比索洛尔、拉西地平和赖诺普利对高血压病患者24小时血压的影响

目的比较比索洛尔、拉西地平和赖诺普利对２９例高血压病患者的降压疗效。方法采用随机、单盲和交叉的方法，运用２４小时动态血压监测。结果三药均能显著降低血压，彼此间降低偶测血压的幅度无显著差异。比索洛尔和拉西地平降低２４小时平均和白天平均血压的幅度大于赖诺普利。三药均能有效控制清晨血压高峰期的血压，它们的降压谷／峰比值都超过６５％。结论比索洛尔、拉西地平和赖诺普利均可每日服用１次，前二药控制２４小时血压及清晨醒后的高峰期血压较后者为佳。     

Different hemodynamic (24-h ambulatory blood pressure monitoring) and renin-inhibiting effect of a 1-week treatment with enalapril and lisinopril.

Ambulatory blood pressure and heart rate monitoring were used for comparing the antihypertensive effect of a 1-week treatment with enalapril and lisinopril 10 mg once daily (double-blind crossover placebo-controlled study). Twelve outpatients with mild to moderate hypertension were treated. Both drugs had a significant and identical hypotensive effect. Neither drug affected the diurnal rhythm of blood pressure or heart rate. Therefore the two drugs are equipotent antihypertensive agents. Both drugs inhibited ACE activity to a highly significant extent, but in this regard lisinopril was more effective than enalapril. However, lisinopril's greater ACE inhibition was not accompanied by a greater hypotensive effect. The clinical value of this difference is not yet established.     

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.     

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夜间高血压患者靶器官损害及心血管事件风险显著增加。交感神经系统和肾素-血管紧张素-醛固酮系统活性增加及盐敏感和盐摄入量过高是夜间高血压重要发病机制。夜间高血压发生还与多种伴随疾病密切相关。改变生活方式、合理选择降压药物及治疗伴随疾病是控制夜间高血压的主要方法。     

Efficacy and safety of high-dose lisinopril in chronic heart failure patients at high cardiovascular risk, including those with diabetes mellitus. Results from the ATLAS trial.

AIMS: An analysis was designed to determine whether chronic heart failure patients at high cardiovascular risk benefited to the same extent from high-dose lisinopril as the whole ATLAS population. METHODS AND RESULTS: A retrospective analysis was performed on high-risk heart failure patients in the Assessment of Treatment with Lisinopril And Survival (ATLAS) trial (total number of patients 3164) comparing highdose (32.5-35 mg. day(-1)) vs low-dose (2.5-5 mg. day(-1)) lisinopril for a median of 46 months. These high-risk patients included those with hypotension, hyponatraemia, compromised renal function, the elderly and patients with diabetes mellitus at baseline. In the whole study population, high-dose lisinopril led to a trend in risk reduction of all-cause mortality (primary end-point P=0.128) and a significant risk reduction in all-cause mortality plus hospitalization (principal secondary end-point P=0.002). Subgroup analyses were performed for these end-points. There were no consistent interactions between age, baseline sodium, creatinine or potassium values, and treatment effect. Diabetics showed a beneficial response to high-dose therapy that was at least as good as that in non-diabetics. The underlying higher morbidity/mortality rates in diabetics mean that high-dose lisinopril has potential for a larger absolute clinical impact in these patients. CONCLUSION: Long-term high-dose lisinopril was as effective and well-tolerated in high-risk patients, including those with diabetes mellitus, as for the ATLAS study population as a whole.     

Acute effects of the ACE inhibitor lisinopril on cardiac electrophysiological parameters of isolated guinea pig hearts.

