Decrease in urinary albumin excretion associated with the normalization of nocturnal blood pressure in hypertensive subjects

Previous results have indicated that valsartan administration at bedtime as opposed to on wakening improves the diurnal/nocturnal ratio of blood pressure without loss in efficacy and therapeutic coverage. We hypothesized that increasing this ratio could reduce microalbuminuria. We conducted a prospective, randomized, open-label, blinded endpoint trial on 200 previously untreated nonproteinuric patients with grade 1 to 2 essential hypertension, assigned to receive valsartan (160 mg/d) as a monotherapy either on awakening or at bedtime. Blood pressure was measured by ambulatory monitoring for 48 consecutive hours before and after 3 months of treatment. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately calculate the diurnal and nocturnal means of blood pressure on a per-subject basis. The significant blood pressure reduction after 3 months of therapy was similar for both treatment times. The diurnal/nocturnal blood pressure ratio was unchanged after valsartan on awakening, but significantly increased from 7.5 to 12.2 (P<0.001) when valsartan was administered at bedtime. Urinary albumin excretion was significantly reduced by 41% after bedtime treatment. This reduction was independent of the 24-hour blood pressure decrease but highly correlated with the decrease in nocturnal blood pressure and mainly with the increase in diurnal/nocturnal ratio (P<0.001). Bedtime valsartan administration improves the diurnal/nocturnal blood pressure ratio to a more dipper profile. This normalization of the circadian blood pressure pattern is associated with a significant decrease in urinary albumin excretion and plasma fibrinogen, and could thus reduce the increased cardiovascular risk in nondipper hypertensive patients.     

Effects of telmisartan 80 mg and valsartan 160 mg on ambulatory blood pressure in patients with essential hypertension

OBJECTIVES: This trial investigated and compared the antihypertensive efficacy of telmisartan and valsartan, two angiotensin II receptor blockers, used in monotherapy at their maximum recommended dose in hypertensive patients. METHODS: We studied 70 subjects (32 men and 38 women) aged 47.6 +/- 12.2 (mean +/- SD) years, with mild to moderate essential hypertension; they were randomly assigned to receive monotherapy with either telmisartan (80 mg) or valsartan (160 mg), in the form of a single daily tablet upon awakening. Blood pressure was measured by ambulatory monitoring every 20 min during the day and every 30 min at night for 48 consecutive hours before and after 3 months of treatment. Physical activity was simultaneously monitored every minute by wrist actigraphy to calculate accurately the diurnal and nocturnal means of blood pressure on a per subject basis. RESULTS: There was a highly significant blood pressure reduction during the 24 h with both drugs. The blood pressure reduction in the 24-h mean was significantly larger for valsartan 160 mg (18.6 and 12.1 mmHg for systolic and diastolic blood pressure, respectively) than for telmisartan 80 mg (10.8 and 8.4 mmHg; P < 0.001 between treatment-groups). There was also a highly significant reduction (P < 0.001) of 6.5 mmHg in the 24-h mean of pulse pressure after valsartan administration only. The trough : peak ratio and the smoothness index were slightly higher in systolic, but similar in diastolic blood pressure, for telmisartan as compared to valsartan. CONCLUSIONS: Despite a shorter half-life, 160 mg/day valsartan was more effective in lowering blood pressure over 24 h than 80 mg/day telmisartan. Furthermore, valsartan was also more effective in lowering arterial pulse pressure, an observation that may have important therapeutic implications, given the mounting evidence that pulse pressure may be a risk factor for future cardiovascular events.     

