Salt-induced exacerbation of morning surge in blood pressure in patients with essential hypertension

The morning surge in blood pressure (BP) is related to the morning occurrence of lethal cardiovascular events. We tested the hypothesis that salt intake may be associated with the morning surge in BP in essential hypertension. Seventy-six patients were admitted and placed on a low salt diet (2 g/day) for 7 days followed by a high salt diet (20-23 g/day) for another 7 days. At the end of each salt diet, 24-h ambulatory BP and heart rate monitorings and head-up tilt (HUT) test were performed. Patients whose average mean BP (MBP) was increased by more than 10% by salt loading were assigned to the salt-sensitive (SS) group (n = 37); the remaining patients, whose MBP was increased by less than 10%, were assigned to the non-salt-sensitive (NSS) group (n = 39). The increase in ambulatory MBP during 6.30-8.00 am above the baseline (2.00-4.00 am) was significantly enhanced by salt loading in the NSS group (P < 0.05), but not in the SS group. The coefficient of variation of 24-h MBP and heart rate was increased by salt loading only in the NSS group. The significant elevation of plasma noradrenaline concentration after awakening, which was noted during the low salt diet period, was unchanged during the high salt diet period in the NSS group, but abolished in the SS group. Salt loading enhanced HUT-induced decrease in systolic BP without affecting the heart rate response only in the NSS group. We conclude that the morning surge in BP is enhanced by salt loading in the NSS type of essential hyper- tension, presumably by the excessive activation of the sympathetic nervous system. Journal of Human Hypertension (2000) 14, 57-64.     

Role of ambulatory blood pressure monitoring for the management of hypertension in Asian populations

Out‐of‐clinic blood pressure (BP) measurement, eg, ambulatory BP monitoring, has a strong association with target organ damage and is a powerful predictor of cardiovascular events compared with clinic BP measurement. Ambulatory BP monitoring can detect masked hypertension or various BP parameters in addition to average 24‐hour BP level. Short‐term BP variability assessed by standard deviation or average real variability, diminished nocturnal BP fall, nocturnal hypertension, and morning BP surge assessed by ambulatory BP monitoring have all been associated with target organ damage and cardiovascular prognosis. Recently, the authors compared the degree of sleep‐trough morning BP surge between a group of Japanese and a group of Western European untreated patients with hypertension and found that sleep‐trough morning BP surge in Japanese persons was significantly higher than that in Europeans. Although Asian persons have been known to have a higher incidence of stroke than heart disease, the difference in characteristics of BP indices assessed by ambulatory BP monitoring might be the cause of racial differences in stroke incidence between Asian and Western populations. This review focuses on Asian characteristics for the management of hypertension using ambulatory BP monitoring.     

奥美沙坦与坎地沙坦治疗轻、中度原发性高血压的疗效及安全性比较

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

Comparison of the efficacy and safety of azilsartan with that of candesartan cilexetil in Japanese patients with grade I-II essential hypertension: a randomized, double-blind clinical study

Azilsartan is a novel angiotensin receptor blocker being developed for hypertension treatment. This 16-week, multicenter, randomized, double-blind study compared the efficacy and safety of azilsartan (20-40 mg once daily by forced titration) and its ability to provide 24-h blood pressure (BP) control, with that of candesartan cilexetil (candesartan; 8-12 mg once daily by forced titration) in 622 Japanese patients with grade I-II essential hypertension. Efficacy was evaluated by clinic-measured sitting BP, and by ambulatory BP monitoring (ABPM) at week 14. Participants (mean age: 57 years, 61% males) had a mean baseline sitting BP of 159.8/100.4 mm Hg. The mean change from baseline in sitting diastolic BP at week 16 (primary endpoint) was -12.4 mm Hg in the azilsartan group and -9.8 mm Hg in the candesartan group, demonstrating a statistically significant greater reduction with azilsartan vs. candesartan (difference: -2.6 mm Hg, 95% confidence interval (CI): -4.08 to -1.22 mm Hg, P=0.0003). The week 16 (secondary endpoint) mean change from baseline in sitting systolic BP was -21.8 mm Hg and -17.5 mm Hg, respectively, a significant decrease with azilsartan vs. candesartan (difference: -4.4 mm Hg, 95% CI: -6.53 to -2.20 mm Hg, P<0.0001). On ABPM, the week 14 mean changes from baseline in diastolic and systolic BP were also significantly greater with azilsartan over a 24-h period, and during the daytime, night-time and early morning. Safety and tolerability were similar among the two groups. These data demonstrate that once-daily azilsartan provides a more potent 24-h sustained antihypertensive effect than that of candesartan but with equivalent safety.     

