Prognostic significance of blood pressure measured on rising.

Previous works using ambulatory blood pressure (BP) monitoring demonstrated that independently of the mean level of BP, the variability in BP, or the day-night range, could have prognostic significance. We have also found that the value of BP on rising in the morning is strongly correlated with left ventricular mass of hypertensive individuals independently of the 24-h value. In the present study, we sought its predictive value for cardiovascular complications in a cohort of hypertensive patients. The population studied belongs to a cohort of initially untreated hypertensive patients recruited since 1983 and followed for more than 5 years. Patients were then treated and followed by their family doctor. At entry, all patients were equipped with a device to measure ambulatory BP. They were requested to trigger a measurement manually on rising in the morning (arising BP). The data on their outcome were collected by a physician unaware of the initial state of the patients. A total of 256 patients have been followed up for 5 years or more, 19 were lost to follow-up. The mean follow-up period was 84 +/- 29 months. Cardiovascular complications were recorded in 23 individuals. The arising systolic BP (SBP) was significantly higher in the group who presented a complication. In a stepwise discriminant analysis including age, office, fitting, arising and 24-h average SBPs only age and arising SBP entered the equation. In conclusion, the single BP value measured by an ambulatory device on rising in the morning seems more discriminant of future cardiovascular events than the value of BP measured on fitting the device or the average of three measurements taken under standardised conditions in the hospital or office.     

Losartan versus atenolol on 24-hour ambulatory blood pressure. A LIFE substudy

Objective. The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study showed that losartan-based treatment reduced risk of the composite endpoint of cardiovascular death, stroke and myocardial infarction compared with atenolol-based treatment in patients with hypertension and left ventricular hypertrophy with similar office blood pressure (BP) reduction. Our aim was to investigate the effect of losartan- and atenolol-based treatment on 24-h ambulatory BP and heart rate (HR) in LIFE. Methods: In 110 patients, 24-h ambulatory BP and heart rate were recorded at baseline and 1 year after randomization. Results: Ambulatory BP was comparably reduced throughout the 24-h period after 1 year of losartan- vs atenolol-based antihypertensive treatment. Office and ambulatory BP were comparably reduced in the follow-up period. Early morning surge in BP was similar between groups. Non-dipping status was more frequent in the losartan group (p = 0.01). From baseline to Year 1 the 24-h HR profile for the losartan group was unchanged, but, as expected, there was a significant decrease in daytime HR in the atenolol group, which was not as large during early night-time. Conclusion: There were no differences in 24-h BP burden and HR that could explain the difference in outcome in favor of losartan vs atenolol in the LIFE study.     

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.     

Effect of doxazosin GITS on 24-hour blood pressure profile in patients with stage 1 to stage 2 primary hypertension

OBJECTIVE: To investigate the effect of the doxazosin gastrointestinal therapeutic system (GITS) on the 24 h blood pressure (BP) profile by ambulatory blood pressure measurements (ABPM) in patients with stage 1 to stage 2 primary hypertension. METHODS AND RESULTS: Seventeen hypertensive patients-either untreated or after a two-week run-in/washout period-underwent office and ABPM monitoring before and six weeks after an open-label once-daily morning dose of 4 mg of doxazosin GITS, an alpha(1)-adrenoceptor antagonist. Fourteen patients responded; three did not. Data analyses refers to the responders: linear analysis demonstrated statistically significant reductions from baseline in daytime, night-time, and total 24 h means for systolic BP (SBP) (7-10 mmHg) and diastolic BP (DBP) (5-10 mmHg) after treatment, with no statistically significant change in heart rate (HR). Rhythm analysis demonstrated statistically significant reductions from baseline in mean mesor (8 mmHg), maximum (6 mmHg) and minimum (10 mmHg) values in SBP, and in mean mesor (5 mmHg), maximum (7 mmHg) and minimum (5 mmHg) values in DBP. Circadian rhythm parameters in BP and HR were not significantly altered by treatment. Treatment with doxazosin GITS was well tolerated. CONCLUSIONS: A single morning dose of doxazosin GITS at 4 mg significantly reduced ambulatory SBP and DBP throughout a 24 h period while preserving a normal 24 h BP and HR rhythm profile in stage 1 to stage 2 hypertensives.     

