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To investigate the effect of amlodipine on baroreflex sensitivity and sympathetic system activity, 36 patients with essential hypertension were randomized to once-daily, double-blind treatment with amlodipine 5 mg or placebo 5 mg for 60 days. Measurements with a Finapres device allowed calculation of baroreflex sensitivity and blood pressure (BP) variability. Adrenergic activity was assessed via measurements of lymphocyte beta2-adrenoceptors and plasma catecholamine concentrations. Compared with placebo, amlodipine significantly decreased BP, but did not significantly alter baroreflex sensitivity. Spectral analysis of Finapres data showed that, compared with placebo, amlodipine decreased the variability of systolic blood pressure, diastolic blood pressure, and RR interval in the low frequency band. There were no simultaneous changes in adrenergic function, however, suggesting that these effects of amlodipine were not mediated via sympathetic nervous system activation.

Background: Many studies have shown definite but weak correlations between 24h blood pressure and left ventricular mass in hypertension., Objective: The present study applied an original multivariate analysis of parameters from ambulatory blood pressure monitoring to predict left ventricular mass in hypertension., Methods: Two hundred untreated hypertensive subjects (age=51+/-13 years, clinic blood pressure=163/98mmHg) had echocardiography and 24h recording of blood pressure. Data from 102 subjects were used to construct a mathematical model for prediction of left ventricular mass. The remaining 98 subjects were used to validate the model., Results: The model included age, weight, height, 24h systolic blood pressure, heart rate over 24h, standard deviations of systolic blood pressure and of heart rate over 24h. Using this model, we explained 63% of the variance of left ventricular mass. Moreover, the model was validated for the correlation (r=0.70) between measured and the estimated left ventricular mass., Conclusions: Systolic blood pressure, heart rate and their standard deviations over 24h contribute to left ventricular mass in hypertensive subjects. Thus, it is important to take into account not only blood pressure but also heart rate in clinical studies.

The role of blood pressure on carotid remodeling, using no indexed and indexed parameters, was studied in essential hypertension. Carotid parameters were also compared to cardiac mass and aortic stiffness. Forty untreated hypertensive men had echocardiography, carotid ultrasonography and carotidfemoral pulse wave velocity measurements. Cross-sectional area index was associated essentially with the 24-hour systolic blood pressure whereas intima-media thickness was related especially to the 24-hour pulse pressure. Carotid intima-media thickness and cross-sectional area indexes were less related to blood pressure variables than non-indexed parameters. There is an independent association between 24-hour pulse pressure and left ventricular mass index and pulse wave velocity. To conclude, blood pressure, particularly pulse pressure, is associated with vascular and cardiac alterations. The indexation by the body surface area do not provide any additional information in the association between carotid and blood pressure parameters.

The intima-media thickness of the carotid artery is a cardiovascular risk factor, especially in hypertensive, diabetic or dyslipidemic patients. Very accurate tools of measurement are essential in order to optimise the analysis of the severity of the vascular lesions. Present methods use computer programmes for ultrasonic image enhancement and have already been shown to be very reproducible. However, there is still room for improvement in the detection of lesions at their initial stage of development and in the follow-up of their progression with or without antihypertensive or lipid lowering drugs.

Turner's syndrome is associated with congenital heart disease in a third of cases. Several reports of aortic dilatation and of death by dissection or rupture of the aorta have been published. The authors undertook a prospective study to assess the incidence of cardiac malformations and aortic dilatation in genetically confirmed Turner's syndrome. Twenty-six out of 34 patients recalled (76%), aged 7 to 30 years (average 17 +/- 6 years) accepted their inclusion in this study and underwent clinical examination, ECG, chest X-ray and echocardiography. Thirteen patients had a monosomy 45X and 13 a mosaic or structural abnormality. Six had a history of cardiovascular disease (operated coarctation: 2 cases, kinking: 2 cases, Hypertension: 2 cases). Eight patients (30%) had one or several anatomical cardiovascular abnormalities: bicuspid aortic valve (19.2%), abnormalities of the aortic isthmus (kinking or coarctation) (15.4%), aortic regurgitation (7.7%), mitral stenosis (3.8%), partial anomalous venous drainage (3.8%), patent ductus arteriosus (3.8%) and left superior vena cava (11.5%). Systematic evaluation of the aorta resulted in the diagnosis of dilatation of the ascending aorta in 1 case and dilatation of the sinus of Valsalva in 2 other cases. The authors conclude that echocardiographic evaluation is essential after the diagnosis of Turner's syndrome. It should be repeated regularly to detect dilatation of the aorta which carries the risk of serious complications, such as rupture or dissection of the aorta.