Exaggerated morning blood pressure surge and cardiovascular events. A 5-year longitudinal study in normotensive and well-controlled hypertensive elderly

Cardiovascular events (CE) occur most frequently in the morning hours in hypertensive subjects. We studied the association between the morning blood pressure (BP) surge and CE in prognosis of 10 normotensive and 32 well-controlled hypertensive elderly, in whom ambulatory BP monitoring was performed and who were followed prospectively for 5 years. The morning surge (MS) of BP was calculated as mean systolic BP during 2 h after awakening − mean systolic BP during 1 h that included the lowest sleep BP. During an average of 60 months, five CE occurred. When the patients were divided into two groups according to MS, those in the top terzile (MS group; MS ≥ 34 mmHg, n = 14) had a higher prevalence of CE (5 versus 0, p = 0.001) during the follow-up period, than the others (non-MS group; MS < 34 mmHg, n = 28). The logistic regression analysis showed the MS sleep-trough surge as predictive variable of CE (odds ratio, OR = 0.794, p = 0.022). In conclusion, in older normotensives and well-controlled hypertensives, a higher BP MS is associated with vascular risk independently of clinical and ambulatory BP. Reduction of the MS could thus be a therapeutic target for preventing vascular events also in non-hypertensive patients.     

Comparison of valsartan and amlodipine on ambulatory and morning blood pressure in hypertensive patients

BACKGROUND: Cardiovascular events occur most frequently in the morning. We aimed to study the effects of monotherapy with the long-acting angiotensin II receptor blocker valsartan compared with the long-acting calcium antagonist amlodipine on ambulatory and morning blood pressure (BP). METHODS: We performed ambulatory BP monitoring before and after once-daily dose of valsartan (valsartan group, n = 38) and amlodipine (amlodipine group, n = 38) therapy in 76 hypertensive patients. To achieve the target BP of < or =140/90 mm Hg, valsartan was titrated from 40 mg/day to 160 mg/day (mean dose 124 mg/day) and amlodipine was titrated from 2.5 mg/day to 10 mg/day (mean dose 6.4 mg/day). RESULTS: Both drugs significantly reduced clinic and 24-h systolic BP (SBP) and diastolic BP (DBP) (P <.002). However, the antihypertensive effect of amlodipine was superior to that of valsartan in clinical SBP (-26 mm Hg v -13 mm Hg, P =.001) and 24-h SBP (-14 mm Hg v -7 mm Hg, P =.008). In addition, morning SBP was significantly reduced by amlodipine from 156 to 142 mm Hg (P <.001) but not by valsartan. Both agents reduced lowest night SBP to a similar extent (amlodipine 121 to 112 mm Hg, P <.001; valsartan 123 to 114 mm Hg, P <.002). Reduction in morning SBP surge (morning SBP minus lowest night SBP) was significantly greater in patients treated with amlodipine compared with those treated with valsartan (-6.1 mm Hg v +4.5 mm Hg, P <.02). CONCLUSIONS: Amlodipine monotherapy was more effective than valsartan monotherapy in controlling 24-h ambulatory BP and morning BP in 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.     

Relationship of circadian blood pressure and morning blood pressure surge with the severity of metabolic syndrome in newly diagnosed hypertensives.