Administration time-dependent effects of valsartan on ambulatory blood pressure in hypertensive subjects

This study investigated the administration time-dependent antihypertensive efficacy of valsartan, an angiotensin II receptor blocker. We studied 90 subjects (30 men and 60 women), 49.0+/-14.3 (mean+/-SD) years of age with stage 1 to 2 essential hypertension; they were randomly assigned to receive valsartan (160 mg/d) as a monotherapy either on awakening or at bedtime. Blood pressure was measured by ambulatory monitoring every 20 minutes during the day and every 30 minutes at night for 48 consecutive hours before and after 3 months of treatment. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately calculate the diurnal and nocturnal means of blood pressure on a per-subject basis. The highly significant blood pressure reduction after 3 months of treatment with valsartan (P<0.001) was similar for both treatment times (17.0 and 11.3 mm Hg reduction in the 24-hour mean of systolic and diastolic blood pressure with morning administration and 14.6 and 11.4 mm Hg reduction with bedtime administration; P>0.174 for treatment time effect). Valsartan administration at bedtime as opposed to on wakening resulted in a highly significant average increase by 6% (P<0.001) in the diurnal-nocturnal ratio of blood pressure; this corresponded to a 73% relative reduction in the number of nondipper patients. The findings confirm that valsartan efficiently reduces blood pressure throughout the entire 24 hours, independent of treatment time. They also suggest that time of treatment can be chosen according to the dipper status of a patient to optimize the effect of antihypertensive therapy, an issue that deserves further investigation.     

Differing administration time-dependent effects of aspirin on blood pressure in dipper and non-dipper hypertensives

Aspirin is a potent antioxidative agent that reduces vascular production of superoxide, prevents angiotensin II-induced hypertension, and induces NO release. Low-dose aspirin administered at bedtime, but not on awakening, has also been shown to reduce blood pressure, possibly enhancing the nocturnal trough in NO production. Because endothelium-dependent vasodilation is blunted through a decrease in NO release in non-dipper compared with dipper patients, we compared the administration time-dependent influence of aspirin on ambulatory blood pressure in dipper and non-dipper hypertensive subjects. We studied 257 patients with mild hypertension (98 men and 159 women), 44.6+/-12.5 years of age, randomly assigned to receive 100 mg per day of aspirin either on awakening or at bedtime. Ambulatory blood pressure was measured for 48 hours at baseline and after 3 months of intervention. Blood pressure was slightly elevated after aspirin on awakening (increase of 1.5/1.0 mm Hg in the 24-hour mean of systolic/diastolic blood pressure; P<0.028). A highly significant blood pressure reduction was observed in patients who received aspirin at bedtime (decrease of 7.2/4.9 mm Hg in systolic/diastolic blood pressure; P<0.001). The reduction in nocturnal blood pressure mean was double in non-dippers (11.0/7.1 mm Hg) compared with dippers (5.5/3.3 mm Hg; P<0.001). This prospective trial corroborates the significant administration time-dependent effect of low-dose aspirin on blood pressure, mainly in non-dipper hypertensive patients. The timed administration of low-dose aspirin could thus provide a valuable approach, beyond prevention of cardiovascular disease, in the blood pressure control of patients with mild hypertension.     

Comparison of the efficacy of morning versus evening administration of telmisartan in essential hypertension

Valsartan administration at bedtime as opposed to on wakening improves the sleep time-relative blood pressure decline toward a more dipper pattern without loss in 24-hour efficacy. Yet to be determined is whether this administration time-dependent efficacy is a class-related feature, characteristic of all angiotensin receptor blockers or specific only to valsartan. Terminal half-life is a major difference between angiotensin receptor blockers, being largest ( approximately 24 hours) for telmisartan. This trial investigated the administration time-dependent antihypertensive efficacy of telmisartan. We studied 215 patients with hypertension (114 men and 101 women), 46.4+/-12.0 years of age, randomly assigned to receive telmisartan (80 mg/d) as a monotherapy either on awakening or at bedtime. Blood pressure was measured for 48 hours before and after 12 weeks of treatment. The significant blood pressure reduction after treatment was similar for both groups. Bedtime administration of telmisartan, however, was more efficient than morning dosing in reducing the nocturnal blood pressure mean. The sleep time-relative blood pressure decline was slightly reduced after telmisartan on awakening but significantly increased with bedtime dosing, thus reducing the prevalence of nondipping from baseline by 76%. Telmisartan administered at bedtime, as opposed to morning dosing, improved the sleep time-relative blood pressure decline toward a more dipper pattern without loss in 24-hour efficacy. Nocturnal BP regulation is significantly better achieved with bedtime dosing of telmisartan. Results from this prospective trial suggest that these beneficial features of bedtime dosing may be class related for angiotensin receptor blockers. These results should be taken into account when prescribing this class of antihypertensive medication for treatment of essential hypertension.     

