Associations between nondipping of nocturnal blood pressure decrease and cardiovascular target organ damage in strictly selected community-dwelling normotensives

BACKGROUND: In hypertensives, nondippers are more likely than dippers to suffer silent, as well as overt, hypertensive target organ damage. In this study, we investigated whether a nondipper status was associated with target organ damage in normotensives. METHODS: We performed ambulatory blood pressure (BP) monitoring, echocardiography, and carotid ultrasonography and measured natriuretic peptides and urinary albumin (UAE) in 74 normotensive subjects with the following criteria: 1) clinical BP <140/90 mm Hg; 2) average 24-h ambulatory BP <125/80 mm Hg. RESULTS: The left ventricular mass index (LVMI) and the relative wall thickness (RWT) measured by echocardiography were greater in nondippers than dippers (LVMI: 103 +/- 26 v 118 +/- 34 g/m(2), P <.05; RWT: 0.38 +/- 0.07 v 0.43 +/- 0.09, P <.01). Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were higher in nondippers than dippers (ANP: 14 +/- 10 v 36 +/- 63 pg/mL, P <.01; BNP: 16 +/- 12 v 62 +/- 153 pg/mL, P <.05). There were no significant differences in UAE and intima-media thickness measured by carotid ultrasonography. CONCLUSIONS: Normotensive nondipping may not reflect renal damage, but may have a predominant effect on cardiac damage. Nondipping of nocturnal BP seems to be a determinant of cardiac hypertrophy and remodeling, and may result in a cardiovascular risk independent of ambulatory BP levels in normotensives.     

Adiponectin, insulin resistance, and left ventricular structure in dipper and nondipper essential hypertensive patients

BACKGROUND: Adiponectin is an adipocyte-derived protein with insulin-sensitizing and antiatherogenic properties. Failure to decrease blood pressure (BP) normally during night in hypertensive patients has been independently associated with left ventricular hypertrophy. METHODS: We examined the relationship between adiponectin levels, insulin sensitivity, and left ventricular structure in 40 newly diagnosed never-treated patients with essential hypertension, including 20 patients with a normal night-time pressure decrease (ie, dippers) and 20 patients with BP persistently elevated throughout the 24-h period (ie, nondippers). All subjects had grade 1-2 hypertension, aged 18 to 65 years, no diabetes mellitus, no obesity, no hyperlipidemia, and no cardiopulmonary, renal, or hepatic disease. RESULTS: The two groups of patients were similar for age, sex, body mass index, and had no differences for clinic, 24-h, and diurnal BP, and 24-h, diurnal, and nocturnal heart rate, as well as glucose, total cholesterol, and triglyceride levels. Plasma insulin and homeostasis model assessment (HOMA index) were higher (P < .01), and adiponectin levels were lower (P < .005) in nondippers than in dippers. Adiponectin correlated inversely with HOMA index and insulin levels (r = -0.58, and r = -0.62, respectively, P < .001) in the entire population. Nondippers showed left ventricular mass, relative wall thickness, and measure of early and late diastolic peak flow velocity ratio similar to those of dippers. CONCLUSIONS: In the absence of major cardiovascular risk factors, nondipper essential hypertensive patients show more prominent insulin resistance and lower adiponectin compared to dippers. Therapeutic modulation of adiponectin or insulin resistance might provide additional benefit to the conventional antihypertensive treatment.     

Is HOMA index a predictor of nocturnal nondipping in hypertensives with newly diagnosed type 2 diabetes mellitus?