The role of pulse pressure (PP) in cardiovascular remodelling was studied in 61 never treated hypertensive subjects who were selected on the criteria of ambulatory blood pressure (BP) monitoring (mean BP over 24 h: 147 +/- 14/96 +/- 10 mm Hg). Echocardiography and carotid ultrasonography were performed and the vascular images analysed using a specific automatic measuring program. Thirty percent of subjects had left ventricular hypertrophy (LVH). Left ventricular mass index (LVMI) was related to the clinic (r = 0.35) and ambulatory (r = 0.41 over 24 h, r = 0.38 daytime and r = 0.42 night-time) PP and to the systolic BP. PP was higher when there was LVH. Vascular thickening was found in 6.6% of subjects (carotid intima-media thickness (IMT) >/=1.0 mm). Among the BP parameters, IMT and cross-sectional area (CSA) were related only to the clinic PP (r = 0.27, r = 0.29 respectively) and to the ambulatory PP (over 24 h: r= 0.29, r = 0.28; daytime: r = 0.22, r = 0.23; night-time: r = 0.32, r = 0.30). In men, the relationship between CSA and PP (clinic and over 24 h) was independent of age. A total of 16.7% of subjects with LVH had intima-media thickening in contrast to 2.3% in the group without LVH. LVMI was related to the CSA (r = 0.37) and to the IMT (r = 0.31). However, after multivariate analysis taking into account the PP, relationships between IMT or CSA and LVMI disappeared. Our data showed that the PP was the most important BP parameter in the development of cardiac and arterial remodelling in hypertension. Journal of Human Hypertension (2000) 14, 23-30.

Aims: Cardiac failure patients were studied systematically using polysomnography 1 month after recovering from acute pulmonary oedema, and again after 2 months of optimal medical treatment for cardiac failure., Methods and Results: This prospective study of consecutive patients was conducted in a cardiac care unit of a university hospital. V o(2)measurements and left ventricular ejection fraction were recorded. Thirty-four patients, initially recruited with pulmonary oedema, improved after 1 month of medical treatment to NYHA II or III. They were aged less than 75 years and had a left ventricular ejection fraction less than 45% at the time of inclusion. Age was 62 (9) years, body mass index= 27 (5) kg x m(-2)and an ejection fraction= 30 (10)%. Eighteen of the 34 patients (53%) had coronary artery disease. Twenty-eight of the 34 had sleep apnoea syndrome with an apnoea+hypopnoea index >15 x h(-1)of sleep. Thus, the prevalence of sleep apnoea in this population was 82%. Twenty-one of 28 (75%) patients had central sleep apnoea and seven of 28 (25%) had obstructive sleep apnoea. Patients with central sleep apnoea had a lower Pa co(2)than those with obstructive sleep apnoea (33 (5) vs 37 (5) mmHg, P<0.005). Significant correlations were found between apnoea+hypopnoea index and peak exercise oxygen consumption (r= -0.73, P<0.01), and apnoea+hypopnoea index and Pa co(2)(r= -0.42, P = 0.03). When only central sleep apnoea patients were considered, a correlation between apnoea+hypopnoea index and left ventricular ejection fraction was also demonstrated (r= -0.46, P<0.04). After 2 months of optimal medical treatment only two patients (both with central sleep apnoea) showed improvement (apnoea+hypopnoea index <15 x h(-1))., Conclusions: We have demonstrated a high prevalence of sleep apnoea, which persisted after 2 months of medical treatment, in patients referred for acute left ventricular failure. Central sleep apnoea can be considered a marker of the severity of congestive heart failure., (Copyright 1999 The European Society of Cardiology.)