Effects of time of day of treatment on ambulatory blood pressure pattern of patients with resistant hypertension

Patients with resistant hypertension present high prevalence of a non-dipper blood pressure pattern. Recent results indicate that non-dipping is related partly to the absence of 24-hour therapeutic coverage in patients treated with single morning doses. Accordingly, we investigated the impact of treatment time on the blood pressure pattern in 700 patients with resistant hypertension on the basis of clinic measurements who were studied by 48-hour ambulatory monitoring. Among them, 299 patients received all their medication on awakening, and 401 were taking > or =1 antihypertensive drug at bedtime. The percentage of patients with controlled ambulatory blood pressure was double in patients taking 1 drug at bedtime (P=0.008). Among the 578 patients with true resistant hypertension, subjects receiving 1 drug at bedtime showed a significant reduction in the 24-hour mean of systolic and diastolic blood pressure (3.1 and 1.6 mm Hg, respectively; P<0.011). This reduction was much more prominent during nighttime (5.1 and 3.0 mm Hg; P<0.001). Accordingly, the diurnal/nocturnal blood pressure ratio was significantly increased by 2.7 and the prevalence on non-dipping reduced (56.9 versus 81.9%; P<0.001) in patients taking 1 drug at bedtime. Compared with patients receiving all drugs on awakening, subjects with 1 drug at bedtime also showed significant reductions in the average values of glucose, cholesterol, fibrinogen, and urinary albumin excretion (P<0.011). In patients with resistant hypertension, pharmacological therapy should take into account when to treat with respect to the rest-activity cycle of each patient to improve control and to avoid the non-dipper pattern associated to higher cardiovascular risk.     

Diurnal variation of hemodynamic indices in non-dipper hypertensive patients.

The purpose of this study was to elucidate the underlying mechanisms of blunted nocturnal blood pressure reduction in non-dipper hypertensive patients. We studied the diurnal variations in systemic hemodynamic indices and baroreflex sensitivity. In 45 subjects with essential hypertension (24 men; mean age, 49+/-1 years), intra-arterial pressure was monitored telemetrically. Non-dippers were defined as those with a nocturnal reduction of systolic blood pressure of less than 10% of daytime systolic blood pressure. Stroke volume was determined using Wesseling's pulse contour method, calibrated with indocyanine green dilution. Baroreflex sensitivity was calculated as deltapulse interval/deltasystolic blood pressure on spontaneous variations. The mean values of the hemodynamic parameters were calculated every 30 min. Twenty-six subjects were classified as non-dippers. Daytime blood pressure was not significantly different between dippers (149+/-4/87+/-3 mmHg) and non-dippers (147+/-3/82+/-2 mmHg), while the nighttime blood pressure was significantly reduced in dippers (131+/-3/77+/-2 mmHg) but not in non-dippers (145+/-3/80+/-2 mmHg). Nocturnal decreases in both cardiac index and stroke index were smaller in non-dippers (-12.0+/-1.2% and 1.5+/-1.0%) than in dippers (-17.5+/-1.4% and -2.2+/-1.1%). Baroreflex sensitivity significantly increased at nighttime both in dippers (6.5+/-0.6 to 8.0+/-0.7 ms/mmHg) and in non-dippers (5.1+/-0.3 to 6.4+/-0.4 ms/mmHg). Neither daytime nor nighttime baroreflex sensitivity was significantly different between the groups. We conclude that the hemodynamics of non-dipper essential hypertension are characterized by an inadequate nocturnal decrease in cardiac index and stroke index, suggestive of relative volume expansion or malsuppressed sympathetic activity.     