OBJECTIVE: Insulin resistance is involved in glucose intolerance, type 2 diabetes mellitus and hypertension. We aimed to analyze relationship between insulin resistance and nocturnal nondipping. METHODS: Patients underwent physical and biochemical evaluation, clinic and ambulatory blood pressure measurements. The homeostasis model assessment (HOMA) index was calculated. RESULTS: Ninety-six essential hypertensive patients, of whom 42 were dippers, with newly diagnosed type 2 diabetes mellitus were included. Nighttime average heart rate and mean arterial pressure of nondippers were higher than dippers (P<0.0001 and 0.001). Nondippers had higher fasting plasma glucose, serum insulin levels and HOMA indices than dipper patients (P=0.006, <0.0001 and <0.0001). Ten dippers and 36 nondippers were insulin resistant (P<0.0001). Clinic (r=+0.22, P=0.031), daytime average (r=+0.27, P=0.007), nighttime average (r=+0.33, P=0.001), 24-h average systolic (r=+0.25, P=0.015) and nighttime average diastolic blood pressures (r=+0.31, P=0.002) were positively correlated with homeostasis model assessment index. Nighttime mean arterial pressure and heart rates (daytime, nighttime, 24-h average) showed positive correlation with homeostasis model assessment index. In multivariate analysis, high homeostasis model assessment index was associated with increased nondipping risk (odds ratio: 1.85, confidence interval: 1.24-2.76, P=0.003). After adjustment of several factors, average nighttime systolic (P<0.0001), diastolic (P<0.0001) and 24-h diastolic blood pressure (P=0.029) and heart rate (P=0.001) measurements of insulin resistant patients were higher than nonresistant patients. CONCLUSIONS: Insulin resistance is related with diurnal blood pressure variation. The HOMA index may be a predictor of nocturnal nondipping in patients with essential hypertension and newly diagnosed type 2 diabetes mellitus.     

Reduced nocturnal fall in blood pressure,assessed by two ambulatory blood pressure monitorings and cardiac alterations in early phases of untreated essential hypertension

To investigate whether in recently diagnosed essential hypertensives a reduced nocturnal fall in blood pressure (BP), established on the basis of two 24-h ambulatory blood pressure monitorings (ABPM) is related to a greater cardiovascular damage. In all, 355 consecutive, recently diagnosed, never-treated essential hypertensives referred for the first time to our outpatient clinic were included in the study. Each patient underwent the following procedures: (1) two 24-h ABPMs performed within 3 weeks, (2) 24-h urinary collection for microalbuminuria, (3) nonmydriatic photography of ocular fundi, (4) echocardiography, (5) carotid ultrasonography. We defined nondipping profile as a night-day systolic and diastolic fall < or =10 % (mean of two ABPMs). A dipper BP profile was found in 238 patients, whereas in 117 patients a nondipper profile was present. The two groups were similar for age, gender, body mass index, smoking habit, clinic BP, 48-h BP and heart rate, while, by definition, night-time systolic and diastolic BP were significantly higher in nondippers than in dippers (130/81 vs 121/74 mmHg, P < 0.0001).The prevalence of left ventricular hypertrophy (LVH) defined by four different criteria: (a) LV mass index (LVMI) > or = 125 g/m(2) in both genders; (b) LVMI > or = 134 gm(2) in men and > or = 110 in women; (c) LVMI> or = 125 g/m(2) in men and > or = 110 g/m(2) in women; (d) LVMI > or = 51 g/m(2.7) in men and > or = 47 g/m(2.7) in women was significantly higher in nondippers than in dippers (a: 12 vs 7%, P < 0.05; b: 16 vs 7%, P < 0.01; c: 20 vs 11%, P < 0.01; d: 35 vs 23% P < 0.02) and this finding was associated with a significant increase in aortic root and left atrium dimensions. There were no differences between the two groups in the prevalence of carotid and retinal changes and microalbuminuria. In conclusion our findings suggest that never-treated hypertensives with a reduced BP fall in the night time, defined on the basis of two ABPMs, have a higher prevalence of TOD than dippers, in terms of echocardiographic LVH. In this population setting, cardiac structural alterations are a more sensitive marker of the impact of the nocturnal BP load on cardiovascular system than other extracardiac signs of TOD.     

