Effects of graded-release diltiazem versus ramipril, dosed at bedtime, on early morning blood pressure, heart rate, and the rate-pressure product

Background

Therapeutic agents for the treatment of hypertension may differ in their efficacy during the early morning period, a time when both morbid and mortal cardiovascular events are increased compared to other times of the day.

Methods

We studied the effects of a graded-release delivery system of diltiazem (diltiazem HCL extended release tablets) versus ramipril, both dosed at bedtime, on blood pressure (BP), heart rate, and the heart rate-systolic BP product during the first 4 hours after awakening in a double-blind, titration-to-effect trial. There were 261 men and women enrolled in the trial with an untreated sitting diastolic BP of 90 to 109 mm Hg and ambulatory daytime diastolic BP of 85 to 109 mm Hg. Patients were randomized to either diltiazem extended release (ER) tablets each evening (240 mg titrated to 360 mg and to 540 mg) or ramipril each evening (5 mg titrated to 10 mg and to 20 mg). Early morning assessments of BP, heart rate, and the heart rate-systolic BP product were performed using 24-hour ambulatory recordings after 10 weeks of therapy.

Results

In each therapeutic group, 76% of patients were titrated to the highest possible dose. After 10 weeks of treatment, reductions in early morning BP by diltiazem ER tablets were significantly greater (−18/−15 mm Hg) than reductions by ramipril (−13/−8 mmHg , P < .005 for systolic BP and P < .001 for diastolic BP). Diltiazem ER tablets also led to greater reductions in morning heart rate and the heart rate-pressure product compared to ramipril. Reductions in mean 24-hour diastolic BP, heart rate, and the rate-pressure product were greater in patients treated with diltiazem ER tablets compared to ramipril, while reductions in 24-hour systolic BP were similar in each group. The observed adverse effects were not serious and incidences were similar for the 2 treatment groups.

Conclusions

These data demonstrate that bedtime administration of diltiazem ER, an agent designed to parallel the circadian rhythm of BP and heart rate, led to significantly greater early morning hemodynamic effects compared to the angiotensin-converting enzyme inhibitor ramipril, also dosed in the evening.     

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

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

24-Hour and Nighttime Blood Pressures in Type 2 Diabetic Hypertensive Patients Following Morning or Evening Administration of Olmesartan

Ambulatory blood pressure monitoring (ABPM) allows determining of the nocturnal blood pressure fall (NBPF). An NBPF below 10% (nondipper pattern) has been related to increased cardiovascular risk, and it is a common finding in type 2 diabetic hypertensive patients. The authors evaluated the impact on 24-hour blood pressure, NBPF, and albuminuria of olmesartan 40 mg, administered in a morning- vs a nocturnal-based dosing scheme, in type 2 diabetic patients with newly diagnosed hypertension. Using a crossover design, 40 patients (42.1% men) received olmesartan 40 mg once daily at wake up or bedtime for 8 weeks. Patients underwent 24-hour ABPM at baseline and at weeks 8 and 16, and albumin to creatinine ratio was measured at baseline and 8 weeks. Night systolic blood pressure (BP) ( P =.007) and mean BP ( P =.012) were significantly reduced following the bedtime dose, compared with morning dosing. Night BP fall (%) was significantly reduced by bedtime dosing, compared with morning dosing ( P =.0001). No differences were seen for urinary albumin excretion between both arms at week 8. Without affecting 24-hour BP control, night dosing of olmesartan increases nocturnal BP fall significantly more than conventional morning dosing, increasing the number of dipper diabetic hypertensive patients.     

Preventing increases in early-morning blood pressure,heart rate,and the rate-pressure product with controlled onset extended release verapamil at bedtime versus enalapril,losartan, and placebo on arising