Objective: To study the relationships between evolution of changes in blood pressure (BP) over the 24 hour cycle and their cardiac and vascular consequences in mild to moderate hypertensive (HT) subjects (WHO criteria)., Material and Methods: 151 patients presenting with mild to moderate essential HT (Age 49 +/- 12 yrs, 63 M 44W)--ambulatory measurement of BP over 24 hours (Spacelabs 90207) automatic determination of the diurnal cycle by Fourier analysis (5 harmonics) and calculation of the slope of BP variation (mmHg/hr) at the point of transition from day to night (nocturnal dip slope (NDS)), and at the change from night to day (morning rise slope (MRS). Patients with inversion of the day-night cycle were excluded, day-night being arbitrarily defined as 7 to 22 h and 22 to 7 h. Echography of left ventricular mass index (LVMI)/Penn convention, formula of Devereux, and carotido-femoral distensibility by pulse wave velocity (PWV, Complior Colson France)., Results: Ambulatory measures of BP and HR and of cardiovascular parameters were as follows. [table: see text] The slope of nocturnal fall (NDS) and morning rise in SBP (MRS) is significantly correlated with LVMI (NDP r = -0.02, p = 0.049, MPP r = 0.21, p = 0.029) and with PWV (MPP: r = 0.32, p = 0.005). No relationship was found with the DBP values. By multivariate analysis taking into account age, sex, 24 h SBP, MPP slope velocity was the only variable which was significantly related with the model of PWV and LVMI (p < 0.001)., Conclusion: Dipper and non-dipper studies have been performed to examine the consequences of day night variations in BP. The evolution of diurnal changes in BP seems to have an effect on the vessels and heart and may be a simple analysis tool for assessing prognosis and therapeutic effects.

Unlabelled: This work tests a new ambulatory blood pressure device: Save 33 II. The evaluation is conducted according to the phases II and IV of the British Hypertension Society (BHS) protocol: the phases I and III (before and after use) are not performed as this device has received the European quality label 'CE' that guarantees a +/- 3 mmHg accuracy before and after 10,000 simulated cycles. Two trained observers (hearing test and certification done according to the BHS recommendations) have performed 7 sequential BP measurements with conventional and automatic method, at the same arm, among 85 patients. The ranges of mean blood pressure are 78-203 mmHg, for SBP and 53-130 mmHg for DBP., Results: The Save 33 II monitor satisfies the grade B of BHS evaluation for both systolic and diastolic pressures. This device also satisfies the Association for the Advancement of Medical Instrumentation (AAMI) protocol: mean difference between methods and standard deviation less than 5 +/- 8 mmHg: -2.7 +/- 6.8 mmHg for SBP and -0.86 +/- 6.6 mmHg for DBP. The in-use assessment is conform to BHS criteria for 20 recordings (less than 20% invalid values during day and night); the 5 other recordings have not enough night values, due to batteries failure (2 cases), sleeping discomfort (2 cases) and a cuff withdraw., Conclusion: This device, in the tested configuration, agrees the B grade of BHS and can be recommended for ambulatory blood pressure measurement.

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.