Impact of abnormal nocturnal blood pressure fall on vascular function

BACKGROUND: It is well known that nondipping pattern of arterial hypertension has a harmful effect on target organs such as the brain, heart, and kidneys. However, it remains uncertain whether abnormal dipping patterns of nocturnal blood pressure (BP), such as extreme and reverse dipping, influence vascular function. METHODS: This study comprised consecutive 2800 individuals (1554 men and 1246 women). All were nondiabetic and had uncomplicated, untreated essential sustained hypertension based on office measurements. After a 2-week wash-out period, 24-h ambulatory BP recordings were obtained and patients were classified by their nocturnal systolic BP fall (132 extreme dippers with >20% nocturnal systolic BP fall; 1235 dippers with >10% but <20% fall; 1146 nondippers with >0% but <10% fall; and 287 reverse dippers with <0% fall). Microalbumin, ACR (albumin/creatinine ratio), and microglobulin values were measured in all groups. RESULTS: Extreme dippers did not differ from dippers with regard to microalbumin, microglobulin excretion, or ACR. On the contrary, reverse dippers had significantly (P <.0001) higher values, compared with nondippers, for microalbumin (49.5 v 37.2 mg/dL), microglobulin (10.33 v 8.71 mg/dL), ACR (104.9 v 65.2), and percentages of abnormal values for these parameters. CONCLUSIONS: Microalbuminuria, an index of vascular function, differentiates reverse dippers from nondippers, but not extreme dippers from dippers among hypertensive patients.     

High-density lipoprotein cholesterol and insulin resistance are independent and additive markers of left ventricular hypertrophy in essential hypertension.

We examined whether plasma high-density lipoprotein-cholesterol (HDL-C) levels and glucose metabolism parameters are independent or additive predictors of left ventricular hypertrophy (LVH) in patients with untreated essential hypertension. The study group consisted of 41 Japanese patients with untreated essential hypertension and LVH (left ventricular mass index [LVMI] >125 g/m2; age 58+/-6 years, mean+/-SD), and the control group consisted of 39 age-matched patients with untreated essential hypertension without LVH (LVMI 相似文献   

Lack of correlation between QTc dispersion and morning blood pressure surge in recently diagnosed essential hypertensive patients.

BACKGROUND: Cardiovascular events are known to occur more frequently in patients with a high morning surge in blood pressure (BP), but the correlation between a morning BP surge and corrected QT dispersion (QTc) has not been confirmed to date. METHODS AND RESULTS: The correlation between the morning BP surge and QTc was studied in 82 patients recently diagnosed with high BP (47 males, 35 females). Twenty-four-hours BP monitoring was conducted to classify patients into dipper (n=45) or nondipper (n=37) groups according to the degree of nocturnal BP reduction. QTc was found to be significantly longer in the nondippers compared with the dippers (36.1+/-17.2 vs 47.6+/-20.7, p<0.001). In addition, there was a significant increase in the end-diastolic interventricular septum thickness (IVSd), left ventricular posterior wall thickness in diastole (PWT) and left ventricular mass index (LVMI) in the nondippers vs the dippers (respectively, 0.93+/-0.09 vs 1.03+/-0.05, p<0.001, 0.94+/-0.09 vs 1.01+/-0.04, p<0.01, 109.7+/-12.8 vs 129.1+/-20.9, p<0.001). QTc had a significant positive correlation with nighttime BP, IVSd, PWT, and LVMI, but negatively correlated with the nocturnal BP reduction rate. These results were maintained even after adjusting for age and gender. However, a significant correlation between the morning BP surge and QTc was not confirmed. CONCLUSION: In the present nondipper hypertensive patients, QTc, nighttime BP, LVMI, and wall thickness were significantly greater than in the dipper patients. However, there was no significant correlation between the morning BP surge and QTc.     

Insulin resistance is associated with reduced nocturnal falls of blood pressure in normotensive, nonobese type 2 diabetic subjects

To assess the relationship between insulin resistance and ambulatory blood pressure (BP) pattern, we determined glucose infusion rate (GIR) as a marker of insulin resistance using a glucose clamp method, and measured 24-h BPs in 25 normotensive, nonobese type 2 diabetic subjects. They were divided into two groups: 11 dippers and 14 nondippers. Clinical characteristics were similar in the two groups except for orthostatic fall in systolic BP. The median GIR level was significantly lower in nondippers than in dippers (P < 0.05). Spearman's rank correlation revealed that the GIRs were negatively correlated with the systolic, diastolic and mean BPs during nighttime (P < 0.05 or less), but not with daytime or whole day BPs. Moreover, based on a logistic regression analysis, the GIR as well as orthostatic fall in systolic BP discriminated independently between dippers and nondippers. Thus, our results suggest that insulin resistance is associated with decreased nocturnal BP fall in type 2 diabetic subjects.     