Angiotensin-converting enzyme (ACE) inhibitors are of benefit in life-threatening ventricular arrhythmias in patients with congestive heart failure and ventricular tachycardia caused by the onset of myocardial ischemia as well as by reperfusion of an ischemic area. The aim of the present study was to investigate whether direct electrophysiological effects are responsible for these observations. Therefore, we investigated the electrophysiological effects of lisinopril on the whole cardiac conduction and pacemaker system in isolated guinea pig hearts perfused by the method of Langendorff at concentrations of 0.01, 0.1, 1, and 10 microM. Lisinopril did not affect heart rate, atrioventricular, His bundle, or intraventricular conduction at any of the concentrations tested. Likewise the frequency-dependent QT duration was unchanged. At a concentration of 10 microM, lisinopril prolonged effective refractory period evaluated by premature beats (46 +/- 15%, n = 8, p less than 0.01) as well as the rate-dependent effective refractory period (31 +/- 12, n = 8, p less than 0.01) of the atrioventricular conduction. These effects can be explained by lisinopril's action as a minor calcium antagonist at a toxic concentration of 10 microM. The present results show that electrophysiological parameters are not substantially altered by lisinopril. Therefore, several other mechanisms such as the unloading of the left ventricle and/or the suppression of noradrenalin release and the electrolyte (potassium and magnesium) repletion and/or regression of left ventricular hypertrophy as long-term effects may play a major role in the antiarrhythmic efficacy of ACE inhibitors.     

Temporal Analysis of Blood Pressure by Ambulatory 24 H Blood Pressure Monitoring

In order to study the circadian rhythm of BP in man. we performed 24-hour non invasive BP on 15 hospitalized patients. Each subject was monitored twice, with an interval of 24–48 h between the two monitorings. In 14 of the 15 subjects MBP showed a statistically significant circadian rhythm. The curve fitted by the single cosinor method to the mean of the first rhythmometric measurements performed on all 15 subjects was characterized by an acrophase at 12.53, an amplitude of 4.68 mmHg and a mesor of 87.49 mmHg. The same parameters for the second rhythmometric measurements were: acrophase at 13.57, amplitude 4.1 mmHg and mesor 88.35 mmHg. In both cases, overall circadian rhythm resulted to be similar in all the subjects (p < 0.01). Multivariate analysis of variance showed that each subject has his own characteristic circadian rhythm. Our findings support the hypothesis of a identifiable circadian rhythm of BP in man.     

高血压合并阻塞性睡眠呼吸暂停综合征患者昼夜血压的变化

目的研究轻中度高血压合并阻塞性睡眠呼吸暂停综合征(OSAS)患者昼夜血压变化的特点。方法入选心功能(NHYA)Ⅰ级的轻中度高血压患者177例,经多导睡眠呼吸监测后,按睡眠呼吸暂停指数分为4组,单纯高血压组(A组)42例,高血压合并轻度OSAS组(B组)66例,高血压合并中度OSAS组(C组)25例和高血压合并重度OSAS组(D组)44例,进行24 h动态血压监测。结果 D组患者昼间和夜间血压水平明显高于A组(P<0.05,P<0.01),与A组比较,B、C和D组夜间舒张压显著升高(P<0.05,P<0.01)。夜间低血氧水平与醒时、醒后舒张压、昼间、夜间收缩压和舒张压呈负相关(P<0.05)。结论轻中度高血压合并OSAS患者的夜间舒张压更高,合并重度OSAS的高血压患者全天血压水平均明显高于单纯高血压患者,血压升高幅度与夜间低氧血症程度呈负相关。     

24-hour efficacy of once-daily diltiazem in essential hypertension.

The safety and effectiveness of a once daily formulation of diltiazem hydrochloride (diltiazem CD) in the treatment of essential hypertension was assessed in a total of 127 patients with supine diastolic blood pressures (DBP) of 95 to 110 mmHg randomized to diltiazem CD (n = 61) or placebo (n = 66). Patients were titrated to doses of 120, 240, or 360 mg to achieve DBP reduction to less than 90 mmHg. At end study diltiazem CD changed trough supine SBP and DBP by -8.4 +/- 1.7 (p = 0.0009) and -8.6 +/- 1.1 mmHg (p = 0.0075), respectively. Heart rate was not significantly changed (-1.3 +/- 1.1 beats/min, p = 0.4362). The average dose of diltiazem CD was 268 mg with 69% achieving a clinical response. A subset of 47 patients underwent ambulatory blood pressure monitoring to assess the consistency of the effect over the full 24-h dosing interval. Diltiazem CD lowered DBP and SBP throughout the dosing interval. The overall side effect profile was similar to placebo. This study provides evidence of 24-h efficacy of this new, once daily formulation of diltiazem.     

