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.     

Chronotherapy improves blood pressure control and reverts the nondipper pattern in patients with resistant hypertension

Therapeutic strategies in resistant hypertension include adding another drug or changing drugs in search for a better synergic combination. Most patients, however, receive all of their drugs in a single morning dose. We have evaluated the impact on the circadian pattern of blood pressure on modifying the time of treatment without increasing the number of prescribed drugs. We studied 250 hypertensive patients who were receiving 3 antihypertensive drugs in a single morning dose. Patients were randomly assigned to 1 of 2 groups according to the modification in their treatment strategy: changing 1 of the drugs but keeping all 3 in the morning or the same approach but administering the new drug at bedtime. Blood pressure was measured for 48 hours before and after 12 weeks of treatment. There was no effect on ambulatory blood pressure when all of the drugs were taken on awakening. The baseline prevalence of nondipping (79%) was slightly increased after treatment (86%; P=0.131). The ambulatory blood pressure reduction was statistically significant (9.4/6.0 mm Hg for systolic/diastolic blood pressure; P<0.001) with 1 drug at bedtime. This reduction was larger in the nocturnal than in the diurnal mean of blood pressure. Thus, whereas only 16% of the patients in this group were dippers at baseline, 57% were dippers after therapy (P<0.001). Results indicate that, in resistant hypertension, time of treatment may be more important for blood pressure control and for the proper modeling of the circadian blood pressure pattern than just changing the drug combination.     

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.     

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.     

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.     

Administration time-dependent effects of aspirin on blood pressure in untreated hypertensive patients

Previous studies on the potential influence of aspirin on blood pressure have not taken into consideration the chronopharmacological effects of nonsteroidal anti-inflammatory drugs. This pilot study investigates the effects of aspirin on blood pressure in untreated hypertensive patients who received aspirin at different times of the day according to their rest-activity cycle. We studied 100 untreated patients with mild hypertension (34 men and 66 women), 42.5+/-11.6 (mean+/-SD) years of age, randomly divided into 3 groups: nonpharmacological hygienic-dietary recommendations; the same recommendations and aspirin (100 mg/d) on awakening; or the same recommendations and aspirin before bedtime. Blood pressure was measured every 20 minutes during the day and every 30 minutes at night for 48 consecutive hours before and after 3 months of intervention. The circadian pattern of blood pressure in each group was established by population multiple-component analysis. After 3 months of nonpharmacological intervention, there was a small, nonsignificant reduction of blood pressure (<1.1 mm Hg; P>0.341). There was no change in blood pressure when aspirin was given on awakening (P=0.229). A highly significant blood pressure reduction was, however, observed in the patients who received aspirin before bedtime (decrease of 6 and 4 mm Hg in systolic and diastolic blood pressure, respectively; P<0.001). Results indicate a statistically significant administration time-dependent effect of low-dose aspirin on blood pressure in untreated patients with mild hypertension. The influence of aspirin on blood pressure demonstrated in this study indicates the need to quantify and control for aspirin effects in patients using this drug in combination with antihypertensive medication.     

急性脑卒中患者血压特点的分析

目的研究急性脑卒中患者血压影响因素及动态血压特点。方法82例发病在7天内的急性脑卒中患者。记录患者住院诊室血压及24 h动态血压。血压≥140/90 mm Hg(1 mm Hg=0.133 kPa)为诊室血压升高;24 h动态血压平均值≥130/80 mm Hg、日间平均值≥135/85 mm Hg、夜间平均值≥125/75 mm Hg为动态血压升高。结果既往高血压病史对急性脑卒中患者诊室血压升高有影响(P<0.05)。有高血压病史者平均诊室血压(146.02±18.89)/(86.36±11.52)mm Hg,无高血压病史者平均诊室血压(136.22±14.63)/(82.61±11.86)mm Hg,二者收缩压水平差异有显著性意义(P<0.05)。急性脑卒中患者动态血压表现为夜间血压负荷增加,24 h平均血压于发病后4~5天明显升高,6~7天降低。诊室血压升高与诊室血压正常比较,血压形态均以非杓形和反杓形为主,2组差异无显著性意义(P>0.05)。结论急性脑卒中诊室血压升高与高血压病史有关,急性脑卒中随发病时间延长,血压呈下降趋势。     

Short-term reproducibility of a non-dipping pattern in type 2 diabetic hypertensive patients