OBJECTIVES: Twenty-four-hour ambulatory blood pressure (BP) data and the presence of metabolic syndrome (MS) are both good discriminators of cardiovascular risk. We examined the relationship between metabolic syndrome scores as defined by the International Diabetes Federation 2005 report (IDF-2005) and 24h ambulatory BP data in newly diagnosed hypertensives. METHODS: We evaluated 352 non-diabetic subjects (male/female: 167/185, aged 49+/-13). Based on IDF-2005 criteria, 212 subjects fulfilled 0, 1 or 2 criteria (no metabolic syndrome) and 140 fulfilled 3, 4 or 5 criteria (metabolic syndrome). Patients were divided into two groups (MS and non-MS), matched for age and casual BP All underwent 24h ambulatory blood pressure monitoring. RESULTS: No significant differences were found between non-MS and MS for casual BP (153/92+/-17/8 vs. 154/92+/-16/8 mmHg), age (48+/-14 vs. 50+/-12 years), 24h ambulatory BP (131/82+/-14/10 vs. 133/82+/-14/9 mmHg), daytime BP (135/86+/-14/11 vs. 137/85+/-14/9 mmHg), nighttime BP (122/74+/-15/11 vs. 124/74+/-15/10 mmHg), nighttime fall (9+/-6 vs. 9+/-6 %), BP on arising (131/82+/-20/15 vs. 135/82+/-21/15 mmHg), evening surge (7+/-14 vs. 10+/-15 mmHg), percentage of dippers (42.5 vs. 37.1%) or percentage of non-dippers (50.9 vs. 50.7%). However, significant differences between non-MS and MS were found for morning BP surge (25+/-12 vs. 28+/-15 mmHg, p<0.03). Also, when patients were divided into four groups according to MS scores (0/1, 2, 3 or 4/5), significant differences between groups were observed only for BP on arising (group 2 vs. 4/5, 132/79+/-21/15 vs. 140/84+/-10/15 mmHg, p<0.05; group 3 vs. 4/5, 131/81+/-20/15 vs. 140/84+/-20/15, p<0.005) and for morning BP surge (group 0/1 vs. 4/5, 24+/-11 vs. 29+/-15 mmHg, p<0.003). CONCLUSIONS: We conclude that in newly diagnosed hypertensive subjects there is no significant relationship between the severity of metabolic syndrome and ambulatory blood pressure data or circadian variations. The only exception found was a greater morning BP surge in patients with MS, whose importance as a determinant of cardiovascular risk needs to be clarified by further studies.     

A comparison of morning blood pressure surge in African Americans and whites

African Americans have twice the risk of suffering a stroke compared to whites, but the reasons for this disparity have yet to be elucidated. Recent data suggest that the morning blood pressure (BP) surge is an independent predictor of strokes. Whether African Americans and whites differ with respect to morning BP surge is unknown. African-American (n=183) and white (n=139) participants, age 18-65, were studied with 24-hour ambulatory BP monitoring. Morning surge was defined as morning BP minus the trough BP during sleep. The morning surge was significantly lower in African Americans than in whites (23 mm Hg vs. 27 mm Hg; both SEM=1.0; p=0.009). This relationship was no longer evident after adjusting for gender, age, and body mass index (23 mm Hg vs. 26 mm Hg; SE=1.0 and 1.1; p=nonsignificant). Morning BP surge is unlikely to account for differences in stroke incidence between African Americans and whites.     

Ambulatory blood pressure, blood pressure variability and the prevalence of carotid artery alteration: the Ohasama study