Background Therapeutic agents for the treatment of hypertension may differ in their efficacy during the early-morning period, a time when both morbid and mortal cardiovascular events are increased compared with other times of the day. Methods We studied the effects of a chronotherapeutic delivery system of verapamil (controlled-onset extended release [COER]-24 system) dosed at bedtime versus conventional morning administration of both enalapril and losartan on the blood pressure (BP), heart rate, and the heart rate systolic BP product during the first 4 hours after awakening in a placebo-controlled, forced-titration trial. There were 357 men and women enrolled in the trial with an untreated sitting diastolic BP of 95 to 114 mm Hg and ambulatory daytime diastolic BP ≥85 mm Hg. Patients were randomized to either COER-verapamil hydrochloride each evening (240 mg titrated to 360 mg), enalapril each morning (10 mg titrated to 20 mg), losartan each morning (50 mg titrated to 100 mg), or placebo. Early morning assessments of BP, heart rate, and the heart rate systolic BP product were performed by use of 24-hour ambulatory recordings after 4 weeks (low dose) and 8 weeks (high dose) of therapy. Results Results were similar at weeks 4 and 8 for all treatment groups except that the magnitude of change was greater at week 8. After 8 weeks of treatment, reductions in early morning BP by COER-verapamil were significantly greater (−15/−10 mm Hg) than enalapril (−9/−7 mm Hg, P < .01) and losartan (−8/−5 mm Hg, P < .001). COER-verapamil also led to greater reductions in morning heart rate, the rate-pressure product, and the rate-of-rise of BP compared with the other 2 active treatment groups. Reductions in mean 24-hour BP were greater in patients treated with COER-verapamil compared with placebo and losartan, and similar to reductions in patients treated with enalapril. Conclusions Bedtime administration of an agent designed to parallel the circadian rhythm of BP and heart rate led to significantly greater early morning hemodynamic effects compared with other conventional once-daily antihypertensive agents dosed in the morning. (Am Heart J 2002;144:657-65.)     

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

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

Therapeutic effects of evening administration of guanabenz and clonidine on morning hypertension: evaluation using home-based blood pressure measurements

OBJECTIVE: To clarify the effects of bedtime administration of the centrally acting alpha(2)-agonists, guanabenz and clonidine, on morning hypertension. METHODS: Patients with morning hypertension were assigned to receive once-daily evening administration of guanabenz (2 mg/day, n = 81; 4 mg/day, n = 2) or clonidine (75 microg/day, n = 40; 150 microg/day, n = 10) for 4 weeks, and the blood pressure (BP)-lowering effects of these drugs in the morning and evening were evaluated by assessing self-monitored BP in the home environment. The subjects were then subdivided into different groups according to their evening BP, and the effects of guanabenz and clonidine on evening BP were evaluated further for each group. In addition, as a substitute for the trough/peak ratio, the evening/morning (E/M) ratio was calculated to assess the duration of action of the two alpha(2)-agonists. RESULTS: Evening dosing with guanabenz or clonidine lowered morning BP significantly. Both drugs decreased evening BP in the subgroup of subjects with a high evening BP, but not in those with a normal evening BP. The individual E/M ratios for guanabenz, but not for clonidine, were significantly greater in those with a high evening BP than in those with a normal evening BP. In the early treatment period, treatment with guanabenz resulted in a higher diastolic E/M ratio in those subjects with a high evening diastolic BP than did treatment with clonidine. CONCLUSION: The results suggest that evening administration of the central alpha(2)-agonists guanabenz and clonidine effectively suppresses the morning BP elevation in treated hypertensive patients.     

Morning blood pressure surge and hypertensive cerebrovascular disease: role of the alpha adrenergic sympathetic nervous system

BACKGROUND: The morning surge of blood pressure (BP) is associated with alpha-adrenergic activity. We studied the association between the alpha-adrenergic morning surge in BP and silent cerebrovascular disease in elderly patients with hypertension. METHODS: We conducted ambulatory BP monitoring three times (twice at baseline and after nighttime dosing of the alpha1-blocker doxazosin) in 98 elderly hypertensive patients in whom the presence of silent cerebral infarcts (SCI) was assessed by brain magnetic resonance imaging. The morning BP surge (MBPS) was calculated as the mean systolic BP during the 2 h after waking minus the mean systolic BP during 1 h that included the lowest sleep BP. The alpha-adrenergic MBPS was calculated as the reduction of MBPS by doxazosin. RESULTS: The prevalence of multiple SCI was higher in the Surge group (top quartile: MBPS > or = 45 mm Hg, n = 24) than in the Nonsurge group (MBPS < 45 mm Hg, n = 74) (54% v 31%, P = .04), and in the higher alpha-adrenergic surge group (top quartile: alpha-adrenergic MBPS > or = 28 mm Hg, n = 25) than in the lower alpha-adrenergic surge group (< 28 mm Hg, n = 73) (68% v 26%, P < .0001). In the Surge group, subjects with higher alpha-adrenergic surge (n = 17) had a markedly higher frequency of multiple SCI, whereas none in the lower alpha-adrenergic surge group had multiple SCI (n = 7) (77% v 0%, P = .001). The alpha-adrenergic MBPS was closely associated with multiple SCI (10 mm Hg increase: OR = 1.96, P = .006), independently of age, MBPS, 24-h systolic BP, and other confounding factors. CONCLUSION: The morning BP surge, particularly that dependent on alpha-adrenergic activity, is closely associated with advanced silent hypertensive cerebrovascular disease in elderly individuals.     

