An alpha-adrenergic blocker titrated by self-measured blood pressure recordings lowered blood pressure and microalbuminuria in patients with morning hypertension: the Japan Morning Surge-1 Study

BACKGROUND: The impact on microalbuminuria of strict treatment aimed at lowering of self-measured morning blood pressure using an adrenergic blockade is unclear. METHODS: We conducted an open-label multicenter trial, the Japan Morning Surge-1 Study, that enrolled 611 hypertensive patients, whose self-measured morning systolic blood pressure levels were more than 135 mmHg while taking antihypertensive drugs. These were randomly allocated to an experimental group, whose members received bedtime administration of 1-4 mg doxazosin (doxazosin group) or a control group whose members continued without any add-on medication (control group). The urinary albumin/creatinine ratio was investigated at the baseline and 6 months after the randomization. RESULTS: Both the morning and evening blood pressures and urinary albumin/creatinine ratio (-3.4 vs. 0.0 mg/gCr for urinary albumin/creatinine ratio; P < 0.001) were more markedly reduced in the doxazosin group than in the control group. This difference in the urinary albumin/creatinine ratio between the two groups was more marked in the patients with microalbuminuria (n = 238, -27.9 vs. -8.1 mg/gCr, P < 0.001). The reduction of urinary albumin/creatinine ratio was significantly associated with the use of doxazosin, and the change in all self-measured blood pressures (morning, evening, the average morning-evening), and these associations were independent of each other (P < 0.001). CONCLUSION: Adding a bedtime dose of an alpha-adrenergic blocker titrated by self-measured morning blood pressure in treated hypertensive patients with uncontrolled morning hypertension significantly reduced blood pressure and urinary albumin excretion rate, particularly in those with microalbuminuria.     

Time-dependent effects of imidapril administration in patients with morning hypertension measured as home blood pressure

We investigated the effect of the timing of imidapril administration in patients with morning hypertension (home blood pressure [HBP] in the morning [morning HBP] > or =135/85 mmHg). Eighty-seven patients (mean age, 61 years; 48% women) with morning hypertension each measured HBP in the early morning, before going to bed for the final five days of the observation, and during treatment. Imidapril (2.5 or 5.0 mg) was administered once every morning (n = 57) or at bedtime (n = 30) for four weeks (monotherapy: n = 30, 34%; combined with other antihypertensive drugs: n = 57, 66%). The morning (M) versus evening (E) effect (M/E ratio) and the evening versus morning effect (E/M ratio) were calculated to assess the duration of imidapril action. Morning HBP was significantly reduced (all p < 0.05) except when 2.5 mg of imidapril was administered once at bedtime. The individual M/E ratios expressed as means +/- standard deviation for systolic HBP were 0.9 +/- 0.7 and 0.7 +/- 0.7 for the morning administration of 2.5 and 5.0 mg of imidapril, respectively. The corresponding E/M ratios for bedtime administration were 0.3 +/- 0.5 and 1.0 +/- 0.7, respectively. One daily dose of imidapril taken either in the morning or at bedtime lowered morning HBP, indicating that imidapril is useful for controlling morning hypertension.     

Chronotherapy with nifedipine GITS in hypertensive patients: improved efficacy and safety with bedtime dosing

BACKGROUND: Previous studies have shown that the circadian pattern of blood pressure (BP) remains unchanged after either morning or evening dosing of several calcium-channel blockers (CCBs), including amlodipine, isradipine, verapamil, nitrendipine, and cilnidipine. This trial investigated the administration-time dependent antihypertensive efficacy of the slow-release, once-a-day nifedipine gastrointestinal-therapeutic-system (GITS) formulation. METHODS: We studied 180 untreated hypertensives (86 men and 94 women), 52.5 +/- 10.7 years of age, randomly assigned to receive nifedipine (30 mg/day) as a monotherapy either upon awakening or at bedtime. BP was measured for 48 h before and after 8 weeks of treatment. RESULTS: The BP reduction after treatment was significantly larger with bedtime dosing mainly during night time sleep (P < 0.012). The number of patients with controlled ambulatory BP after treatment was greater with bedtime than morning treatment (P = 0.016). The baseline prevalence of nondipping was unaltered after ingestion of nifedipine on awakening, but reduced from 51 to 35% after bedtime dosing (P = 0.025). The morning surge of BP, a risk factor for stroke, was significantly reduced (P < 0.001) only after bedtime administration of nifedipine. Bedtime in comparison to awakening-time ingestion of nifedipine was also associated with a reduction in the incidence of edema from 13 to 1% (P < 0.001). CONCLUSIONS: The increased efficacy on ambulatory BP as well as the significantly reduced prevalence of edema after bedtime as compared to morning ingestion of nifedipine should be taken into account when prescribing this medication to patients with essential hypertension.     