BACKGROUND: Little information is available on the reproducibility of nocturnal variations in blood pressure in type 2 diabetic hypertensive patients. OBJECTIVE: We aimed to compare the intrasubject short-term reproducibility of a nocturnal non-dipping pattern and the prevalence of cardiac and extracardiac signs of target organ damage, in a group of type 2 diabetic hypertensive patients and in an age/gender-matched group of non-diabetic hypertensive subjects. METHODS: Thirty-six treated hypertensive patients with long-lasting type 2 diabetes (> 10 years duration) consecutively attending our hospital out-patient hypertension clinic (group I; mean age, 65 +/- 9 years), and 61 untreated non-diabetic subjects with grade 1 and grade 2 uncomplicated essential hypertension, matched for age and gender, and chosen from patients attending an outpatient clinic (group II; mean age, 65 +/- 5 years), were considered for this analysis. All patients underwent blood sampling for routine blood chemistry, 24-h urine collection for microalbuminuria, two 24-h periods of ambulatory blood pressure monitoring (ABPM) within a 4-week period, echocardiography, and carotid ultrasonography. A dipping pattern was defined as a greater than 10% reduction in the average systolic and diastolic blood pressure at night compared with average daytime values. RESULTS: A reproducible nocturnal dipping and non-dipping profile was found in 11 (30.6%) and 21 (58.3%) diabetic patients, respectively; while only in four (11.1%) patients was a variable dipping profile observed. Of the 23 patients with a non-dipping pattern during the first ABPM period, 21 (91.3%) also had this type of pattern during the second ABPM recording. In group II (non-diabetic hypertensive patients), 30 patients (49.2%, P < 0.05) had a dipping pattern, 13 patients (21.3%, P < 0.01) had a non-dipping profile pattern and 18 patients (29.5%, P < 0.01) had a variable dipping pattern. Of the 20 patients with a non-dipping pattern during the first ABPM period, 13 (65.0%) confirmed this type of pattern during the second ABPM recording. Finally, the prevalence of left ventricular hypertrophy (77.7 versus 41.4%, P < 0.01), carotid plaques (80.5 versus 38.3%, P < 0.01), carotid intima-media thickening (54.3 versus 44.0%, P < 0.05) and microalbuminuria (11.1 versus 2.0%, P < 0.01) was significantly higher in group I than in group II. According to a logistic regression analysis, diabetes, left ventricular hypertrophy and carotid plaques were the main independent predictors of the non-dipping (pattern in the overall population. CONCLUSIONS: These findings indicate that intrasubject variability of non-dipper pattern is lower in diabetic than in non-diabetic hypertensive patients, that classification of diabetic hypertensive patients as dipper or non-dipper on the basis of a single ABP recording is more reliable than in non-diabetic patients, and that the more frequent and reproducible non-dipping (pattern in diabetic patients is associated with a more prominent cardiac and extracardiac target organ damage.     

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.     

Addition of spironolactone in patients with resistant arterial hypertension (ASPIRANT): a randomized, double-blind, placebo-controlled trial

There is currently limited data on which drug should be used to improve blood pressure (BP) control in patients with resistant hypertension. This study was designed to assess the effect of the addition of 25 mg of spironolactone on BP in patients with resistant arterial hypertension. Patients with office systolic BP >140 mm Hg or diastolic BP >90 mm Hg despite treatment with at least 3 antihypertensive drugs, including a diuretic, were enrolled in this double-blind, placebo-controlled, multicenter trial. One hundred seventeen patients were randomly assigned to receive spironolactone (n=59) or a placebo (n=58) as an add-on to their antihypertensive medication, by the method of simple randomization. Analyses were done with 111 patients (55 in the spironolactone and 56 in the placebo groups). At 8 weeks, the primary end points, a difference in mean fall of BP on daytime ambulatory BP monitoring (ABPM), between the groups was -5.4 mm Hg (95%CI -10.0; -0.8) for systolic BP (P=0.024) and -1.0 mm Hg (95% CI -4.0; 2.0) for diastolic BP (P=0.358). The APBM nighttime systolic, 24-hour ABPM systolic, and office systolic BP values were significantly decreased by spironolactone (difference of -8.6, -9.8, and -6.5 mm Hg; P=0.011, 0.004, and 0.011), whereas the fall of the respective diastolic BP values was not significant (-3.0, -1.0, and -2.5 mm Hg; P=0.079, 0.405, and 0.079). The adverse events in both groups were comparable. In conclusion, spironolactone is an effective drug for lowering systolic BP in patients with resistant arterial hypertension.     