Differential effects of morning and evening dosing of nisoldipine ER on circadian blood pressure and heart rate

The time of administration of once-daily antihypertensive agents may have a significant impact on blood pressure control during awake and sleep periods. Using 24-h ambulatory monitoring, we compared the effects of morning and evening dosing of the long-acting dihydropyridine calcium channel blocker, nisoldipine extended-release (ER), on circadian blood pressure (BP) and heart rate in patients with mild-to-moderate hypertension. After completing a 3-week placebo run-in period, 85 patients were randomized to morning versus evening nisoldipine ER treatment at a fixed 20-mg dose. Patients were treated for 4 weeks, followed by crossover to the alternate dosing regimen for 4 additional weeks. Twenty-four–hour ambulatory monitoring was performed at baseline and at 4 and 8 weeks after randomization. Awake and sleep times were determined by electronic activity recorders (Actigraphy). Similar least-squares (±SE) mean changes from baseline in 24-h BP (systolic BP/diastolic BP: −11.9/−7.4 ± 0.6/0.5 v −11.6/−6.5 ± 0.6/0.5 mm Hg) and heart rate (1.0/1.7 ± 0.4/0.4 beats/min) occurred with morning and evening administration, respectively. A significantly greater effect on awake diastolic BP (systolic BP/diastolic BP: −12.6/−8.1 ± 0.7/0.4 v −11.3/−6.4 ± 0.7/0.4 mm Hg; P = .16/.01) was observed with morning dosing compared with evening dosing. In addition, small increases in sleep and early morning heart rate were seen with evening compared with morning administration of nisoldipine (sleep, 3.1 ± 0.4 v 0.4 ± 0.4 beats/min; P < .001; early morning, 3.5 ± 0.7 v 0.5 ± 0.7 beats/min; P = .002). These differential effects on awake BP and sleep heart rate were also observed in patients who had normal (dippers) and elevated (nondippers) BP values during sleep. Appropriate evaluation of the efficacy and safety of long-acting antihypertensive agents is essential when evening administration is being considered. In the present study, the timing of nisoldipine ER administration had no effect on mean changes in BP and heart rate over a 24-h period. However, nisoldipine ER had some differential effects during sleep and awake periods with morning relative to evening dosing.     

Telemonitoring of blood pressure self measurement in the OLMETEL study

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

Differential Effects of Morning or Evening Dosing of Amlodipine on Circadian Blood Pressure and Heart Rate

Objectives: To compare the effects of morning and evening dosing of amlodipine on both circadian blood pressure (BP) and heart rate (HR) in mild-to-moderate essential hypertension. Design: A perspective, double-blind, randomized, crossover design with dose titration. Patients and methods: Sixty-two patients recruited in the study were aged 21–77 years and had mild-to-moderate essential hypertension. At the end of a 2-week single-blind, placebo run-in period, eligible patients were randomly assigned to morning (7 AM) and evening (9 PM) amlodipine treatment. The initial dose was 5 mg. After 2 weeks of double-blind therapy, patients with a seated diastolic blood pressure 90 mm Hg had their doses titrated upward to 10 mg, while the other patients remained on their original 5 mg doses for another 4 weeks period, than crossover to the alternate dosing regimen for 6 additional weeks. The 24-h ambulatory monitoring was performed at baseline and at 6 and 12 weeks after randomization. Results: 24-h diastolic BP load (11.0 ± 17.5% vs. 6.5 ± 9.1%, P < 0.05) and night-time BP load (28.5 ± 31.4%/17.7 ± 28.2% vs. 20.0 ± 27.9%/9.2 ± 17.8%, P < 0.05/0.05) were significantly greater with evening dosing compared with morning dosing. Nocturnal fall of BP was greater with morning dosing than with evening dosing (9.8 ± 6.7/7.4 ± 5.3 vs. 6.7 ± 6.6/5.4 ± 5.4 mm Hg, P < 0.01/0.05). Percentage of nocturnal BP fall was greater with morning dosing versus with evening dosing (7.9 ± 5.3%/9.6 ± 6.8% vs. 5.4 ± 7.0%/7.0 ± 6.9%, P < 0.01/0.05). Conclusions: Morning administered amlodipine had a better effect on the circadian BP compared with evening administrated amlodipine in mild-to-moderate essential hypertension.     

