Efficacy of combination antihypertensive therapy with low-dose indapamide: assessment by blood pressure self-monitoring at home

We examined the effects of the addition of low-dose indapamide to antihypertensive drugs of other classes, as well as its duration of action, using blood pressure (BP) self-monitoring at home. Seventy-six patients undergoing monotherapy with a calcium channel blocker (CCB), angiotensin converting-enzyme inhibitor (ACEI), or angiotensin AT1-receptor blocker (ARB), but had an average morning home systolic BP (SBP) > or =135 mmHg or diastolic BP (DBP) > or =85 mmHg, were studied. Indapamide (1 mg) was added to their existing treatment once daily for 4 weeks. The additional hypotensive effects of indapamide were evaluated by casual and home BPs, and the results were compared among the three groups of subjects classified according to their initial drug treatment classes. The morning/evening (M/E) ratio of BP reduction was calculated to assess the duration of the effect. Overall, indapamide significantly (P < 0.001) lowered morning home BP (147 +/- 12/87 +/- 9 mmHg to 135 +/- 12/81 +/- 9 mmHg), evening home BP (138 +/- 15/79 +/- 10 mmHg to 126 +/- 12/73 +/- 9 mmHg), and casual BP (145 +/- 21/86 +/- 14 mmHg to 136 +/- 17/81 +/- 13 mmHg). All groups showed significant indapamide-induced home SBP/DBP decreases, whereas only the ACEI and ARB groups, but not the CCB group, showed a home pulse pressure (PP) reduction. Evening SBP and PP decreases were significantly greater in the ARB group than in the CCB group. The mean M/E ratio with indapamide was 0.95 for SBP and 0.85 for DBP. Low-dose indapamide used in combination can provide additional anti-hypertensive efficacy lasting for 24 h. The added effect of indapamide may be more prominent on ARBs than on CCBs.     

Morning rise of blood pressure assessed by home blood pressure monitoring is associated with left ventricular hypertrophy in hypertensive patients receiving long-term antihypertensive medication.

To assess the influence of morning rise of systolic blood pressure (SBP) as assessed by home blood pressure monitoring on the left ventricular mass index (LVMI) in relation to the blood pressure control status, we evaluated M-mode cardiac echocardiography in 626 hypertensive subjects (412 men and 214 women; mean age, 61.3+/-10.1 years) who were receiving antihypertensive medication. The subjects were requested to measure their blood pressure at home in the morning and evening over a 3-month period. They were distributed into the following four groups by the average (ME Ave) and the difference (ME Dif) of the morning and evening SBP. The well-controlled hypertensives with a morning rise of SBP (ME Ave<135 mmHg and ME Dif>or=10 mmHg; n=45; 7.2%) had a greater LVMI (122.9+/-22.7 vs. 92.7+/-15.6 g/m2, p<0.001) than the well-controlled hypertensives without a morning rise of SBP (ME Ave<135 mmHg and ME Dif<10 mmHg; n=367; 58.6%). The uncontrolled hypertensives with a morning rise of SBP (ME Ave>or=135 mmHg and ME Dif>or=10 mmHg; n=91; 14.5%) also had a greater LVMI (136.8+/-21.9 vs. 100.2+/-17.5 g/m2, p<0.001) than the uncontrolled hypertensives without a morning rise of SBP (ME Ave>or=135 mmHg and ME Dif<10 mmHg; n=123; 19.6%). A stepwise multivariate regression analysis revealed that the ME Dif was the most important factor related to the LVMI (r2=35.1% for all subjects, p<0001; r2=39.7% for men, p<0.001; and r2=18.7% for women, p<0.001). These results suggest that morning rise of blood pressure is an important factor influencing the development of left ventricular hypertrophy in hypertensive patients on antihypertensive medication.     