Objective: To analyse the performance of a Windkessel blood pressure (BP) modeling of arterial compliance adjusted in a dynamic fashion according to a non-linear relationship between the arterial compliance (AC) and BP. Non invasive measurements of the radial BP waveform (MILLAR tonometry) were compared to those constructed by an electric simulator reproducing the model in a symmetrical network subdivided into 121 segments. We introduced at cardiac level the aortic stroke volume (Doppler echocardiography) and the dynamic values of compliance (relation of compliance-to pressure, constant or variable) whether the model was linear or non linear, measured by high resolution Doppler (NIUS 02) for each subject., Results: At the radial artery segment the modelled BP obtained by the non linear model of AC was not significantly different from the measured BP wave, while in the linear model (AC constant at mean BP level) the systolic BP was significantly underestimated. (*P < 0.05)., Conclusion: This work shows the limits inherent in simplification of arterial compliance in the Windkessel model using constant parameters. This demonstrates the influence of the dynamic properties of the arterial wall in a conduction artery on the level of systolic and diastolic BP.

The 24-h ambulatory systolic blood pressure (ASBP) recording has become a helpful tool in the diagnosis of hypertension and evaluation of the efficiency of anti-hypertensive drugs. Yet, the very high variability of ASBP makes the analysis of the recording rather difficult. A potential solution to reduce ASBP variability has been studied and is presented in this article. It consists of equipping the portable ASBP recorder device with other sensors, a three axes accelerometer and a heart rate recorder, so as to enable an analysis to be undertaken of the arterial pressure profile in the light of these concomitant data. A database has been collected, and a model linking ASBP variations with body acceleration and heart rate measurements is developed. Its performance is tested in prediction and the results compared with those obtained from one of the solutions currently used by physicians to deal with ASBP variability. The results obtained with 16 young subjects from the database, for whom two 24-h recordings are available, are significantly improved and very encouraging.

Unlabelled: The Windkessel model is a linear model which does not take into account the structural and functional variations of the arteries related to the pulsatility of the blood pressure (BP) and its variations between systole and diastole., Objective: To analyse the performance of a BP modelisation where the parameters of AC are adjusted in a dynamic fashion according to a curvilinear relationship of the arterial properties (compliance) in relationship to the BP between systole and diastole., Design and Methods: 9 control subjects (age 25 +/- 3). The non invasive measures of the radial BP waveform (Millar tonometry) was compared to that constructed by an electric simulator reproducing the model in a sysmetrical network subdivised into 121 segments where we introduced for each subject: at cardiac level, the aortic stroke volume (Doppler echocardiography), and at the radial level, the dynamic values of compliance and diameter according to an arc-tangent model (measured by arterial echography NiUS02)., Results: The BP obtained by the adjusted model, where the AC parameter follows the curvilinear, relationship dV/dP measured experimentally, was not significantly different from the experimental, while in the constant model (AC at mean BP level) the systolic BP was different., Conclusion: This work shows in an experimental way the limits inherent in simplification in the Windkessel modelisation of the vascular system with constant parameters. It shows in a conduction artery the influence of the functional properties of the arterial wall on the level of systolic and diastolic BP.

The HOT study is the largest controlled therapeutic trial conducted to date in hypertension. This international, prospective, randomised trial is designed to determine the optimal blood pressure to be obtained during treatment, in order to achieve optimal reduction of complications and cardiovascular mortality. The HOT study is conducted according to the PROBE methodology (Prospective Randomised Open Blinded Endpoints. It has three objectives: 1) to evaluate the relationship between the development of major cardiovascular events and the DBP target level (DBP < or = 90, DBP < or = 85 or DBP < or = 80 mmHg. 2) to evaluate the relationship between the development of major cardiovascular events and real DBP observed, 3) to determine whether low-dose acetylsalicylic acid (75 mg/day) provides an additional benefit in terms of cardiovascular morbidity and mortality in treated hypertensive subjects. Between April 1992 and October 1994, 18,790 patients, between the ages of 50 and 80 years (26 countries), were randomised to these 3 target DBP groups and several parameters likely to influence the blood pressure fall were identified. The reduction of DBP was all the more pronounced the higher the baseline DBP. For a baseline DBP equal to 100 mmHg, the mean fall was 18 mmHg and for a baseline DBP equal to 110 mmHg, the mean fall was 27 mmHg. Advanced age was also found to be a factor promoting reduction of DBP, which increased after the age of 65 years. Analysed in relation to the type of treatment, this more marked reduction in the elderly showed that monotherapy with a calcium channel blocker was very effective on DBP and especially after the age of 75 years. The data of the study also showed that SBP decreased in parallel to DBP, but to an even greater extent. Thus, a 10 mmHg reduction of DBP induces a reduction of SBP by approximately 20 mmHg. This reduction of SBP related to the level of DBP was even more marked the higher the baseline SBP and the higher the target DBP objective. Thus 80% of patients in the DBP < or = 80 mmHg group had an SBP < or = 150 mmHg during treatment. Among the other factors, weight appeared to clearly influence reduction of DBP, as the reduction of DBP was more marked the lower the patient's weight. In contrast, the body mass index was poorly correlated with the reduction in blood pressure. The blood pressure reduction, regardless of weight, was more marked when a stricter blood pressure objective was adopted (DBP < or = 80 mmHg). Finally, in the particular case of elderly subjects, treatment with a calcium channel blocker appeared to be very effective in reducing the blood pressure.

