Antihypertensive effects of beta-blockers administered once daily: 24-hour measurements

Whole-day automated ambulatory blood pressure (BP) monitoring was used to assess the duration of the antihypertensive actions of the beta-blockers atenolol (50 to 100 mg; n = 20) and acebutolol (400 to 800 mg; n = 19) each given once daily at 9 AM. When compared with its pretreatment 24-hour average, atenolol decreased diastolic BP by 10 +/- 2 mm Hg (p less than 0.01) and systolic BP by 12 +/- 2 mm Hg (p less than 0.01). Acebutolol decreased the 24-hour diastolic BP by 11 +/- 1 mm Hg (p less than 0.01) and systolic BP by 13 +/- 2 mm Hg (p less than 0.01). More specifically, a comparison of the two drugs during the final 6 hours (3 AM to 9 AM) of the dosing interval showed that the mean decrease in diastolic BP of 10.2 +/- 1.5 mm Hg with acebutolol was greater (p less than 0.05) than the decrease of 6.2 +/- 1.3 mm Hg with atenolol. Moreover, this final 6-hour effect of atenolol was less (p less than 0.01) than that observed during the first 18 hours of the day. The late effects of acebutolol did not change significantly from its early effects. The two agents also differed in their trough (final 2-hour decrease in diastolic BP) and peak (maximum 2-hour decrease in diastolic BP) effects: for atenolol the peak-to-trough difference was 7.8 +/- 3.1 mm Hg (p less than 0.05), whereas for acebutolol it was 3.8 +/- 4.2 mm Hg (N.S.). This study confirms the efficacy of atenolol and acebutolol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term efficacy of combination therapy with losartan and low-dose hydrochlorothiazide in patients with uncontrolled hypertension

We evaluated the long-term efficacy of losartan and low-dose hydrochlorothiazide combination therapy in the treatment of hypertension. We enrolled 15 Japanese hypertensive outpatients whose 24-hour ambulatory blood pressure was >or= 135/80 mmHg after candesartan 8 mg (CND group; n = 10) monotherapy or amlodipine 5 mg (AML group; n = 5) monotherapy for 2 months or more. The monotherapy was then switched to losartan 50 mg and hydrochlorothiazide 12.5 mg combination therapy. Ambulatory blood pressure and indices of glucose and lipid metabolism were measured at the end of the monotherapy and after 3 and 12 months of the combination therapy. In the CND group, 24-hour blood pressure decreased significantly from 137 +/- 9/89 +/- 4 to 126 +/- 8/81 +/- 7 mmHg after 3 months (P < 0.05/ P < 0.001) and to 123 +/- 7/81 +/- 4 mmHg after 12 months (P < 0.01/P < 0.001). In the AML group, 24-hour blood pressure decreased significantly from 137 +/- 11/81 +/- 7 to 125 +/- 12/75 +/- 6 mmHg after 3 months (P < 0.05/P < 0.05) and to 124 +/- 9/77 +/- 7 mmHg after 12 months (P < 0.05/NS). There were significant decreases in systolic blood pressure during the daytime (6:00-21:30), nighttime (22:00-5:30) and early morning (6:00-8:00) after 12 months in both groups. No adverse changes in the indices of glucose or lipid metabolism were observed in either group. In conclusion, long-term combination therapy with losartan and low-dose hydrochlorothiazide was effective in the treatment of hypertensive patients whose blood pressure was not controlled by candesartan or amlodipine monotherapy alone.     