Bedtime administration of cilnidipine controls morning hypertension

Morning blood pressure (BP) level plays an important role in the incidence of cardiovascular disease. Recently, Kario, et al proposed the usefulness of ME difference (morning minus evening systolic BP) and ME average (average of morning and evening systolic BP) for the evaluation of antihypertensive treatment. Cilnidipine is a novel calcium channel blocker (CCB) that exerts inhibitory actions not only on L-type but also on N-type calcium channels. We investigated the effect of bedtime administration of cilnidipine (10 mg) in addition to the antihypertensive treatment for uncontrolled morning hypertension. Twenty-three hypertensive outpatients (13 males and 10 females; mean age, 66.9 years) with stable antihypertensive medication and uncontrolled morning BP were studied using self-measured BP monitoring in the morning and evening. Morning SBP (P < 0.001) and DBP (P < 0.001) decreased significantly from 150.2 +/- 8.7 and 87.8 +/- 9.3 to 132.7 +/- 7.4 and 77.5 +/- 8.5 mmHg, respectively, after the addition of cilnidipine. Morning heart rate did not change (63.3 +/- 7.0 to 64.1 +/- 9.4). The evening SBP, but not DBP, decreased significantly after treatment. Both the ME average (P < 0.001) and ME difference (P < 0.01) significantly decreased from 143.0 +/- 9.2 and 14.3 +/- 12.4 to 131.3 +/- 7.2 and 2.8 +/- 9.2 mmHg after treatment, respectively. The microalbuminuria decreased from 39.6 +/- 13.2 to 27.3 +/- 8.4 mg/g Cr. In conclusion, L-/N-type CCB cilnidipine may be useful for patients with uncontrollable morning hypertension by reducing both ME average and ME difference.     

Add-on effect of bedtime dosing of the alpha(1)-adrenergic receptor antagonist doxazosin on morning hypertension and left ventricular hypertrophy in patients undergoing long-term amlodipine monotherapy.

High morning blood pressure is related to target organ damage and future cardiovascular events. Chronobiologic therapies focusing on the early morning period may be an important strategy for antihypertensive therapy. The aim of this study was to clarify the add-on effects of bedtime dosing of the alpha(1)-adrenergic receptor antagonist doxazosin on morning blood pressure in patients with essential hypertension who were under long-acting calcium channel blocker amlodipine monotherapy. The add-on effects of doxazosin at the maximum dose of 6 mg at bedtime on home blood pressure and left ventricular geometry for 1 year were investigated in 49 subjects (37 men and 12 women, aged 57.5+/-9.1 years) with morning hypertension who had been treated with amlodipine alone for more than 1 year. Doxazosin induced a significant decrease in morning blood pressure (145.6+/-5.6/91.5+/-5.4 to 132.4+/-3.7/83.6+/-5.6 mmHg, p相似文献   

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.     

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.     

Prevalence of Masked Hypertension in Subjects Treated with Antihypertensive Drugs as Assessed by Morning versus Evening Home Blood Pressure Measurements: the J-HOME study

To investigate the relationship between morning and evening home blood pressure (BP) measurements to make a diagnosis of masked hypertension, we collected information on the characteristics of 3,303 essential hypertensive outpatients receiving antihypertensive medication in Japan using a physician, self-administered questionnaire. All patients were asked to measure their home BP once every morning and once every evening for two weeks. Morning and evening home BP values of each patient were defined as the average of all morning and all evening home BP values, respectively. The mean BP values of all study subjects were 142.8/80.6 mmHg for office BP, 139.8/81.8 mmHg for morning home BP, 133.7/76.9 mmHg for evening home BP, and 136.8/79.3 mmHg for the average of the morning and evening home BPs. Masked hypertension was defined as an office BP < 140/90 mmHg and a home BP > or = 135/85 mmHg. The prevalence of masked hypertension diagnosed using morning home BP (23.1%) was higher than that diagnosed by evening home BP (14.7%); the prevalence was 19.0% when diagnosed using the average of the morning and evening home BPs. Among the 1,386 patients with a normal office BP, the diagnosis of masked hypertension based on morning and evening home BP values differed in 28.8% of patients for systolic BP and 20.9% for diastolic BP (kappa coefficient = 0.43). The present study showed that the prevalence of masked hypertension was underestimated when the diagnosis of masked hypertension was made on the basis of evening home BP.     