Clinical characteristics of resistant hypertension evaluated by ambulatory blood pressure monitoring

Strict control of blood pressure is important to prevent cardiovascular disease, although it is sometimes difficult to decrease blood pressure to target levels. The aim of this study was to investigate the clinical characteristics of resistant hypertension evaluated by ambulatory blood pressure monitoring. One hundred in-hospital patients, whose 24-hour average blood pressure was higher than 130/80?mmHg even after treatment with more than three antihypertensive drugs, were included in the present analysis. Circadian variation of blood pressure was evaluated by nocturnal fall in systolic blood pressure. Average blood pressures of all patients were high in both daytime and nighttime, 150.0/82.9 and 143.8/78.2?mmHg, respectively. Twenty patients had been treated with hemodialysis or peritoneal dialysis. In 63 patients out of the other 80 patients (79%), estimated glomerular filtration rate (eGFR) was also decreased (<60?mL/min/1.73 m²). The patients classified into dipper, non-dipper, riser and extreme-dipper were 20%, 43%, 34% and 3%, respectively. In addition, in 17 patients whose eGFR was preserved, 12 patients showed a non-dipper or riser pattern, suggesting that it was difficult to account for this altered circadian blood pressure variation only by renal dysfunction. These results show that a large number of the patients with resistant hypertension suffered from renal dysfunction, although it was difficult to explain altered circadian blood pressure variation based on renal dysfunction alone.     

Masked Hypertension Defined by Ambulatory Blood Pressure Monitoring Is Associated With an Increased Serum Glucose Level and Urinary Albumin‐Creatinine Ratio

J Clin Hypertens(Greenwich). 2010;12:578–587. © 2010 Wiley Periodicals, Inc. The authors evaluated the relationship of hypertensive target organ damage to masked hypertension assessed by ambulatory blood pressure (BP) and home blood pressure (HBP) monitoring in 129 participants without taking antihypertensive medication. Masked hypertension was defined as office BP ≤140/90 mm Hg and 24-hour ambulatory BP ≥130/80 mm Hg. The masked hypertensive participants defined by 24-hour ambulatory BP (n=13) had a higher serum glucose level (126 vs 96 mg/dL, P=.001) and urinary albumin-creatinine ratio (38.0 vs 7.5 mg/gCr, P<.001) than the normotensive participants (n=74); however, these relationships were not observed when the authors defined groups using HBP (≥135/85 mm Hg). Masked hypertension by both 24-hour ambulatory BP and HBP had a higher urinary albumin-creatinine ratio than normotension by both 24-hour ambulatory BP and HBP (62.1 vs 7.4 mg/gCr, P=.001), and than masked hypertension by HBP alone (9.3 mg/gCr, P=.009). Masked hypertension defined by 24-hour ambulatory BP is associated with an increased serum glucose level and urinary albumin-creatinine ratio, but these relationships are not observed in masked hypertension defined by HBP.     

Aspirin administered at bedtime, but not on awakening, has an effect on ambulatory blood pressure in hypertensive patients.

OBJECTIVES: The purpose of this research was to investigate in untreated hypertensive patients the effects on ambulatory blood pressure (BP) of aspirin (ASA) administered at different times of the day. BACKGROUND: Previous studies have shown that ASA produces an administration time-dependent inhibition of angiotensin II. Low-dose ASA has also been shown to reduce BP when administered before bedtime, as opposed to upon awakening, in normotensive and hypertensive volunteers, and in pregnant women at high risk for preeclampsia. METHODS: We studied 328 untreated patients with grade 1 hypertension, 44.0 +/- 12.6 years of age, randomly divided into three groups: nonpharmacological hygienic-dietary recommendations, the same recommendations and ASA (100 mg/day) on awakening, or the same recommendations and ASA before bedtime. Blood pressure was measured every 20 min during the day and every 30 min at night for 48 consecutive h before and after 3 months of intervention. RESULTS: After three months of nonpharmacological intervention, there was a small and nonsignificant reduction of BP (<0.2 mm Hg; p = 0.648). Blood pressure was slightly elevated after aspirin on awakening (2.6/1.6 mm Hg in the 24-h mean of systolic/diastolic BP; p = 0.002). A significant BP reduction, however, was observed in the patients who received aspirin before bedtime (6.8/4.6 mm Hg in systolic/diastolic BP; p < 0.001). CONCLUSIONS: This prospective trial documents a significant administration time-dependent effect of low-dose ASA on BP in untreated hypertensive patients. The timed administration of low-dose ASA could provide a valuable approach, beyond the secondary prevention of cardiovascular disease, in the added BP control of patients with mild essential hypertension.     