氨氯地平及达爽对高血压患者血压昼夜变化规律的影响

目的 观察高血压患者血压昼夜变化节律,并按照时间治疗学的原则,探讨氨氯地平(络活喜)及达爽在不同给药时间对高血压患者血压昼夜规律的影响.方法 130例2级或3级高血压患者来源于2008年5月-2009年11月在哈尔滨市第一医院心内科门诊及住院治疗的病人.在监测24 h动态血压后,根据动态血压昼夜变化节律将病人分为杓型和非杓型.杓型(n=34)血压者晨起(6:00)一次性给予达爽5mg、络活喜5mg;非杓型血压者均衡性别、年龄因素后分为3组,Ⅰ组(n=30)晨起(6:00)给予达爽5mg、络活喜5mg;Ⅱ组(n=32)晨起(6:00)给予达爽5 mg,晚间(18:00)给予络活喜5 mg;Ⅲ组(n=34)晨起(6:00)给予络活喜5 mg,晚间(18:00)给予达爽5 mg.4周后,复查24 h动态血压(1 Pa=13.3 mmHg),分析治疗前后24 h平均收缩压(24hSBP)、24 h平均舒张压(24 hDBP);白天、夜间平均收缩压(dSBP,nSBP);白天、夜间平均舒张压(dDBP,nDBP).结果 ①杓型血压者晨起一次给药,24 hSBP、24 hDBP和dSBP、dDBP分别由(154.3±5.6)、(95.4±3.1)mmHg和(158.7±6.5)、(99.6±3.7)mmHg下降至(137.2±3.9)、(82.5±2.7)mmHg和(139.7±3.8)、(85.2±3.5)mmHg(t值分别为2.124、2.356,2.278、2.449,P均<0.05).②非杓型Ⅰ、Ⅱ、Ⅲ组高血压患者治疗后24 hSBP[(139.6±4.1)、(134.5±4.6)、(133.4±3.5)mmHg]和24 hDBP[(83.5±4.2)、(80.8±5.6)、(81.6±4.7)mmHg]与治疗前[(154.4±6.1)、(156.7±6.7)、(156.6±5.2)mmHg和(95.8±2.8)、(94.9±3.8)、(95.7±3.2)mmHg]比较明显下降(t值分别为2.038、2.040、2.135,2.142、2.213、2.216,P均<0.05);治疗后dSBP[(138.9±5.4)、(136.7±4.1)、(137.4±6.4)mmHg]和dDBP[(85.8±5.3)、(83.6±5.1)、(83.9±5.2)mmHg]与治疗前[(158.6±3.5)、(158.4±5.6)、(159.5±4.3)mmHg和(98.4±3.7)、(99.6±3.7)、(83.9±5.2)mmHg]比较明显下降(t值分别为2.021、2.252、2.261,2.217、2.167、2.076,P均<0.05);治疗后nSBP[(133.7±4.6)、(129.8±5.7)、(127.6±2.8)mmHg]和nDBP[(87.8±2.9)、(78.5±6.4)、(77.8±4.8)mmHg]与治疗前[(146.7±6.9)、(149.8±3.9)、(150.2±4.1)mmHg和(93.7±4.2)、(95.7±4.3)、(93.4±3.3)mmHg]比较明显下降(t值分别为1.798、2.032、2.014,1.864、2.157、2.166,P均<0.05).治疗后nSBP、nDBP,Ⅰ、Ⅱ、Ⅲ组组间比较差异有统计学意义(F值分别为2.32、2.17,P均<0.05);其中Ⅱ组和Ⅲ组效果优于Ⅰ组(q值分别为3.17、4.03,3.32、4.19,P均<0.05),但Ⅱ组和Ⅲ组间效果相似(P>0.05).结论 高血压患者应重视血压节律的检测,杓型血压者晨起一次给药即可有效控制血压;非杓型者早晚分次给药较晨起顿服两种药物更能有效控制患者的夜间血压,达到有效平稳降压.     

Circadian rhythm of blood pressure in patients with obstructive sleep apnea.

AIMS: The aims of this study were to examine the circadian variation in blood pressure (BP) in obstructive sleep apnea (OSA) and to compare this between normotensive and hypertensive subjects. METHODS: We measured 24-hour ambulatory BP (ABP) in 72 men (mean age 51 +/- 8 years), with OSA diagnosed on overnight sleep study. Measurements of BP were made at 15 min intervals for 24 h using either an Oxford Medilog ABP or Spacelabs 90207 recorder. All recordings were performed after > or = 3 week washout of anti-hypertensive drugs. The day-time monitoring period was defined as 07:00 hrs to 22:00 and night-time 22:00 to 07:00. The ratio of night:day systolic and diastolic BP was calculated. RESULTS: The patients were obese (mean body mass index 33 +/- 5 kg/m2) with a central pattern of obesity (waist:hip ratio 0.99 +/- 0.14, normal < 0.94). The mean 24-h ABP (systolic/diastolic) was 138 +/- 18/88 +/- 12 mmHg. The mean daytime ABP was 143 +/- 18/93 +/- 12 and night-time ABP 128 +/- 20/80 +/- 12 Hg. The night:day BP ratio was 0.90 +/- 0.07 (systolic) and 0.87 +/- 0.09 (diastolic) indicating that average BP was lower during the night. This pattern was similar in normotensive and hypertensive subjects. In contrast there was a significant relationship between increasing BMI and night:day blood pressure ratio (r = 0.56, p < 0.001) independent of the effects of OSA. CONCLUSION: In contrast to previous studies, men with OSA have a normal diurnal pattern of blood pressure levels. These findings suggest that any influence of OSA on BP is manifested throughout the 24-h period.     

