Chronobiological analysis by ambulatory blood pressure monitoring of the hyperbaric and hypobaric indexes for evaluation of the antihypertensive effect of long-acting nifedipine.

BACKGROUND: It has been suggested that chronobiology can provide new insights into the evaluation and treatment of cardiovascular disease. In the present study the hyperbaric index (hyperBI) and hypobaric index (hypoBI) were compared with the mean blood pressure (BP) over 24 h to evaluate the antihypertensive effect of long-acting nifedipine on essential hypertension. METHODS AND RESULTS: Fourteen patients were treated with nifedipine CR (20-40 mg/day) for 6 months. Ambulatory BP monitoring was performed before and after treatment. The hyperBI (mmHg . h/day) was calculated as the integrated BP area above the conventional upper limit (140/90 mmHg for the daytime and 120/80 mmHg at night), and the hypoBI was calculated as the integrated BP area below the conventional lower limit (110/60 mmHg for the daytime and 100/50 mmHg at night). At baseline, both the systolic and diastolic 24-h hyperBI values closely correlated with the 24-h mean BP (r=0.994 and 0.935, p<0.0001). Treatment with nifedipine significantly lowered both the 24-h mean systolic and diastolic BP (143+/-14/89 +/-12 to 124+/-16/80+/-8 mmHg, p<0.001/p=0.001), as well as the casual BP (167+/-11/101 +/-8 to 140+/-13/86+/-10 mmHg, p<0.001/p<0.01). Reduction of both the systolic and diastolic hyperBI values was statistically significant over the 24-h period (274+/-266 to 90+/-155, p=0.009; 145+/-187 to 41+/-63, p=0.024), as well as during the daytime (200+/-181 to 66+/-116, p=0.014; 105+/-120 to 24+/-38, p=0.017) and at night (systolic, 74+/-106 to 24+/-52, p=0.021). The 24-h mean BP was normalized, but a small excess BP load persisted despite treatment. There was no significant increase of systolic hypoBI during the 24-h period (1+/-2 to 25+/-30, p=0.065), the daytime (0+/-0 to 14+/-38, p=0.20), or at night (1+/-3 to 11+/-19, p=0,052). Similar findings were obtained for diastolic hypoBI. CONCLUSIONS: Nifedipine CR improved the 24-h hyperBI and mean BP without causing excessive hypotension. These 2 parameters have a close relationship when assessment is done by 24-h BP monitoring. The hyperBI and hypoBI may assist in providing adequate antihypertensive therapy for individual patients by detecting an excessive BP load or hypotension, respectively.     

Rosiglitazone reduces office and diastolic ambulatory blood pressure following 1-year treatment in non-diabetic subjects with insulin resistance

OBJECTIVE: Rosiglitazone (RSG) has been reported to reduce blood pressure (BP) in patients with type-2 diabetes, but similar effects in non-diabetic people with insulin resistance is less clear. Our aim was to test the long-term BP-lowering effects of RSG compared with placebo. METHODS: We recruited participants for BP evaluation of RSG treatment from a larger intervention trial. Office BP was recorded in 355 non-diabetic subjects with insulin resistance randomized to receive either RSG or placebo for 52 weeks. Ambulatory BP monitoring (ABPM; Spacelab 90207) was performed in a subgroup of 24 subjects (RSG: n = 11; placebo n = 13). RESULTS: After 1 year, the office BP decreased by -3.1 mmHg systolic (p<0.05) and -3.8 mmHg diastolic (p<0.001) in the RSG group versus placebo. In patients treated with RSG, at 1 year there was a trend for a reduction from baseline for mean 24-h diastolic BP (DBP), daytime DBP and night-time DBP (-4.39, -5.26 and -2.93 mmHg, respectively). However, only daytime DBP was significantly lower in the RSG group compared with control (adjusted mean difference: -4.41 mmHg, p = 0.007). There was also a non-significant trend for a reduction in mean 24-h systolic BP (SBP), daytime SBP and night-time SBP (-2.70, -2.51 and -3.35 mmHg, respectively). CONCLUSIONS: RSG treatment for 1 year was associated with a small but significant decrease in diastolic 24-h ambulatory diastolic BP, and both systolic and diastolic office BPs in non-diabetic people with insulin resistance.     