缬沙坦对非勺型高血压患者血压昼夜节律的影响

目的观察缬沙坦对非勺型高血压患者血压昼夜节律的影响。方法选择经24h动态血压监测且诊断为非勺型2级高血压的患者60例为研究对象,将其按电脑数字表法随机均分为治疗组30例：上午7：00和晚上7：00各服缬沙坦80mg;对照组30例：上午7：00服缬沙坦160mg,两组用药8周后复测24h动态血压。比较两组血压昼夜节律的变化。结果两组治疗后24h、白昼、夜间收缩压及舒张压均较治疗前显著下降,差异有统计学意义（P〈0．05）。治疗组的夜间收缩压、舒张压及白昼、夜间血压负荷较对照组显著下降,差异有统计学意义（P〈0．05）。治疗组血压昼夜节律改变有效率明显高于对照组,差异有统计学意义（收缩压：73．33％抵46．67％,P〈0．05;舒张压：76．67％眠43．33％,P〈0．01）。结论应用缬沙坦治疗非勺型高血压,可以很好地控制2级高血压,并改变血压昼夜节律,早晚两次服用,效果更好。     

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.     

Diurnal variation of blood pressure; reproducibility and association with left ventricular hypertrophy in hemodialysis patients

OBJECTIVE: The objective of this paper is to describe the pattern of diurnal blood pressure (BP) change in hemodialysis patients, determine the association of the non-dipping pattern of diurnal BP with left ventricular mass index (LVMI), and to determine if the nocturnal profile of BP is reproducible when repeated over time. METHODS: In a cross-sectional study, ambulatory blood pressure monitoring (ABPM) was performed over a midweek 44-h period and echocardiography was performed on the interdialytic day. Patients with a night/day systolic and diastolic BP ratio on both days >0.9 were defined as non-dippers. Ambulatory blood pressure monitoring was repeated at 6 and 12 months follow-up. RESULTS: Of the 59 patients, 88% were African-American, and 48% were non-dippers. Mean LVMI was significantly higher in the non-dipper (68.3+/-25 g/height) compared to the dipper patients (55.6+/-16, P<0.05). Mean nocturnal systolic BP (r=0.35) and the night/day systolic BP ratio (r=0.39) had a higher correlation with M-mode LVMI than pre-dialysis (r=0.32). After adjustment for 44-h mean SBP, night/day systolic BP ratio remained independently associated with LVMI (beta coefficient 147.62, P=0.004). Of 12 patients who had a non-dipper profile at baseline, 11 (92%) demonstrated the same profile after 6 months and 1 year of follow-up. CONCLUSION: Many hemodialysis patients demonstrate a non-dipper profile; the degree of decline in nocturnal BP is independently associated with LVMI even after adjustment for mean BP. Patients who are identified as non-dippers consistently reproduce the same profile over time.     

Clinical trial of arotinolol in the treatment of hypertension: dippers vs. non-dippers.