Casual versus 24-hour ambulatory blood pressure recording in the evaluation of chronic administration of sustained-release verapamil

Although ambulatory blood pressure monitoring has been used widely for the evaluation of antihypertensive treatment, little information is available regarding the comparison between this method and casual BP measurement during drug trials. In our study, we tested the efficacy of a new formulation of verapamil, 240 mg sustained-release tablets, and compared the degree of BP reduction as detected by casual (standard mercury manometer) and by 24-hour ambulatory recording (Spacelab ICR 5300). A statistically significant fall in casual BP was observed after verapamil with respect to placebo. Moreover, 24-hour, waking and sleeping ambulatory BPs were significantly reduced by verapamil. The mean BP reduction was similar for office (20.1/16.1 +/- 4.3/3.1 mmHg) and for day-time ambulatory monitoring (13.4/10.7 +/- 4.2/1.9 1.9 mmHg), but no correlation was found between BP fall recorded by the two techniques for individual subjects. This study suggests that sustained-release verapamil is an effective antihypertensive drug. Individual mean BP reduction outside the clinic may not be predicted from office readings and therefore ambulatory BP recording seems to provide a better basis for testing the efficacy of drugs.     

The normal limits of arterial pressure registered with portable methods: an approach to the problem

In the present paper the problem of the normalcy limits of whole-day ambulatory blood pressure has been faced by evaluating the difference between casual and ambulatory blood pressure in a population of 522 subjects with blood pressure values covering the whole blood pressure range. On the basis of the casual blood pressure levels, 60 subjects were normotensives, 110 borderline hypertensives, 214 mild, 103 moderate and 35 severe hypertensives. The differences between casual and median 24-hour blood pressure averaged 18.4/9.6 mmHg. The difference between casual and median day-time was 14.2/6.7 mmHg. This difference was independent from the ambulatory blood pressure values and unrelated to the sex or age of subjects. The upper normal limits of ambulatory blood pressure were established by subtracting the above differences from the normal limits established by the WHO for casual blood pressure (140/90 mmHg). For 24-hour blood pressure the upper limits were 121.6/80.4 mmHg and for day-time blood pressure these were 125.8/83.3 mmHg. Contrary to previous studies conducted on normotensive populations with this approach the selection of patients based on casual blood pressure is avoided and the WHO normalcy limits are taken into account.     

Effect of indomethacin on blood pressure lowering by captopril and losartan in hypertensive patients

NSAIDs are known to attenuate the effects of some antihypertensive medications. It is not known whether the new class of angiotensin II receptor antagonists is similarly affected. We conducted a multicenter study assessing the effect of indomethacin on the antihypertensive effects of losartan and captopril. After 4 weeks of placebo washout, hypertensive patients received 6 weeks of active antihypertensive therapy with either 50 mg losartan once daily (n=111) or 25 mg captopril twice daily for 1 week, which was increased to 50 mg twice daily for 5 weeks (n=105). This was followed by 1 week of concomitant therapy with indomethacin (75 mg daily). The primary outcome measure was the change in mean 24-hour ambulatory diastolic blood pressure after the addition of indomethacin. Both captopril and losartan significantly lowered ambulatory diastolic blood pressure (losartan -5.3 mm Hg, P:<0.001; captopril -5.6 mm Hg, P:<0.001) after 6 weeks of therapy. Indomethacin significantly attenuated the 24-hour ambulatory diastolic blood pressure for both losartan (2.2 mm Hg, P:<0.05) and captopril (2.7 mm Hg, P:<0.001) and also attenuated the effect of captopril on trough sitting diastolic blood pressure. Changes in daytime diastolic blood pressure (7:00 AM to 11:00 PM) were similar to the 24-hour response in both groups. Nighttime diastolic blood pressure (11:01 PM to 6:59 AM) was significantly attenuated in captopril-treated patients (2.0 mm Hg, P:<0.05), but losartan was unaffected (0.4 mm Hg). Thus, concurrent treatment with indomethacin similarly attenuates the 24-hour antihypertensive response to losartan and captopril.     

Blood pressure and Turner syndrome

INTRODUCTION: Elevated blood pressure (BP) is an important predictor of morbidity and mortality from cardiovascular disease. Patients with Turner syndrome (TS) have a higher morbidity and mortality in middle age than the normal population. As BP in childhood or early adulthood is predictive of BP later in adult life, we assessed manual and 24 h ambulatory BP in patients with TS to determine whether the BP pattern is altered at an early stage in these patients who are known to be at risk of cardiovascular disease. PATIENTS AND METHODS: We studied manual and 24 h ambulatory BP profiles in 75 girls with Turner syndrome, age range 5.4-22.4 years. A monitor with an oscillometric device (SpaceLabs model 90207) and an appropriate sized cuff was used. BP was measured during the day-time (0800-2000 h) and the night-time periods (2200-0800 h). The BP measured were compared with population standards. The effect of different growth promoting agents on BP was also evaluated. RESULTS: Mean manual and 24 h ambulatory BP measurements were 118/77 mmHg (range 95/60-140/102) and 115/70 mmHg (range 93/57-154/99), respectively. There was minimal difference between the two methods with a positive bias of 2.4 mmHg for diastolic BP and a negative bias of 2.1 mmHg for systolic BP. The mean standard deviation scores (SDS) corresponding to the mean BP recordings were 24 h systolic + 0. 81 (range - 1.26 to + 4.45), 24 h diastolic + 0.43 (range - 0.85 to + 3.42), day-time systolic + 1.08 (range - 0.95 to + 4.72), day-time diastolic + 0.70 (range - 0.94 to + 3.71), night-time systolic + 0. 22 (range -2.2 to + 3.64) and night-time diastolic - 0.18 (range -2. 0 to + 2.43). The SDS for both the mean 24 h and day-time systolic and diastolic BP were shifted to the right of the normal distribution. 57% of the girls had less than the normal 10% reduction in nocturnal systolic blood pressure. 17% had diastolic and 21% had systolic blood pressure above the 95th percentile for age and sex. There was no significant difference in the BP SDS between girls on no treatment and those receiving treatment. CONCLUSION: Over 50% of girls with Turner syndrome have an abnormal BP circadian rhythm, which is similar to adult patients with secondary hypertension. Patients with Turner syndrome have higher blood pressure measurements compared to published population standards, as evidenced by the shift to the right of both the systolic and diastolic BP SDS. These findings suggest that girls with Turner syndrome should be carefully monitored in childhood and adulthood for blood pressure and other cardiovascular risk factors.     

