奥美沙坦与坎地沙坦治疗轻、中度原发性高血压的疗效及安全性比较

目的 评价奥美沙坦24 h降压尤其是降低晨峰血压的效果.方法 120例轻、中度原发性高血压患者随机双盲服用奥美沙坦20 mg或坎地沙坦8 mg,共8周.服药前、服药后8周行动态血压监测(ABPM),比较两组24 h,白昼,下一次给药前4 h、2 h ABPM达标的患者比例.结果 8周后奥美沙坦和坎地沙坦均能有效降低血压,奥美沙坦治疗的24 h血压和白天血压达标率高于坎地沙坦,分别为37%比25%和25%比15%,在动态血压监测的最后2 h、4 h,血压的达标比例奥美沙坦高于坎地沙坦,分别为30%比20%和40%比25%.结论奥美沙坦治疗的高血压患者24 h血压和晨峰血压达标率比例高.奥美沙坦不仅能较好地控制24 h血压,而且能降低与晨峰血压高有关的心血管事件.     

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.     

Effect of Low-Dose Manidipine on Ambulatory Blood Pressure in Very Elderly Hypertensives

Summary. To evaluate the effect of manidipine 10 mg on 24-hour ambulatory blood pressure (BP) and heart rate (HR) in very elderly hypertensive patients, 54 patients aged 76–89 years (mean age 81.8 years) with systolic blood pressure (SBP) >160 mmHg and diastolic blood pressure (DBP) >90 mmHg were studied. After a 4-week placebo washout period, patients were randomized to receive manidipine 10 mg or placebo, both administered once daily for 8 weeks. Patients were checked after the initial run-in placebo phase and every 4 weeks thereafter. At each visit casual BP and HR were measured. At the end of the placebo period and after 8 weeks of active treatment, noninvasive 24-hour ambulate blood pressure measurement ABPM was performed. Manidipine significantly lowered casual sitting and standing SBP (P <0.001) and DBP (P <0.001) at the trough level. ABPM showed a significant decrease in 24-hour SBP and DBP values (P < 0,001), daytime SBP and DBP (P <0.001), and night-time SBP (P <0.001) and DBP (P <0.005). In addition, ABPM confirmed a consistent antihypertensive activity throughout the 24-hour dosing interval, without effect on the circadian BP profile. The trough/peak ratio was 0.67 for SBP and 0.59 DBP. No statistically significant change in HR was observed. The treatment was well tolerated, and there were no serious side effects. In conclusion, in very elderly hypertensive patients, once-daily administration of manidipine 10 mg was well tolerated and effective in reducing casual as well ambulatory BP.     

Proposal of RAS-diuretic vs. RAS-calcium antagonist strategies in high-risk hypertension: insight from the 24-hour ambulatory blood pressure profile and central pressure

I here propose an individualized renin angiotensin system (RAS) inhibitor-based combination therapy with calcium-channel blockers (CCBs) or with diuretics, based on the 24-hr ambulatory blood pressure (BP) profiles and central pressure in relation to the target organ damage in high-risk hypertensive patients. For high-risk patients with increased circulating volume, such as that caused by chronic kidney disease (CKD) or congestive heart failure (CHF), who are likely to exhibit a non-dipper/riser pattern of nocturnal BP fall, diuretics are recommended in combination with a RAS inhibitor to reduce nocturnal BP preferentially. For high-risk patients with arterial diseases such as cardiovascular disease and increased arterial stiffness, who are likely to exhibit exaggerated BP variability, such as morning BP surge and day-to-day BP variability, a CCB is recommended for use in combination with a RAS inhibitor to reduce BP variability and central BP. In particular, bedtime dosing of a RAS inhibitor targeting sleep-early morning activation of RAS may be particularly effective for cardiorenal protection.     