Blood pressure effects of naproxcinod in hypertensive patients

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

The relationship between a blunted morning surge and a reversed nocturnal blood pressure dipping or “riser” pattern

The authors sought to determine the association between the blunted morning blood pressure (BP) surge and nocturnal BP dipping of the “riser” pattern in 501 patients with hypertension enrolled in the ACHIEVE‐ONE (Ambulatory Blood Pressure Control and Home Blood Pressure [Morning and Evening] Lowering by the N‐Channel Blocker Cilnidipine) trial. The patients' sleep‐trough morning BP surge and prewaking surge were calculated and then classified according to their nocturnal systolic BP reduction pattern as extreme dippers, dippers, nondippers, and risers. The prevalence of the riser pattern was significantly higher in both the lowest sleep‐trough morning BP surge decile and the prewaking surge decile (blunted surge group) compared with the remaining deciles (56.0% vs 10.4% [P<.0001] and 59.2% vs 10.2% [P<.0001], respectively). The riser pattern was a significant determinant of both blunted sleep‐trough morning BP surge (odds ratio, 73.3; P<.0001) and blunted prewaking surge (odds ratio, 14.8; P<.0001). The high prevalence of the riser pattern in patients with blunted morning BP surges may account for the cardiovascular risk previously reported in such patients.     

Nebivolol: Comparison of the Effects of dl-Nebivolol, d-Nebivolol, l-Nebivolol, Atenolol, and Placebo on Exercise-Induced Increases in Heart Rate and Systolic Blood Pressure

The effects of racemic nebivolol, 2.5, 5.0, and 10.0 mg; d-nebivolol, 2.5 mg; l-nebivolol, 2.5 mg; atenolol, 50 mg; and placebo, each given once daily for 7 days, on exercise-induced increases in heart rate and systolic blood pressure were compared in a seven-way double-blind randomized crossover trial in 14 healthy male volunteers. Observations on these variables were made 3 and 24 hours after dosing on the first and last days of therapy. Similar effects on both exercise-induced tachycardia and increases in systolic blood pressure were seen with nebivolol 5.0 mg and with d-nebivolol 2.5 mg; l-nebivolol 2.5 mg was no different from placebo. These data show that the beta-blocking effects of nebivolol reside in the d-isomer. A dose-related response was evident with racemic nebivolol in inhibiting exercise-induced tachycardia over the range of doses studied. Whereas the effects of atenolol on both exercise-induced tachycardia and increases in systolic blood pressure were fully evident on the first day of treatment, those of nebivolol, especially with regard to heart rate, and, to a lesser degree, systolic pressure, were greater on the final than on the first day. Nebivolol had a clearly superior trough-to-peak efficacy ratio than atenolol.     

Effects of the angiotensin II receptor blockers telmisartan versus valsartan on the circadian variation of blood pressure: impact on the early morning period