老年原发性高血压患者血压晨峰与左心室肥厚的关系

目的探讨老年原发性高血压患者血压晨峰与左心室肥厚的关系。方法选择老年原发性高血压患者80例,根据24 h动态血压监测分为2组:血压晨峰值≥55 mm Hg(1 mm Hg=0.133 kPa)为晨峰组,血压晨峰值<55mm Hg为非晨峰组,每组40例,均常规行超声心动图检查,计算左心室重量指数(LVMI)。结果晨峰组24h、昼间、夜间收缩压及血压晨峰均明显高于非晨峰组(P<0.05),晨峰组LVMI明显高于非晨峰组;左心室肥厚比例明显高于非晨峰组(P<0.05)。结论老年原发性高血压患者血压晨峰与左心室肥厚密切相关。     

Coronary flow reserve in dipper and non-dipper hypertensive patients

Background. Failure to decrease blood pressure (BP) normally during night-time, which is called non-dipping, in hypertensive individuals is associated with higher cardiovascular morbidity and mortality. In addition, non-dipping BP leads to structural changes in the left ventricle; however, the effect of non-dipping BP on coronary flow reserve (CFR) has not been studied yet. Methods. In this study, we measured CFR of 22 subjects with non-dipper hypertension, and 15 subjects with dipper hypertension using transthoracic second-harmonic Doppler echocardiography (Acuson Sequoia C256®). None of the subjects had any systemic disease or coronary risk factor except hypertension. Results. Age, gender, body mass index, lipids and echocardiographic findings including left ventricular mass index were similar between the groups. Office BP recordings were similar between non-dipper and dipper groups (147.9±6.1/93.9±4.3 vs 144.0±8.0/93.0±3.7). Daytime and 24-h ambulatory BP measurements were similar within the groups, but night-time BPs were significantly greater in non-dipper group than those were in dipper group. Left ventricular diastolic and systolic functions, and both baseline and hyperemic peak diastolic coronary velocity as well as CFR, were similar between the non-dipper and dipper groups (CFR: 2.47±0.59 vs 2.39±0.47). Conclusion. CFR were similar in patients with non-dipper and dipper hypertension in the absence of excessive left ventricular hypertrophy and other cardiovascular risk factors.     

White-Coat Resistant Hypertension

The aim of this study was to evaluate whether sustained hypertensives with high clinic blood pressure, despite multiple drug treatment, show a true resistant hypertension or a “white-coat effect,” and whether the pretreatment white-coat effect is maintained despite pharmacological therapy. The occurrence of resistant hypertension was determined in 250 consecutive essential hypertensives who had had an ambulatory blood pressure monitoring before treatment assignment. Twenty-seven of 250 hypertensives with persistently high clinic blood pressure despite 3 months of adequate pharmacological therapy underwent further ambulatory blood pressure monitoring. Using our internal standards, seven patients had a true resistant hypertension whereas 20 subjects showed a large white-coat effect (white-coat resistant hypertension), ie, high clinic blood pressure (>140/90) but “normal” ambulatory daytime (<139/90 mm Hg) and 24 h (135/85 mm Hg) blood pressure. Using other cutoff points for ambulatory blood pressure, 134/90 and 135/85 mm Hg for daytime blood pressure, 10 and 13 patients, respectively, were reclassified as true resistant hypertensives and 17 and 14, respectively, were white-coat resistant hypertensives. Interestingly, in white-coat resistant hypertensives the large differences between clinic and ambulatory daytime blood pressure (white-coat effect), recorded before treatment assignment, were not affected by drugs and remained constant over time. Left ventricular mass index in white-coat resistant hypertensives was significantly lower than in truly resistant hypertensives, suggesting that prognosis could differ between these groups. In this study, using either our internal standards or some other cutoffs reported in the literature, the white-coat phenomenon was an important cause of resistant hypertension. The use of ambulatory blood pressure monitoring in these patients may avoid misdiagnosis of resistant hypertension, unnecessary overtreatment, and expensive procedures to look for possible secondary hypertension.     