Azilsartan in Patients With Mild to Moderate Hypertension Using Clinic and Ambulatory Blood Pressure Measurements

This was a phase 2, multicenter, randomized, parallel-group, double-blind dose-ranging study. Hypertensive adults (n=555) received one of five doses of azilsartan (AZL; 2.5, 5, 10, 20, 40 mg), olmesartan medoxomil (OLM) 20 mg, or placebo once daily. The primary endpoint was change in trough clinic diastolic blood pressure (DBP) at week 8. Compared with placebo, all AZL doses (except 2.5 mg) provided statistically and clinically significant reductions in DBP and systolic blood pressure (SBP) based on both clinic blood pressure (BP) and 24-hour ambulatory BP monitoring (ABPM). AZL 40 mg was statistically superior vs OLM. Clinic BP was associated with a pronounced placebo effect (−6 mm Hg), whereas this was negligible with ABPM (±0.5 mm Hg). Adverse event frequency was similar in the AZL and placebo groups. Based on these and other findings, subsequent trials investigated the commercial AZL medoxomil tablet at doses 20 to 80 mg/d using 24-hour ABPM.     

Comparative efficacy of two different beta-blockers on 24-hour blood pressure control.

Atenolol and metoprolol succinate, dosed once daily, have different pharmacokinetic profiles. This study tests the hypothesis that differences that are especially noted in the early morning period, when cardiovascular risk is highest, in 24-hour blood pressure (BP) control exist between these 2 beta-blockers. This was a small, randomized open-label study with blinded end point evaluation in 36 hypertensive patients. All participants received hydrochlorothiazide 12.5 mg for 2 weeks before randomization to either 50 mg atenolol or metoprolol succinate given every morning; both treatments were force-titrated to 100 mg/d at 4 weeks. The primary end point was the change in early morning ambulatory systolic BP. Early morning (12 AM-6 AM) systolic BP differences were 3+/-14 mm Hg with atenolol vs -7+/-8 mm Hg with metoprolol succinate (P=.03). The overall 24-hour changes in systolic BP were 1+/-15 mm Hg with atenolol vs -9+/-11 mm Hg with metoprolol (P=.03). In conclusion, metoprolol succinate was more effective in sustaining 24-hour and early morning BP reductions compared with atenolol in a small group of hypertensive patients also treated with once-daily low-dose hydrochlorothiazide. It is possible that differences in outcome between atenolol-based and other therapies may be the result of inadequate dosing of atenolol, a medication that may not be effective for the entire 24-hour period.     

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.     

Melatonin reduces night blood pressure in patients with nocturnal hypertension

Purpose

Nocturnal hypertension is associated with a high risk of morbidity and mortality. A blunted nocturnal surge in melatonin excretion has been described in nondipping hypertensive patients. We therefore studied the potency of melatonin to reduce nighttime blood pressure (BP) in treated hypertensive patients with nocturnal hypertension.

Patients and Methods

Thirty-eight treated hypertensive patients (22 males, mean age 64 ± 11 years) with confirmed nocturnal hypertension (mean nighttime systolic BP >125 mm Hg), according to repeated 24-hour ambulatory blood pressure monitoring (ABPM), were randomized in a double-blind fashion to receive either controlled release (CR)-melatonin 2 mg or placebo 2 hours before bedtime for 4 weeks. A 24-hour ABPM was then performed.

Results

Melatonin treatment reduced nocturnal systolic BP significantly from 136 ± 9 to 130 ± 10 mm Hg (P = .011), and diastolic BP from 72 ± 11 to 69 ± 9 mm Hg (P = .002), whereas placebo had no effect on nocturnal BP. The reduction in nocturnal systolic BP was significantly greater with melatonin than with placebo (P = .01), and was most prominent between 2:00 am and 5:00 am (P = .002).

Conclusions

Evening CR-melatonin 2 mg treatment for 4 weeks significantly reduced nocturnal systolic BP in patients with nocturnal hypertension. Thus, an addition of melatonin 2 mg at night to stable antihypertensive treatment may improve nocturnal BP control in treated patients with nocturnal hypertension.     