BACKGROUND: Ambulatory blood pressure (BP) monitoring has shown that BP typically declines by 10% to 20% during sleep and increases fairly rapidly in the early morning period. Because the early morning period has been associated with both loss of hypertension control and increased rates of myocardial infarction and stroke, there has been interest in evaluating the effects of antihypertensive therapy at this particular time of the day. The purpose of this study was to assess the effects of a long half-life (telmisartan, 24 h) versus intermediate half-life (valsartan, 6 to 9 h) on early morning BP in two scenarios: after an active dose and after a missed dose of each agent. METHODS: The study was a double-blind, randomized trial that compared telmisartan (40 to 80 mg once daily) versus valsartan (80 to 160 mg once daily) on early morning BP in 490 patients with hypertension. Ambulatory BP recordings were performed at baseline after a placebo period and again after 6 and 8 weeks of double-blind therapy in a randomized cross-over design. The monitoring patients received either an active dose or a placebo dose (to mimic a "missed" dose). The primary study end point was reduction in the BP in the early morning period (last 6 h of the dosing period). RESULTS: After the active dose, telmisartan reduced the BP during the last 6 h of the dosing period by -11/-7.6 +/- 0.8/0.6 mm Hg compared to -8.7/-5.8 +/- 0.8/0.6 mm Hg on valsartan (P = .02 for systolic BP and.01 for diastolic BP). On the day of the missed dose, telmisartan reduced the early morning BP by -9.0/-6.3 +/- 0.7/0.6 mm Hg versus -7.4/-5.1 +/- 0.7/0.4 mm Hg on valsartan (P = .09 for systolic BP and.06 for diastolic BP). On the day of the missed dose, reductions in 24-h average BP for the two antihypertensive agents were -10.3/-6.9 mm Hg for telmisartan versus -8.7/-5.9 mm Hg for valsartan (P = .06 for systolic BP and.056 for diastolic BP). CONCLUSIONS: On a day of active therapy, telmisartan lowered both systolic and diastolic BP to a greater extent than valsartan for the last 6 h of the dosing interval. On a day in which a dose was missed, there was a notable trend for greater BP reduction during the latter part of the dosing interval on telmisartan versus valsartan. These results demonstrate that telmisartan achieved a greater effect than valsartan on BP during the early morning period in patients with hypertension.     

Morning versus evening amlodipine treatment: effect on circadian blood pressure profile in essential hypertensive patients

OBJECTIVE: To determine the antihypertensive efficacy and the potential impact on circadian blood pressure pattern of morning versus evening administration of amlodipine to essential hypertensive patients. METHODS: Twelve mild-to-moderate essential hypertensives were investigated in this open, randomized cross-over study. Blood pressure and heart rate were measured by use of ambulatory blood pressure monitoring after a wash-out period of 1 week and after treatment schedules with 5 mg amlodipine once a day either at 0800 h or at 2000 h for 3 weeks. Effects were evaluated by linear and rhythm analysis using the ABPM-FIT program. RESULTS: Both morning and evening administrations of amlodipine significantly (P < 0.01) reduced the elevated systolic and diastolic blood pressures during daytime. However, due to baseline values being lower during night-time, a significant (P < 0.05) reduction was observed only in systolic, not in diastolic, blood pressure. Maximal blood pressure values were significantly (P 相似文献   

Antihypertensive efficacy of night-time graded-release diltiazem versus morning amlodipine in African Americans

BACKGROUND: The effect of a once daily night-time (10 pm) graded-release diltiazem (GRD) on early morning blood pressure (BP), heart rate (HR), and rate-pressure product (RPP) were compared with the effect of morning (8 am) amlodipine in 262 African American individuals with hypertension. METHODS: The multicenter, randomized, double-blind, parallel-group, dose-to-effect trial evaluated changes from baseline in BP, HR, and RPP (HR x systolic BP) by ambulatory BP monitoring during the first 4 h after awakening (diastolic BP = primary), between 6 am and 12 noon, and over a 24-h period. Patients were randomized to night-time GRD 360 mg (n = 132) or morning amlodipine 5 mg (n = 130) for 6 weeks, and were titrated to GRD 540 mg or amlodipine 10 mg after 6 weeks if clinic systolic BP/diastolic BP (SBP/DBP) was > or = 130/85 mm Hg. RESULTS: Compared with amlodipine, GRD showed significantly greater DBP reductions of 3.5 mm Hg (P < .0049) and 3.2 mm Hg (P < .0019) during the first 4 h after awakening and between 6 am and 12 noon respectively, as well as comparable reduction for the 24-h mean DBP. The SBP reductions during the morning periods were comparable, but the reduction in the 24-h mean SBP was 3.4 mm Hg greater (P < .0022) for amlodipine. Mean reductions in HR and RPP were significantly greater (P < or = .0008) for GRD during all intervals; amlodipine increased whereas diltiazem reduced HR with mean differences of 6.7 to 9.3 beats/min. Both treatments were well tolerated. CONCLUSIONS: Night-time GRD was more effective than morning amlodipine in reducing early morning DBP, HR, and RPP, as well as 24-h HR and RPP in African American individuals with hypertension. Amlodipine was more effective in reducing SBP over the 24-h period.     