Determinants of exaggerated difference in morning and evening blood pressure measured by self-measured blood pressure monitoring in medicated hypertensive patients: Jichi Morning Hypertension Research (J-MORE) Study

BACKGROUND: Morning blood pressure (BP) surge in ambulatory BP monitoring was a risk factor for stroke in our previous study. We studied the determinants of the morning minus evening systolic BP difference (ME difference) in self-measured BP monitoring, as a possible risk factor for stroke in medicated hypertensive patients. METHODS: Nine hundred sixty-nine hypertensive outpatients receiving stable antihypertensive drug treatment were studied using self-measured BP monitoring in the morning and evening. RESULTS: The ME difference ranged from -37.3 to 53.3 mm Hg (mean 7.9 mm Hg). The highest quartile (Q4) of the ME difference group (>15.0 mm Hg) had older age (68.0+/-9.8 years v 66.2+/-10.3 years, P=.01) and higher prevalence of men (48.3% v 39.9%, P=.02), regular alcohol drinkers (34.7% v 26.0%, P=.01) and beta-blocker use (26.9% v 19.9%, P=.03) than the other quartile groups (Q1 to Q3), whereas there was no significant difference in the average of morning and evening (ME average) BP. In logistic regression analysis controlling for ME average and other confounding factors, independent risks for Q4 of ME difference were older age (10 years older: odds ratio [OR] 1.21, P=.01, 95% confidence interval (CI) 1.04-1.42), regular alcohol drinker (OR 1.51, P=.04, 95% CI 1.01-2.26), and beta-blocker use (OR 1.50, P=.02, 95% CI 1.06-2.12). CONCLUSIONS: Older age, beta-blocker use, and regular alcohol drinking were significant determinants of the exaggerated ME difference in medicated hypertensive patients.     

The effect of combination therapy with an L/N-Type Ca(2+) channel blocker, cilnidipine, and an angiotensin II receptor blocker on the blood pressure and heart rate in Japanese hypertensive patients: an observational study conducted in Japan.

Recently, the use of combination therapy with a calcium channel blocker (CCB) and an angiotensin II receptor blocker (ARB) has been rapidly increasing. Although this combination therapy is accepted as a standard treatment hypertension, there have been few large-scale, multicenter studies examining its safety and efficacy. The present study was designed to investigate the safety and efficacy of adding cilnidipine, a dual L/N-type CCB, to the regimen of patients whose blood pressure had been poorly controlled (systolic blood pressure [SBP] >140 mmHg or diastolic blood pressure [DBP] >90 mmHg) by antihypertensive monotherapy with an ARB. The percentage achievement of the blood pressure goals recommended by the JSH 2000 guidelines was also assessed for at least 12 weeks of treatment. A total of 2,920 patients were enrolled in the study at 471 institutions in Japan from February 2003 to July 2004. The incidence of adverse reactions related to cilnidipine was as low as 2.5%. A significant reduction from the baseline was found both in SBP (from 164.1 +/- 15.3 to 139.2 +/- 15.3 mmHg, p<0.0001) and DBP (from 91.7 +/- 11.4 to 79.3 +/- 10.7 mmHg, p<0.0001). A total of 31.5% of the patients achieved the blood pressure goals recommended by the JSH 2000 guidelines. Moreover, the heart rate also significantly decreased in these patients, particularly in those with a higher baseline heart rate. Our results indicate that cilnidipine can be used in combination with an ARB to control blood pressure without any significant adverse effects, and also that cilnidipine successfully reduces elevated heart rate, which is a possible risk factor for cardiovascular events.     

Comparison of the effects of cilnidipine and amlodipine on ambulatory blood pressure.

Cilnidipine is a novel and unique 1,4-dydropyridine derivative calcium antagonist that exerts potent inhibitory actions not only on L-type but also on N-type voltage-dependent calcium channels. Blockade of the neural N-type calcium channel inhibits the secretion of norepinephrine from peripheral neural terminals and depresses sympathetic nervous system activity. The purpose of this study was to assess the effect of cilnidipine and amlodipine on ambulatory blood pressure (BP) levels. We performed 24-h ambulatory BP monitoring before and after once-daily use of cilnidipine (n=55) and amlodipine (n=55) in 110 hypertensive patients. Both drugs significantly reduced clinic and 24-h systolic BP (SBP) and diastolic BP (DBP) (p < 0.005). However, the reductions of 24-h (-1.19+/-6.78 vs. 1.55+/-6.13 bpm, p=0.03), daytime (-1.58+/-6.72 vs. 1.68+/-7.34 bpm, p=0.02) and nighttime (-1.19+/-5.72 vs. 1.89+/-6.56 bpm, p=0.01) pulse rate (PR) were significantly greater in the cilnidipine group than the amlodipine group. There was no correlation between the degree of daytime SBP change and that of daytime PR change after amlodipine treatment (r=-0.08, n.s.), but there was a significant negative correlation between the degree of daytime SBP change and that of day-time PR change after cilnidipine treatment (r=-0.27, p<0.05). N-type calcium channel blockade by cilnidipine may not cause reflex tachycardia, and may be useful for hypertensive treatment.     