Left Ventricular Mass Is Better Correlated With Arising Blood Pressure Than With Office or Occasional Blood Pressure

The peak incidence of cardiovascular complications in the morning points to a possible role of the abrupt increase in blood pressure on arising. However, there is as yet no firm evidence linking the extent of the elevation in blood pressure on arising and the risk of cardiovascular complications. We sought a correlation between blood pressure on arising and left ventricular mass in a population of 181 previously untreated hypertensive patients. Ambulatory blood pressure was measured over a 24-h period, and each patient was requested to trigger a blood pressure determination immediately after standing on arising in the morning. Left ventricular mass was measured with M-mode echocardiography and indexed for height, height^2.7, and body surface area. The systolic blood pressure on arising was significantly (P <.01) better correlated than office blood pressure with left ventricular mass index and wall thickness. On multivariate analysis, the values of systolic blood pressure on arising and mean 24-h systolic blood pressure contributed significantly and independently to the correlation with left ventricular mass and wall thickness. These observations point to the significance of the arising blood pressure. A marked abrupt daily elevation in blood pressure on arising, then maintained for a certain time, could contribute to the development of left ventricular hypertrophy and may constitute a trigger for cardiovascular complications.     

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

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

Peak blood pressure‐guided monitoring may serve as an effective approach for blood pressure control in the out‐of‐office setting

We aimed to explore whether diurnal blood pressure (BP) peak characteristics have a significant influence on the association between left ventricular damage with the two BP components (morning BP vs. afternoon peak BP) in untreated hypertensives. This cross‐sectional study included 1084 hypertensives who underwent echocardiography and 24‐h ambulatory BP monitoring. Participants were stratified according to the relationship between morning systolic BP (MSBP; average SBP within 2 h of waking up) and afternoon peak systolic BP (ASBP; average SBP between 16:00 and 18:00). Afternoon and morning hypertension was defined as ≥ 135/85 mm Hg. The morning and afternoon peak BPs occurred at around 7:00 and 17:00, respectively. In general hypertensives, morning BP and afternoon peak BP are significantly different in absolute values (for binary SBP, McNemar''s χ² = 6.42; p = .014). ASBP was more pronounced than MSBP in 602 patients (55.5%), in whom 24‐h SBP showed higher consistency with ASBP than with MSBP (Kappa value: 0.767 vs 0.646, both p < .01). In subjects with ASBP ≥ MSBP, ASBP was associated with left ventricular hypertrophy independent of MSBP (logistic regression analysis odds ratio: 1.046, p < .01), and left ventricular mass index was more strongly correlated with ASBP than with MSBP (multiple regression coefficient β: 0.453, p < .01), in which the relationships held true independently of 24‐h SBP. The opposite results were obtained in subjects with MSBP > ASBP. Peak BP‐guided monitoring may serve as an effective approach to out‐of‐office hypertension monitoring and control, providing the best consistency with 24‐h average SBP and highest discrimination performance for target organ damage, independently of 24‐h SBP.     

Blood pressure on arising, morning blood pressure surge and blood pressure variability in white coat hypertensives and in matched normotensives and sustained hypertensives.