OBJECTIVES: To investigate the association between ambulatory blood pressure (BP) variables (level, short-term variability, circadian variation and morning pressor surge) and carotid artery alteration in a general population. METHODS: We measured ambulatory BP every 30 min in 775 participants (mean age 66.2 +/- 6.2 years, 68.8% women) from the Japanese general population. Short-term BP variability during the daytime and night-time were estimated as within-subject standard deviation of daytime and night-time BP, respectively. Circadian BP variation was calculated as the percentage decline in nocturnal BP. Morning pressor surge was defined as morning BP minus pre-waking BP. The extent of carotid artery alteration was evaluated as the average of common carotid intima-media thickness (IMT) and the presence of focal carotid plaque. RESULTS: Daytime and night-time BP values were more closely associated with carotid artery alteration than casual BP. With mutual adjustment for daytime and night-time BP, the latter (P < 0.0001) was more closely associated with IMT, which represents diffuse arterial thickening and arteriosclerosis, than daytime BP (P = 0.2). Night-time systolic BP variability was positively associated with carotid plaque (focal atherosclerotic lesions) independently of possible confounding factors, including night-time systolic BP (P = 0.01). A diminished nocturnal decline in systolic BP was associated with a greater IMT after adjustment for confounding factors (P = 0.03). A morning pressor surge was not associated with carotid artery alteration. CONCLUSION: Ambulatory BP levels and BP variability were closely associated with carotid artery alteration, suggesting that these parameters are independent risk factors or predictors of carotid artery alteration.     

Effectiveness of using long-acting angiotensin II type 1 receptor blocker in Japanese obese patients with metabolic syndrome on morning hypertension monitoring by using telemedicine system (FUJIYAMA Study)

Aim: Recently, obesity patients have been diagnosed as metabolic syndrome. The aim of this study was to evaluate which angiotensin type 1 receptor blockers (ARBs), telmisartan or candesartan, is superior for the control of home blood pressure (BP) in the morning when the outpatient clinic BP was well controlled in the patients with metabolic syndrome.

Methods: The patients with metabolic syndrome were enrolled. Home BP was monitored by using a telemedicine system. After a 2- to 4-week control period to establish baseline home BP values, these patients were randomly divided into telmisartan (20–80?mg) and candesartan (4–12?mg) groups. These end points were evaluated by using the telemedicine system during steady-state active therapy. A total of 356 patients attending 60 outpatient Japanese centers were recruited.

Results: On a day of active therapy, telmisartan significantly lowered both systolic and diastolic home BP in the morning to a greater extent compared to candesartan. At the end of the study, reductions in systolic and diastolic home BP in the morning, in telmisartan group were significantly larger compared to the changes in the candesartan group (systolic; Tel: 12.0?±?8.9 versus Can: 8.1?±?17.1?mmHg, p?=?0.0292, diastolic; Tel: 7.4?±?6.1 versus Can: 3.7?±?6.8?mmHg, p?=?0.0053). Additionally in the telmisartan treated group, LDL-cholesterol showed significant reduction (p?=?0.037), but candesartan did not.

Conclusion: The present study by using the telemedicine system clearly demonstrated that telmisartan has a strong effect on reducing morning home BP, and a good effect on lipid metabolism in patients with metabolic syndrome.     

A comparison of the efficacy and duration of action of candesartan cilexetil and losartan as assessed by clinic and ambulatory blood pressure after a missed dose, in truly hypertensive patients: a placebo-controlled, forced titration study. Candesartan/Losartan study investigators