Twenty-four-hour ambulatory blood pressure in men and women aged 17 to 80 years: the Allied Irish Bank Study.

In order to determine reference values for ambulatory blood pressure, a sample of 815 healthy bank employees (399 men and 416 women), aged 17-79 years, were investigated. Ambulatory blood pressure was recorded over 24 h, taking measurements at 30-min intervals. Blood pressure was also measured by trained observers in the clinic. Ambulatory blood pressure in the 815 subjects averaged 118/72 mmHg over 24 h, 124/78 mmHg during the day (1000-2259 h) and 106/61 mmHg at night (0100-0659 h). Office blood pressure, measured by an observer, was 4/2 mmHg lower (p less than 0.0001) than daytime ambulatory pressure. The 95th centiles for the daytime ambulatory pressure in men were: 114/88 mmHg for the age group 17-29 years (n = 107); 143/91 mmHg from 30-39 years (n = 123); 150/98 mmHg from 40-49 years (n = 109); and 155/103 mmHg in 50-79 year old men (n = 60); for the corresponding age groups in women, the 95th centiles of the daytime pressure were: 131/83 mmHg (n = 174); 132/85 mmHg (n = 149); 150/94 mmHg (n = 55); and 177/97 mmHg (n = 38).     

Clinical utility and applicability of smoothness index, normalized smoothness index and individualized RDH index during treatment of essential hypertension

The purpose of this study was to assess the clinical utility of the smoothness index (SI) and normalized SI (SIn), measures of duration and homogeneity of blood pressure (BP) reduction, during an observation period without antihypertensive therapy followed by a treatment period using dihydropyridines (DHP) in 54 newly diagnosed and previously untreated subjects (age 46.9 +/- 9.1 years) with essential hypertension. In addition, we aimed to describe the reduction-duration-homogeneity (RDH) index for statistical assessment of the BP reduction in the individual patient. Twenty-four-hour BP was lowered during treatment (139.2 +/- 13.9/ 91.0 +/- 7.6 mmHg vs 130.9 +/- 11.3/85.2 +/- 5.2 mmHg, p < 0.001/p = 0.001). SI showed great interindividual variation, and increased from zero to 0.9 +/- 0.8 (systolic BP) and 0.8 +/- 0.7 (diastolic BP) after treatment (p < 0.001 for both), similar results were obtained for SI(n). The RDH index revealed BP reduction in agreement with the change in individual 24-h, daytime and night-time BP. Although SI and SI(n) may add important information regarding the homogeneity of the antihypertensive effect in a group of patients, and the RDH index for the individual patient, conclusions regarding antihypertensive efficacy can be obtained from assessment of the 24-h, daytime and night-time BP changes and ambulatory BP profiles. Based on our findings, we do not recommend the use of SI or RDH index in the clinical practice.     

An epidemiological approach to ambulatory blood pressure monitoring:the Belgian Population Study