INTRODUCTION: It is still controversial whether subjects with white-coat hypertension (WCHT) exhibit higher cardiovascular risk compared to normotensive subjects (NT). In subjects with WCHT it is not known whether the abnormal blood pressure (BP) reaction in the office also occurs at other times of day, particularly on arising and immediately after waking, i.e. the times at which the majority of cardiovascular events are reported to occur. OBJECTIVE AND METHODS: To evaluate with 24h ambulatory BP measurement the values of morning BP surge, BP on arising and BP variability in subjects with WCHT in comparison with age-, gender- and weight-matched normotensives (BP) and untreated sustained hypertensives (BP). RESULTS: Groups of BP, WCHT and BP were matched for age, gender and body weight: BP: n=69, age 49 +/- 7 years, 54 % female, BMI 26 +/- 1, casual BP 126/79 +/- 5/4 mmHg, daytime BP 124/80 +/- 6/6 mmHg; WCHT: n=74, age 52 +/- 8 years, 57% female, BMI 26 +/- 2, casual BP 152/95 +/- 7/7 mmHg, daytime BP 126/80 +/- 5/6 mmHg; HT: n=79, age 53 +/- 7 years, 56% female, BMI 27 +/- 2, casual BP 154/97 +/- 9/8 mmHg, daytime BP 143/89 +/- 12/10 mmHg. Of the three groups, subjects with WCHT exhibited BP on arising (121/81 +/- 13/8 mmHg) similar to that of NTs (120/80 +/- 13/9 mmHg, NS), both significantly lower than that of HTs (137/92 +/- 17/10 mmHg, p < 0.01), suggesting the absence of an alerting BP reaction in WCHT at that time. By contrast, subjects with WCHT showed higher values of systolic morning BP surge vs. NTs (25 +/- 10 vs. 22 +/- 11 mmHg, p < 0.05), both lower than that observed in hypertensives (33 +/- 11 mmHg, p < 0.01 vs. NT and WCHT) and greater daytime variability (systolic BP standard variation), i.e. 12 2 vs. 10 +/- 2 mmHg, p < 0.05, both lower than that observed in hypertensives (14 +/- 3 mmHg, p < 0.01 vs. NT and WCHT). CONCLUSIONS: Although subjects with WCHT did not show any alerting blood pressure reaction on arising, morning BP surge and BP variability were greater in these subjects than in control normotensives, although lower than sustained hypertensives. Although this is still speculative, we cannot exclude the possibility that even a slight increase in morning BP surge might in the long term constitute an additional load on the circulation that could increase cardiovascular risk in subjects with WCHT compared to matched normotensives.     

Day-night dip and early-morning surge in blood pressure in hypertension: prognostic implications

We investigated the relationship between the day-night blood pressure (BP) dip and the early morning BP surge in an cohort of 3012 initially untreated subjects with essential hypertension. The day-night reduction in systolic BP showed a direct association with the sleep trough (r = 0.564; P < 0.0001) and the preawakening (r = 0.554; P < 0.0001) systolic BP surge. Over a mean follow-up period of 8.44 years, 268 subjects developed a major cardiovascular event (composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and heart failure requiring hospitalization) and 220 subjects died. In a Cox model, after adjustment for predictive covariates, including age, sex, diabetes mellitus, cigarette smoking, total cholesterol, left ventricular hypertrophy on ECG, estimated glomerular filtration rate, and average 24-hour systolic BP, a blunted sleep trough (≤ 19.5 mm Hg; quartile 1) and preawakening (≤ 9.5 mm Hg; quartile 1) BP surge was associated with an excess risk of events (hazard ratio, 1.66 [95% CI, 1.14-2.42]; P = 0.009; hazard ratio, 1.71 [95% CI, 1.12-2.71]; P = 0.013). After adjustment for the same covariates, neither the dipping pattern nor the measures of early morning BP surge were independent predictors of mortality. In conclusion, in initially untreated subjects with hypertension, a blunted day-night BP dip was associated with a blunted morning BP surge and vice versa. In these subjects, a blunted morning BP surge was an independent predictor of cardiovascular events, whereas an excessive BP surge did not portend an increased risk of events.     

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.     

Prognostic significance of 24-h ambulatory blood pressure characteristics for cardiovascular morbidity in a population of elderly men

OBJECTIVE: This study aimed to investigate the prognostic significance of 24-h ambulatory systolic (SBP), diastolic (DBP) and pulse pressure (PP), and blood pressure (BP) variability for cardiovascular morbidity in elderly men. DESIGN AND METHODS: Twenty-four hour ABP monitoring was performed in 70-year-old men (n = 872) participating in a longitudinal population-based study. The population was followed for up to 9.5 years, and the relationship between different blood pressure components and cardiovascular (CV) morbidity was assessed by Cox proportional hazard analysis. RESULTS: During follow-up, 172 CV events occurred (2.97 per 100 person-years). SBP and PP, both office and ambulatory, were significant predictors of CV morbidity. Twenty-four hour ambulatory PP [hazard ratio (HR) for 1 SD increase in BP 1.32, 95% confidence interval (CI) 1.15-1.52] and daytime ambulatory PP (HR 1.29, 95% CI 1.13-1.48) predicted CV morbidity independently of office PP and other established CV risk factors. Addition of night-time PP to a regression model with daytime PP and covariates did not increase the predictive value. However, the variability of daytime SBP (adjusted HR 1.24, 95% CI 1.07-1.42) provided additional prognostic power, independently of the 24-h SBP level. CONCLUSIONS: Ambulatory PP was a powerful predictor of CV morbidity in elderly men, independently of office PP and other established cardiovascular risk factors. Moreover, variability of daytime SBP added important prognostic information, suggesting that 24-h ambulatory BP monitoring may contribute to an improved risk assessment in elderly subjects.     