The purpose of this double-blind, forced titration study was to compare the antihypertensive effect duration of candesartan cilexetil, which has a longlasting binding to the human AT1-receptor, to that of losartan on ambulatory BP (ABP) not only during the 24-h dosing interval but also during the day of a missed dose intake. After a 4-week placebo lead-in period, 268 patients with sitting diastolic BP 95 to 110 mm Hg and mean awake ambulatory DBP > or =85 mm Hg were randomized to receive either 8 mg of candesartan, 50 mg of losartan, or placebo for a 4-week period. Thereafter, the doses were doubled in all patients for an additional 4-week period. Ambulatory BP monitoring was performed for 36 h after dosing and clinic BP measured 48 h after dosing. Candesartan cilexetil (16 mg) reduced ABP to a significantly greater extent than 100 mg of losartan, particularly for systolic ABP during daytime (P<.05), nighttime (P<.05), and 24-h (P<.01) periods, systolic (P<.01) and diastolic (P<.05) ABP between 0 and 36 h, and both systolic (P<.001) and diastolic (P<0.001) ABP during the day of a missed dose. Clinic BP at 48 h after dosing was significantly reduced exclusively with 16 mg of candesartan. The differences in BP reduction between 8 mg of candesartan and 50 mg of losartan were statistically significant for systolic ABP during daytime (P<.01), nighttime (P<.05), 24-h (P<.01), 0 to 36 h (P<.05) and during the day of missed dose (P<.05). Moreover, although losartan did not significantly reduce ambulatory BP in a dose-related manner, ambulatory systolic and diastolic BP reductions with 16 mg of candesartan were significantly greater (P<.01 and <.001) than those seen with 8 mg of candesartan during every period at the ABP supporting a dose-response relationship. In conclusion, this forced titration study in ambulatory hypertensive patients demonstrates that candesartan cilexetil provides significant dose-dependent reduction in both clinic and ambulatory BP in doses ranging from 8 to 16 mg once daily. Furthermore, candesartan cilexetil is superior to losartan in reducing systolic ABP and in controlling both systolic and diastolic ABP on the day of a missed dose. The differences observed between both agents are most likely attributable to a tighter binding to, and a slower dissociation from, the receptor binding site with candesartan cilexetil.     

苯那普利和硝苯地平缓释片对高血压病清晨疗效的比较

目的 :为了探讨苯那普利和硝苯地平缓释片对于清晨血压 ,心率及心率收缩压乘积的效果。方法 :选取 6 0例轻、中度高血压患者 ,分别给予苯那普利或硝苯地平缓释片治疗。利用动态血压监测观察治疗前和 2 0d后清晨血压 ,心率及心率收缩压乘积的变化。结果 :两种药物对清晨血压下降无统计学差异 ,而在清晨心率和心率收缩压乘积有统计学差异。结论 :苯那普利组清晨心率轻微下降 ,硝苯地平缓释片组则稍上升 ,苯那普利组清晨心率收缩压乘积下降更明显。     

Prognostic significance of morning surge in blood pressure: which definition, which outcome?

The prognostic significance of morning surge in blood pressure (BP) remains obscure because the findings of the four prospective studies available [ambulatory BP monitoring (ABPM) substudy of the Syst-Eur trial, the Jichii Medical School ABPM-wave1 study, the Bordeaux hypertensive cohort study, and the Ohasama study] have generated conflicting results partly because of small number of events and differences in definitions, measurement conditions, target outcomes, and study populations. A large morning surge was associated with a significantly lower risk of total cardiovascular events in the Syst-Eur study. On the contrary, a large morning surge was associated with a significantly higher risk of total stroke events in the Jichii Medical School ABPM-wave1 study, and of total cardiovascular events in the Bordeaux hypertensive cohort study. The Ohasama study found that a large morning surge was not associated with the risk of total stroke events, but rather with a significantly higher risk of cerebral hemorrhage. More prospective studies or meta-analyses are required to better elucidate the prognostic significance of the morning surge in BP.     

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。     

Association between sleep disorders and morning blood pressure in hypertensive patients

Sleep disorders are known to increase the risk of hypertension, yet few studies have investigated the relation between sleep disorders and morning blood pressure (BP). This study aimed to determine, whether the morning BP is associated with sleep quality and sleep-disordered breathing. A total of 144 hypertensive patients were included in this cross-sectional study. Each subject underwent anthropometric measurements, biochemical testing, 24-h ambulatory BP monitoring, and polysomnography (PSG). Sleep quality and sleep-disordered breathing were determined by PSG parameters of sleep architecture and sleep respiratory. There were no significant differences between subjects with and without morning hypertension in the parameters of sleep architecture and sleep respiratory. In multiple regression analysis, morning BP was independently associated with night-time BP and morning BP surge, but not with the parameters of sleep architecture and sleep respiratory. Further analysis showed that both night-time BP and morning BP surge were independently associated with the sleep respiratory parameters. In conclusion, sleep-disordered breathing might indirectly affect the morning BP by elevated night-time BP, yet neither poor sleep quality nor sleep-disordered breathing was major determinants of elevated morning BP in hypertensive patients.     