Objective: To determine how much of the variations of blood pressure during a 24 hour period could be accounted for by a change in activity using an accelerometer to detect the physical activity and establish a predictive model., Materials and Methods: 18 healthy subjects (mean age 25 +/- 2 yrs) were studied during daily life (24 hours) twice one week apart. The systolic and diastolic blood pressure, heart rate (HR), and time of measure were recorded by ambulatory monitoring using Spacelabs (4 measures per hour). A portable digital memory device was designed for the 24 hours ambulatory monitoring of HR (ECG) and physical activity. This device consists of an ECG Holter (ELA medical model Cinesis with digital memory) and a three piezoresistive type accelerometer sensors (prototype ELA research) able to record physical activity in the 3 space dimension., Results: The data of the first recording were compared to the predicated values from the application of a logarithmic model of activity to the second recording. The model then predicted 53 +/- 19% of the systolic BP values of the test day. The mean individual difference for a given time period of one hour between the measured and the predicted systolic BP from the model was 1.45 +/- 3.1 mmHg with a range of [-6.9; 3.4 mmHg]. The mean individual systolic BP difference for the same given time period of one hour but without predictive model was 1.29 +/- 10 mmHg with a range of [-28; 43 mmHg]., Conclusion: This study show that 3 D accelerometer is an easy tool to program individual model of ambulatory blood pressure variability. The introduction of this qualitative method seems logical in therapeutic trial.

Like all laboratory parameters, measurement of heart rate must comply with certain theoretical conditions. In practice, it results from a compromises between the defined objectives, the material and the conditions of measurement. Effort are made to reproduce baseline conditions. The questions of the duration of measurement, it reproductibility, expression of the results, and the methods themselves are discussed. Standardization is required.

A number of retrospective epidemiological and clinical arguments described in this article demonstrate that elevated heart rate (HR) is a predictive factor of cardiovascular risk due to activation of the sympathetic system which increases blood pressure and increases the risk of atherosclerosis and its complications. However, no epidemiological study has prospectively studied HR as the primary endpoint.