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.     

Morning rise, morning surge and daytime variability of blood pressure and cardiovascular target organ damage. A cross-sectional study in 743 subjects.

OBJECTIVE: To evaluate in a large population the relationship between cardiovascular target organ damage and values of the night-to-morning rise of systolic blood pressure (MR-BP), the morning surge of BP at the moment of rising (BP surge) and daytime BP variability (standard deviation [SD] of daytime BP). METHODS: This was a cross-sectional study, evaluating 743 subjects, aged 30-75 years, 416 female, with normal renal function and no previous cardiovascular events. The population included: I-174 patients with type 2 diabetes, II-317 hypertensive patients with ongoing treatment over at least the previous 6 months, III-127 hypertensive patients untreated in the last 6 months, IV-125 healthy normotensive subjects. All underwent 24-hour ambulatory BP monitoring to calculate MR-BP, BP surge and SD of daytime BP. Target organ evaluation included: pulse wave velocity (PWV) (an indicator of aortic stiffness) in 711 subjects, left ventricular mass index (LVMI) in 185 subjects and 24-hour albuminuria in 239 subjects. RESULTS: In the population as a whole, BP surge, MR-BP and SD of daytime BP correlated significantly with PWV (r = 0.434, p < 0.0001; r = 0.126, p < 0.001; 0.337, p < 0.001, respectively), with LVMI (r = 0.447, p < 0.0001; r = 0.307, p < 0.001; 0.162, p < 0.05, respectively) and to a lesser degree with albuminuria (r = 0.126, p < 0.05; r = 0.083, NS; 0.082, NS, respectively). In the upper quintile of distribution of BP surge, the percentage of cases with abnormal PWV (>12 m/s) (21%), cardiac hypertrophy (53 %) and microalbuminuria (47 %) was significantly greater (p < 0.03) than that observed in the lower quintile (1%, 14% and 27%, respectively). BP surge correlated more strongly with indices of target organ damage than did MR-BP or SD of daytime BP, independently of night-time BP and nocturnal BP fall. CONCLUSIONS: In this large population, MR-BP, BP surge and daytime BP variability are strongly correlated with target organ damage severity, and are probably related to organ deterioration. Of the three, morning surge of BP at the moment of rising is more strongly related to organ damage than MR-BP, perhaps because unlike MR-BP, BP surge is independent of night-time BP values.     

A multicenter, 14-week study of telmisartan and ramipril in patients with mild-to-moderate hypertension using ambulatory blood pressure monitoring