To compare the effects of an alpha, beta blocker, arotinolol, in the treatment of essential hypertension between patients with a dipper and those with a non-dipper profile by means of 24-h ambulatory blood pressure monitoring (ABPM), a multicenter single blind parallel trial was carried out in five clinical centers. After a one-week single blind placebo run-in period, the patients underwent ABPM if their clinic diastolic blood pressure (DBP) ranged from 90-109 mmHg and their clinic systolic blood pressure (SBP) was <180 mmHg. They were divided into two groups according to the absence (non-dipper group, 24 cases) or presence (dipper group, 23 cases) of nocturnal BP reduction > or =10% of daytime BP. ABPM was measured again at the end of the active treatment phase. All patients were given Arotinolol 10-20 mg twice daily for 4 weeks. Twenty four-hour systolic and diastolic average BPs (MSBP, MDBP), 24-h systolic and diastolic blood pressure load (LS BP, LDBP), daytime systolic and diastolic average BPs (dMSBP, dMDBP), daytime systolic and diastolic blood pressure load (dLSBP, dLDBP), nighttime systolic and diastolic average BPs (nMSBP, nMDBP) and nighttime systolic and diastolic blood pressure load (nLSBP, nLDBP) were calculated. Arotinolol was effective in 78.2% of dippers and 54.2% of non-dippers, but the difference in effectiveness between these groups was not statistically significant. After treatment, SBP and DBP-including 24-h, daytime and nighttime systolic and diastolic BPs- were significantly reduced in both groups. During the daytime period, the systolic and diastolic blood pressures were significantly reduced in both dippers and non-dippers, while nighttime systolic and diastolic blood pressures were significantly reduced only in the non-dipper group. No significant changes were found in the dipper group over this period. In conclusion, Arotinolol, which can be dosed twice daily, is an effective antihypertensive agent which effectively lowers blood pressure during the day while reducing nighttime blood pressure more in non-dippers than in dippers, without excessive lowering blood pressure in the latter.     

Evaluation of dosing time-related anti-hypertensive efficacy of valsartan in patients with type 2 diabetes

The aim of this study was to evaluate which administration timing of valsartan provides satisfactory blood pressure (BP) control, once daily in the morning, once daily in the evening, or twice daily in total 160 mg. Hypertensive patients with mild-to-moderate diabetic nephropathy were enrolled, but those with more than three anti-hypertensive agents, renal insufficiency (serum creatinine ≥ 3 mg/ dL), or hepatic insufficiency were excluded. They were randomized to receive valsartan 160mg once daily in the morning, valsartan 160 mg once daily in the evening, or valsartan 80 mg twice daily for 12 weeks according to a three-period crossover design. Office blood pressure (OBP), home blood pressure (HBP) self-measured by patients, and urinary albumin excretion adjusted by creatinine excretion (UAE) were measured every 12 weeks. In 34 patients, (male: 18, mean age: 57.5 ± 10.3), valsartan with ether all administration timing demonstrated significant reductions in OBP and HBP compared to baseline: valsartan 160 mg once daily in the morning: -12.2/-9.5 mmHg (p < 0.01); valsartan 160 mg once daily in the evening: -14.2/-10.3 mmHg (p < 0.01); valsartan 80 mg twice daily: -15.0/-10.2 mmHg (p < 0.01) There was no statistically significant differences in a decrease in OBP and HBP, and reduction of UAE among three administration timing. In conclusion, these data indicate that the efficacy on BP-lowering does not depend on administration timing of valsartan in patients with diabetic nephropathy.     

Reference thresholds for 24-h, diurnal, and nocturnal ambulatory blood pressure mean values in pregnancy

OBJECTIVES: Several studies have indicated that the use of the 24-h mean of blood pressure, mainly using reference thresholds derived from the general non-pregnancy practice, does not provide a proper test for diagnosis of hypertension in pregnancy. This prospective study examines previously derived reference thresholds for the 24-h, diurnal, and nocturnal mean of blood pressure as potential screening tests for the diagnosis of hypertension in pregnancy. METHODS: We studied 235 normotensive and 168 hypertensive pregnant women, who provided 2430 blood pressure series sampled every 20 min during the day and every 30 min at night for 48 consecutive hours once every 4 weeks from the first obstetric visit until delivery. Sensitivity and specificity for each parameter are based on the comparison of the distributions of mean blood pressure values with reference thresholds previously established from an independent population of 113 pregnant women also evaluated monthly by 48-h ambulatory monitoring throughout gestation. RESULTS: Sensitivity of mean blood pressure values, above 70% at all stages of pregnancy, was higher than that obtained from clinic blood pressure measurements, which were always below 14%. The poorest results were consistently obtained for the nocturnal mean. Sensitivity was similar for the 24-h and the diurnal mean, with values ranging from 71% for diastolic blood pressure in the first trimester of pregnancy to 93% for systolic blood pressure in the third trimester. Systolic blood pressure consistently provided better sensitivity than diastolic blood pressure at all gestational ages. CONCLUSIONS: This prospective study on women systematically studied by 48-h ambulatory monitoring throughout gestation indicates that mean ambulatory blood pressure values provide higher sensitivity and specificity than conventional measurements. Moreover, results indicate that diagnosis of hypertension in pregnancy based on ambulatory blood pressure should be established from thresholds much lower than those currently used in clinical practice.     