BACKGROUND: In order to determine reference values for ambulatory blood pressure, a random population sample of 1057 persons, 20-88 years old, was investigated in a geographically defined area of Belgium. This article is the final report on the cross-sectional phase of this population survey. METHODS:Twenty-four-hour ambulatory pressure was recorded at 20 min intervals from 0800 to 2200 h and at 45 min intervals from 2200 to 0800 h. Conventional blood pressure was measured by trained nurses at the participants' homes and also in a subgroup of 532 persons at a locally organized clinic. A conventional blood pressure exceeding 140 mmHg systolic or 90 mmHg diastolic and the taking of antihypertensive drugs were the criteria used to distinguish between normotensive and hypertensive persons. RESULTS: In the 1057 patients, of whom 328 were hypertensive, 24 h, daytime (2200 to 0800 h) and night-time (0000 to 0600 h) pressures averaged 119/71, 125/77 and 108/62 mmHg, respectively. Compared with daytime values, blood pressures at home were 3.5/1.5 mmHg lower in 729 normotensive people but 11.6/4.5 mmHg higher in 328 hypertensive patients. In the normotensive subgroup the 95th percentiles of the 24 h, daytime and night-time pressures were 129/80, 137/88 and 121/72 mmHg, respectively. These boundaries were not materially altered when we considered only the 275 participants who had been normotensive both at home and at the clinic (127/79, 135/87 and 118/72 mmHg, respectively). When, in addition to the Belgian data, other reports on large cohorts were also analysed, the transition from normotension to hypertension on ambulatory measurement was likely to be within the ranges of 130-135/80-85, 135-140/85-90 and 120-125/70-75 mmHg for 24 h, daytime and night-time pressures, respectively. CONCLUSION: In comparison with other population surveys and with the earlier interim reports on the Belgian study, the present analysis produced remarkably consistent results with respect to the distributions of the ambulatory measurements. The working definitions of normality based on the 95th percentiles of the ambulatory measurements in the normotensive participants in the present survey and various other studies need further validation in terms of the incidence of cardiovascular complications. For this purpose, the Belgian participants as well as other cohorts are being prospectively followed.     

Using different methods to evaluate the efficacy of olmesartan medoxomil in Chinese patients with mild to moderate essential hypertension according to ambulatory blood pressure monitoring

OBJECTIVE: To evaluate the efficacy of olmesartan medoxomil in Chinese patients with mild to moderate essential hypertension using different methods according to ambulatory blood pressure monitoring. METHODS: Chinese patients 18-75 years of age with clinic diastolic blood pressure (BP) 90-109 mmHg and systolic BP less than 180 mmHg were treated with olmesartan medoxomil 20-40 mg once daily for 24 weeks to reach the goal BP (<140/90 and <130/80 mmHg in diabetes) in a multicenter study. The trough-to-peak ratio (T/P ratio) and the smoothness index (SI) for systolic/diastolic BP were calculated using different methods according to ambulatory blood pressure monitoring. RESULT: Olmesartan medoxomil 20-40 mg once daily reduced the systolic/diastolic ambulatory BP for 24-h, daytime, and night-time by 13.3±16.3/7.6±9.5, 13.9±17.4/8.0±10.4, and 12.3±18.1/6.8±10.2 mmHg in all eligible patients at week 24 from baseline (n=87, P<0.0001). The global and individual T/P ratios were 0.64/0.62 and 0.32/0.30 (n=87) for systolic/diastolic BP, whereas these were 0.71/0.70 and 0.31/0.39 in fair responders (n=71). Global and individual SI were 6.81/5.37 and 0.92/0.67 (n=87) for systolic/diastolic BP, whereas these were 7.04/5.44 and 1.03/1.03 in fair responders (n=71). Global and individual T/P ratios for systolic/diastolic BP were 0.75/0.82 and 0.45/0.46 in the 20 mg subgroup (n=41), whereas these were 0.44/0.59 and 0.30/0.29 in the 40 mg subgroup (n=30). Global and individual SI were 5.70/5.32 and 1.03/0.87 for systolic/diastolic BP in the 20 mg subgroup (n=41), but these were 3.64/2.46 and1.01/0.60 in the 40 mg subgroup (n=30). CONCLUSION: The duration of the antihypertensive action of olmesartan medoxomil with 20-40 mg once daily can be assessed by the global T/P ratio and SI rather than the individual values, even in different populations and dosages.     

Comparison of antihypertensive therapies by noninvasive techniques

We compared the antihypertensive effects of the beta-blocker atenolol and the converting enzyme inhibitor lisinopril during 12 weeks of treatment in patients with mild to moderate essential hypertension. Atenolol (n = 10) significantly decreased conventionally measured blood pressure from 144/103 to 135/93 mm Hg and lisinopril (n = 9) from 150/104 to 130/92 mm Hg. Based on data derived from automated 24-h ambulatory blood pressure monitoring, atenolol decreased the average whole-day systolic pressure by 18 +/- 6 mm Hg (p less than 0.02) and the diastolic pressure by 11 +/- 2 mm Hg (p less than 0.01). Lisinopril produced decreases of 27 +/- 5 mm Hg (p less than 0.01) and 13 +/- 2 mm Hg (p less than 0.001). Examination of the 24-h blood pressure patterns showed that the efficacies of the two drugs were similar. Each appeared to be effective throughout the whole-day monitoring period, although only lisinopril significantly decreased blood pressure during the final four-h period (4 AM to 8 AM) preceding the next day's dose. Neither drug produced significant echocardiographic changes in left ventricular wall thickness or muscle mass during the short-term treatment. Lisinopril and atenolol effectively decrease blood pressure during a 24-h period. Moreover, we found that automated whole-day blood pressure monitoring is a useful tool for comparing the efficacy and duration of action of differing antihypertensive agents.     