BACKGROUND: Blood pressure (BP) has a circadian pattern with a morning surge that is associated with an increased risk of acute coronary and cerebrovascular events. In a prospective, randomized, open-label, blinded-endpoint, parallel-group, multicenter, forced-titration study of telmisartan and ramipril, the efficacy of both drugs on mean ambulatory diastolic BP (DBP) and systolic BP (SBP) during the last 6 h of a 24-h dosing interval was evaluated. METHODS: After screening and a single-blind run-in phase, 812 adults with mild-to-moderate hypertension (defined as a mean seated DBP > or =95 mm Hg and < or =109 mm Hg and a 24-h ABPM mean DBP 7 > or = 85 mm Hg) were randomized to the open-label, 14-week, forced-titration, active-treatment phase as follows: telmisartan 40 mg/80 mg/80 mg (n = 405) or ramipril 2.5 mg/5 mg/10 mg (n = 407), once daily in the morning. The primary efficacy variable was change from baseline in the last 6-h mean DBP and SBP at 8 and 14 weeks as assessed by ambulatory BP monitoring (ABPM). Secondary efficacy variables were changes from baseline in BP control during each of the 24-h periods and in-clinic trough cuff BP. RESULTS: Telmisartan 80 mg was superior to ramipril 5 mg and 10 mg in change from baseline in the last 6-h ABPM mean DBP and SBP at both 8 and 14 weeks (both P < .0001), respectively. At 14 weeks, the adjusted mean change from baseline in DBP for telmisartan 80 mg was -8.8 mm Hg compared with that for ramipril 10 mg of -5.4 mm Hg (P < .0001). For SBP, the adjusted mean change from baseline for telmisartan 80 mg was -12.7 mm Hg compared with that for ramipril 10 mg of -7.9 mm Hg (P < .0001). At 14 weeks, telmisartan 80 mg also yielded superior reductions from baseline in trough cuff BP compared with ramipril 10 mg (DBP: -11.0 mm Hg v -7.8 mm Hg, respectively; SBP: -14.3 mm Hg v -9.1 mm Hg, respectively; both P < .0001). Measures of 24-h BP control favored telmisartan 80 mg versus ramipril 10 mg (P < .0001), as did other secondary ABPM endpoints during the daytime, night-time, and morning periods. Treatment-related adverse events were uncommon; patients treated with ramipril had a higher incidence of cough than those treated with telmisartan (10.1% v 1.5%, respectively). CONCLUSIONS: Telmisartan 80 mg was consistently more effective than ramipril 10 mg in reducing both DBP and SBP during the last 6 h of the dosing interval, a measure of the early morning period when patients are at greatest risk of life-threatening cardiovascular and cerebrovascular events. Telmisartan 80 mg was also more effective than ramipril 10 mg in reducing BP throughout the entire 24-h dosing interval. Both drugs were well tolerated.     

No impact of blood pressure variability on microalbuminuria and left ventricular geometry: analysis of daytime variation, diurnal variation and 'white coat' effect

OBJECTIVE: To investigate the influence of blood pressure variability on target organ involvement. METHODS: Using a cross-sectional study of a hypertension clinic at a district general hospital, 420 patients with newly diagnosed untreated essential hypertension referred on a consecutive basis from general practice and 146 normal subjects drawn at random from the Danish National Register underwent a variety of measurements which included: echocardiography with determination of left ventricular mass index and relative wall thickness and early morning urine albumin/creatinine ratio. Mean, standard deviation and coefficient of variation of automated clinic values; daytime, night-time and full 24-h period were extracted from 24-h ambulatory blood pressure (ABP) monitoring. 'White coat' effect and dip were calculated. Hypertensives were classified into subjects with high or low variability, into 'white coat' hypertensives or established hypertensives and into dippers or non-dippers. RESULTS: Standard deviation of daytime blood pressure (BP) was positively associated with target organ damage and BP level, which was not the case when variability was expressed as a coefficient of variation. Patients with high variability exhibited no more significant target organ damage than patients with low variability, but patients with established hypertension had significantly more target organ damage than the 'white coat' hypertensives. The 'white coat' effect as such was not associated with increased target organ involvement. Non-dippers had significantly more cardiac target organ damage than dippers, but the difference disappeared after correction for different 24-h BP level. CONCLUSION: BP variability data obtained by non-invasive ABP monitoring does not seem to improve the information inherent in the BP level.     

Pulsatile and steady 24-h blood pressure components as determinants of left ventricular mass in young and middle-aged essential hypertensives

In order to explore the relations between left ventricular mass (LVM) and the pulsatile (pulse pressure) and steady (mean pressure) components of the blood pressure (BP) curve, 304 young and middle-aged essential hypertensive patients were studied by means of 24-h ambulatory BP monitoring and echocardiography. In the overall study population, both the BP components showed significant correlations with LVM. These correlations were unevenly distributed in the subgroups of subjects younger and in those older than 50 years. While in this latter subgroup, in multivariate analysis, both 24-h mean BP (24-MBP) (beta = 0.27; P = 0.008) and 24-h pulse pressure (24-h PP) (beta = 0.23; P = 0.02) were associated with LVM, in the subset of younger hypertensives only 24-h MBP (beta = 0.21; P = 0.009) was related to LVM, independent of other covariates. The relations observed between 24-h PP and LVM in the entire study population and in the patients older than 50 years lost statistical significance when the effect of 24-h systolic blood pressure (24-h SBP) was taken into account, in a multiple regression model in which 24-h MBP was replaced by 24-h SBP. Our findings seem to suggest that the association of PP with LVM in middle-aged hypertensives may partially explain the increased cardiovascular risk, documented in subjects with high PP. However, this relation is not independent, but is mediated by SBP.     