Reduction of white coat effect by cilnidipine in essential hypertension.

Stress elevates blood pressure (BP) by increased sympathetic nerve activity. Cilnidipine, a novel dihydropyridine calcium antagonist that has inhibitory actions on N-type as well as L-type voltage-dependent calcium channels, has been reported to attenuate the cold stress-induced increase in plasma norepinephrine and BP in rats. Because white coat effect is associated with an enhanced pressor response to mental stress, we postulated that cilnidipine would attenuate white coat effect in patients with essential hypertension. Sixty-one consecutive outpatients (50 men, 11 women) with essential hypertension were studied prospectively. Twenty-nine patients were treated with either cilnidipine (n = 15) or nifedipine, a representative L-type voltage-dependent calcium antagonist (n = 14). Gender, age, body mass index, duration of hypertension, target organ damage of hypertension, and BP and heart rate (HR) were not significantly different between cilnidipine and nifedipine groups, and both systolic (SBP) and diastolic BP (DBP) were significantly decreased after treatment in both groups. White coat effects on systolic and DBP and HR were not significantly different between groups before antihypertensive treatment. Cilnidipine, but not nifedipine, significantly reduced white coat effects on SBP and HR. Furthermore, white coat effects on systolic BP and HR were significantly lower after treatment in the cilnidipine group compared with the nifedipine group. These data suggest that cilnidipine may reduce white coat effect in hypertensive patients by N-type calcium channel antagonism.     

Efficacy of Combination Antihypertensive Therapy with Low-Dose Indapamide: Assessment by Blood Pressure Self-Monitoring at Home

We examined the effects of the addition of low-dose indapamide to antihypertensive drugs of other classes, as well as its duration of action, using blood pressure (BP) self-monitoring at home. Seventy-six patients undergoing monotherapy with a calcium channel blocker (CCB), angiotensin converting-enzyme inhibitor (ACEI), or angiotensin AT₁-receptor blocker (ARB), but had an average morning home systolic BP (SBP) ≥ 135 mmHg or diastolic BP (DBP) ≥ 85 mmHg, were studied. Indapamide (1 mg) was added to their existing treatment once daily for 4 weeks. The additional hypotensive effects of indapamide were evaluated by casual and home BPs, and the results were compared among the three groups of subjects classified according to their initial drug treatment classes. The morning/evening (M/E) ratio of BP reduction was calculated to assess the duration of the effect. Overall, indapamide significantly (P < 0.001) lowered morning home BP (147 ± 12/87 ± 9 mmHg to 135 ± 12/81 ± 9 mmHg), evening home BP (138 ± 15/79 ± 10 mmHg to 126 ± 12/73 ± 9 mmHg), and casual BP (145 ± 21/86 ± 14 mmHg to 136 ± 17/81 ± 13 mmHg). All groupsshowed significant indapamide-induced home SBP/DBP decreases, whereas only the ACEI and ARB groups, but not the CCB group, showed a home pulse pressure (PP) reduction. Evening SBP and PP decreases were significantly greater in the ARB group than in the CCB group. The mean M/E ratio with indapamide was 0.95 for SBP and 0.85 for DBP. Low-dose indapamide used in combination can provide additional anti-hypertensive efficacy lasting for 24 h. The added effect of indapamide may be more prominent on ARBs than on CCBs.     