Comparison of different methods of blood pressure measurements

OBJECTIVE: To compare different methods of measuring and averaging blood pressure readings, and see how they affect classification of patients as normotensive or hypertensive. METHODS: The comparisons were made in up to 145 suitable patients in the first and last week of a 6-week surveillance. Ambulatory blood pressure measurements were taken from the nondominant arm, as the average of up to 78 measurements over 24 h (24-h ambulatory blood pressure measurements), or 60 from 0700 h to 2200 h (daytime ambulatory blood pressure measurements), or 18 from 2200 h to 0700 h (night-time ambulatory blood pressure measurements). Office blood pressure measurements were taken by the outpatient department nurse in triplicate from both arms, and the averages were taken of the second and third of each triplicate. Home blood pressure measurements were taken in duplicate each morning and evening, entered by patients into diaries, and the available readings of up to four values per day were averaged for the first and sixth week. The classifications of normotensive versus hypertensive produced by criterion values of 24-h ambulatory blood pressure measurements of 125/80 and 130/80 mmHg were compared with the classifications produced by the other measurements with a range of criterion values. RESULTS: The home blood pressure measurements and office blood pressure measurements of systolic values underestimated the corresponding 24-h ambulatory blood pressure measurements values by 3-9 average (SD 9-18) mmHg, and the diastolic values overestimated them by averages of 3-6 (SD 6-13) mmHg. Daytime ambulatory blood pressure measurement systolic and diastolic values overestimated them by 2-4 (SD 2-4) mmHg and night-time ambulatory blood pressure measurement values underestimated them by 7-12 (SD 5-9) mmHg. In comparing the 24-h ambulatory blood pressure measurement classifications of hypertensives versus normotensives with those produced from the other types of measurements, it was easiest to detect criterion values for daytime ambulatory blood pressure measurement that gave the best agreement and they appeared different for the different criterion values of 24-h ambulatory blood pressure measurement. For the other types of measurement, the agreement was generally worse and it was harder to detect a best criterion value for agreement with either of the 24-h ambulatory blood pressure measurement classifications. A subsample of 63 patients identified as needing institution, maintenance or modification of antihypertensive treatment excluded about half of the patients classified as hypertensive by either 24-h ambulatory blood pressure measurement criterion. CONCLUSION: Limited agreement existed between different ways of classifying patients. The utility of the classifications depends on the purpose to which they are put.     

Ambulatory recording of blood pressure. Study of the reproducibility of findings in 25 subjects

The reproducibility of a novel ambulatory blood pressure (B.P.) monitoring was tested, for clinical trial in hypertension. The spacelabs apparatus is based on standard auscultatory and oscillometric blood pressure measurements. Ten normotensive patients and 15 hypertensive patients were investigated as follows: their blood pressure was monitored twice over a 24 hr period at an interval of 30 and 15 days respectively. The monitoring data were expressed as the mean of the average blood pressure over day-time (7 hr-22 hr) and 24 hr as well as 24 hr. B.P. profiles (means of 4 measurements per hour). The statistical analysis of the two subpopulations of patients showed a satisfaction reproducibility of both the 24 hr B.P. curves (normotensive patients: PAS: r = 0.94; PAD: r = 0.92; Hypertensive patients PAS: r = 0.82; PAD: r = 0.64 p less than 0.001). and blood pressure levels (normotensive patients: J1: 113 +/- 10/70 +/- 6 mmHg; J30: 110 +/- 10/68 +/- 6 mmHg. Hypertensive patients: J1: 150 +/- 10/98 +/- 9 mmHg; J15: 155 +/- 15/96 +/- 8 mmHg). In contrast, analyzing each patient individually exhibited a correct reproducibility of the B.P. levels but the 24 hr--profiles of either the diastolic or systolic blood pressure could not be correlated with sufficient reliability (normotensive patients: 7 times out of 10 for PAS, and 4 times out of 10 for PAD; hypertensive patients: 5 times out of 15 for PAS, and 3 times out of 15 for PAD). In addition, the patient activity, should be carefully controlled during ambulatory blood pressure measurements.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regression of left ventricular mass is accompanied by improvement in rapid left ventricular filling following antihypertensive therapy with metoprolol