Efficacy of once-daily tobramycin monotherapy for acute pulmonary exacerbations of cystic fibrosis: a preliminary study

Our objective was to compare the efficacy, safety, and microbiology of once-daily intravenous (IV) tobramycin with conventional 8-hourly tobramycin/ceftazidime IV therapy for acute Pseudomonas aeruginosa (PA) pulmonary exacerbations in cystic fibrosis (CF). CF patients with PA-induced pulmonary exacerbations were allocated to receive either once-daily tobramycin (Mono) or conventional therapy with tobramycin/ceftazidime given 8-hourly (Conv). The two longitudinal groups received therapy in a double-blind, randomized manner over a period of 2 years. Tobramycin doses were adjusted to achieve a daily area under the time-concentration curve of 100 mg x hr/L in both groups. Results were assessed for both short-term changes (efficacy and safety after 10 days of IV antibiotics during acute exacerbations) and long-term changes (efficacy, safety, and sputum microbiology between study entry and exit). Pulmonary function tests (PFTs) on admission were similar in both groups. After 10 days of IV antibiotics, absolute mean improvements in percent of predicted PFTs were 12.8, 12.1, and 13.7 for forced expiratory volume in 1 sec (FEV(1)), forced vital capacity (FVC), and forced expired flow between 25--75% of FVC (FEF(25--75%)) in the Conv group (n = 51 admissions) compared to 10.6, 9.9, and 10.6 in the Mono group (n = 47)(P<0.05 for all). Sixteen percent in the Conv group and 15% of patients in the Mono group did not respond to therapy by day 10. Long-term PFT patterns were similar for the Conv and Mono groups. The time between admissions did not differ. The Mono group showed a significant increase in tobramycin minimum inhibitory concentrations (MICs) against PA from study entry to study exit (P = 0.02, n = 27 strains); this failed to reach significance in the Conv group (P = 0.08, n = 25). There was no significant increase in the number of isolates, with MIC> or =8 mg/L in both groups. No short- or long-term changes in audiology or serum creatinine were found in either group. After 10 days of IV therapy, the urinary enzyme N-acetyl-beta-d-glucosaminidase/creatinine ratios increased in both groups (P0.05). This increase was greater in the Conv compared to the Mono group (P < 0.05). We conclude that this pilot study indicates once-daily tobramycin therapy to be as effective and safe as conventional 8-hourly tobramycin/ceftazidime therapy. Combination antibacterial therapy appears to offer no clinical advantage over once-daily tobramycin monotherapy. Tobramycin once-daily monotherapy is a potential alternative to conventional IV antibacterial therapy which deserves further investigation, including the impact on susceptibility of PA to tobramycin.     

高血压患者治疗后的血压昼夜节律与心脏结构改变的相关性研究

目的 探讨高血压患者治疗后的血压昼夜节律与心脏结构改变的关系。方法 根据诊所血压控制水平将179例患者分为3组：Ⅰ组患者诊所血压控制满意（血压〈140／90mmHg）；Ⅱ组患者诊所血压未控制（血压≥140／90mmHg）但自测血压正常；Ⅲ组患者为顽固性高血压。应用24h动态血压监测和超声心动图观察并比较患者的血压昼夜节律与心脏结构、功能的特点。夜间血压下降率〈10％为非勺型组，≥10％为勺型组。结果 Ⅲ组的非勺型患者（66．7％）较Ⅰ组（44．4％）及Ⅱ组（48．0％）显著增多（P〈0．01）。Ⅲ组的左室肥厚患者（62．7％）较Ⅰ组（11．7％）及Ⅱ组（34．1％）显著增多（P〈0．01）。3组勺型和非勺型患者间的左室肥厚比较均差异无显著性。结论 治疗后的原发性高血压患者其血压控制水平、血压昼夜节律与心脏结构改变无相关性。     