Analysis of the acidity index and integrated intragastric acidity in 645 patients presenting with gastroesophageal reflux disease symptoms

OBJECTIVE: In a recent study of patients receiving proton-pump inhibitor (PPI) therapy, a new parameter, the acidity index, was described as being less complicated to calculate and of comparable accuracy (r = 0.93) to integrated intragastric acidity (IA) in assessing intragastric pH control. The aim of this study was to correlate AI with IA using a large database of ambulatory 24-h pH-metry studies in untreated patients presenting with gastroesophageal reflux disease (GERD) symptoms. MATERIAL AND METHODS: We retrospectively analyzed 645 studies obtained from 1995 to 2001. Daytime (0800 h-2200 h), night-time (2200 h-0800 h) and 24-h IA and AI were calculated according to age, gender and the presence or absence of GERD, and correlations between these parameters were assessed using linear regression with F-statistic values, p-values and Akaike's Information Criterion values. GERD was defined as total esophageal pH time <4.0, 5 cm above the lower esophageal sphincter, for > or =4.2% of the day. IA and AI were calculated as follows: IA (mmol x h/l) = summation operator(acid in mmol/l at time "t" + acid in mmol/l at time "t - 1")/2 x ("t"-"t - 1"); AI = (%time pH < 4-%time pH < 3) x 1+(%time pH < 3-%time pH < 2) x 10+(%time pH < 2-%time pH < 1) x 100 + (%time pH < 1-%time pH < 0.8) x 1000. RESULTS: Overall, the mean 24-h IA value was 882.0+/-820.0 mmol x h/l (daytime 392.0+/-400.0, night-time 490.0+/-486.0). The mean 24-h AI value was 102.0+/-87.0 (daytime 86.0+/-80.0, night-time 120.0+/-114.0, p < 0.001). The mean 24-h IA value was 1057.0+/-829.4 mmol x h/l (daytime 459.8+/-406.0, night-time 597.2+/-500.4, p < 0.001) in GERD patients and 713.0+/-775.0 mmol x h/l (daytime 326.0+/-383.0, night-time 387.0+/-448.5) in non-GERD patients (p < 0.001). The mean 24-h AI value was 122.1+/-88.1 (daytime 101.4+/-82.5, night-time 145.3+/-120.7) in GERD patients and 83.0+/-81.0 (daytime 71.0+/-73.9, night-time 96.4+/-102.6) in non-GERD patients (p < 0.001). Our statistical modeling demonstrated that the correlation between the acidity index and IA becomes progressively poorer with increasing values of acidity. CONCLUSIONS: We conclude that gastric acid production assessed by both IA and AI is higher during evening hours in comparison with daytime hours and the difference between night-time and daytime values is statistically significant. In addition, gastric acid production assessed by both IA and AI is significantly higher in GERD patients than non-GERD patients. This difference is primarily due to differences in nocturnal acid production. The AI correlates poorly with measured IA, especially at higher levels of gastric acidity. Therefore, AI is not an acceptable surrogate for IA in assessing gastric acid production.     

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.     

The population RDH index: a novel vector index and graphical method for statistical assessment of antihypertensive treatment reduction, duration, and homogeneity

Current indices used in the evaluation of antihypertensive treatment duration and homogeneity such as the trough-peak, smoothness index, and normalized smoothness index were designed to be applied to ambulatory blood pressure monitoring recordings from individual participants. Evaluation of antihypertensive treatment in populations is often carried out by calculating these individual indices for each of the participants and providing summarizing statistics about the population, such as the mean and median. We describe a new population vector index and graphical method for the statistical assessment of antihypertensive treatment reduction, duration, and homogeneity (RDH) from ambulatory blood pressure monitoring. The population (RDH) was specifically designed as a tool to evaluate and compare blood pressure coverage offered by antihypertensive drugs over 24 h in populations. The population RDH is a three-component vector index that incorporates information about the reduction, duration, and homogeneity of antihypertensive treatment, as well as their statistical significance over the 24 h period. In addition to defining the RDH index, in this paper we also demonstrate its usefulness and advantages as an index and graphical method for antihypertensive treatment duration and homogeneity assessment by using it to analyze two data sets.     