Morning blood pressure predicts hypertensive organ damage in patients with renal diseases: effect of intensive antihypertensive therapy in patients with diabetic nephropathy

Blood pressure (BP) measured at home early in the morning (HBP) has been recognized as a useful predictor for organ damage and has been viewed as an important therapeutic target in patients with hypertension. The present study was aimed to determine whether this notion holds true in patients with progressive renal disease.The study enrolled patients with mild to moderate renal impairment. They were all directed to record self-measured HBP to evaluate the adequacy of BP control. In addition to the conventional antihypertensive therapy, intensive treatment to more efficiently reduce elevated morning HBP was applied, especially in patients with diabetic nephropathy. The results were as follows: 1) The status of BP control assessed using HBP and office/clinic BP (OBP) shows predominance of morning hypertension. The prevalence of patients with well-controlled systolic HBP was 38%, those with poorly-controlled HBP 30%, masked hypertension 20% and white coat hypertension 12%. 2) Early morning systolic HBP in diabetics was significantly higher than that in non-diabetics. However, when evaluated on systolic OBP, both groups were comparable.3)Logistic regression analysis showed that the predictive variables to explain morning hypertension (more than 130 mmHg and increased systolic HBP) were age, amount of daily urinary protein excretion and left ventricular mass index (LVMI).4)Following conventional therapy, intensive antihypertensive therapy consisting of calcium channel blockers (CCB) and/or diuretics given in the morning, and angiotensin receptor blockers (ARB) given in the evening, together with alpha1-blockers given at bedtime, efficaciously reduced elevated HBP in the morning. This result was associated with significant reduction in daily urinary protein excretion and in serum plasminogen-activator inhibitor (PAI-1) concentration.The present study indicates that, regardless of ongoing conventional antihypertensive therapy, the majority of patients with renal disease had morning hypertension, suggesting that these patients are at a higher risk for cardiovascular disease. For the purpose of improving morning hypertension, intensive treatments with combined CCB, ARB and alpha1-blockers could have substantial benefit on the morbidity and prognosis in patients with diabetic nephropathy.     

Prediction of stroke by home "morning" versus "evening" blood pressure values: the Ohasama study

Predictive power of self-measured blood pressure at home (home BP) for cardiovascular disease risk has been reported to be higher than casual-screening BP. However, the differential prognostic significance of home BP in the morning (morning BP) and in the evening (evening BP), respectively, has not been elucidated. In the Ohasama study, 1766 subjects (>or=40 years) were followed up for an average of 11 years. The predictive power for stroke incidence of evening BP was compared with that of morning BP as continuous variables. The Cox regression model demonstrated that evening BP and morning BP predicted future stroke risk equally. Subjects were also assigned to 1 of 4 categories based on home BP. In this analysis, stroke risk in morning hypertension ([HT] morning BP >or=135/85 mm Hg and evening BP <135/85 mm Hg; relative hazard (RH): 2.66; 95% CI:1.64 to 4.33) and that in sustained HT(morning BP and evening BP >or=135/85 mm Hg; RH: 2.38; 95% CI: 1.65 to 3.45) was significantly higher than that in normotension (morning BP and evening BP <135/85 mm Hg). The risk in morning HT was more remarkable in subjects taking antihypertensive medication (RH: 3.55; 95% CI: 1.70 to 7.38). Although the risk in evening HT (morning BP <135/85 mm Hg and evening BP >or=135/85 mm Hg) was higher than that in normotension, the differences were not significant. In conclusion, morning BP and evening BP provide equally useful information for stroke risk, whereas morning HT, which indicates HT specifically observed in the morning, might be a good predictor of stroke, particularly among individuals using anti-HT medication.     