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.     

氯沙坦对高血压病人24小时血压的影响

目的观察氯沙坦对高血压病人24小时血压的影响,探讨其临床意义。 方法20例Ⅰ-Ⅱ级高血压病人,入院后停药2周,服氯沙坦50mg,qd,疗程12周,1个月后血压若未降至140/90mmHg以下,可加大剂量到100mg,qd,治疗前后复查24小时动态血压。以二次给药间距终末时血压下降数除以给药间距中最大血压下降数值作为药物降压的谷/峰比(T∶P),以夜间血压均值与白昼血压均值比较时下降10%或大于10mmHg者为夜间血压下降或"杓型者",反之为夜间血压不下降者或"非杓型者"。 结果　发现(1)氯沙坦能明显降低高血压病人的24小时平均血压(mmHg)(SBP134±14比113±8,DBP89±12比71±5,P<0.01);有效率为85.0%.(2)氯沙坦降压的SBP和DBPTP比率分别为78.6%(48%～93.9%)和76.2%(46.4%～89.6%).SBP,DBP和MBP的平滑曲线指数分别是1.23±0.32,1.36±0.41和1.32±0.38.(3)对夜间血压高于正常值(120/80mmHg)的高血压患者,氯沙坦明显降低夜间血压(mmHg)(SBP142.6±8.8降至116.3±11.4,DBP89.2±9.6降至74.3±6.8,P<0.01),对夜间血压已属正常者,氯沙坦无进一步降压作用(SBP120.3±3.7比116.3±6.8;DBP78.2±6.1比74.3±7.2,P>0.05).(3)24小时SBP,DBP下降幅度与治疗前SBP,DBP明显相关,r分别为0.803和0.797,P<0.01. 结论　氯沙坦是一种安全有效的降压药,其主要优点是24小时平稳降压,谷峰比满意,夜间无过度降压的危险,晨间血压上升受到明显抑制,基础血压越高,降压效果越好。     

Predictors of controlled ambulatory blood pressure in treated hypertensive patients with uncontrolled office blood pressure.

Although some treated hypertensive patients have controlled 24-h ambulatory blood pressure (ABP) despite their uncontrolled office blood pressure (BP), the factors relating to the control of 24-h ABP remain unknown. We conducted a study to assess 24-h ABP and its association with other cardiovascular risk factors, including echocardiographic left ventricular hypertrophy (LVH), in elderly hypertensive patients (n =41) with uncontrolled office BP (>140/90 mmHg) during long-term medication. Although a majority of the patients had isolated elevation of office systolic BP (SBP), there was no significant relationship between office SBP and 24-h SBP, and about half of the patients had controlled 24-h ABP (125+/-8/69+/-6 mmHg). Patients with controlled 24-h ABP (125+/-8/69+/-6 mmHg) had similar office BP (150+/-6/77+/-5 vs. 150+/-7/79+/-7 mmHg), but lower left ventricular mass index (LVMI) (123+/-34 vs. 156+/-34 g/m(2)) and body mass index (BMI) (24.4+/-2.1 vs. 26.4+/-3.6 kg/m(2)) compared with those with uncontrolled 24-h ABP (149+/-13/78+/-7 mmHg). Multivariate analysis showed that LVMI and BMI were independently associated with controlled 24-h ABP, and the control status of 24-h ABP was highly dependent on the presence of LVH and obesity. Therefore, absence of LVH and obesity may be useful for predicting the level of control of 24-h ABP in treated patients whose office BP is uncontrolled without ABP measurements.     