24-hour ambulatory blood-pressure effects of valsartan and hydrochlorothiazide combinations compared with amlodipine in hypertensive patients at increased cardiovascular risk: a VAST sub-study

BACKGROUND: There is a lack of data on the effects of angiotensin-receptor blocker and diuretic combinations on ambulatory blood pressure (ABP) in hypertensive patients with additional cardiovascular risk factors. METHODS: In a randomized, double-blind trial, the effects on 24-h ABP of the combination valsartan 160 mg od and hydrochlorothiazide 25 or 12.5 mg during 24 weeks of therapy were compared with the effects of amlodipine 10 mg monotherapy (group A10) in 474 stage-II hypertensive patients with additional cardiovascular risk factors. After a two-week single-blind placebo run-in period, patients were randomized to receive valsartan 160 mg od or amlodipine 5 mg od. At week 4, HCTZ 12.5 mg (group V160/HCTZ12.5) and 25 mg (group V160/HCTZ25) were added to the valsartan groups and in the A10 patients the amlodipine dose was force-titrated to 10 mg od. RESULTS: All three treatments reduced 24-h BP as well as night-time and daytime BP levels from baseline. Twenty-four hour systolic blood pressure (SBP) was reduced by 15.9+/-1.0 mmHg (least-squares mean change+/-SE), 19.3+/-1.0 mmHg and 16.1+/-1.1 mmHg in the V160/HCTZ12.5, V160/HCTZ25 and A10 groups, respectively and 24-h diastolic blood pressure (DBP) was reduced by 9.3+/-0.6 mmHg, 11.4+/-0.6 mmHg and 9.6+/-0.7 mmHg in the three groups. The differences between the V160/HCTZ25 group and the A10 group were significant (p<0.05) for the changes in 24-h systolic BP as well as for changes in daytime systolic BP and night-time diastolic BP. Control rates defined as ABPM < or =130/80 mmHg were: 48.4%, 60.8% and 50.9% in the V160/HCTZ12.5, V160/25 and A10 groups, respectively. The differences in control rates between the V160/HCTZ25 group and the other two treatment groups were significant at p<0.05. CONCLUSIONS: The fixed-dose combination of valsartan 160 mg+HCTZ 25 mg od is an attractive therapeutic option measured on the effects on 24-h ABPM, night-time and daytime BP reduction and control rates in hypertensive patients at additional cardiovascular risk.     

The impact of dipper and non-dipper characteristics in the fluctuation of arterial blood pressure. A study of a population of 484 diabetic patients

Abnormal pattern of circadian blood pressure variations carries a high risk of cardiovascular complications. The aim of this study was to assess the frequency of abnormal blood pressure rhythm in diabetes and its consequences on micro and macrovascular complications. 484 diabetes mellitus patients were submitted to 24-h ambulatory blood pressure monitoring. They were divided into two groups according to the absence (non-dipper: group 1; n = 167) or presence (dipper: group 2; n = 317) of nocturnal BP reduction = 10% of daytime BP. Following data were collected and compared between these two groups: body mass index, glycated haemoglobin, urinary albumin excretion, research of retinopathy by fundoscopy, tests for presence of a macrovascular disease. There were no significant differences among the two groups in sex, body mass index, type and duration of diabetes and glycemic control. Clinical SBP and DBP did not differ from significant manner between non-dipper and dipper (140 +/- 18/81 +/- 1 versus 138 +/- 19/81 +/- 10 mmHg). Non-dipper 24-h SBP and 24-h DBP were higher than those of dipper (129 +/- 16/76 +/- 9 versus 122 +/- 15/73 +/- 8 mmHg; p < 0.001). Non-dipper were older than dipper (59.9 +/- 13 versus 55.8 +/- 15 years; p < 0.001) and there was more hypertensive patients in group 1 than in group 2 (50% versus 39%; p < 0.01). Macro- and microvascular diabetes complications were more common in non-dipper. In conclusion high blood pressure is frequently observed in diabetic patients. Its association with a diminished nocturnal BP fall could explain a higher risk of complications, especially retinopathy, nephropathy and cardiac events.     

White coat effect in treated and untreated patients with high office blood pressure. Relationship with pulse wave velocity and left ventricular mass index.