Differential Effects of Amlodipine on Ambulatory Blood Pressure in Elderly Hypertensive Patients With Different Nocturnal Reductions in Blood Pressure

Previous studies have discovered that amlodipine given once daily can reduce blood pressure (BP) throughout the day and night. The effects of amlodipine on day and night BP have not been fully investigated in groups of hypertensives with different diurnal variations. In a prospective study, we performed 24-h ambulatory BP monitoring before and after once-daily use of amlodipine in three groups of asymptomatic elderly hypertensive patients with different nocturnal BP reductions, as follows: 10 extreme dippers with nocturnal reduction of systolic BP ≥ 20% of daytime systolic BP, 17 dippers (reduction by ≥ 10% to < 20%), and 23 nondippers (reduction by < 10%). At baseline, the office and the awake BP were similar in all three groups, whereas the nighttime BP was significantly higher in the nondippers than in the dippers and in the dippers than in the extreme dippers. After treatment, the office and the daytime BP were both equally reduced in all three groups. On the other hand, the nighttime BP was significantly reduced both in the nondippers and, to a lesser extent, in the dippers. In the extreme dippers, however, no further reductions of nocturnal BP were found. Significant positive correlations were found between baseline BP levels and the BP reduction after amlodipine therapy was begun. No BP reduction > 10 mm Hg was observed when the baseline systolic/diastolic BP was < 120/70 mm Hg. Multiple linear regression analysis disclosed that the nighttime BP reduction afforded by amlodipine was dependent on the baseline nighttime BP levels, but not on the baseline nocturnal fall of BP. Once-daily use of amlodipine reduced BP levels throughout the day and night in hypertensive patients who show minimal or mild nocturnal BP fall, but it had no effects on nocturnal BP in those who show a substantial nighttime BP reduction. Thus, when we controlled using daytime office BP, amlodipine might not further reduce nocturnal BP to the extent that it accelerates the brain ischemia in some hypertensive patients with marked nocturnal BP reduction.     

From treatment to organ damage; a 5-year follow-up study of ambulatory blood pressure in essential hypertension. Diversity between development of left ventricular hypertrophy and urinary albumin excretion

This study aimed to assess blood pressure (BP) profile, BP control, left ventricular hypertrophy (LVH) and albumin/creatinine ratio (ACR) in urine after 5 years of antihypertensive treatment in subjects with newly diagnosed essential hypertension. Fifty-four subjects were included and prescribed calcium-channel blocker in monotherapy during an 8-week period, and later 46 subjects (34 men, 12 women, 53.1+/-8.6 years) attended a 5-year follow-up visit at the hypertension clinic. They underwent 24-h ambulatory BP monitoring (ABPM), ECG and ACR at baseline and after 5 years. Echocardiography performed after 5 years revealed LVH in 54% of the subjects, while there was no change in Cornell product, an ECG criterion for LVH. BP control assessed by office BP was 33%, and only 20% using 24-h ABP. Night-time fall in BP was significantly attenuated from 13.2+/-5.9% to 10.7+/-6.0%, p = 0.01 for systolic BP and from 13.3+/-6.9% to 9.8+/-6.8%, p = 0.004 for diastolic BP. The number of dippers decreased after 5 years, but this did not reach statistical significance. In contrast to the lack of change in Cornell product, there was a significant decrease in ACR, and 93% of the subjects had ACR<1.5 mg/mmol after 5 years compared with 57% at baseline (p<0.001). Thus, ABPM should be encouraged in the follow-up of all hypertensive subjects as it reveals better inadequate BP control than office BP and gives information about night-time fall, as this may explain the high prevalence of LVH. The diversity in development of LVH and ACR during antihypertensive treatment needs to be verified.     