A home blood pressure monitoring study comparing the antihypertensive efficacy of two angiotensin II receptor antagonist fixed combinations

BACKGROUND: The objective of this prospective, randomized, open-label, blinded-endpoint study was to compare the antihypertensive efficacy of valsartan 80 mg v irbesartan 150 mg when combined with hydrochlorothiazide (HCTZ) 12.5 mg. METHODS: Untreated or uncontrolled hypertensive adults (n = 800) were enrolled by primary care physicians. After a 5-week open-label lead-in phase in which all patients received 12.5 mg HCTZ once daily, subjects whose blood pressure (BP) remained uncontrolled were randomized (n = 464) to valsartan/HCTZ (80/12.5 mg) or irbesartan/HCTZ (150/12.5 mg) for 8 weeks. Home BP monitoring (HBPM) was performed in the morning and in the evening for 5 days, at baseline, and after 8 weeks. Office BP measurements were obtained at baseline and after 8 weeks. RESULTS: Irbesartan/HCTZ produced greater reductions in average systolic BP (SBP) and diastolic BP (DBP) measured by HBPM than valsartan/HCTZ (SBP: -13.0 v -10.6 mm Hg, P = .0094; DBP: -9.5 v -7.4 mm Hg, P = .0007). These differences were more pronounced in the morning (trough) than in the evening. Office BP measurements also showed greater reductions in trough seated SBP and DBP with irbesartan/HCTZ compared with valsartan/HCTZ. Normalization rates observed with HBPM (SBP <135 mm Hg and DBP <85 mm Hg) were significantly greater with irbesartan/HCTZ than with valsartan/HCTZ (50.2 v 33.2%; P = .0003). The overall safety was similar in the two groups. CONCLUSIONS: The superior BP-lowering potency of the fixed combination irbesartan/HCTZ (150/12.5 mg) over valsartan/HCTZ (80/12.5 mg), evidenced independently from the investigators by HBPM, supports the use of this technique in trials with prospective, randomized, open-label, blinded-endpoint designs.     

Morning versus evening administration of a calcium channel blocker in combination therapy for essential hypertension by ambulatory blood pressure monitoring analysis

Patients with moderate to severe hypertension may need more than two antihypertensive drugs in combination to achieve ideal blood pressure (BP) control. The purpose of this study was to compare the efficacy and safety of administering the antihypertensive agents either all together in the morning or separately with two agents in the morning and one calcium channel blocker (CCB) in the evening. Twenty-four-hour ambulatory BP monitoring (ABPM) was performed among 15 patients (mean, 59 years) with moderate to severe essential hypertension. All patients received at least 3 antihypertensive drugs for ideal BP control. Two treatment regimens were given to each patient: Regimen 1: All antihypertensive agents were given once a day in the morning; Regimen 2: All antihypertensive agents were given in the morning, except the CCB which was given at 4:00 pm. After receiving regimen 1 for 4 weeks, each patient underwent 24-hour ABPM to analyze the BP control. After the first ABPM, each patient was switched to regimen 2. After 4 weeks of treatment with regimen 2, each patient underwent the second ABPM measurement. The pretreatment mean systolic and diastolic BP were 179.6 +/- 21.7 and 107.4 +/- 19.9 mmHg, respectively. Between the two regimens, there was no significant difference in the mean 24-hour BP (126.1 +/- 5.8/73.3 +/- 3.8 versus 130.2 +/- 6.2/75.1 +/- 4.7 mmHg), daytime BP (128.2 +/- 6.5/75.3 +/- 3.8 versus 132.4 +/- 5.8/77.2 +/- 4.4 mmHg), nighttime BP (125.2 +/- 4.9/72.4 +/- 3.3 versus 130.9 +/- 6.2/73.8 +/- 4.1 mmHg), and 24-hour heart rate (65.1 +/- 3.8 versus 64.2 +/- 3.4 bpm). The circadian BP and heart rate profiles were almost identical between regimen 1 and regimen 2. We conclude that in patients with moderate to severe hypertension treated with at least 3 antihypertensive agents, administering a CCB simultaneously with other antihypertensive agents in the morning or separately in the evening did not affect the 24-hour BP control.     