老年高血压患者血压昼夜波动与肾小球滤过率下降的关系

目的探讨老年高血压患者血压昼夜波动与肾小球滤过率(glomerular filtration rate,GFR)下降的关系。方法对178例老年高血压患者测定血清肌酐,以Cockroff-Gault公式计算GFR估测值(eGFR),根据eGFR≥90ml/(min·1.72 m~2)、60～89 ml/(min·1.72 m~2)、40～59 ml/(min·1.72 m~2)、<40 ml/(min·1.72 m~2)分为A组44例、B组59例、C组46例、D组29例,并行24 h动态血压监测,测定空腹血糖、TC、TG、LDL-C、HDL-C,计算体重指数。结果 A组、B组、C组和D组随着eGFR的下降,夜间收缩压、24 h脉压、昼间脉压、夜间脉压、收缩压晨峰逐渐升高;舒张压波动幅度、夜间收缩压下降率、夜间脉压下降率逐渐降低,差异有统计学意义(P<0.05)。Pearson相关分析显示,病程、夜间收缩压、收缩压晨峰、24 h脉压、夜间脉压及夜间舒张压下降率与eGFR呈负相关,夜间舒张压、舒张压波动幅度、夜间收缩压下降率、夜间脉压下降率与eGFR呈正相关(P<0.05,P<0.01)。结论血压昼夜节律和波动幅度的异常与eGFR下降密切相关,尤以夜间脉压增大为著。     

Captopril Administered at Night Restores the Diurnal Blood Pessure Rhythm in Adequately Controlled,Nondipping Hypertensives

The aim of our study was to evaluate whether captopril administered at night, can shift the circadian blood pressure (BP) from a nondipper to a dipper pattern in adequately controlled hypertensive patients, who continued their antihypertensive therapy. In a prospective, randomized, double blind, placebo-controlled designed study, we enrolled 121 treated, adequately controlled nondipping hypertensive patients. All patients were randomly assigned to 12.5 mg captopril or placebo treatment administered at night. In case of nondippers, the dosage of captopril or placebo was doubled after two weeks of treatment, while for dippers antihypertensive regimens were not changed. After another two weeks, all patients underwent ambulatory BP monitoring. Our results show that at the end of the active treatment period, the prevalence of a dipping diurnal BP pattern in the captopril group (70%) was significantly higher than that in the placebo group (9.8%, P < 0.001). Nighttime BP, night/day BP ratio, nighttime BP load and 24-h systolic BP were significantly lower after 4 weeks nighttime captopril treatment compared to baseline. In conclusion, the present study demonstrates for the first time that captopril administered at night can restore the diurnal BP rhythm and decrease the elevated night/day BP ratio in appropriately controlled, nondipper hypertensive patients. These results were mainly due to the decrease of nighttime BP.     

Efficacy of eplerenone versus enalapril as monotherapy in systemic hypertension

This study compared the efficacy and tolerability of eplerenone and enalapril in 499 patients with stage 1 or 2 hypertension who were randomized to receive eplerenone or enalapril for 6 months in a 3-step titration-to-effect study. After 6 months, patients whose diastolic blood pressure (BP) was <90 mm Hg had their dosages down-titrated were followed for an additional 6 months. Diastolic BP was the primary end point. Eplerenone was as effective as enalapril in reducing both systolic BP (eplerenone, -14.5 mm Hg; enalapril, -12.7 mm Hg; p = 0.199) and diastolic BP (eplerenone, -11.2 mm Hg; enalapril, -11.3 mm Hg; p = 0.910) at 6 months. BP reductions at 12 months were also similar between groups (-16.5/-13.3 mm Hg for eplerenone, -14.8/-14.1 mm Hg for enalapril; p = 0.251 and 0.331, respectively). Withdrawal rates for adverse events (eplerenone 7.9%, enalapril 9.3% at 6 months) and treatment failures (eplerenone 23.3%, enalapril 22.8% at 6 months) were also equivalent. Approximately 2/3 of each group had normal BP with monotherapy treatment at 6 months. BP response was independent of renin levels in the eplerenone group, but not in the enalapril group. Both agents reduced albuminuria in patients who had an elevated value at baseline, with significantly greater improvement in patients treated with eplerenone versus enalapril (-61.5% vs -25.7%; p = 0.01). Both agents were similarly well tolerated, and there was no increased incidence of any sexual adverse events in the eplerenone group. Patients taking enalapril had a higher rate of cough. Both agents increased serum potassium levels, but <1% in each group reported adverse events from hyperkalemia. Eplerenone was as effective as enalapril as monotherapy in patients with stage 1 or 2 hypertension, was more effective in reducing albuminuria, and was well tolerated for 12 months.     

