209) followed in double-blind fashion for 1 year. The overall incidence of the primary endpoints was 9.3% with no significant between-group difference. Total mortality was also similar between groups. CONCLUSIONS: In elderly patients with isolated systolic hypertension, administration of lacidipine or chlorthalidone markedly reduced systolic blood pressure with no difference in the incidence of cardiovascular events and total mortality.     

Cardiac hypertrophy in experimental hypertension: interaction of the sodium ion, blood pressure and lisinopril

The interaction of blood pressure, salt intake and the inhibition of angiotensin converting enzyme activity with cardiac hypertrophy were examined in the Dahl rat model. Eight-week-old salt sensitive and salt resistant rats were each separated into two colonies, one of which was maintained on a low salt and the other on a high salt diet for three weeks, at the end of which time both salt sensitive colonies were hypertensive. Each colony was then separated into two groups, one received no medication the other was given lisinopril until normotension was achieved. After 11 weeks of therapy, intra-arterial blood pressures and heart rates were recorded. The rats were sacrificed and heart weight to body weight ratios were determined. Both untreated salt sensitive groups displayed marked cardiac hypertrophy which correlated well with diastolic blood pressure irrespective of salt intake. Lisinopril therapy lowered blood pressures to normotensive levels in all groups except for salt sensitive rats ingesting a high salt diet where, despite a 10-fold increase in drug dose, normotension was not achieved. Significant cardiac regression accompanied lisinopril therapy in rats receiving low salt diets but high salt intake severely attenuated regression in both strains. There was no significant correlation between heart weight and blood pressure in the treated groups. The results suggest that cardiac regression appears to be mediated by other factors besides ventricular afterload pressure and that high salt intake adversely affects blood pressure and heart weight response to lisinopril therapy.     

Comparison of the cardiovascular protection by omapatrilat and lisinopril treatments in DOCA-salt hypertension

OBJECTIVE: To compare the cardiovascular protection provided by omapatrilat and lisinopril in an experimental model of hypertension. METHODS: Four-week deoxycorticosterone acetate (DOCA)-salt hypertensive (HT) and age-matched normotensive (NT) rats were treated either with omapatrilat (40 mg/kg per day) or lisinopril (20 mg/kg per day) for 2 weeks before sacrifice, and compared with untreated HT and NT rats sacrificed at ages corresponding to either before or after the drug regimens. RESULTS: Systolic arterial pressure (SAP) of 2 and 4 week HT rats was increased in comparison to age-matched NT rats (P <0.05). Treatment with omapatrilat or lisinopril reduced SAP in HT (P <0.05) similarly by about 10%. Cardiac interstitial collagen, perivascular collagen and media/lumen ratio of coronary arterioles were increased in HT rats. Both treatments partially prevented the rise in perivascular collagen and completely corrected the increased media/lumen ratio in small arterioles from HT (P <0.05). In contrast to NT rats, only a weak coronary dilatation to bradykinin was observed in Langendorff hearts isolated from untreated-HT. This response was slightly improved by lisinopril and markedly improved by omapatrilat (P <0.05). The coronary dilatation to SNP which was reduced in 4-week HT (P <0.05), was partially improved by omapatrilat treatment but not by lisinopril. The enhanced superoxide anion production in aorta from HT rats was partially corrected with omapatrilat and lisinopril. Finally, omapatrilat, unlike lisinopril, markedly reduced mortality in a more severe form of DOCA-salt hypertension. CONCLUSIONS: Omapatrilat and lisinopril regressed coronary remodelling and cardiac collagen deposition, and reduced vascular oxidative stress in DOCA-salt hypertensive rats. However, despite similar antihypertensive efficacy, omapatrilat was superior to lisinopril in improving the endothelial-dependent coronary dilatation, suggesting a better vascular protection in the DOCA-salt model of hypertension.     

Effect of therapy with lisinopril on the state of cerebral blood flow in women with hypertension in peri- and postmenopause

Blood flow in extra and intracranial arteries was assessed by doppler ultrasound in 26 hypertensive women without history of stroke. Studies were performed before treatment, after acute test with lisinopril and in 1 month of therapy with lisinopril. Baseline investigation revealed changes of velocity characteristics of blood flow and resistance indexes indicative of impaired cerebral hemodynamics both at extra- and intracranial level. After treatment with lisinopril signs of improvement of blood flow in extra- and intracranial arteries were found. Most important finding was normalization of ability of extracranial arteries to spasm and dilation presumably associated with restoration of hemodynamic reserve of cerebral vessels.     

Effect of carvedilol on portal hypertension depends on the degree of endothelial activation and inflammatory changes

OBJECTIVE: Bleeding from esophageal varices is a major complication of liver cirrhosis. Non-selective beta-blockers exert an influence on the functional part of portal hypertension, thereby reducing the risk of bleeding. Direct measurement of this functional part is not possible; nevertheless, pro-inflammatory markers as well as parameters of endothelial dysfunction might serve as surrogate markers. The aim of study was to assess the correlation between the therapeutic efficacy of carvedilol and markers of endothelial dysfunction and systemic inflammation in patients with liver cirrhosis and portal hypertension. MATERIAL AND METHODS: Thirty-six patients with cirrhosis and portal hypertension were given carvedilol, 25 mg q.i.d. for 30 days. Hepatic venous pressure gradient (HVPG) and biochemical determinations were performed prior to and after the treatment. Eight healthy individuals served as controls for comparison of biochemical markers. RESULTS: In the whole group of cirrhotic patients, HVPG decreased from 17.7+/-3.8 to 14.9+/-4.8 mmHg (p<0.001). Complete response was seen in 15 patients (42%). Baseline serum levels of E-selectin were significantly higher in responders than in non-responders (119.8+/-70.6 versus 52.6+/-25.7 ng/ml; p=0.023) and in controls (28.8+/-22.2 ng/ml; p=0.004). Furthermore, baseline TNF-alpha levels were significantly higher in responders than in non-responders (22.8+/-15.7 versus 7+/-8.9; p=0.047) and in controls (5.5+/-5.9 pg/ml; p=0.005). Serum levels of ICAM-1 showed the same trend (4360+/-2870 versus 2861+/-1577 versus 651+/-196 ng/ml), although differences did not reach statistical significance. CONCLUSIONS: Markers of systemic inflammation and endothelial dysfunction seem to predict the hypotensive effect of carvedilol on portal hypertension in patients with liver cirrhosis and may be useful in the assessment of the efficacy of the therapy.     