OBJECTIVE: To evaluate in hypertensive patients whether the white coat effect is associated with target-organ damage and whether it is modified by anti-hypertensive therapy. METHODS: In a cross-sectional study we evaluated blood pressure (BP) measured in the office and by 24-h ambulatory blood pressure monitoring (ABPM), carotid-femoral pulse wave velocity (PWV) as an index of aortic stiffness, and left ventricular mass index (LVMI) in 88 subjects (aged 49 +/- 2 years) with white-coat hypertension (WCH, office BP > 140/90, daytime BP < 130/84 mmHg), 31 under antihypertensive therapy, 57 untreated, and in 115 patients with office and ambulatory hypertension (HT, aged 51 +/- 2 years, office BP > 140/90, daytime BP > 135/85), 65 under antihypertensive therapy, 50 untreated. In a longitudinal study in 15 patients with HT and in 11 patients with WCH we evaluated the influence of antihypertensive therapy (> 6 months) on office and ambulatory BP and on PWV. RESULTS: The intensity of the white coat effect (office BP-daytime BP) was greater in WCH than in HT. Taking all subjects, the white coat effect did not correlate with PWV (r = 0.08, ns) or with LVMI (r = 0.01, ns), whereas daytime BP correlated significantly with PWV (r = 0.41, p < 0.01) and with LVMI (r = 0.32, p < 0.05). WCH subjects showed lower PWV and LVMI than HT subjects. Treated and untreated WCH, with similar office and daytime BP, showed similar values of PWV and LVMI. Treated and untreated HT showed similar office BP values but treated HT showed lower daytime BP and PWV values. In the longitudinal study, antihypertensive therapy significantly reduced daytime BP and PWV values in the 15 HTs, whereas in the 11 WCH it did not alter daytime BP or PWV values. CONCLUSIONS: 1. In both WCH and HT (treated and untreated) the intensity of the white coat effect does not reflect either the severity of hypertension measured by target organ damage or the efficacy of antihypertensive treatment. 2. In WCH antihypertensive therapy does not improve either ambulatory BP values or damage to target organs.     

Role of blood pressure monitoring in non-pharmacological management of hypertension

Ambulatory blood pressure monitoring (ABPM) and home blood pressure (BP) measurement appear to be useful in the assessment of the effects of non-pharmacological treatment of hypertension because they can detect small changes in BP without observer bias. We studied the effects of various lifestyle modifications using ABPM and home BP measurement in Japanese patients with hypertension. Weight reduction by a hypocaloric diet (average 4 kg) was associated with decreases in 24-h BP (10/4 mmHg) as well as casual BP (9/6 mmHg). The reductions in daytime and night-time BPs were comparable. The effects of daily walking without weight loss on office, home, and 24-h BPs were 2-3/1-2 mmHg. The changes in home and 24-h BPs were more significant than those in office BP. A low-salt diet (25 mmol/day versus 250 mmol/day) decreased 24-h BP by 9/4 mmHg. This hypotensive effect was observed throughout the day. Potassium supplementation (64 mmol/day) decreased office, home and 24-h BPs by 3-4/1-2 mmHg. The changes in home and 24-h BPs were highly significant compared with office BP. Supplementation of magnesium (20 mmol/day) also reduced those BPs significantly. However, the effects of calcium supplementation (25 mmol/day) were small (1-2/1 mmHg) and were significant only for home BP. Alcohol restriction for 4 weeks decreased daytime BP by 3/2 mmHg but increased night-time BP by 4/2 mmHg. Average 24-h BP did not change. Smoking cessation lowered daytime BP without affecting night-time BP. Monitoring of 24-h BP and home BP can detect small changes in BP produced by lifestyle modifications. Ambulatory BP monitoring is particularly suitable in the assessment of changes in lifestyle affecting the circadian pattern of BP such as alcohol consumption and smoking.     

Improved automatic analysis of ambulatory blood pressure data based on precise detection of individual night-time from diurnal profile of heart rate

BACKGROUND: Software programs sold with ambulatory blood pressure monitoring (ABPM) devices are designed to use some set 'typical' night-time (e.g. 2300-0700) to estimate daytime/night-time blood pressure (BP) with limited accuracy. Alternative use of individual periods of sleep/wakefulness from patient diaries is time consuming and subjective. We developed a simple mathematical algorithm for the detection of the 'night-time' as a period of low values in diurnal profiles of heart rate (HR) allowing accurate automatic analysis of daytime/night-time blood pressure. To test this technique we designed a software application allowing automatic analysis of ABPM data based on the different night-time definitions, including the developed algorithm and compared reproducibility of the degree of BP dipping produced by the different methods across two days of 48-h ABPM. METHODS: A 48-h ABPM study was performed in 33 patients with uncomplicated stage II hypertension. Means and standard deviations (SD) of the differences in the degree of BP dipping between two 24-h periods of 48-h ABPM were obtained separately for three methods of night-time definition: automatic detection from individual HR profiles, fixed 2300-0700 h interval and sleep time from patient diaries. RESULTS: Reproducibility of the BP dip estimation across 2 days of BP monitoring was significantly better for night-time detected from individual HR profiles than for the fixed 2300-0700 h interval or sleep time from diary. The SD of the differences was 6.7/8.2 compared with 13.5/18.3 and 13.0/14.8 respectively (systolic BP/diastolic BP, mmHg). CONCLUSIONS: Implementation of the developed method of night-time definition may significantly improve automatic analysis of ABPM data.     