Comparative Efficacy of Two Different β-Blockers on 24-Hour Blood Pressure Control

Atenolol and metoprolol succinate, dosed once daily, have different pharmacokinetic profiles. This study tests the hypothesis that differences that are especially noted in the early morning period, when cardiovascular risk is highest, in 24-hour blood pressure (BP) control exist between these 2 β-blockers. This was a small, randomized open-label study with blinded end point evaluation in 36 hypertensive patients. All participants received hydrochlorothiazide 12.5 mg for 2 weeks before randomization to either 50 mg atenolol or metoprolol succinate given every morning; both treatments were force-titrated to 100 mg/d at 4 weeks. The primary end point was the change in early morning ambulatory systolic BP. Early morning (12 am –6 am ) systolic BP differences were 3±14 mm Hg with atenolol vs −7±8 mm Hg with metoprolol succinate ( P =.03). The overall 24-hour changes in systolic BP were 1±15 mm Hg with atenolol vs −9±11 mm Hg with metoprolol ( P =.03). In conclusion, metoprolol succinate was more effective in sustaining 24-hour and early morning BP reductions compared with atenolol in a small group of hypertensive patients also treated with once-daily low-dose hydrochlorothiazide. It is possible that differences in outcome between atenolol-based and other therapies may be the result of inadequate dosing of atenolol, a medication that may not be effective for the entire 24-hour period.     

Early alterations of blood pressure in normotensive and normoalbuminuric Type 1 diabetic patients

With the objective to examine patterns of blood pressure (BP) in normotensive and normoalbuminuric Type 1 diabetic patients during 24 h ambulatory blood pressure monitoring (ABPM) we studied 28 Type 1 diabetic patients aged 27+/-7.1 years with a disease duration of 9+/-6.6 years, and 28 non-diabetic normotensive subjects aged 25+/-6.5 years matched to the diabetic group for age, gender, skin color, weight, height, body mass index, clinic BP and absence of microalbuminuria. Systolic BP (sBP) and diastolic BP (dBP) were recorded for 24 h, daytime and nighttime. SBP and dBP burden, night/day BP ratios and percent nighttime BP fall were determined. Subjects with a nocturnal fall in either sBP or dBP of less than 10% of daytime values were classified as non-dippers. Both sBP (111+/-7.1 vs. 104+/-9 mmHg; P=0.003) and dBP nighttime (66+/-6.1 vs. 61+/-5.3 mmHg; P=0.001) were higher in diabetic patients than non-diabetic subjects. Night/day ratios for sBP (0.93+/-0.04 vs. 0.89+/-0.05; P=0.006) and dBP (0.86+/-0.06 vs. 0.82+/-0.06; P=0.007) were higher in diabetics. The loss of a fall in sBP was more prevalent in diabetic subjects (78 vs. 39%; P=0.007). Non-dippers for sBP and dBP in the diabetic group had higher BP burden during the nighttime (21.4+/-16.6 vs. 3.2+/-3.9%; P=0.01 and 21.9+/-10 vs. 3.7+/-5.5%; P<0.001, respectively). Our data demonstrate higher sBP and dBP during the nighttime and loss of the nocturnal fall in BP in Type 1 diabetic patients. Further prospective studies are needed to define if high BP burden in diabetic non-dippers during the night could represent a risk for nephropathy and cardiovascular disease.     

Blood pressure effects of naproxcinod in hypertensive patients

The blood pressure (BP) effects of naproxcinod and naproxen were assessed in an 8-week, double-blind, crossover study in 131 hypertensive patients aged 50 to 74 years. Patients received naproxcinod 750 mg twice daily or naproxen 500 mg twice daily, then the alternate treatment, each for 14 days, with placebo run-in/washout before each active treatment period and 24-hour ambulatory BP monitoring conducted before and after each active treatment period. Mean change from baseline in average 24-hour systolic BP (SBP) after 2 weeks of treatment numerically favored naproxcinod 750 mg twice daily (least-squares [LS] mean for naproxcinod minus naproxen: -1.6 mm Hg; P=.12). Post hoc analyses showed statistically significant SBP differences favoring naproxcinod for the 8 elapsed hours (LS mean: -4.4 mm Hg; P<.0001) and the 24 hours following morning dosing (LS mean: -2.4 mm Hg; P=.006). Naproxcinod may be a beneficial alternative for patients with osteoarthritis requiring nonsteroidal anti-inflammatory drugs.     