Evaluation of the activity of the autonomic nervous system in "dipper" and "non dipper" essential hypertensives. Gender differences]

OBJECTIVES: 1) To compare the autonomic nervous system activity parameters obtained from a photoplethysmographic recording in dipper and non dipper hypertensive. 2) To look for an interaction between dipper/non dipper status and gender. METHODS: Prospective study involving 245 untreated hypertensives (51 +/- 13 years, 146 men, 99 women). All of the patients underwent a 24-hour ambulatory blood pressure measurement (ABPM) as well as an echocardiography for left ventricular mass index determination (LVMI) and a photoplethysmographic recording of blood pressure (BP). Nondippers were defined as those whose nocturnal decrease in systolic BP (SBP) and/or diastolic BP (DBP) was < 10% of daytime BP. Spectral powers were obtained from the photoplethysmographic recording using a fast Fourier transform over the low frequency band (LF) and the high frequency band (HF). Baroreflex sensitivity (BRS) was evaluated by the sequences method. RESULTS: Of the 245 patients, 159 were dippers (98 men, 61 women) and 86 were non dippers (48 men and 38 women). Clinic BP was significantly higher in non dippers than in dippers (168/101 vs 161/98 mmHg; p < 0.01 for SBP and p < 0.05 for DBP) whereas daytime ABPM and LVMI were not different, whatever the gender. LF spectral powers were significantly lower in non dippers than in dippers for SBP (respectively 25 +/- 11% vs 30 +/- 13%; p < 0.01) for DBP (respectively 35 +/- 14% vs 41 +/- 15%; p < 0.01) and for HR (respectively 34 +/- 15% vs 38 +/- 15%; p = 0.03). They showed a positive correlation with the nocturnal SBP fall (r = 0.21, p < 0.001 for SBP and DBP spectral powers, r = 0.19; p < 0.005 for HR spectral power) and with the nocturnal DBP fall, too (r = 0.19; p < 0.005 for SBP spectral power, r = 0.20; p < 0.002 for DBP spectral power, r = 0.19; p < 0.005 for HR spectral power). HF spectral powers tended to be higher in non dippers than in dippers but in a non significative way. BRS was roughly the same in dippers and non dippers (7.5 +/- 2.7 vs 7.0 +/- 3.1 ms/mmHg, NS). The interaction between non dipper/dipper status and sex was non significant whatever the LF spectral power. CONCLUSIONS: 1) The greater the nocturnal BP fall, the higher the sympathetic activity indexes. 2) This relationship was found both in males and females.     

INSULIN RESISTANCE IS ASSOCIATED WITH REDUCED NOCTURNAL FALLS OF BLOOD PRESSURE IN NORMOTENSIVE,NONOBESE TYPE 2 DIABETIC SUBJECTS

To assess the relationship between insulin resistance and ambulatory blood pressure (BP) pattern, we determined glucose infusion rate (GIR) as a marker of insulin resistance using a glucose clamp method, and measured 24-h BPs in 25 normotensive, nonobese type 2 diabetic subjects. They were divided into two groups: 11 dippers and 14 nondippers. Clinical characteristics were similar in the two groups except for orthostatic fall in systolic BP. The median GIR level was significantly lower in nondippers than in dippers (P < 0.05). Spearman's rank correlation revealed that the GIRs were negatively correlated with the systolic, diastolic and mean BPs during nighttime (P < 0.05 or less), but not with daytime or whole day BPs. Moreover, based on a logistic regression analysis, the GIR as well as orthostatic fall in systolic BP discriminated independently between dippers and nondippers. Thus, our results suggest that insulin resistance is associated with decreased nocturnal BP fall in type 2 diabetic subjects.     

Neurohumoral characteristics of older hypertensive patients with abnormal nocturnal blood pressure dipping