Can an angiotensin-converting enzyme inhibitor with a short half-life effectively lower blood pressure for 24 hours?

Twenty-four-hour noninvasive ambulatory blood pressure monitoring was used to study the antihypertensive effect of morning (8 AM) versus evening (10 PM) administration of the new angiotensin-converting enzyme inhibitor quinapril, 20 mg. Eighteen patients with mild to moderate hypertension were studied in a double-blind, crossover fashion after 2 weeks of placebo for 4 weeks of each of the two active treatments. The results show that 20 mg of quinapril given once daily is effective in lowering blood pressure levels throughout a 24-hour period. The 24-hour blood pressure profiles showed a more sustained antihypertensive effect with an evening dose of quinapril compared with a morning dose of quinapril; with the morning dose a smaller reduction in blood pressure was observed during nighttime hours. Evening administration seems preferable, because it produces a more sustained and stable 24-hour blood pressure control probably through a more favorable modulation of tissue angiotensin-converting enzyme inhibition or effect on the adrenergic-induced rise in blood pressure that occurs during early morning hours.     

老年原发性高血压患者晨峰现象对早期肾损害的影响

目的探讨老年原发性高血压患者晨峰现象（MBPS）对早期肾功能的影响。方法根据24h动态血压监测结果将134例老年原发性高血压患者,分为晨峰组和非晨峰组,常规检查血脂,空腹血糖,尿微量白蛋白（mAlb）、血β2微球蛋白（β2-microglobulin,β2-MG）、血清胱抑素C（CystainC）、血清肌酐（Scr）、动态血压监测（ambulatory bloodpressure monitoring,ABPM）,计算体重指数（BMI）并做对比分析。结果晨峰组的24h、白昼、夜间平均收缩压均显著高于非晨峰组（P〈0.05）,晨峰组血β2-MG、尿mAlb、血清胱抑素C明显高于非晨峰组,两组差异有统计学意义（P〈0.05）;而BMI、血脂谱、空腹血糖、血清肌酐差异无统计学意义。结论具有MBPS的高血压患者较无MBPS的患者更容易出现早期肾损害。     

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。     

Increased morning blood pressure surge and coronary microvascular dysfunction in patient with early stage hypertension

Morning blood pressure surge (MBPS) is defined as an excessive increase in blood pressure (BP) in the morning from the lowest systolic BP during sleep, and it has been reported as a risk factor for cardiovascular events in current clinical studies. In this study, we evaluated the association between the rate of BP variation derived from ambulatory BP monitoring data analysis and coronary microvascular function in patients with early stage hypertension. One hundred seventy patients with prehypertension and Stage 1 hypertension who fulfilled the inclusion and exclusion criteria were included in the study. We divided our study population into two subgroups according to the median value of coronary flow reserve (CFR). Patients with CFR values <2.5 were defined as the impaired CFR group, and patients with CFR values ≥2.5 were defined as the preserved CFR group, and we compared the MBPS measurements of these two subgroups. CFR was measured using transthoracic Doppler echocardiography (TTDE). Ambulatory 24-hour systolic and diastolic BP, uric acid, systolic MBPS amplitude, diastolic MBPS amplitude, high-sensitivity C-reactive protein, and mitral flow E/A ratio were statistically significant. These predictors were included in age- and gender-adjusted multivariate analysis; ambulatory 24-hour systolic BP (ß = 0.077, P < .001; odds ratio [OR] = 1.080; 95% confidence interval [CI] [1.037–1.124]) and systolic MBPS amplitude (ß = 0.043, P = .022; OR = 1.044; 95% CI [1.006–1.084]) were determined to be independent predictors of impaired CFR (Hosmer–Lemeshow test, P = .165, Nagelkerke’s R² = 0.320). We found that increased changes in MBPS values in patients with prehypertension and Stage 1 hypertension seemed to cause microvascular dysfunction in the absence of obstructive coronary artery disease.