The Effects of an Olmesartan Medoxomil–Based Treatment Algorithm on 24-Hour Blood Pressure Levels in Elderly Patients Aged 65 and Older

This study examined the effect of olmesartan medoxomil (OM) ± hydrochlorothiazide (HCTZ) on mean 24-hour ambulatory blood pressure, mean seated cuff (Se) blood pressure (BP), and SeBP goal achievement in elderly (65 years and older) patients with hypertension. After a 2- to 3-week placebo run-in period, patients received OM 20 mg, up-titrated to OM 40 mg, and then added HCTZ 12.5  mg to 25 mg in a stepwise manner at 3-week intervals if SeBP remained ≥120/70 mm Hg. The primary end point was change from baseline in mean 24-hour ambulatory systolic BP. At study end, mean 24-hour ambulatory BP had decreased by 25.7/12.3 mm Hg (n=150) and mean SeBP by 25.4/10.5 mm Hg (n=176; all P <.00001 vs baseline). Drug-related treatment-emergent adverse events, most commonly dizziness (3.4%), hypotension (2.2%), and headache (1.1%), were observed in 11.8% of patients. An OM-based treatment algorithm effectively lowers BP in an elderly patient population throughout the 24-hour dosing interval without compromising tolerability.     

Should pulse pressure and day/night variations in blood pressure be seen as independent risk factors requiring correction or simply as markers to be taken into account when evaluating overall vascular risk?

Patients with a blunted fall in nocturnal BP (known as non-dippers) have a high risk of micro- and macrovascular complications, particularly if they have hypertension, but also in normotensive patients with diabetes. A blunted fall in nocturnal BP reflects the high level of CV risk in these patients. ABPM data indicating an altered circadian BP rhythm reverse circadian BP profile should alert the physician to the potential risk of complications and should lead to efforts to treat hypertension effectively, especially at night, and to check for sleep apnoea syndrome, particularly in cases of resistant hypertension, or autonomic neuropathy (postural hypotension), a well known risk factor for cardiovascular (CV) events. Patients should be carefully screened for nephropathy. However, the definitions of "non-dipper" vary widely. Suitable treatments are poorly defined, but angiotensin-converting enzyme inhibitors (ACEi), diuretics, salt restriction and the maintenance of continuous positive airway pressure (CPAP) can be used as non-specific treatments. The efficacy of taking blood pressure-lowering drugs at bedtime rather than in the morning is still debated but deserves attention. In the diabetic population, brachial pulse pressure (PP) is an independent predictor of cardiovascular mortality, but not of all-cause mortality. It is also associated with complications of both type 2 and type 1 diabetes, this effect being stronger for nocturnal than for diurnal PP, and is strongly predictive of coronary heart disease in patients with type 2 diabetes. The stronger association between PP and age in diabetic than in non-diabetic populations suggests that diabetes accelerates vascular ageing. In patients with incipient nephropathy or overt renal failure, PP increases CV risk. However, misinterpretation could be related to confusion between brachial PP and central PP. The therapeutic implications of PP measurement remain poorly documented in diabetes.     