Left ventricular hypertrophy is associated with abnormal left ventricular diastolic filling in patients with hypertension. To assess the effects of antihypertensive therapy on the heart in nine previously untreated patients with echocardiographically-detected left ventricular hypertrophy, left ventricular mass and rapid left ventricular filling rate were compared before and after 6 months of treatment with metoprolol monotherapy. Metoprolol was given in doses of 100 to 400 mg/day (average dose, 167 mg/day in two divided doses) and significantly reduced both casual, office blood pressure (150/101 to 130/86 mm Hg, p less than 0.01) and 24-hour ambulatory blood pressure (139/91 to 126/79 mm Hg, p less than 0.05 for systolic, p less than 0.01 for diastolic). Following treatment with metoprolol, left ventricular mass index decreased from 135 +/- 20 to 120 +/- 13 gm/m2 (p less than 0.05), while rapid left ventricular filling rate increased from 1.89 +/- 0.24 to 2.09 +/- 0.27 end-diastolic volumes/sec (p less than 0.01). The reduction in left ventricular mass index was secondary to decreased posterior and septal wall thicknesses (13% and 11%, respectively, p less than 0.05 for both), as there were no changes in the left ventricular internal dimensions. Neither resting nor exercise left ventricular ejection fraction changed on metoprolol therapy compared to the baseline values. These data demonstrate that regression of left ventricular hypertrophy in never-previously-treated hypertensive patients is accompanied by improved diastolic performance following beta-adrenergic blocker monotherapy.     

Role of nocturnal blood pressure in the onset of diabetic nephropathy

The aim of this study was to assess the responsibility of night-time blood pressure in the onset of nephropathy in diabetic patients. PATIENTS AND METHODS: This study included 98 diabetic patients (mean age: 54 +/- 15 years, diabetes duration: 15 +/- 10 years). An evaluation of diabetes and a 24-h ambulatory blood pressure were performed at the initial evaluation (Y0) and about five years later (Y5). At Y0, all patients had normal urinary albumin excretion (UAE) (<30 mg/24h). They were separated into two groups according to urinary albumin excretion at Y5: group (N +): UAE>30 mg/24h and group (N-): UAE<30 mg/24h. Twenty four hours ambulatory blood pressure, clinical and biological parameters recorded at Y0 were compared in both. RESULTS: At Y5, there was 18 patients in group (N +) and 78 in group (N-). Patients of group (N +) were older than those of group (N-): 62.9 +/- 9.5 vs. 52.6 +/- 15.7 years, p<0.01, and their BMI was higher (28 +/- 5 vs. 25 +/- 4 kg/m2, p<0.03). Diabetes duration and Hb A1c levels did not differ from significant manner in both. At Y0, UAE was significantly higher in group (N +) than in group (N-): 13 +/- 7 vs. 8 +/- 6 mg/24h, p<0.01. At the initial evaluation, daytime systolic and diastolic blood pressures did not differ from significant manner in both. Systolic and diastolic BP night-time were higher in diabetic patients who developed microalbuminuria (SBP: 122 +/- 19 vs. 113 +/- 13 mmHg, p<0.05 and DBP: 70 +/- 6 vs. 65 +/- 10 mmHg, p<0.03). UAE collected at Y5 was correlated to night-time BP recorded at Y0 (SBP: r=0.381, p=0.001 and PAD: r=0.294, p=0.004) and night-time systolic BP explained 12.3% of the UAE variance. Progression of UAE between the two evaluations was found to be correlated to the night-time systolic BP recorded at Y0 (r=0.335, p=0.0008) and night-time systolic BP explained 11.7% of the progression variance. There was a negative correlation between UAE at A5 and the difference between daytime and night-time BP recorded during the same evaluation (r=- 0.230, p=0.024 with SBP and r=- 0.243, p=0.017 with DBP). CONCLUSION: The results underlign the resposability of night-time blood pressure, and more especially of nighttime systolic blood pressure, for the onset of nephropathy in diabetic patients.     

Efficacy of manidipine/delapril versus losartan/hydrochlorothiazide fixed combinations in patients with hypertension and diabetes

BACKGROUND: Hypertension markedly increases the already high risk for cardiovascular complications in patients with diabetes mellitus. Less than one in eight patients with hypertension and type 2 diabetes have adequately controlled blood pressure. As a result, antihypertensive combinations are now widely used in management of hypertension associated with diabetes. METHODS: This double-blind study investigated efficacy of a new fixed dose combination of a calcium antagonist, manidipine 10 mg, and an angiotensin-converting enzyme inhibitor, delapril 30 mg, compared with a combination of an angiotensin receptor blocker, losartan 50 mg, and a diuretic, hydrochlorothiazide 12.5 mg. Patients with hypertension (blood pressure > or = 130/80 mmHg) with controlled type 2 diabetes (HbA1c < or = 7.5%) were randomized to manidipine/delapril (n = 153) or losartan/hydrochlorothiazide (n = 161), administered once daily for 12 weeks. Patients underwent ambulatory blood pressure monitor evaluation at baseline and end of treatment. RESULTS: Mean decreases in 24-h systolic blood pressure were seen with both manidipine/delapril (-9.3 mmHg) and losartan/hydrochlorothiazide (-10.7 mmHg) combinations. The mean (95% confidence interval) treatment difference was -1.4 (-4.5/1.8) mmHg, demonstrating noninferiority of the manidipine/delapril combination. Reduction in 24-h diastolic blood pressure (-4.6 versus -4.5 mmHg) and daytime (systolic blood pressure -10.5 versus -11.1 mmHg) and night-time (systolic blood pressure -7.1 versus -9.3 mmHg) blood pressure were also not significantly different between treatments. Compliance and adverse events were comparable for both groups. CONCLUSION: The study demonstrated that the combination of manidipine and delapril is as effective as losartan and hydrochlorothiazide in treatment of hypertension in type 2 diabetes.     