Comparison of the effects on 24-h ambulatory blood pressure of valsartan and amlodipine, alone or in combination with a low-dose diuretic, in elderly patients with isolated systolic hypertension (Val-syst Study)

OBJECTIVE: The aim of this study was to compare the time-effect profiles of a once-daily administration of valsartan and amlodipine, each given alone or in combination with hydrochlorothiazide, in terms of ambulatory blood pressure (BP) and heart rate in elderly patients with isolated systolic hypertension. METHODS: One hundred and sixty-four elderly outpatients with systolic hypertension received valsartan 80 mg (n=79) or amlodipine 5 mg (n=85) once daily for eight weeks, after which the patients with poorly controlled office BP were up-titrated to valsartan 160 mg or amlodipine 10 mg once daily. If their office systolic BP was still >140 mmHg after eight weeks at these doses, 12.5 mg hydrochlorothiazide was added for a further eight weeks. The hourly BP decreases in all of the patients were calculated on the basis of 24-h ambulatory recordings made after the placebo period and at the end of active treatment. The trough/peak ratio and smoothness index were calculated in the responders. RESULTS: Both the valsartan- and amlodipine-based treatments effectively lowered mean 24-h, daytime and night-time systolic ambulatory BP (all p<0.001) without any significant differences between the two regimens. Ambulatory heart rate decreased in the subjects on valsartan and slightly increased in those on amlodipine (the differences in 24-h and daytime heart rate were significant (p=0.008 and 0.002 respectively). Among the 138 responders, the valsartan-based treatment had a greater anti-hypertensive effect during the daytime hours (p=0.02), a difference that was also significant for average 24-h BP (p=0.02). The mean systolic BP trough/peak ratio was 0.56 in the patients on valsartan, and 0.77 in those on amlodipine (NS). The smoothness index was respectively 1.70 and 1.58 (NS). CONCLUSIONS: The present results show that both the valsartan- and amlodipine-based treatments lead to a similar long-term reduction in 24-h systolic BP. However, in treatment responders, valsartan has a greater anti-hypertensive effect during the daytime.     

A smooth blood pressure control is obtained over 24 h by delapril in mild to moderate essential hypertensives.

OBJECTIVE: To assess the homogeneity of the antihypertensive effect of delapril over 24 h. DESIGN AND METHODS: After 2 weeks of placebo 50 mild to moderate essential hypertensives (age 54+/-5 years) were subjected to 8 weeks of treatment with delapril 30 mg once daily. At the end of each period, blood pressure (BP) was assessed by conventional sphygmomanometry (clinic or CBP) and ambulatory (A) BP monitoring. Twenty-four-hour means, trough-to-peak ratio (T/P) and smoothness index (SI, the ratio between the average of the 24-h BP changes after T and its standard deviation) were calculated for systolic (S) and diastolic (D) BP. RESULTS: CBP and ABP were significantly reduced by treatment. Pulse pressure (PP, the SBP-DBP difference) was also significantly (p < 0.01) reduced by delapril (5.7+/-6.2 and 3.3+/-3.8 mmHg, CPP and APP). The median T/P was higher (0.51 and 0.62, SBP and DBP) in the 43 responders at trough than in the whole group (0.44 and 0.51). The SI was similarly high in the whole group (1.3+/-0.6 and 1.4+/-0.6, SBP and DBP) and in the responders (1.4+/-0.5 and 1.5+/-0.6). CONCLUSIONS: Delapril effectively and smoothly reduces BP over 24 h, this effect being evident also on PP, a parameter with a relevant prognostic value.     