Telemonitoring of blood pressure self measurement in the OLMETEL study

OBJECTIVE: To investigate the feasibility of blood pressure (BP) telemonitoring in previous uncontrolled hypertensives treated with olmesartan medoxomil in a clinical practice setting. METHODS: Patients (n = 53) with untreated, uncontrolled or insufficiently treated hypertension were selected by physicians to receive olmesartan medoxomil 10-40 mg/day for 12 weeks. Office BP values were determined by a physician at baseline and after 12 weeks' treatment; BP self-measurement (BPSM) was conducted throughout the 12-week treatment period using a TensioPhone TP2 telemonitoring device; BP values were stored and automatically downloaded to a remote service centre via standard telephone lines. RESULTS: Olmesartan medoxomil produced statistically significant reductions from baseline in both systolic and diastolic office BP and BPSM values. In contrast to office BP, telemonitoring of BPSM allowed the early identification of responders (e.g., after 2-3 weeks' treatment). Blood pressure reduction with olmesartan medoxomil was greater for office BP than for BPSM values. Normalization of BP was achieved in 64.2% of the patients using office BP measurement compared with 36.4% using BPSM. Blood pressure self-measurement showed no significant difference between morning and evening BP measurements or between the morning : evening BP ratio at baseline and after nine weeks of olmesartan medoxomil treatment. Compliance and tolerability were good or very good in most patients. CONCLUSION: In a 'real-life' clinical practice setting, telemonitoring of BPSM was an effective technique that was partially affected by patient non-compliance. Olmesartan medoxomil provided effective and reliable BP-lowering, which was maintained throughout the 24-hour period.     

Efficacy and safety of a once daily graded-release diltiazem formulation in essential hypertension

BACKGROUND: The efficacy and safety of a chronotherapeutic, graded-release diltiazem HCl extended-release (GRD) 120-, 240-, 360- and 540-mg dose administered once-daily at bedtime (10 PM) were evaluated in a 7-week randomized, double-blind comparison to placebo and to GRD 360 mg administered once-daily at 8 AM in 478 patients with moderate-to-severe essential hypertension. METHODS: We assessed the change from baseline to end point in trough diastolic blood pressure (DBP) at 6 PM to 10 PM and in mean DBP from 6 AM to 12 noon between GRD 360 mg PM and GRD 360 mg AM, measured by ambulatory BP monitoring (ABPM). RESULTS: Bedtime doses of GRD showed dose-related mean reductions in trough DBP that were significant for GRD doses of 240 mg and higher. Bedtime GRD 360 mg was associated with a significantly greater reduction in mean DBP between 6 AM and 12 noon compared to morning GRD 360 mg with a least squares mean for treatment difference of -3.3 mm Hg (P =.0004). Similar dose-related and significant reductions in systolic BP (SBP) and heart rate (HR) were obtained. Incidence of adverse events (AEs) for all GRD groups (44.5%) was less than that obtained for the placebo group (49.3%). The 540-mg group showed an incidence of AEs (43.5%) similar to that observed for the 240-mg group (42.6%). CONCLUSIONS: The GRD dose-dependently significantly reduces BP and HR over the 24-h interval after once-daily bedtime dosing. Further greater reductions were obtained between 6 AM and 12 noon, when circadian BP is highest, compared to morning administration of the same dose. The 540-mg GRD was safe, well tolerated, and offers further therapeutic option for patients with severe hypertension who required additional BP control.     