Sustained beneficial effects on blood pressure during long time retrospective follow-up after endovascular treatment of renal artery occlusion

We retrospectively evaluated short- and long-term effects of percutaneous transluminal renal angioplasty (PTRA) with or without stent placement of renal artery occlusion (RAO) upon blood pressure (BP), serum (s)-creatinine, and the need for antihypertensive treatment in 34 RAO patients who underwent PTRA during 1996-2002. In 24/34 (71%) treatment was considered technically successful, 22/24 (92%) were treated with PTRA + stent, two with only PTRA. Patients were followed for mean 2.6 (range 0-8) years, during which 14/34 (41%) patients died. In all 34 patients, systolic and diastolic BP (SBP and DBP) before treatment were 184 +/- 30/95 +/- 15 mmHg and had decreased at discharge (to 157 +/- 21/80 +/- 10 mmHg; P < 0.001 for both SBP and DBP), and remained lower after 1 year (154 +/- 20/83 +/- 7 mmHg; P < 0.001 for SBP and P < 0.01 for DBP), and at last follow-up (148 +/- 20/80 +/-12 mmHg; P < 0.001 for both SBP and DBP). No changes occurred in s-creatinine or the number of antihypertensive drugs. Similar results were seen in the subgroup of 24/34 (71%) patients in whom treatment was technically successful. Among the 24 patients undergoing technically successful PTRA, absence of nephrosclerosis (P = 0.035) and a shorter duration of hypertension (P = 0.020) predicted favourable clinical outcome. No adverse effects upon s-creatinine or the need for antihypertensive medication were seen in patients in whom treatment was considered a technical failure. Seven of these patients were treated with PTRA of another renal artery than the occluded, or with embolisation. In conclusion, RAO can be treated with endovascular techniques. Technically successful results with decreasing blood pressure levels were obtained in 71% of patients.     

Early morning home blood pressure control among treated patients with controlled office blood pressure

Elevated morning blood pressure (BP) has a significantly increased risk of cardiovascular events, so morning BP is of substantial clinical importance for the management of hypertension. This study aimed to evaluate early morning BP control and its determines among treated patients with controlled office BP. From May to October 2018, 600 treated patients with office BP < 140/90 mm Hg were recruited from hypertension clinics. Morning BP was measured at home for 7 days. Morning home systolic blood pressure (SBP) increased by an average of 11.5 mm Hg and that morning home diastolic blood pressure (DBP) increased by an average of 5.6 mm Hg compared with office BP. Morning home SBP, DBP, and their moving average were more likely to be lower among patients with a office SBP < 120 mm Hg than among patients with a office SBP ranging from 120 to 129 mm Hg and from 130 to 139 mm Hg (P < .001). A total of 45% of patients had early morning BP < 135/85 mm Hg. The following factors were significantly correlated with morning BP control: male sex, age of <65 years, absence of habitual snoring, no drinking, adequate physical activity, no habit of high salt intake, office BP < 120/80 mm Hg, and combination of a calcium channel blocker (CCB) and angiotensin receptor blocker or angiotensin‐converting enzyme inhibitor (ARB/ACEI). Less than half of patients with controlled office BP had controlled morning BP and that positive changes may be related to an office BP < 120/80 mm Hg, combination of a CCB and ACEI/ARB and a series of lifestyle adjustments.     

Rate of morning increase in blood pressure is elevated in hypertensives

BACKGROUND: We applied a new logistic curve fitting procedure to ambulatory blood pressure (ABP) recordings to determine whether the rate of increase in systolic (SBP), mean (MBP) and diastolic blood pressure (DBP) and heart rate (HR) in the morning is related to the level of BP in subjects. METHODS: The rate of transition in the morning and evening period was determined using a six-parameter double-logistic equation applied to 528 ABP recordings from a cardiovascular risk assessment clinic. Based on daytime BP (MBP, SBP, or DBP), the upper quartile (UQ, n = 132) and lower quartile (LQ) were compared. RESULTS: Subjects in the UQ of daytime MBP were hypertensive and showed greater day-night differences compared to normotensive subjects in the LQ (29 +/- 1 mm Hg for MBP compared to 20 +/- 1 mm Hg). The rate of morning increase in SBP and DBP was 42% and 30% greater in UQ subjects compared to the LQ subjects (P < .05). The rates of evening decrease in all BPs were 69% to 84% greater in the subjects in the UQ. Similar results were obtained if subjects were divided according to daytime SBP or DBP. The rate of morning increase in MBP was correlated with daytime BP, but not night-time or 24 h MBP. CONCLUSIONS: The rate of morning increase in BP is greater in those subjects with the highest daytime BP. The exaggerated rate of morning increase in BP in this group, which were all hypertensive, may also be important for greater cardiovascular risk.     