不同服药方法对高血压患者降压有效性和平稳性的影响

目的 探讨不同服药方法 对于高血压治疗有效性和平稳性的影响.方法 采用随机、单盲、平行对照设计,对90例2级及以上原发性高血压患者,随机分为早晨服用非洛地平和缬沙坦组(A组30例,男15例,女15例),早晨服用缬沙坦晚上服非济地平组(B组30例,男17例,女13例),早晨服用非洛地平晚上服缬沙坦组(C组30例,男16例,女14例),患者均于服药前及服药后2周进行动态血压监测求得平滑指数等指标.结果 服药2周后,各组夜间时段及24 h的平均收缩压的下降值依此为:19.3、28.8、30.5、22.9、28.3及29.1 mm Hg(1 mm Hg=0.133 kPa).组间比较,A组0.05).夜间及24 h平均收缩压平滑指数符组依次为:2.43,3.12,3.22及1.92,2.49,2.27,组间比较,夜间平均收缩压平滑指数A组0.05).结论 联合用药的降压效果显著,早晚分次服药较早晨顿服两种药物能更有效控制夜间血压,早晚分次服药使夜间及24 h血压下降更平稳.     

Prevalence of Masked Hypertension in Subjects Treated with Antihypertensive Drugs as Assessed by Morning versus Evening Home Blood Pressure Measurements: The J-HOME Study

To investigate the relationship between morning and evening home blood pressure (BP) measurements to make a diagnosis of masked hypertension, we collected information on the characteristics of 3,303 essential hypertensive outpatients receiving antihypertensive medication in Japan using a physician, self-administered questionnaire. All patients were asked to measure their home BP once every morning and once every evening for two weeks. Morning and evening home BP values of each patient were defined as the average of all morning and all evening home BP values, respectively. The mean BP values of all study subjects were 142.8/80.6 mmHg for office BP, 139.8/81.8 mmHg for morning home BP, 133.7/76.9 mmHg for evening home BP, and 136.8/79.3 mmHg for the average of the morning and evening home BPs. Masked hypertension was defined as an office BP < 140/90 mmHg and a home BP ≥ 135/85 mmHg. The prevalence of masked hypertension diagnosed using morning home BP (23.1%) was higher than that diagnosed by evening home BP (14.7%); the prevalence was 19.0% when diagnosed using the average of the morning and evening home BPs. Among the 1,386 patients with a normal office BP, the diagnosis of masked hypertension based on morning and evening home BP values differed in 28.8% of patients for systolic BP and 20.9% for diastolic BP (kappa coefficient = 0.43). The present study showed that the prevalence of masked hypertension was underestimated when the diagnosis of masked hypertension was made on the basis of evening home BP.     

Orthostatic hypertension: home blood pressure monitoring for detection and assessment of treatment with doxazosin

To determine the role of home blood pressure (BP) monitoring for a reproducible assessment of orthostatic hypertension (OHT) and the effectiveness of hypertension control by doxazosin. In this study, 605 medicated hypertensive outpatients were enrolled. Home BP in the sitting and standing positions was monitored in all patients in the morning and evening for 6 months. According to an open-label multicenter trial design, the patients were randomly allocated to either an intervention group that took doxazosin (1-4 mg) at bedtime or to a control group that did not receive any add-on medication. The patients were divided into deciles of orthostatic BP change as evaluated by home BP monitoring at baseline. Those in the top decile, in the lowest decile and in deciles two through eight were then assigned to the OHT group, the orthostatic hypotension group and the orthostatic normotension group, respectively.Orthostatic BP in the OHYPO group did not change, whereas that of the OHT group was markedly reduced by doxazosin (P<0.01). In the control group, classification into orthostatic BP categories using home BP monitoring was more reproducible (κ coefficient: 0.42-0.50) than when using clinical BP (κ coefficient: 0.13-0.24). In all groups, a reduction in the urinary albumin/creatinine ratio was significantly associated with a reduction in orthostatic BP doxazosin (P<0.001).The identification of OHT based on home BP monitoring was highly reproducible. The administration of doxazosin might control OHT and consequently prevent target organ damage.     

Reproducibility of masked hypertension determined from morning and evening home blood pressure measurements over a 6-month period.