Increased nocturnal blood pressure in healthy prepubertal twins

AIM: To compare ambulatory blood pressure monitoring (ABPM) in twin children to a published singleton population, and to examine the influence of birthweight and fasting plasma cortisol on blood pressure. DESIGN: A cross-sectional study of monozygotic and dizygotic twins compared with a similar previously published normative control population. METHODS: Forty-four healthy prepubertal twin children aged 4-11 years (20 monozygotic, 22 male) were studied. All subjects had 24-h ABPM and a fasting early morning plasma cortisol. RESULTS: Twins had higher 24-h systolic blood pressure (BP) compared with controls with similar daytime and elevated night-time systolic BP (P > 0.3 and P < 0.01, respectively). Twins had reduced systolic and diastolic nocturnal BP dipping compared with controls (P < 0.0001 for both), and 61% of twins exhibited a < 10% fall in nocturnal BP. In the twin cohort there was no association between birth weight and daytime systolic BP (P = 0.6), nor any other ABPM parameter. There was no difference in BP parameters between dizygotic and monozygotic twins, and no difference between the lighter and heavier birthweight twins for any ABPM parameter. Fasting plasma cortisol was not associated with either birthweight (P = 0.2) or daytime systolic BP (P = 0.4). CONCLUSIONS: Healthy prepubertal twins have increased nocturnal BP and reduced nocturnal BP dipping independent of zygosity or birthweight. These abnormalities may be a risk factor for the later development of hypertension in twins. As these BP abnormalities are not associated with twin birth weight, the twin model may not be appropriate in investigating the fetal origins of disease in later adult life.     

Urinary arginine methylation index associated with ambulatory blood pressure abnormalities in children with chronic kidney disease

Arginine (ARG) metabolites are interrelated and are involved in chronic kidney disease (CKD) and cardiovascular disease. Twenty-four-hour ambulatory blood pressure monitoring (ABPM) appears to correlate with cardiovascular outcomes. We investigated the relationship between ARG metabolites, and their combined ratios in urine, and the ABPM profiles of children and adolescents with CKD. This cross-sectional study included 45 children and adolescents (age, 5–18 years) with stage 1 to 4 CKD. Each child underwent office blood pressure (BP) measurements, 24-hour ABPM, and urinary ARG metabolite determinations. Seventy percent of children with CKD had abnormal 24-hour ABPM profiles, including nocturnal hypertension, increased BP load, and nondipping nocturnal BP. The urinary ARG-to-asymmetric dimethylarginine (ADMA) ratio was lower, and the ADMA-to-symmetric dimethylarginine (SDMA) ratio was higher in children with advanced CKD (stages 2–4) than those with stage 1 CKD. CKD patients with BP abnormalities also had reduced urinary ARG and dimethylamine (DMA) levels. The higher urinary (ADMA+SDMA)-to-ARG ratios were correlated to ABPM abnormalities, including increased systolic BP load and non-dipping nocturnal BP. ABPM abnormalities were significantly associated with a high urinary (ADMA+SDMA)-to-ARG ratio, suggesting the possible involvement of methylated ARG in the development of hypertension among children with CKD.     

Angiotensin II type 1 receptor blocker, olmesartan, restores nocturnal blood pressure decline by enhancing daytime natriuresis

OBJECTIVE: We have shown that as renal function deteriorated, night-time fall in both blood pressure and urinary sodium excretion were diminished. We have also reported that sodium intake restriction and diuretics both normalized circadian blood pressure rhythm from nondipper to dipper patterns. In this study, we investigated whether an angiotensin II receptor blocker, olmesartan, could restore night-time blood pressure fall. METHODS: Twenty patients with chronic kidney disease (13 men, seven women; mean age 44.8 +/- 18.1 years; BMI 22.9 +/- 3.5 kg/m2) were studied. At baseline and 8 weeks after the treatment with olmesartan medoxomil (10-40 mg/day), 24-h blood pressure monitoring and urinary sampling for both daytime (0600-2100 h) and night-time (2100-0600 h) were repeated to compare the circadian rhythms of blood pressure and urinary sodium excretion. RESULTS: The 24-h mean arterial pressure was lowered by olmesartan, while urinary sodium excretion remained unchanged. On the other hand, daytime urinary sodium excretion was increased from 4.8 +/- 2.2 to 5.7 +/- 2.1 mmol/h, while night-time urinary sodium excretion tended to be reduced from 3.9 +/- 1.7 to 3.4 +/- 1.6 mmol/h. Night/day ratios of mean arterial pressure (0.98 +/- 0.1 to 0.91 +/- 0.08; P = 0.01) and urinary sodium excretion (0.93 +/- 0.5 to 0.68 +/- 0.4; P = 0.0006) were both decreased. Olmesartan enhanced night-time falls more in mean arterial pressure (r = 0.77; r2 = 0.59; P < 0.0001) and urinary sodium excretion (r = 0.59; r2 = 0.34; P = 0.007), especially in patients whose baseline night-time falls were more diminished. CONCLUSIONS: These findings demonstrated that olmesartan could restore night-time blood pressure fall, as seen with diuretics and sodium restriction, possibly by enhancing daytime sodium excretion. Since nocturnal blood pressure is a strong predictor of cardiovascular events, olmesartan could relieve cardiorenal load through normalization of circadian blood pressure rhythm besides having powerful ability to block the renin-angiotensin system.     