Relation between nocturnal arterial oxygen desaturation and morning blood pressure

OBJECTIVE: Arterial oxygen saturation (SpO2) in volunteers had been previously investigated, and the possibility that a decrease in SpO2 leads to an increase in blood pressure (BP) in airline passengers experiencing oxygen desaturation at high altitudes was reported. It was also shown that mean nocturnal SpO2 was lower in subjects with high-normal BP or mild hypertension than in those with normal BP. The present study investigated nocturnal SpO2, evening BP, and morning BP of volunteers during daily life and examined the relation between nocturnal SpO2 and change in BP (morning BP minus evening BP) to determine the influence of SpO2 on BP. METHODS: Sixty-two volunteers (31 men and 31 women) aged 40-87 years (mean: 55.9 +/- 12 [SD] years) underwent measurement of SpO2 and heart rate with a ring-shaped pulse oximeter during sleep at home. Evening BP and morning BP were measured by automatic BP recorder. Subjects that were classified as having high SpO2 (mean nocturnal SpO2 >or= 95%; n = 23, 10 men and 13 women; mean age: 53.2 +/- 12 years) or low SpO2 (mean nocturnal SpO2 < 94%; n = 21, 12 men and 9 women; mean age: 58.7 +/- 13 years) were compared. The relation between mean nocturnal SpO2 and morning BP and the relation between mean nocturnal SpO2 and change in BP were investigated. RESULTS: There was a significant negative correlation between mean nocturnal SpO2 and morning systolic BP (SBP; r = -0.50, p < 0.01) and between mean nocturnal SpO2 and morning diastolic BP (DBP; r = -0.37, p < 0.01). A significant negative correlation between mean nocturnal SpO2 and change in SBP was observed (r = -0.57, p < 0.01). Morning BP was significantly higher in the low nocturnal SpO2 group than in the high nocturnal SpO2 group (p < 0.001). CONCLUSION: The increase in morning BP from evening BP was significantly greater in subjects with a low nocturnal SpO2. The decrease in SpO2 during sleep may affect morning BP rise.     

Status of home blood pressure measured in morning and evening: evaluation in normotensives and hypertensives in Japanese urban population.

To assess home blood pressure status in a Japanese urban population, we analyzed home blood pressure values in normotensive subjects determined by casual blood pressure (< 140/90 mmHg), hypertensive subjects without medication (> or = 140/90 mmHg) and treated hypertensive patients. The subjects (468 male, 232 female; mean age 41 years old) were recruited from a company located in Tokyo. Home blood pressure was measured with a semi-automatic device (Omron HEM-759P). Subjects were instructed to perform triplicate morning and evening measurements on 7 consecutive days. In the treated hypertensive group (n = 70), there was a significant difference between morning (139 +/- 12/88 +/- 9 mmHg) and evening (130 +/- 12/79 +/- 8 mmHg) home blood pressure. In the normotensive group (n = 558), however, only the diastolic blood pressure (DBP) component of the home blood pressure was significantly different between morning (115 +/- 13/72 +/- 9 mmHg) and evening (114 +/- 12/68 +/- 8 mmHg). In the nontreated hypertensive group (n = 72), casual blood pressure (145 +/- 14/92 +/- 9 mmHg) was higher than morning (138 +/- 16/89 +/- 11 mmHg) and evening (134 +/- 16/83 +/- 11 mmHg) home blood pressure, but no difference was seen between morning and evening systolic blood pressure (SBP). According to the reference value of the Japanese Society of Hypertension 2004 (SBP > or = 135 mmHg and/or DBP > or = 85 mmHg), 7.2% (systolic) and 8.7% (diastolic) of subjects in the normotensive group were classified as hypertensive by home blood pressure. Casual blood pressure in the treated hypertensive group was normal in 64.3% for SBP and 70.0% for DBP. However, their morning SBP (32.9%), morning DBP (40.0%), evening SBP (10.0%), and evening DBP (17.1%) were classified as hypertensive by home blood pressure. Furthermore, patients who were taking antihypertensive drug(s) only in the morning (n = 52) showed higher morning SBP (6 mmHg, p = 0.086) and morning DBP (6 mmHg, p = 0.005) than patients taking drug(s) by other administration schedules (n = 18), but no difference in evening home blood pressure was observed. In conclusion, a proportion of the subjects defined as normotensive by casual blood pressure were classified as hypertensive by home blood pressure in the present urban population. Furthermore, morning home blood pressure control in the treated hypertensive group classified as under control by casual blood pressure was insufficient, especially in patients who were taking medication only in the morning.     