Sleep disturbance is associated with decreased daily activity and impaired nocturnal reduction of blood pressure in dementia patients

Our aim was to investigate the relationships between sleep disturbance and activities of daily living (ADL) and 24-h blood pressure patterns in institutionalized dementia patients. Using 107 institutionalized dementia patients (32 males and 75 females, mean age 76.3 years), patients with a mini mental state examination (MMSE) score <24 were classified into four groups based on ADL (normal or declined) and nocturnal reduction in blood pressure (dipper or non-dipper). The sleep/wake state was visually monitored hourly for 14 consecutive days, and daytime and nighttime sleep ratios were determined. MMSE scores were significantly lower in the declined ADL group than in the normal ADL group. The nighttime sleep ratio of the non-dipper/declined ADL group was significantly lower than in the other groups. Sleep disturbance was associated with the deterioration of MMSE scores, low ADL, and impaired nocturnal reduction in blood pressure in dementia patients.     

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.     

Sleep disturbance is associated with decreased daily activity and impaired nocturnal reduction of blood pressure in dementia patients

Our aim was to investigate the relationships between sleep disturbance and activities of daily living (ADL) and 24-h blood pressure patterns in institutionalized dementia patients. Using 107 institutionalized dementia patients (32 males and 75 females, mean age 76.3 years), patients with a mini mental state examination (MMSE) score <24 were classified into four groups based on ADL (normal or declined) and nocturnal reduction in blood pressure (dipper or non-dipper). The sleep/wake state was visually monitored hourly for 14 consecutive days, and daytime and nighttime sleep ratios were determined. MMSE scores were significantly lower in the declined ADL group than in the normal ADL group. The nighttime sleep ratio of the non-dipper/declined ADL group was significantly lower than in the other groups. Sleep disturbance was associated with the deterioration of MMSE scores, low ADL, and impaired nocturnal reduction in blood pressure in dementia patients.     

Effects of bedtime vs. morning administration of the long-acting lipophilic angiotensin-converting enzyme inhibitor trandolapril on morning blood pressure in hypertensive patients.

Cardiovascular events occur most frequently in the morning. To study the effects of the long-acting lipophilic angiotensin-converting enzyme (ACE) inhibitor trandolapril on morning blood pressure (BP), we performed ambulatory BP monitoring (ABPM) before and after administration of trandolapril just before going to bed (bedtime-administered group: n=17) or in the morning (morning-administered group: n=20) in 37 hypertensive patients. Both sets of ABPM data were available in 30 patients. The 24-h systolic BP (SBP) levels were significantly decreased by 7.2 mmHg in the morning-administered group (p=0.02) and by 5.2 mmHg in the bedtime-administered group (p=0.04). In the bedtime-administered group, prewaking SBP (the average of the 2-h SBP values just before waking) and morning SBP (the average of the 2-h SBP values just after waking) were significantly decreased by 11 mmHg (p=0.005) and by 8.4 mmHg (p=0.03), respectively. On the other hand, in the morning-administered group, the reduction of prewaking SBP (3.9 mmHg, n.s.) and morning SBP (6.6 mmHg, n.s.) did not reach the level of statistical significance. However, the differences in the reductions of prewaking and morning SBPs between the two groups were not statistically significant. There was no additional reduction of the nighttime lowest BP in either administration group. In conclusion, bedtime administration of the long-acting ACE inhibitor trandolapril seems to be a safe and effective means of controlling morning BP in hypertensive patients without an excessive fall in nocturnal BP.     