Pulse pressure or dipping pattern: which one is a better cardiovascular risk marker in resistant hypertension?

OBJECTIVE: Nocturnal blood pressure (BP) reduction and ambulatory pulse pressure (PP) are well known prognostic markers obtained from ambulatory BP monitoring (ABPM). The aim of this study is to investigate which one of these ABPM parameters is related to high cardiovascular risk profile in resistant hypertension, based on their associations with target organ damage (TOD). METHODS: Clinical-demographic, laboratory and ABPM variables were recorded in a cross-sectional study involving 907 resistant hypertensive patients. Nocturnal systolic BP reduction and 24-h PP were assessed both as continuous and dichotomized variables (PP at the upper tertile value: 63 mmHg). Statistical analyses included bivariate tests and multivariate logistic regression with each TOD as the dependent variable. RESULTS: Patients with the nondipping pattern and high 24-h PP shared some characteristics: they were older, had higher prevalence of cerebrovascular disease and nephropathy, higher office and 24-h BP levels, increased serum creatinine and microalbuminuria, and higher left ventricular mass index than their counterparts. Additionally, patients with high PP had a greater prevalence of diabetes and other TOD. In multivariate logistic regression, high PP was independently associated with all TODs even after adjustment for sex, age, BMI, cardiovascular risk factors, 24-h mean arterial pressure and antihypertensive treatment, whereas nondipping pattern was only associated with hypertensive nephropathy. Furthermore, PP was more strongly associated with the number of TOD than the nocturnal systolic blood pressure (SBP) fall. CONCLUSIONS: In a large group of resistant hypertensive patients, an increased 24-h PP shows a closer correlation with high cardiovascular risk profile than the nocturnal BP reduction.     

Treatment of non-dipper hypertension with bedtime administration of valsartan

BACKGROUND: Previous results have indicated that valsartan administration at bedtime, as opposed to upon wakening, may improve the diurnal: nocturnal ratio of blood pressure without loss in 24-h coverage and efficacy. OBJECTIVES: To investigate the administration time-dependent antihypertensive efficacy of valsartan in non-dipper patients. METHODS: We studied 148 non-dipper patients with grade 1-2 essential hypertension, aged 53.0+/-12.6 years, who were randomly assigned to receive valsartan (160 mg/day) as a monotherapy either on awakening or at bedtime. Blood pressure was measured 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 accurately calculate the diurnal and nocturnal means of blood pressure on a per subject basis. RESULTS: The significant blood pressure reduction after 3 months of valsartan (P<0.001) was similar for both treatment times (13.1 and 8.5 mmHg reduction in the 24-h mean of systolic and diastolic blood pressure with morning administration; 14.7 and 10.3 mmHg with bedtime administration; P>0.126 for treatment-time effect). The diurnal: nocturnal ratio of blood pressure was significantly increased only when valsartan was administered before bedtime, which resulted in 75% of the patients in this group reverting to dippers, a significant increase in the percentage of patients with controlled blood pressure over 24 h, and a reduction in urinary albumin excretion. CONCLUSIONS: In non-dipper hypertensive patients, dosing time with valsartan should be chosen at bedtime, for improved efficacy during the nocturnal resting hours, as well as the potential associated reduction in cardiovascular risk.