Divergent results using clinic and ambulatory blood pressures: report of a darusentan-resistant hypertension trial

Patients with resistant hypertension are at increased risk for cardiovascular events. The addition of new treatments to existing therapies will help achieve blood pressure (BP) goals in more resistant hypertension patients. In the current trial, 849 patients with resistant hypertension receiving ≥3 antihypertensive drugs, including a diuretic, at optimized doses were randomized to the selective endothelin A receptor antagonist darusentan, placebo, or the central α-2 agonist guanfacine. The coprimary end points of the study were changes from baseline to week 14 in trough, sitting systolic BP, and diastolic BP measured in the clinic. Decreases from baseline to week 14 in systolic BP for darusentan (-15±14 mm Hg) were greater than for guanfacine (-12±13 mm Hg; P<0.05) but not greater than placebo (-14±14 mm Hg). Darusentan, however, reduced mean 24-hour systolic BP (-9±12 mm Hg) more than placebo (-2±12 mm Hg) or guanfacine (-4±12 mm Hg) after 14 weeks of treatment (P<0.001 for each comparison). The most frequent adverse event associated with darusentan was fluid retention/edema at 28% versus 12% in each of the other groups. More patients withdrew because of adverse events on darusentan as compared with placebo or guanfacine. We conclude that darusentan provided greater reduction in systolic BP in resistant hypertension patients as assessed by ambulatory BP monitoring, in spite of not meeting its coprimary end points. The results of this trial highlight the importance of ambulatory BP monitoring in the design of hypertension clinical studies.     

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.     

Effects of the renin inhibitor MK-8141 (ACT-077825) in patients with hypertension

The renin inhibitor MK-8141 (ACT-077825) demonstrates substantial immunoreactive active renin (ir-AR) increase (sevenfold) without a persistent plasma renin activity (PRA) decrease. The present study assessed the antihypertensive efficacy of MK-8141 in hypertensive patients. In this double-blind, placebo- and active comparator-controlled study, 195 patients with hypertension (trough sitting diastolic blood pressure ≥92 to <105 mm Hg, trough sitting systolic blood pressure <170 mm Hg, and 24-hour mean diastolic blood pressure [DBP] ≥80 mm Hg) were randomized to one of four treatments (stratified by race, black versus others): MK-8141 250 mg, MK-8141 500 mg, enalapril 20 mg, or placebo. Blood pressure was measured at trough and as 24-hour ambulatory blood pressure monitoring. The primary end point was change from baseline in 24-hour mean ambulatory DBP measured after 4 weeks. At week 4, the change from baseline in 24-hour mean (95% CI) ambulatory DBP compared with placebo was ?1.6 mm Hg (?4.2, 1.1), ?1.1 mm Hg (?3.9, 1.6), and ?4.9 (?7.5, ?2.2) for MK-8141 250 mg, MK-8141 500 mg, and enalapril 20 mg, respectively. Only mean ambulatory DBP-lowering with enalapril 20 mg was statistically significant. Enalapril, but not MK-8141, also significantly lowered 24-hour mean ambulatory systolic blood pressure (SBP) compared with placebo (?6.7 mm Hg [?10.5, ?2.8]). Neither enalapril nor MK-8141 significantly lowered trough DBP and SBP compared with placebo. MK-8141 was generally well tolerated. In patients with hypertension, MK-8141 (ACT-077825) did not produce significant blood pressure–lowering efficacy despite a demonstrated effect of the drug on ir-AR, in the absence of durable PRA suppression.     

Appropriate time interval to repeat ambulatory blood pressure monitoring in patients with white-coat resistant hypertension

Resistant hypertension is defined as uncontrolled office blood pressure, despite the use of ≥3 antihypertensive drugs. Ambulatory blood pressure monitoring (ABPM) is mandatory to diagnose 2 different groups, those with true and white-coat resistant hypertension. Patients are found to change categories between controlled/uncontrolled ambulatory pressures without changing their office blood pressures. In this way, ABPM should be periodically repeated. The aim of this study was to evaluate the most appropriate time interval to repeat ABPM to assure sustained blood pressure control in patients with white-coat resistant hypertension. This prospective study enrolled 198 patients (69% women; mean age: 68.9±9.9 years) diagnosed as white-coat resistant hypertension on ABPM. Patients were submitted to a second confirmatory examination 3 months later and repeated twice at 6-month intervals. Statistical analyses included Bland-Altman repeatability coefficients and multivariate logistic regression. Mean office blood pressure was 163±20/84±17 mm Hg, and mean 24-hour blood pressure was 118±8/66±7 mm Hg. White-coat resistant hypertension diagnosis presented a moderate reproducibility and was confirmed in 144 patients after 3 months. In the third and fourth ABPMs, 74% and 79% of patients sustained the diagnosis. In multivariate regression, a daytime systolic blood pressure ≤115 mm Hg in the confirmatory ABPM triplicated the chance of white-coat resistant hypertension status persistence after 1 year. In conclusion, a confirmatory ABPM is necessary after 3 months of the first white-coat-resistant hypertension diagnosis, and the procedure should be repeated at 6-month intervals, except in patients with daytime systolic blood pressure ≤115 mm Hg, in whom it may be repeated annually.