Recently, the existence of so-called masked hypertension has attracted attention. In this study, the reproducibility of masked hypertension determined from morning and evening home blood pressure measurements was examined over a 6-month period. Home blood pressure measurements were taken consecutively for 7 days in volunteers at a company in 2002 and again in 2003. The 503 Japanese subjects (329 male, 174 female, mean age: 39.4 years), who were not taking antihypertensive drugs, were asked to measure their home blood pressure three times every morning and three times every evening. We defined casual blood pressure > or =140 (systolic) or > or =90 (diastolic) mmHg and home blood pressure > or =135 or > or =85 mmHg as hypertension. We also defined normotension as <140 and <90 mmHg in casual blood pressure and <135 and <85 mmHg in home blood pressure. We examined the reproducibility of four blood pressure categories (normotension, hypertension, white-coat hypertension, and masked hypertension) over a 6-month period. When measured in morning home blood pressure, the reproducibility of masked hypertension (59.1%) was significantly higher than that of white-coat hypertension (25.0%) and similar to that of hypertension (67.6%). However, the reproducibility of masked hypertension (23.5%) was similar to that of white-coat hypertension (32.0%) and significantly lower than that of hypertension (66.7%) when determined using evening home blood pressure. The concordances in the four blood pressure categories between the two periods were 0.582 (kappa coefficient) and 0.463 when determined using morning and evening home blood pressure data, respectively. In conclusion, the reproducibility of masked hypertension over a 6-month period was moderate in an urban Japanese population when evaluated by morning home blood pressure.     

The bedtime administration of doxazosin controls morning hypertension and albuminuria in patients with type-2 diabetes: evaluation using home-based blood pressure measurements

The control of high blood pressure (BP) after awakening in the morning (morning hypertension) as determined by home BP (HBP), as well as BP control throughout the day, may prevent diabetic vascular complications. We examined the effect of an alpha-adrenergic blocker (doxazosin) on BP measurements taken by HBP after awakening and during clinic visits (CBP) in 50 patients with type-2 diabetes and morning hypertension. We evaluated the urinary albumin excretion rate as an indicator of nephropathy. Doxazosin was taken orally once at bedtime for 1 to 3 months. The mean (+/- SD) dose was 2.9 +/- 2.1 mg/day (1 to 8 mg/day). The BP was measured monthly at the clinic during the day and at home after awakening in the morning. In this short-term trial (2.8 +/- 0.4 months), the systolic HBP decreased significantly from 164 +/- 17 mmHg before treatment to 146 +/- 19 mmHg after treatment, and the diastolic HBP decreased significantly from 85 +/- 14 mmHg before treatment to 80 +/- 9 mmHg after treatment. The systolic, but not the diastolic CBP, decreased significantly after treatment. There was no significant difference in the systolic or diastolic values between the HBP and the CBP after treatment. The percentage change in the systolic HBP after treatment was three times greater than for the systolic CBP. The median (interquartile) urinary albumin excretion rate decreased significantly (P < 0.001) from 62 (25-203) mg/g creatinine before treatment to 19 (9-76) mg/g creatinine after treatment. On multiple regression analysis, the decrease in the systolic HBP with treatment positively correlated with the reduction in urinary excretion of albumin. The control of morning hypertension reduced the albuminuria found in both untreated and treated hypertensive patients with type-2 diabetes. Bedtime administration of doxazosin appears to be safe and effective in reducing morning hypertension as measured by HBP. This finding also demonstrates that HBP taken in the morning has a stronger predictive power for the albuminuria level than does CBP.     

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.     

Morning hypertension: the strongest independent risk factor for stroke in elderly hypertensive patients.