Effects of GH replacement on 24-h ambulatory blood pressure and its circadian rhythm in adult GH deficiency

OBJECTIVE: Increased prevalence of hypertension and cardiovascular mortality have been reported in hypopituitary patients who had been appropriately replaced with conventional pituitary hormones except GH. Growth hormone replacement (GHR) results in improvement of surrogate markers of cardiovascular function. Data on effects of GHR on blood pressure (BP) in adult growth hormone deficiency (AGHD), however, remain contradictory. There are as yet no reports on BP circadian rhythms in untreated or treated AGHD. Therefore, in a 12-month follow-up study, we evaluated the effects of GHR on ambulatory blood pressure (ABP) in AGHD patients. STUDY DESIGN: A prospective, open treatment design study to determine the effects of GHR on ABP and heart rate in AGHD patients. GH was commenced at a daily dose of 0.5 IU, and titrated up by increments of 0.25 IU at 4-weekly intervals to achieve and maintain IGF-I standard deviation score (IGF-I SD) between the median and upper end of the age-related reference range. PATIENTS: Twenty-two, post-pituitary surgery, severe AGHD patients (11 men), defined as peak GH response < 9 mU/l to provocative testing were recruited. The mean age +/- SEM was 48.8 +/- 2.5 years. Twenty-one patients required additional pituitary replacement hormones following pituitary surgery and were on optimal doses at recruitment. MEASUREMENTS: Twenty-four-hour ABP and heart rate (HR), body mass index (BMI), waist hip ratio (WHR) and total body water (TBW) were measured before and after 12 months on GHR. Cosinor analysis was used to analyse BP and HR circadian rhythm parameter estimates. RESULTS: Target IGF-I SD was achieved within 3 months of commencement of GHR in all patients (-3.5 +/- 0.4 at baseline vs. 0.8 +/- 0.2 at 3 months, P < 0.001) and remained within range at 12 months (1.1 +/- 0.2, P < 0.001 compared to baseline). A significant increase in TBW (45.8 +/- 1.2 vs. 47.8 +/- 1.5 kg, P < 0.05) but no significant change in BMI (30.7 +/- 2.2 vs. 31.8 +/- 2.7, P = NS) or WHR (0.95 +/- 0.02 vs. 0.93 +/- 0.02, P = NS) was observed after 12 months on GHR. The 24-h mean systolic ABP (SBP; 126.2 +/- 2.8 vs. 120.1 +/- 2.7 mmHg, P < 0.001) and diastolic ABP (DBP; 78.2 +/- 1.6 vs. 71.4 +/- 1.8 mmHg, P < 0.001) significantly decreased following GHR with a parallel increase in 24-h mean HR (69.6 +/- 2.5 vs. 73.8 +/- 2.5 beats/min; P < 0.001). A significant nocturnal decrease in SBP and DBP was observed both before (SBP; daytime, 129.1 +/- 2.8 vs. night time, 115.9 +/- 3.0 mmHg, P < 0.001 and DBP; daytime, 80.7 +/- 1.6 vs. night time, 69.2 +/- 1.8 mmHg, P < 0.001) and following GHR (SBP; daytime, 122.8 +/- 2.6 vs. night time, 110.0 +/- 3.6 mmHg, P < 0.001 and DBP; daytime, 73.9 +/- 1.8 vs. night time, 62.0 +/- 2.3 mmHg, P < 0.001). Individual and population-mean cosinor analysis demonstrated significant circadian rhythms for SBP, DBP and HR before and after 12 months on GHR (P < 0.001), suggesting that SBP, DBP and HR circadian rhythms were not altered by GHR. There was, however, a significant reduction in SBP (124.2 +/- 2.8 vs. 118.4 +/- 2.8 mmHg, P < 0.001) and DBP (77.0 +/- 1.6 vs. 70.2 +/- 1.8 mmHg, P < 0.001) MESOR with an increase in HR MESOR (68.9 +/- 2.5 vs. 72.2 +/- 2.4 beats/min, P < 0.01) following GHR. CONCLUSIONS: Systolic and diastolic BP and HR circadian rhythms are preserved in AGHD following 12 months of GHR. However, there is a significant decrease in 24-h mean SBP and DBP and increase in 24-h mean HR after 12 months on GHR. We postulate that this decrease in 24-h mean SBP and DBP may result in a reduction of cardiovascular morbidity and mortality and may explain the beneficial effects of GHR on cardiovascular system previously reported in AGHD patients.