Safety and efficacy of the oral direct renin inhibitor aliskiren in elderly patients with hypertension

OBJECTIVES: To evaluate the efficacy, safety and tolerability of aliskiren in elderly patients (> or =65 years old) with essential hypertension. METHODS: In this double-blind, multicenter study, 355 elderly patients with hypertension [office mean sitting systolic blood pressure (msSBP) > or =145-<180 mmHg and mean 24-h ambulatory systolic BP (ASBP) > or =135 mmHg] were randomized to once-daily treatment for 8 weeks with aliskiren 75 mg (n = 91), 150 mg (n = 84), 300 mg (n = 94) or the comparator lisinopril 10 mg (n = 86). The primary efficacy variable was change in mean 24-h ASBP. RESULTS: At endpoint, aliskiren 75 mg, 150 mg, 300 mg and lisinopril 10 mg lowered mean 24-h ASBP (least-squares mean+/-SEM) by 8.4+/-0.8, 7.1+/-0.8, 8.7+/-0.8 and 10.2+/-0.9 mmHg, and mean 24-h ambulatory diastolic BP by 4.5+/-0.5, 3.6+/-0.5, 3.9+/-0.5 and 6.3+/-0.5 mmHg, respectively, with no significant difference between aliskiren doses. The trough-to-peak ratio for ASBP reduction with aliskiren 75 mg, 150 mg, 300 mg and lisinopril 10 mg was 0.77, 0.64, 0.79 and 0.87, respectively. All treatments lowered office msSBP and mean sitting diastolic BP (msDBP) compared with baseline. A significantly greater proportion of patients receiving aliskiren 300 mg achieved BP control (msSBP/msDBP <140/90 mmHg) compared with those receiving aliskiren 75 mg (36.2% vs 24.2%, p = 0.033). There was no evidence of dose-related increases in the rate of adverse events with aliskiren treatment. CONCLUSIONS: Aliskiren, a novel direct renin inhibitor, provides effective 24-h BP lowering with no evidence of dose-related increases in the incidence of adverse events in elderly patients with hypertension.     

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.     

Effects of a low dose of indapamide, a diuretic, given daily or every-other-day on blood pressure and metabolic parameters.

To investigate the effects of the diuretic, indapamide, on blood pressure (BP) and metabolic parameters, thirty hypertensive patients were treated with 1 mg of indapamide either every day or every other day. BP, fasting plasma glucose, lipids, serum potassium and uric acid were determined at baseline and after 3 months of a stable regimen of the drug. At the termination of the study, 48-h ambulatory blood pressure monitoring (ABPM) was performed. Three patients received only indapamide, while other patients were treated in combination with additional antihypertensive medications. Patients treated with daily indapamide showed a BP reduction from 162 +/- 2.9/85 +/- 2.4 mmHg to 134 +/- 2.4/71 +/-2.6 mmHg (p < 0.001). The BP reduction was similar in those patients receiving the drug every other day (137 +/- 3.4/71 +/- 3.6 mmHg). While plasma lipids and serum potassium did not differ significantly with the intervention, uric acid increased significantly with daily treatment and normalized with every-other-day treatment. Glycosylated hemoglobin A1c (HbA1c) was not altered (5.6 +/- 0.1% vs. 5.4 +/- 0.2%), and did not differ between patients with and without diabetes mellitus. ABPM revealed an average 24-h BP of 134 +/- 3.3/75 +/- 1.7 mmHg on days in which patients received the medication and 139 +/- 4.9/78 +/- 2.6 mmHg on the intervening day without indapamide (no significant difference). These results suggest that a low dose of indapamide given every day or every other day is effective in lowering BP and does not result in metabolic derangements.     

Effects of GH replacement on 24-h ambulatory blood pressure and its circadian rhythm in adult GH deficiency