Stroke occurs most frequently in the morning hours, but the impact of the morning blood pressure (BP) level on stroke risk has not been fully investigated in hypertensives. We studied stroke prognosis in 519 older hypertensives in whom ambulatory BP monitoring was performed, and who were followed prospectively. During an average duration of 41 months (range: 1-68 months), 44 stroke events occurred. The morning systolic BP (SBP) was the strongest independent predictor for stroke events among clinic, 24-h, awake, sleep, evening, and pre-awake BPs, with a 10 mmHg increase in morning SBP corresponding to a relative risk (RR) of 1.44 (p<0.0001). The average of the morning and evening SBP (Av-ME-SBP; 10 mmHg increase: RR=1.41, p=0.0001), and the difference between the morning and evening SBP (Di-ME-SBP; 10 mmHg increase: RR=1.24, p=0.0025) were associated with stroke risks independently of each other. The RR of morning hypertension (Av-ME-SBP > or = 135 mmHg and Di-ME-SBP > or = 20 mmHg) vs. sustained hypertension (Av-ME-SBP > = 135 mmHg and Di-ME-SBP < or = 20 mmHg) for stoke events was 3.1 after controlling for other risk factors (p=0.01). In conclusion, morning hypertension is the strongest independent predictor for future clinical stroke events in elderly hypertensive patients, and morning and evening BPs should be monitored in the home as a first step in the treatment of hypertensive patients.     

Relationship between morning hypertension identified by home blood pressure monitoring and brain natriuretic peptide and estimated glomerular filtration rate: the Japan Morning Surge 1 (JMS-1) Study

We evaluated whether morning minus evening systolic blood pressure (SBP) difference (MEdif) in home blood pressure measurements can be a marker for hypertensive target organ damage. The authors analyzed 611 hypertensive patients who had high morning SBP levels (>/=135 mm Hg). The patients with morning hypertension (MEdif >/=15 mm Hg, average of morning and evening SBP [MEave] >/=135 mm Hg) were older (P<.001) and had a longer duration of hypertension and antihypertensive medication use, a higher prevalence of left ventricular hypertrophy (LVH) on electrocardiography, a lower glomerular filtration rate by the Cockcroft-Gault equation (P=.002), and a higher brain natriuretic peptide (BNP) level (P<.001) than those with well-controlled blood pressure (MEdif <15 mm Hg, MEave <135 mm Hg). The patients with morning hypertension had a higher BNP level than those with well-controlled blood pressure after adjustment for the confounding factors (28.7 pg/mL vs 20.0 pg/mL; P=.033). In conclusion, morning hypertension is more likely seen among patients with older age and longer duration of hypertension and antihypertensive medication use, and it may be associated with a higher prevalence of LVH and a higher BNP level.     

Losartan/hydrochlorothiazide combination vs. high-dose losartan in patients with morning hypertension--a prospective, randomized, open-labeled, parallel-group, multicenter trial

The treatment of morning hypertension has not been established. We compared the efficacy and safety of a losartan/hydrochlorothiazide (HCTZ) combination and high-dose losartan in patients with morning hypertension. A prospective, randomized, open-labeled, parallel-group, multicenter trial enrolled 216 treated outpatients with morning hypertension evaluated by home blood pressure (BP) self-measurement. Patients were randomly assigned to receive a combination therapy of 50?mg losartan and 12.5?mg HCTZ (n=109) or a high-dose therapy with 100?mg losartan (n=107), each of which were administered once every morning. Primary efficacy end points were morning systolic BP (SBP) level and target BP achievement rate after 3 months of treatment. At baseline, BP levels were similar between the two therapy groups. Morning SBP was reduced from 150.3±10.1 to 131.5±11.5?mm?Hg by combination therapy (P<0.001) and from 151.0±9.3 to 142.5±13.6?mm?Hg by high-dose therapy (P<0.001). The morning SBP reduction was greater in the combination therapy group than in the high-dose therapy group (P<0.001). Combination therapy decreased evening SBP from 141.6±13.3 to 125.3±13.1?mm?Hg (P<0.001), and high-dose therapy decreased evening SBP from 138.9±9.9 to 131.4±13.2?mm?Hg (P<0.01). Although both therapies improved target BP achievement rates in the morning and evening (P<0.001 for both), combination therapy increased the achievement rates more than high-dose therapy (P<0.001 and P<0.05, respectively). In clinic measurements, combination therapy was superior to high-dose therapy in reducing SBP and improving the achievement rate (P<0.001 and P<0.01, respectively). Combination therapy decreased urine albumin excretion (P<0.05) whereas high-dose therapy reduced serum uric acid. Both therapies indicated strong adherence and few adverse effects (P<0.001). In conclusion, losartan/HCTZ combination therapy was more effective for controlling morning hypertension and reducing urine albumin than high-dose losartan.     

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.