Effect on blood pressure of lumiracoxib versus ibuprofen in patients with osteoarthritis and controlled hypertension: a randomized trial

OBJECTIVES: Nonsteroidal anti-inflammatory drugs vary in their impact on blood pressure and the effect of lumiracoxib 100 mg once daily has not been studied previously. To examine whether lumiracoxib 100 mg once daily would result in lower 24-h mean systolic ambulatory blood pressure than ibuprofen 600 mg three times daily in osteoarthritis patients with controlled hypertension, a 4-week, randomized, double-blind, parallel-group study was conducted in 79 centres in nine countries. METHODS: Hypertensive osteoarthritis patients of 50 years at least whose office blood pressure was less than 140/90 mmHg on stable antihypertensive treatment were randomized to lumiracoxib (n = 394) 100 mg once daily or ibuprofen 600 mg three times daily (n = 393) and 24-h ambulatory blood pressure monitoring was performed at baseline and end of study. The primary outcome measure was a comparison of the change in 24-h mean systolic ambulatory blood pressure from baseline to week 4. Secondary analyses included other blood pressure-related endpoints and efficacy (pain) measurements. RESULTS: Compared with baseline, the 24-h mean systolic ambulatory blood pressure (least square mean) decreased in lumiracoxib-treated patients (-2.7 mmHg) and increased in ibuprofen-treated patients (+2.2 mmHg) at 4 weeks, estimated difference -5.0 mmHg (95% confidence interval -6.1 to -3.8) in favour of lumiracoxib. The 24-h mean diastolic ambulatory blood pressure changes were -1.5 mmHg (lumiracoxib), +0.5 mmHg (ibuprofen), difference -2.0 mmHg (95% confidence interval -2.7 to -1.3). Efficacy results were comparable. CONCLUSIONS: Treatment with lumiracoxib 100 mg once daily resulted in clinically significant lower blood pressure compared with ibuprofen 600 mg three times daily in osteoarthritis patients with well controlled hypertension.     

Morning versus evening administration of a calcium channel blocker in combination therapy for essential hypertension by ambulatory blood pressure monitoring analysis

Patients with moderate to severe hypertension may need more than two antihypertensive drugs in combination to achieve ideal blood pressure (BP) control. The purpose of this study was to compare the efficacy and safety of administering the antihypertensive agents either all together in the morning or separately with two agents in the morning and one calcium channel blocker (CCB) in the evening. Twenty-four-hour ambulatory BP monitoring (ABPM) was performed among 15 patients (mean, 59 years) with moderate to severe essential hypertension. All patients received at least 3 antihypertensive drugs for ideal BP control. Two treatment regimens were given to each patient: Regimen 1: All antihypertensive agents were given once a day in the morning; Regimen 2: All antihypertensive agents were given in the morning, except the CCB which was given at 4:00 pm. After receiving regimen 1 for 4 weeks, each patient underwent 24-hour ABPM to analyze the BP control. After the first ABPM, each patient was switched to regimen 2. After 4 weeks of treatment with regimen 2, each patient underwent the second ABPM measurement. The pretreatment mean systolic and diastolic BP were 179.6 +/- 21.7 and 107.4 +/- 19.9 mmHg, respectively. Between the two regimens, there was no significant difference in the mean 24-hour BP (126.1 +/- 5.8/73.3 +/- 3.8 versus 130.2 +/- 6.2/75.1 +/- 4.7 mmHg), daytime BP (128.2 +/- 6.5/75.3 +/- 3.8 versus 132.4 +/- 5.8/77.2 +/- 4.4 mmHg), nighttime BP (125.2 +/- 4.9/72.4 +/- 3.3 versus 130.9 +/- 6.2/73.8 +/- 4.1 mmHg), and 24-hour heart rate (65.1 +/- 3.8 versus 64.2 +/- 3.4 bpm). The circadian BP and heart rate profiles were almost identical between regimen 1 and regimen 2. We conclude that in patients with moderate to severe hypertension treated with at least 3 antihypertensive agents, administering a CCB simultaneously with other antihypertensive agents in the morning or separately in the evening did not affect the 24-hour BP control.