Abnormal patterns of diurnal blood pressure (BP) variation have been reported to be related to advanced target organ damage and poor cardiovascular prognosis. However, the neurohumoral characteristics of patients with such variation have not been fully investigated. We measured BP and plasma levels of neurohumoral factors (norepinephrine [NE], epinephrine, renin, and arginine vasopressin [VP]) during the 70 degree head-up tilt test (10 min supine and 15 min tilting) in 120 older subjects (mean age 71 years) who had sustained hypertension as determined by ambulatory BP monitoring. They who were subclassified according to the nocturnal systolic BP fall as follows: 28 extreme dippers with >20% nocturnal BP fall; 78 dippers with >0% but <20% fall; and 14 nondippers with <0% fall. Plasma renin activity (r = 0.22, P = .02) and VP level (r = 0.36, P < .0001) after tilting were positively associated with the nocturnal systolic BP fall. Plasma NE levels were significantly higher in nondippers than in dippers in both the supine and tilting positions (supine 519 v 315 pg/mL, P = .001; tilting 803 v 550 ng/mL, P < .01), whereas the increase of NE induced by tilting was comparable in the two groups. Plasma renin activity in both the supine and tilting positions was comparable in the three groups, but the increase of this activity caused by tilting was less marked in the nondippers than in the extreme dippers (0.05 v 0.26 ng/mL/min, P = .02) and dippers (0.21 ng/mL/min, P = .07). Plasma VP was markedly increased after tilting in the extreme dippers compared with dippers (3.8 v 2.6 pg/mL, P < .001) and nondippers (v 2.0 pg/mL, P < .001), whereas the levels in the supine position were comparable in the three groups (2.0 pg/mL for extreme dippers, 1.9 pg/mL for dippers, 1.6 pg/mL for nondippers). In conclusion, diurnal BP variation in elderly hypertensive individuals was significantly associated with neurohumoral factors regulating circulating blood volume. Increased VP after tilting in extreme dippers might counteract reduced circulating blood volume, whereas nondippers appear to have alpha- and beta-adrenergic subsensitivity that may be induced by their chronic exposure to high NE levels.     

Candesartan, an angiotensin II receptor blocker, improves left ventricular hypertrophy and insulin resistance

A growing body of evidence indicates that the renin-angiotensin system and insulin resistance play crucial roles in left ventricular hypertrophy (LVH) in patients with essential hypertension (EH). Angiotensin II receptor blockers (ARB) have been reported to regress LVH and improve insulin resistance. We tested the hypothesis that candesartan, an ARB, could regress LVH, in association with improvement of insulin resistance in EH patients. The study participants were nondiabetic and never-treated EH patients (n = 10). Candesartan was administered at a mean final dose of 10.4 +/- 2.1 mg/d for 24 weeks. Candesartan treatment resulted in a significant decrease of systolic and diastolic blood pressures, LV mass index (LVMI), homeostasis model assessment (HOMA) index, and plasma brain natriuretic peptide (BNP). A significant correlation was observed between the percent decrease in LVMI and that of both the HOMA index (r = 0.83, P <.001) and BNP (r = 0.71, P <.005). Stepwise regression analyses revealed that the percent decrease of HOMA index was an independent predictor for both percent decrease in LVMI and plasma BNP. Our findings suggest that pharmacological blockade of angiotensin II receptors by candesartan could improve LVH in never-treated EH patients, which may relate to the improvement of insulin resistance.     

Disturbed circadian blood pressure rhythm and C-reactive protein in essential hypertension

We investigated the effect of the diverse definition criteria of the dipping and non-dipping status on the assessed differences in inflammatory activation between dippers and non-dippers with essential hypertension. 269 consecutive subjects (188 males, aged 50+/-7 years) with untreated stage I-II essential hypertension underwent ambulatory blood pressure (BP) monitoring and high-sensitivity C-reactive protein (hs-CRP) level determination. The population was classified into dippers and non-dippers based on the three following different definitions: true non-dippers (TND): non-dippers (nocturnal fall of systolic and diastolic BP of <10% of the daytime values, n=95) and dippers (the remaining subjects, n=174); true dippers and true non-dippers (TD-TND): non-dippers (nocturnal fall of systolic and diastolic BP<10%, n=95) and dippers (nocturnal fall of systolic and diastolic BP> or =10%, n=75); systolic non-dippers (SND): non-dippers (nocturnal systolic BP fall of <10% of the daytime values, n=145) and dippers (the remaining subjects, n=124). Non-dippers compared to dippers in the TND, TD-TND and SND classification exhibited higher levels of log hs-CRP (by 0.11 mg l(-1), P=0.02; 0.13 mg l(-1), P=0.03 and 0.14 mg l(-1), P=0.02, respectively) and 24 h pulse pressure (PP) (by 4 mm Hg, P=0.006; by 5 mm Hg, P=0.003 and by 5 mm Hg, P<0.0001, respectively). Twenty-four hour PP and nocturnal systolic BP fall were independent predictors of log hs-CRP (P<0.05 for both) in multiple regression analysis. In conclusion, essential hypertensive non-dippers compared to dippers exhibit higher hs-CRP values, irrespective of the dipping status definition. Furthermore, ambulatory PP and nocturnal systolic BP fall interrelate and participate in the inflammatory processes that accompany non-dipping state.     