高龄原发性高血压患者动态血压节律异常与靶器官损害关系的研究

目的探讨高龄原发性高血压患者动态血压特点及其与靶器官受损程度的关系。方法对80例年龄≥80岁的高血压患者进行24 h动态血压监测,根据夜间血压下降率分为杓型组38例和非杓型组42例,比较2组惠者收缩压、舒张压、血压负荷值及靶器官受损的情况。结果与杓型组比较,非杓型组24 h、昼间和夜间收缩压均明显升高(P<0.05),非杓型组和杓型组24 h收缩压负荷值分别为(72.0±11.0)%vs(32.0±8.0)%,P<0.01。非杓型组服用降压药的种类数、冠心病、缺血性脑卒中、肾功能不全及外周动脉疾病的比例显著高于杓型组(P<0.05)。结论高龄非杓型高血压患者的平均收缩压、收缩压负荷及靶器官损害发生率明显高于杓型患者,这类高血压患者更需合理控制血压。     

Onset of action of captopril,enalapril, enalaprilic acid and lisinopril in normal man

Summary The effects of orally administered captopril, enalapril and lisinopril on plasma concentrations of angiotensin converting enzyme (ACE), angiotensin II (ANGII) and renin (PRC) were studied over a period of 6 hours in 6 normal subjects. A further 4 subjects received intravenous enalapril and enalaprilic acid (enalaprilat). Captopril (25 mg) by mouth caused a fall in pANGII that reached a nadir 30 to 40 minutes after administration but an effect was hardly apparent after 6 hours. Enalapril (10 mg) by mouth had less marked effects on pACE and pANGII with a decline in levels first apparent 1 hour after administration and the lowest levels reached between 3 and 6 hours. Lisinopril (10 mg) produced a progressive fall in pACE and pANGII from 1 hour to reach the lowest values 6 hours after treatment. Intravenous enalaprilat (5 mg) produced an immediate sustained fall in both pACE and pANGII but intravenous enalapril (7 mg) had a biphasic inhibitory effect.     

高血压患者血压晨峰与急性冠状动脉事件的关系

目的探讨高血压患者血压晨峰与急性冠状动脉事件的相关性。方法选择186例高血压患者采用动态血压监测仪记录24 h血压。血压晨峰值≥32.6 mm Hg(1 mm Hg=0.133 kPa)患者为晨峰组(42例),血压晨峰值32.6 mm Hg为非晨峰组(144例),并对患者进行3年随访。患者同时具备胸痛、心电图动态变化或心肌酶学变化为急性冠状动脉事件(不稳定性心绞痛、急性心肌梗死)诊断标准。比较2组年龄、动态血压参数、急性冠状动脉事件发生率。结果与非晨峰组比较,晨峰组患者血压晨峰值、清晨动脉压、急性冠状动脉事件发生率均明显升高,差异有统计学意义(P0.05,P0.01);晨峰组24 h平均动脉压、清晨脉压虽高于非晨峰组,但差异无统计学意义(P0.05)。晨峰组患者血压晨峰值与急性冠状动脉事件发生率呈正相关(r=0.9),非晨峰组患者血压晨峰值与急性冠状动脉事件发生率无相关性(r=0.3)。结论高血压患者血压晨峰与急性冠状动脉事件发生密切相关,可能是冠状动脉事件的独立危险因素。