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.     

Which measurement of home blood pressure should be used for clinical evaluation when multiple measurements are made?

OBJECTIVE: We evaluated which home blood pressure (BP) measurement was most useful in clinical evaluation when we measured it three times per sitting. METHODS: Home BP measurements in the morning and evening were performed for 7 days in 572 volunteers (384 men, 188 women, mean age 41.2 years) in 2002 (period 1) and 2003 (period 2). Five sets of measurements were analyzed: A, mean of the first; B, mean of the second; C, mean of the first and second; D, mean of the second and third; and E, mean of all measurements. By analyzing BP in five sets in both periods, their reproducibility was examined. RESULTS: For all five sets of measurements, little difference was found when BP readings were compared between both periods [the differences were -0.6 +/- 6.7 to -0.4 +/- 7.0 mmHg for morning systolic BP (SBP), 0 +/- 4.9 to 0.3 +/- 5.0 mmHg for morning diastolic BP (DBP), -0.1 +/- 7.1 to 0.1 +/- 7.0 mmHg for evening SBP, and 0.1 +/- 5.3 to 0.4 +/- 5.4 mmHg for evening DBP]. Furthermore, BP readings between both periods correlated well; the correlation coefficients were 0.90-0.92 for morning BP and 0.86-0.89 for evening BP. In addition, the concordance rates of three BP categories (normotension, borderline and hypertension) were excellent using morning home BP (kappa coefficient 0.64-0.68) in all five sets, and higher than those using evening home BP (0.52-0.57). CONCLUSIONS: This study has shown that even one measurement on each occasion is as useful as several measurements when 7 consecutive days of home BP measurements are used for clinical evaluation.     

Beneficial effect of cilnidipine on morning hypertension and white-coat effect in patients with essential hypertension.

Home blood pressure has a higher predictive power for cardiovascular events than office blood pressure, and there is a particularly close association between morning blood pressure at home and the incidence of cardiovascular events and mortality in the early morning. In this study, we evaluated the efficacy of a long-acting N-type and L-type calcium channel blocker, cilnidipine, in reducing morning blood pressure at home and in ameliorating the white-coat effect. Fifty-eight subjects diagnosed with both essential hypertension and morning hypertension (43 currently being treated, 15 new patients) were prescribed cilnidipine at a dosage of 10-20 mg per day for 8 weeks. After the addition of or a change to cilnidipine, the morning systolic blood pressure (SBP) was controlled to less than 135 mmHg in 25 (58%) out of the 43 patients currently receiving antihypertensive medication. The office SBP in 24 out of those 25 patients was also maintained under 140 mmHg. In the 15 newly treated patients, the morning SBP of 12 patients (80%) was controlled to less than 135 mmHg after administration of cilnidipine. At baseline, 17 patients showed a clear white-coat effect, in which the difference between office blood pressure and home blood pressure was 20/10 mmHg or more. The white-coat effect was depressed significantly after cilnidipine administration. These results suggest that cilnidipine may serve as a useful antihypertensive medication in the treatment of morning hypertension, and also attenuate the white-coat effect in patients with essential hypertension.     

Cilnidipine, but not amlodipine, ameliorates osteoporosis in ovariectomized hypertensive rats through inhibition of the N-type calcium channel