OBJECTIVE: Increased prevalence of hypertension and cardiovascular mortality have been reported in hypopituitary patients who had been appropriately replaced with conventional pituitary hormones except GH. Growth hormone replacement (GHR) results in improvement of surrogate markers of cardiovascular function. Data on effects of GHR on blood pressure (BP) in adult growth hormone deficiency (AGHD), however, remain contradictory. There are as yet no reports on BP circadian rhythms in untreated or treated AGHD. Therefore, in a 12-month follow-up study, we evaluated the effects of GHR on ambulatory blood pressure (ABP) in AGHD patients. STUDY DESIGN: A prospective, open treatment design study to determine the effects of GHR on ABP and heart rate in AGHD patients. GH was commenced at a daily dose of 0.5 IU, and titrated up by increments of 0.25 IU at 4-weekly intervals to achieve and maintain IGF-I standard deviation score (IGF-I SD) between the median and upper end of the age-related reference range. PATIENTS: Twenty-two, post-pituitary surgery, severe AGHD patients (11 men), defined as peak GH response < 9 mU/l to provocative testing were recruited. The mean age +/- SEM was 48.8 +/- 2.5 years. Twenty-one patients required additional pituitary replacement hormones following pituitary surgery and were on optimal doses at recruitment. MEASUREMENTS: Twenty-four-hour ABP and heart rate (HR), body mass index (BMI), waist hip ratio (WHR) and total body water (TBW) were measured before and after 12 months on GHR. Cosinor analysis was used to analyse BP and HR circadian rhythm parameter estimates. RESULTS: Target IGF-I SD was achieved within 3 months of commencement of GHR in all patients (-3.5 +/- 0.4 at baseline vs. 0.8 +/- 0.2 at 3 months, P < 0.001) and remained within range at 12 months (1.1 +/- 0.2, P < 0.001 compared to baseline). A significant increase in TBW (45.8 +/- 1.2 vs. 47.8 +/- 1.5 kg, P < 0.05) but no significant change in BMI (30.7 +/- 2.2 vs. 31.8 +/- 2.7, P = NS) or WHR (0.95 +/- 0.02 vs. 0.93 +/- 0.02, P = NS) was observed after 12 months on GHR. The 24-h mean systolic ABP (SBP; 126.2 +/- 2.8 vs. 120.1 +/- 2.7 mmHg, P < 0.001) and diastolic ABP (DBP; 78.2 +/- 1.6 vs. 71.4 +/- 1.8 mmHg, P < 0.001) significantly decreased following GHR with a parallel increase in 24-h mean HR (69.6 +/- 2.5 vs. 73.8 +/- 2.5 beats/min; P < 0.001). A significant nocturnal decrease in SBP and DBP was observed both before (SBP; daytime, 129.1 +/- 2.8 vs. night time, 115.9 +/- 3.0 mmHg, P < 0.001 and DBP; daytime, 80.7 +/- 1.6 vs. night time, 69.2 +/- 1.8 mmHg, P < 0.001) and following GHR (SBP; daytime, 122.8 +/- 2.6 vs. night time, 110.0 +/- 3.6 mmHg, P < 0.001 and DBP; daytime, 73.9 +/- 1.8 vs. night time, 62.0 +/- 2.3 mmHg, P < 0.001). Individual and population-mean cosinor analysis demonstrated significant circadian rhythms for SBP, DBP and HR before and after 12 months on GHR (P < 0.001), suggesting that SBP, DBP and HR circadian rhythms were not altered by GHR. There was, however, a significant reduction in SBP (124.2 +/- 2.8 vs. 118.4 +/- 2.8 mmHg, P < 0.001) and DBP (77.0 +/- 1.6 vs. 70.2 +/- 1.8 mmHg, P < 0.001) MESOR with an increase in HR MESOR (68.9 +/- 2.5 vs. 72.2 +/- 2.4 beats/min, P < 0.01) following GHR. CONCLUSIONS: Systolic and diastolic BP and HR circadian rhythms are preserved in AGHD following 12 months of GHR. However, there is a significant decrease in 24-h mean SBP and DBP and increase in 24-h mean HR after 12 months on GHR. We postulate that this decrease in 24-h mean SBP and DBP may result in a reduction of cardiovascular morbidity and mortality and may explain the beneficial effects of GHR on cardiovascular system previously reported in AGHD patients.     

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.     