Circadian Blood Pressure Changes and Myocardial Ischemia in Hypertensive Patients With Coronary Artery Disease

Objectives. We sought to evaluate whether different circadian blood pressure (BP) changes could influence the occurrence of ischemic episodes in untreated and treated hypertensive patients with stable coronary artery disease (CAD).

Background. In hypertensive patients with CAD the occurrence of myocardial ischemia could be influenced by either high or low BP values. Ambulatory monitoring has shown that circadian BP profile is not uniform in hypertensive patients.

Methods. Twenty-one patients with a nighttime BP fall <10% (“nondippers”), 35 with a nighttime BP fall between >10% and <20% (“dippers”) and 14 with a nighttime BP fall >20% (“overdippers”) with CAD underwent simultaneous ambulatory BP and electrocardiographic monitoring before and during drug therapy with nitrates and atenolol or verapamil in a prospective, randomized, open, blinded end point design.

Results. Daytime BP was not significantly different among the groups both before and during therapy. Nighttime BP was different by definition. Treatment significantly reduced BP values in each group (p < 0.05). Daytime ischemic episodes did not differ among the groups either before or during therapy. Drug therapy significantly reduced daytime ischemia (p < 0.05). In untreated patients, nighttime ischemia was more frequent in nondippers than in dippers and overdippers (p < 0.05). Drug therapy significantly reduced nocturnal ischemia in nondippers (p < 0.05), had no significant effect in dippers and significantly increased nighttime ischemia in overdippers (p < 0.05). During treatment, nighttime ischemia was more frequent in overdippers than in dippers and nondippers (p < 0.05). The same results were achieved when ischemic episodes were defined with more restrictive criteria (ST segment depression ≥2 mm).

Conclusions. Circadian BP changes can influence the occurrence of myocardial ischemia in untreated and treated hypertensive patients with CAD. Nocturnal ischemia was found to be more frequent in nondippers among untreated patients and in overdippers among treated patients, potentially suggesting different therapeutic approaches based on circadian BP profile.     

QT Dispersion in Dipper- and Nondipper-Type Hypertension

The aim of this study was to identify the relationship of QT dispersion on 12-lead electrocardiograms and left ventricular mass index on echocardiograms associated with the circadian rhythm of blood pressure (BP). Heart rate and BP were monitored every 30 min for 48 h in 62 patients with essential hypertension using an ambulatory BP monitoring device. The patients were divided into four groups according to gender and circadian BP pattern (nocturnal BP dipper or nondipper). The patients were classified as dippers if their daytime BP decreased by at least 10% during the night and all the other subjects were classified as nondippers. Age, body mass index, and 48-h mean BP were similar among the four groups. During the night-rest period, the systolic and diastolic BP were significantly decreased in dipper-type hypertensives. The maximum QT_c interval and QT_c dispersion were longer in nondippers than in dippers. Left ventricular mass index (LVMI) had a tendency to increase in nondippers. The nocturnal reduction of BP significantly correlated with QT_c dispersion and LVMI. The QT_c dispersion significantly correlated with LVMI and interventricular septum thickness.     

Use of plasma B-type natriuretic peptide level to identify asymptomatic hypertensive patients with abnormal diurnal blood pressure variation profiles: nondippers, extreme dippers, and risers.