Both osteoporosis and high blood pressure are major diseases in aging populations. Recent studies demonstrated that some antihypertensive drugs reduced the risk of bone fracture in elderly patients. Although calcium channel blockers (CCB) are widely used as first-line antihypertensive agents, there is no evidence that they prevent osteoporosis. In this study, we investigated the effects of two types of CCB on bone metabolism: cilnidipine (L-/N-type CCB), which suppresses norepinephrine release from the sympathetic nerve, and amlodipine (L-type CCB). In ovariectomized female spontaneous hypertensive rats, administration of cilnidipine, but not amlodipine, resulted in a significant increase in the ratio of alkaline phosphatase to tartrate-resistant acid phosphatase (TRAP) and a decrease in the number of osteoclasts, as assessed by TRAP staining in the proximal tibia. Bone mineral density, moreover, was significantly higher in the cilnidipine group as compared with the amlodipine group and was associated with a significant decrease in a urinary collagen degradation product (deoxypyridinoline). The degree of prevention of osteoporosis by cilnidipine was similar to that of carvedilol (a β-blocker) because β-blockers reduce fracture risks though the inhibition of osteoclast activation. Interestingly, these effects cannot be attributed to the reduction of blood pressure because all three drugs significantly decreased blood pressure. In contrast, both cilnidipine and carvedilol, but not amlodipine, significantly decreased heart rate, indicating that both cilnidipine and carvedilol suppressed sympathetic nervous activity. Overall, our present data showed that cilnidipine (L-/N-type CCB) ameliorated osteoporosis in ovariectomized hypertensive rats. These pleiotropic effects of antihypertensive drugs such as cilnidipine and carvedilol might provide additional benefits in the treatment of hypertensive postmenopausal women.     

Weekly variation of home and ambulatory blood pressure and relation between arterial stiffness and blood pressure measurements in community-dwelling hypertensives

Although blood pressure (BP) is a major determinant of pulse wave velocity (PWV), some treatments have independent effects on BP and arterial stiffness. Although both ambulatory BP (ABP) and self-measured BP at home (HBP) have become important measures for the diagnosis and management of hypertension, single day recordings may be insufficient for a proper diagnosis of hypertension or the evaluation of treatment efficacy. To evaluate weekly variations in BP using 7-day HBP and 7-day ABP monitoring and to determine the relation between arterial stiffness and BP measurements in community-dwelling patients with hypertension. We enrolled 68 community-dwelling hypertensive subjects in this study. Significant weekly variations in systolic blood pressure (SBP) and diastolic blood pressure (DBP) were found in the awake ABP data (p < .01, respectively), while no significant weekly variations in the asleep ABP or the morning and evening HBP data were observed. In untreated subjects, significant correlations were obtained between the brachial-ankle PWV and the average awake SBP, the average asleep SBP and the average SBP measured by HBP in the evening. In treated subjects, only the average SBP measured by HBP in the morning was significantly correlated with the baPWV. Differences in the weekly variations in BP were observed between HBP and ABP monitoring. In addition, the morning systolic HBP was not correlated with arterial stiffness in untreated subjects with hypertension but was correlated in treated subjects. Relations between the morning HBP and arterial stiffness might be attributed to morning surges in BP and/or trough levels of antihypertensive drugs.     

Weekly Variation of Home and Ambulatory Blood Pressure and Relation Between Arterial Stiffness and Blood Pressure Measurements in Community-Dwelling Hypertensives

Although blood pressure (BP) is a major determinant of pulse wave velocity (PWV), some treatments have independent effects on BP and arterial stiffness. Although both ambulatory BP (ABP) and self-measured BP at home (HBP) have become important measures for the diagnosis and management of hypertension, single day recordings may be insufficient for a proper diagnosis of hypertension or the evaluation of treatment efficacy. To evaluate weekly variations in BP using 7-day HBP and 7-day ABP monitoring and to determine the relation between arterial stiffness and BP measurements in community-dwelling patients with hypertension. We enrolled 68 community-dwelling hypertensive subjects in this study. Significant weekly variations in systolic blood pressure (SBP) and diastolic blood pressure (DBP) were found in the awake ABP data (p < .01, respectively), while no significant weekly variations in the asleep ABP or the morning and evening HBP data were observed. In untreated subjects, significant correlations were obtained between the brachial-ankle PWV and the average awake SBP, the average asleep SBP and the average SBP measured by HBP in the evening. In treated subjects, only the average SBP measured by HBP in the morning was significantly correlated with the baPWV. Differences in the weekly variations in BP were observed between HBP and ABP monitoring. In addition, the morning systolic HBP was not correlated with arterial stiffness in untreated subjectswith hypertension but was correlated in treated subjects. Relations between the morning HBP and arterial stiffness might be attributed to morning surges in BP and/or trough levels of antihypertensive drugs.