Study of representative periods of day-time and night-time levels of blood pressure

The aim of this study is to assess whether it is possible to shorten ambulatory blood pressure (ABP) monitoring while getting measurements that precisely reflect 24 hours and daytime blood pressure (BP). METHODS: three hundred and thirty six young male subjects aged: 21 +/- 2 y, height: 178 +/- 7 cm, weight, 75 +/- 12 kg, with normal or "borderline" BP (casual BP: 138 +/- 13/79 +/- 8 mmHg) participated in the study. BP was recorded in each, every 15 minutes on 24 hours with a Spacelabs 5200 device. Systolic and diastolic BP on 24-h, during the 9 a.m. - 8 p.m. period (daytime) and BP related to the different subperiods included between 15 minutes and 6 hours were calculated. BP values obtained from the 196 subperiods were correlated with 24-h, daytime ABP and causal BP. Results were classified according to the value of correlation coefficient, slope and intercept of regressions. RESULTS: no subperiod accurately predict 24-h systolic BP (SBP) or diastolic BP (DBP) (the best correlation are established with the subperiods: 7 p.m.-01 a.m. for SBP; r = 0.916, p less than 10(-9), y = 0.76 x + 30; and 06 a.m.-12 a.m. for DBP; r = 0.914, p less than 10(-9), y = 0.87 x + 9). Four 6 hours subperiods sampled between 09 a.m.-3 p.m. and 12 a.m.-6 p.m. predict alike and in a reasonable way the daytime BP (SBP: r = 0.971, p less than 10(-9), y = 0.94 x + 8; r = 0.973, p less than 10(-9), y = 0.91 x + 7. Best correlations with casual BP are moderate (SBP: r = 0.674, DBP: r = 0.588). COMMENTS: BP measurements of subperiods smaller or equal to 6 hours cannot accurately predict the average 24-h BP. This is related mainly to the night-time/daytime BP fluctuations. Daytime BP can be estimated with short-term monitoring but the duration must not be smaller than 6 hours.     

Clinical effects of torasemide prolonged release in mild-to-moderate hypertension: a randomized noninferiority trial versus torasemide immediate release

The efficacy of a new torasemide prolonged release (PR) formulation to torasemide immediate release (IR) was compared in a randomized noninferiority double-blind trial. Patients with newly diagnosed mild-to-moderate hypertension or unresponsive or poor tolerability to previous antihypertensive monotherapy received 5 mg/day of torasemide-PR (n = 219) or torasemide-IR (n = 223) for 12 weeks (uptitration to 10 mg/day if no response at 4 or 8 weeks). Mean diastolic blood pressure (DBP) reduction in the torasemide-PR group (11.6 +/- 7.1 mmHg, 95% confidence interval [CI] 10.6-12.5) versus torasemide-IR (11.3 +/- 7.5 mmHg, 95% CI 10.2-12.3) met the noninferiority criterion of a nonsided 97.5% CI lower than the preestablished margin of 2 mmHg. A significantly higher percentage of patients in the torasemide-PR group achieved adequate BP control after 8 and 12 weeks. Ambulatory 24-h BP monitoring (ABPM) measurements in a subset of 100 patients showed greater daytime SBP reductions in the torasemide-PR group (128.4 +/- 9.9 mmHg vs. 133.5 +/- 10.4 mmHg, P < 0.05). Safety and tolerability of both formulations were similar.     

Circadian behavior of blood pressure and heart rate following orthotopic heart transplantation. Studies before and during antihypertensive therapy

The de novo hypertension, which develops in most cardiac transplant recipients within the first postoperative months, is multicausal, though toxic side-effects of cyclosporin A seem to play a key role. In order to analyze the circadian behavior of arterial blood pressure and heart rate after cardiac transplantation (HTX) and to evaluate the effect of an antihypertensive regimen on these parameters, 24-h noninvasive ambulatory blood pressure and heart rate monitoring was performed in 10 hypertensive cardiac transplant recipients on cyclosporin A (mean age 42.3 +/- 11.2 years, 14.3 +/- 8.3 months after HTX) before antihypertensive therapy and after introduction of an antihypertensive regimen with the ACE-inhibitor enalapril plus furosemide alone or combined with verapamil. The study demonstrated a complete loss of the usual nocturnal decline in blood pressure in cardiac transplant recipients (mean systolic and diastolic blood pressure 149 +/- 8 and 102 +/- 7 mm Hg during daytime and 152 +/- 8 and 104 +/- 9 mmHg at night). Antihypertensive therapy lowered the blood pressure level effectively, but did not influence the circadian pattern (mean systolic and diastolic blood pressure 121 +/- 8 and 81 +/- 4 mmHg during daytime and 121 +/- 9 and 83 +/- 3 mmHg at night, all p less than or equal to 0.001). Heart rate, in contrast, showed a significant, though in comparison to normal, a blunted decrease at night (mean heart rate 94 +/- 6 beats per min during daytime and 84 +/- 8 beats per min at night, p less than or equal to 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)