A double-blind, placebo-controlled, dose-response study of the effectiveness and safety of lisinopril for children with hypertension

BACKGROUND: Despite widespread use in hypertensive children, the safety and effectiveness of lisinopril had not been previously tested in a controlled study. METHODS: This study explored the dose-response relationship and safety of lisinopril in 115 hypertensive children, aged 6 to 16 years. Patients were randomized in a double-blind fashion for 2 weeks to one of three doses by body weight at baseline: <50 kg: low (0.625 mg), middle (2.5 mg), high (20 mg), and > or =50 kg: low (1.25 mg), middle (5 mg), high (40 mg). The dose-response for lisinopril was evaluated by analyzing the change in slope in sitting diastolic and systolic blood pressure (BP) by dose after 2 weeks of therapy compared to baseline. Patients then entered a double-blind withdrawal, where patients were either switched to placebo or continued their current lisinopril treatment for up to 2 weeks. Patients completed period II when their BP returned to baseline. Antihypertensive effectiveness, between placebo and lisinopril was determined for all doses. Adverse events were carefully monitored. RESULTS: There was a dose-response relationship between the lowest and each of the higher doses of lisinopril. Blood pressure in the placebo group increased after withdrawal of lisinopril. The dose-response relationship was consistent across all subgroups (ie, age, Tanner stage, ethnicity, gender). CONCLUSIONS: Lisinopril, once daily, is an effective and well-tolerated antihypertensive in children aged 6 to 16 years. An initial dose of 0.07 mg/kg, administered once daily, effectively lowered BP within 2 weeks. Blood pressure was reduced in a dose-dependent fashion.     

Effect of combining electrocardiographic interpretation results on diagnostic accuracy

In order to test the diagnostic performance of various ECG computer programs a reference library of ECGs is being established and evaluation methods are being developed in an international co-operative project. A pilot study was undertaken in which 250 validated electrocardiograms (ECG) and vectorcardiograms (VCG) comprising seven diagnostic groups i.e., normal, left, right and bi-ventricular hypertrophy, anterior, inferior and combined infarction have been analysed independently by 11 different computer programs as well as by six cardiologists. A coding scheme was applied to assign individual diagnostic statements to a common set and to obtain combined program and cardiologist interpretation results. Preliminary results indicate that the accuracy of classification by different programs varies widely. Total accuracy varied between 57.2% and 75.8% (median 69.4%). The cardiologists had a higher accuracy (median 74.3%) than the majority of programs, at least when using the standard ECG. As it is considered premature to stress individual program results, in view of the current sample size, the enhancement in diagnostic accuracy obtained by combining interpretation results is highlighted. Indeed combined cardiologist and program results demonstrated the highest accuracy i.e., respectively 78.7% and 76.1%, higher than the result of any individual reader or program. The combined result of the five most accurate programs was 78.4%, that of the six least accurate was 71.5%, which is again higher than the respective individual components. These findings demonstrate that the combination of expert knowledge of computer programs can, similar to panel review and group analysis in clinical practice, enhance diagnostic accuracy.     

Comparison of lisinopril and nitrendipine on the pulsatility index in mild essential arterial hypertension

Summary A double-blind, randomized crossover study was performed in 21 patients with essential arterial hypertension. Nitrendipine 20 mg o.d. and lisinopril 20 mg o.d. were given in a randomized order during a period of each 8 weeks. Nitrendipine and lisinopril decreased systolic and mean arterial blood pressure to a similar level without a significant increase in heart rate. The mean diastolic blood pressure was smaller with the lisinopril treatment than with the nitrendipine treat. The blood pressure decrease was maintained in the sitting and standing position. Furthermore, only nitrendipine decreased the pulsatility index at the tibial posterior arteries, while lisinopril did not influence it significantly. This finding means that mechanisms other than the blood-pressure lowering effect are involved in the decrease of the pulsatility index.     

Acute and chronic effects of lisinopril on renal and systemic hemodynamics in hypertension

Summary Acute and chronic effects of the converting enzyme inhibitor lisinopril on renal and systemic hemodynamics were studied in 12 patients with mild to moderate essential hypertension. After a washout period, cardiac output (measured by Doppler echography), renal plasma flow, and glomerular filtration rate (measured by isotopic techniques) were determined before and after oral administration of 20 mg lisinopril (vist 1). The same protocol was repeated after 3 months of lisinopril therapy 20 mg once daily (visit 2). Acute administration of lisinopril, both in untreated hypertensive patients (visit 1) and during long-term treatment (visit 2), decreased blood pressure (p < 0.05) and increased renal plasma flow (p < 0.05), while cardiac output and glomerular filtration rate were unchanged. Comparison of baseline parameters between visits 1 and 2 showed that chronic treatment with lisinopril decreased blood pressure and renal vascular resistance and that these effects were still significant 24-hours postdosage. We conclude that lisinopril is an effective antihypertensive agent with favorable renal hemodynamic effects.