An ambulatory blood pressure monitoring study of the comparative antihypertensive efficacy of two angiotensin II receptor antagonists,irbesartan and valsartan

BACKGROUND: The primary objective of this study was to compare the change from baseline in mean diastolic ambulatory blood pressure (ABP) at 24 h post dose (trough measurement) after 8 weeks of treatment with irbesartan or valsartan in subjects with mild-to-moderate hypertension. Secondary objectives included comparing the mean changes from baseline in systolic ABP at trough; 24-h ABP; morning and night-time ABP; self-measured systolic blood pressure (SBP) and diastolic blood pressure (DBP); and office-measured SBP and DBP at trough. DESIGN: After a 3-week, single blind, placebo lead-in period, 426 subjects were randomized to receive either irbesartan 150 mg or valsartan 80 mg for 8 weeks. METHODS: Ambulatory blood pressure measurements were obtained at baseline and at week 8. Self-measured morning and evening DBP and SBP readings were obtained at home over a 7-day period at baseline and at week 8. Office-measured seated DBP and SBP measurements were obtained at trough, at baseline, and at week 8. RESULTS: Irbesartan demonstrated significantly greater reductions than valsartan for mean change from baseline in diastolic ABP at trough (-6.73 versus -4.84 mmHg, respectively; P = 0.035). Irbesartan produced significantly greater reductions than valsartan for mean systolic ABP at trough (-11.62 versus -7.5 mmHg, respectively; P < 0.01) and for mean 24-h diastolic ABP (-6.38 versus -4.82 mmHg, respectively; P = 0.023) and systolic ABP (-10.24 versus -7.76 mmHg; P < 0.01). Irbesartan also produced significantly greater reductions than valsartan for office-measured seated DBP (-10.46 versus 7.28 mmHg, respectively; P < 0.01) and SBP (-16.23 versus -9.96 mmHg, respectively; P < 0.01) and for self-measured morning DBP (-6.28 versus -3.75 mmHg, respectively; P < 0.01) and SBP (-10.21 versus -6.97 mmHg, respectively; P < 0.01). Both drugs were well tolerated. CONCLUSION: Irbesartan was more effective than valsartan in reducing DBP and SBP at trough and in providing greater overall 24-h blood pressure-lowering efficacy.     

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.     

Ambulatory Blood Pressure in Patients with Mesangial Proliferative Glomerulonephritis

Twenty-four-hour ambulatory blood pressure was measured in seven normotensive and 10 hypertensive patients with biopsy proven mesangial proliferative glomerulonephritis (MPG). In normotensive patients, the nocturnal blood pressure variation was seen with a nightly drop in blood pressure while in hypertensive patients with MPG, 24-h blood pressure level was increased both at day- and night-time, but a nocturnal change in blood pressure was also observed in these patients. The pattern of blood pressure variation was not, however, different from the normotensive patients. None of the hypertensive patients with MPG was a so-called non-dipper, showing the same level of blood pressure both at day- and night-time. The hypertensive patients had a rapid increase in blood pressure in the early morning hours from 06.00 to 09.00 h, followed by a relatively abrupt decrease in blood pressure in the evening hours. The patients with high blood pressure were treated with antihypertensive drugs; all patients started with captopril 25 mg once a day, later increasing to twice daily. If the correction of the high blood pressure was not achieved with this drug, amlodipine 5 or 10 mg was added with or without furosemide. Most of the patients needed more than one drug. In all patients, a normal 24-h ambulatory blood pressure could be obtained. The lack of nightly non-dippers in the present hypertensive patients may be explained by a relatively short history of renal disease and the presence of normal or moderately reduced glomerular filtration rate. The abrupt rise in blood pressure during the early morning hours may be due to activation of the renin-angiotensin or sympathetic nervous system in the hypertensive patients with MPG.