We examined the relationship between plasma B-type natriuretic peptide (BNP) level and diurnal variability pattern of blood pressure (BP). Twenty-four-hour ambulatory BP monitoring was performed in 98 patients with asymptomatic essential hypertension, and the patients were classified into four groups according to their circadian BP variation profiles: dippers (n=29), nondippers (n=36), extreme dippers (n=19), and risers (n=14). Plasma BNP was measured by enzyme immunoassay. Based on the distribution pattern of BNP values, the values were analyzed after logarithmic transformation. Significant differences in plasma BNP levels among the types of circadian BP variations were demonstrated by analysis of variance (p<0.0005). Nondippers and risers showed significantly higher plasma BNP levels (mean [range: -1 SD and +1 SD]: 16.1 [6.3, 41.6] pg/mL and 29.2 [15.9, 53.4] pg/mL, respectively) than dippers (8.4 [3.7, 19.1] pg/mL). The area under the receiver operating characteristics curve for distinguishing patients with abnormal circadian BP variation from those with normal variation was 0.72, indicating that plasma BNP levels were useful for distinguishing between these patients. Specificity of 69% and sensitivity of 72% were obtained with a cut-off value of 10.5 pg/mL (log plasma BNP, 1.02) for distinguishing the abnormal diurnal BP profile group from the normal group. In conclusion, hypertensive patients with abnormal diurnal BP variation patterns (nondippers, extreme dippers, and risers) showed higher plasma BNP levels than those with normal circadian BP variation (dippers). Plasma BNP level is clinically useful for the identification of hypertensive patients who have abnormal circadian BP variability, which increases the risk of cardiovascular events.     

Variability of diurnal changes in ambulatory blood pressure and nocturnal dipping status in untreated hypertensive and normotensive subjects

An absent or diminished blood pressure (BP) fall during sleep (so-called "nondipping") has been associated with a higher risk of cardiovascular complications, but the long-term reproducibility of dipper status and the relationship between diurnal changes in BP and perceived sleep quality have not been previously documented in untreated hypertensive patients. Ambulatory BP (ABP) and dipping status were examined in 79 subjects (69 hypertensives and 10 normotensives) at 0, 6, and 12 months. Fifty-six percent of subjects had no change in their dipping status, the majority (53%) dipping normally on all three occasions. However, 44% of patients had variable dipping status, and normal nighttime dipping in BP was observed more often when patients perceived their sleep quality to be good during the period of ABP recording. These results highlight significant intrasubject variability in the diurnal fluctuations in ABP and dipper status, which may in part reflect day-to-day variations in sleep disturbance during ABP monitoring. Classifying hypertensive patients into dippers or nondippers on the basis of a single ABP recording is unreliable and potentially misleading.     

Association of insulin resistance and nocturnal fall of blood pressure in GH-deficient adults during GH replacement

The GH deficiency syndrome in adults is characterized by changes in body composition, metabolic, cardiovascular and psychological profile. Such alterations fit the metabolic syndrome. Changes of blood pressure (BP) levels related to the presence of insulin resistance (IR) may be present in the GH-deficient adult prior to or after therapy with recombinant GH (hGH). The purpose of the study was to assess the relationship between BP and IR in GH-deficient adults after 24 months of replacement with hGH. Thirteen GH-deficient adults were studied [7 men and 6 women, with an average age of 38.6+/-14.14 yr body mass index (BMI) 25.83+/-2.26 kg/m2]. The BP was assessed by means of ambulatory monitoring of BP (AMBP), prior to the treatment and 12 and 24 months after replacement with hGH. Glucose metabolism was assessed by the homeostatic model assessment (HOMA), during the same periods. The average dosage of hGH utilized was 0.67+/-0.15 mg/day. In the analysis of BP levels, we observed a decrease of the diurnal systolic BP (SB P) (p=0.043) and a reduction of the diurnal systolic (p=0.002) and diastolic pressure loads (p=0.038). During the night there were no changes in BP levels. We observed an increase in the percentage of patients with a non-physiological nocturnal fall (non dippers) after replacement with hGH (61.53%). The mean HOMA, insulin and glucose in the fasting state did not present any statistically significant changes. Although the patients within the nondipper group had higher HOMA and insulin levels throughout the study, there were no changes in any of these parameters after GH replacement. All patients with HOMA >2.5 were within the non-dipper group, whereas all dippers had HOMA <2.5. In conclusion, 24 months of therapy with hGH do not seem to have affected glucose homeostasis, and since there is no relationship with the increase of the percentage of non-physiological nocturnal fall, we will need a longer observation time to discover the effects of this finding.