Efficacy and Duration of Action of the Four Selective Angiotensin II Subtype 1 Receptor Blockers,Losartan, Candesartan,Valsartan and Telmisartan,in Patients with Essential Hypertension Determined by Home Blood Pressure Measurements

Our objective was to compare the efficacy and duration of action of 4 angiotensin II receptor blockers (ARBs)—losartan (25–100 mg), candesartan (2–12 mg), valsartan (40–80 mg), and telmisartan (10–40 mg)—in patients with essential hypertension using self-measurement of blood pressure at home (home BP) and to examine the differential effect of the four ARBs on home pulse pressure (home PP). After a 2-week run-in period, each of the 4 ARBs was assigned to subjects who were diagnosed as having hypertension on the basis of home BP and who were over 30 years old. The subjects were asked to take the ARB once daily in the morning and to measure home BP once in the evening and in the morning. We compared the efficacy of each ARB on home BP and home PP and assessed the duration of the BP-lowering effect using the morning effect versus evening effect ratio (M/E ratio). The antihypertensive effects of telmisartan on home systolic BP (SBP) both in the evening and in the morning and on home diastolic BP (DBP) in the morning were significantly greater than those of losartan. The effect of each ARB on home BP in the morning and in the evening was expressed as a ratio (M/E ratio). The M/E ratios of SBP/DBP in patients treated with losartan, candesartan, valsartan, and telmisartan were 0.49/0.16, 0.69/1.01, 0.82/0.88, and 0.88/0.88, respectively. The home PP-lowering effect was greater for valsartan and telmisartan than for losartan and candesartan in the morning. Among the 4 ARBs, the duration of the BP-lowering effect of losartan did not persist throughout 24 hr. The effects of the other 3 ARBs, in particular telmisartan, persisted over 24 hr when they were administered once daily in the morning. In addition, the duration of the PP-lowering effect was similar to that of the BP-lowering effect. Such long-acting property of several ARBs is essential for the modern antihypertensive treatment, and home BP measurements are useful for determining the duration of action of antihypertensive drugs. Losartan, 25 mg a day, which is usually used as an initial dose in Japan, is apparently insufficient to obtain adequate antihypertensive effect and sufficient duration of action.     

Efficacy and duration of action of the four selective angiotensin II subtype 1 receptor blockers, losartan, candesartan, valsartan and telmisartan, in patients with essential hypertension determined by home blood pressure measurements

Our objective was to compare the efficacy and duration of action of 4 angiotensin II receptor blockers (ARBs)--losartan (25-100 mg), candesartan (2-12 mg), valsartan (40-80 mg), and telmisartan (10-40 mg)-in patients with essential hypertension using self-measurement of blood pressure at home (home BP) and to examine the differential effect of the four ARBs on home pulse pressure (home PP). After a 2-week run-in period, each of the 4 ARBs was assigned to subjects who were diagnosed as having hypertension on the basis of home BP and who were over 30 years old. The subjects were asked to take the ARB once daily in the morning and to measure home BP once in the evening and in the morning. We compared the efficacy of each ARB on home BP and home PP and assessed the duration of the BP-lowering effect using the morning effect versus evening effect ratio (M/E ratio). The antihypertensive effects of telmisartan on home systolic BP (SBP) both in the evening and in the morning and on home diastolic BP (DBP) in the morning were significantly greater than those of losartan. The effect of each ARB on home BP in the morning and in the evening was expressed as a ratio (M/E ratio). The M/E ratios of SBP/DBP in patients treated with losartan, candesartan, valsartan, and telmisartan were 0.49/0.16, 0.69/1.01, 0.82/0.88, and 0.88/0.88, respectively. The home PP-lowering effect was greater for valsartan and telmisartan than for losartan and candesartan in the morning. Among the 4 ARBs, the duration of the BP-lowering effect of losartan did not persist throughout 24 hr. The effects of the other 3 ARBs, in particular telmisartan, persisted over 24 hr when they were administered once daily in the morning. In addition, the duration of the PP-lowering effect was similar to that of the BP-lowering effect. Such long-acting property of several ARBs is essential for the modern antihypertensive treatment, and home BP measurements are useful for determining the duration of action of antihypertensive drugs. Losartan, 25 mg a day, which is usually used as an initial dose in Japan, is apparently insufficient to obtain adequate antihypertensive effect and sufficient duration of action.     

Effects of Spironolactone on Dialysis Patients With Refractory Hypertension: A Randomized Controlled Study

The purpose of this study was to evaluate the effects of spironolactone on dialysis patients with refractory hypertension and possible adverse effects. This was a 12‐week prospective, randomized, double‐blind trial of 82 patients randomly assigned to 12‐week treatment with 25 mg/d spironolactone or placebo as add‐on therapy. Visits were scheduled at the start of treatment and after 12 weeks. Measurements of 24‐hour ambulatory blood pressure (BP) monitoring and morning BP were performed. After 12 weeks, spironolactone significantly improved refractory hypertension. Average placebo‐corrected morning BP was reduced by 16.7/7.6 mm Hg. Mean 24‐hour ambulatory BP was reduced by 10.9/5.8 mm Hg. In contrast, serum aldosterone levels in the spironolactone group slightly increased and serum potassium levels insignificantly increased. This study has demonstrated that spironolactone (50 mg) safely and effectively reduces BP in patients with refractory hypertension undergoing dialysis.     

A comparison of the efficacy and duration of action of candesartan cilexetil and losartan as assessed by clinic and ambulatory blood pressure after a missed dose, in truly hypertensive patients : A placebo-controlled, forced titration study

The purpose of this double-blind, forced titration study was to compare the antihypertensive effect duration of candesartan cilexetil, which has a long-lasting binding to the human AT₁-receptor, to that of losartan on ambulatory BP (ABP) not only during the 24-h dosing interval but also during the day of a missed dose intake. After a 4-week placebo lead-in period, 268 patients with sitting diastolic BP 95 to 110 mm Hg and mean awake ambulatory DBP ≥85 mm Hg were randomized to receive either 8 mg of candesartan, 50 mg of losartan, or placebo for a 4-week period. Thereafter, the doses were doubled in all patients for an additional 4-week period. Ambulatory BP monitoring was performed for 36 h after dosing and clinic BP measured 48 h after dosing.

Candesartan cilexetil (16 mg) reduced ABP to a significantly greater extent than 100 mg of losartan, particularly for systolic ABP during daytime (P < .05), nighttime (P < .05), and 24-h (P < .01) periods, systolic (P < .01) and diastolic (P < .05) ABP between 0 and 36 h, and both systolic (P < .001) and diastolic (P < 0.001) ABP during the day of a missed dose. Clinic BP at 48 h after dosing was significantly reduced exclusively with 16 mg of candesartan. The differences in BP reduction between 8 mg of candesartan and 50 mg of losartan were statistically significant for systolic ABP during daytime (P < .01), nighttime (P < .05), 24-h (P < .01), 0 to 36 h (P < .05) and during the day of missed dose (P < .05). Moreover, although losartan did not significantly reduce ambulatory BP in a dose-related manner, ambulatory systolic and diastolic BP reductions with 16 mg of candesartan were significantly greater (P < .01 and < .001) than those seen with 8 mg of candesartan during every period at the ABP supporting a dose–response relationship.

In conclusion, this forced titration study in ambulatory hypertensive patients demonstrates that candesartan cilexetil provides significant dose-dependent reduction in both clinic and ambulatory BP in doses ranging from 8 to 16 mg once daily. Furthermore, candesartan cilexetil is superior to losartan in reducing systolic ABP and in controlling both systolic and diastolic ABP on the day of a missed dose. The differences observed between both agents are most likely attributable to a tighter binding to, and a slower dissociation from, the receptor binding site with candesartan cilexetil.