BACKGROUND: Ambulatory blood pressure measurements allow better evaluation of the effects of antihypertensive drugs on the diurnal profile of blood pressure. Various strategies, such as determining peak: trough ratio and smoothness indexd, with and without smoothing of raw data by Fourier analysis, have been put forward to define the efficacy and duration of action of antihypertensive drugs better. To date there has been little interest in the time scale of maximum effect after intake of the drug and few data regarding effects on variability of heart rate exist.OBJECTIVE: To compare the effects of three antihypertensive agents (10 mg bisoprolol, 2 mg lacidipine and 20 mg lisinopril) on the peak: trough ratio, the smoothness index and the peak response slope for blood pressure and heart rate. METHODS: After a e-week washout period, 99 patients were randomly allocated in double-blind fashion to one of the three drugs. Ambulatory blood pressure measurements were taken upon entry to the study and after 6 weeks of treatment. The diurnal profile of blood pressure was smoothed using fast Fourier analysis. RESULTS: Each of the three treatments had a similar antihypertensive effect over the 24 h. The trough:peak blood pressure ratio for the group as a whole was higher than the value calculated on an individual basis. There was no difference among the peak response slopes for the three treatments; because one integrates three variables (peak, trough and time to maximal effect) this variable expresses large variations in individual cases. We observed differences among the smoothness indices of diastolic blood pressure for the durgs. Studying heart rate during the time of peak effect on blood pressure provides new findings. With bisoprolol, because the heart rate decreased both at the peak and at the trough, the ratio provides a good estimate of a balanced 24 h effect. In contrast, with lacidipine, the rise in heart rate over the 24 h renders use of this ratio impractical. The smoothness index with bisoprolol is significantly higher than those with lacidipine and lisinopril. Examination of individual heart rate slopes shows that there is a large variability for lacidipine and bisoprolol which is not significantly correlated to the slopes of blood pressure. CONCLUSION: To understand the effects of antihypertensive medication fully, various aspects need to be taken into account, namely the trough:peak ratio, the smoothness index and the peak response slope, each one of which is complementary to the analysis of the efficacy. Furthermore, it also seems necessary to study the heart rate, which can be significantly influenced by certain drugs and hence has important implications for the overall haemodynamic state.

Heart rate (HR), which participates in the short-term control of blood pressure and blood flow, depends on an intrinsic system and an extrinsic system via which the central nervous system processus and regulates the afferent stimuli of baroceptors and chemoreceptors. The situations responsible for short-term variations of HR include effort, the "white coat" effect, circadian rhythm, age, gender. The long-term maintenance of the HR level is dependent on nervous mechanisms, and haemodynamic and energetic conditions.

Background: The dynamic elastic modulus of central arteries is very frequency-dependent Although resting heart rate is a potent independent risk factor for morbidity and mortality both from cardiovascular and from noncardiovascular disease, no link between tachycardia and arterial stiffness has ever been established., Objective: To relate arterial stiffness to heart rate in a population with relatively low cardiovascular risk., Methods: Pulse-wave velocity measurements and high-resolution echo-tracking techniques were used to determine the degree of arterial distension (of carotid and femoral arteries, and terminal aorta) and the velocity of the pulse wave (aorta and upper and lower limbs) at the same time as heart rate, in members of a large population of normotensive and hypertensive subjects in a multicenter study in Paris, Fleury-Merogis and Grenoble (France)., Results: A high heart rate was strongly associated with reduced distension and elevated pulse-wave velocity, even after adjustment for age and blood pressure. A high aortic pulse-wave velocity was also negatively associated with a low baroreflex sensitivity. The most significant associations between high heart rate and high arterial rigidity were found for the carotid artery, the thoracic aorta, and the lower limbs, but there was no significant result for the terminal aorta and the arm arteries., Conclusion: This study demonstrates that there is a statistically significant positive link between high heart rate and high arterial stiffness measured at the site of central and lower limb arteries. Since an elevated heart rate has been shown to be associated with cardiovascular risk, such findings may be relevant for future cardiovascular studies in epidemiology.

The regulation of blood pressure (BP) is traditionally described in terms of homeostasis, and indicates that BP although being continuously perturbed by external stimulations always displays the tendency to come back toward a reference set point. Experimental and clinical studies indicate that these fluctuations occurring around the average present a source of complementary information on the mechanism of cardiovascular control. Recently a wide variety of algorithm and models have been proposed to study the cardiovascular system through new technics of continuous non invasive BP or heart rate (HR) measurements. They give new insites for the evaluation of hypertensive patients and relevance to the understanding of the role of the disorder of the tonic regulation of BP, rather than its short-term variability or reactivity. However, if available data unequivocally indicate that the analysis of variability is a useful tool, the interpretation of those data in clinical trials is not always optimal because there is lot of interaction between BP, HR and other biological signals, and furthermore the use of laboratory data introduces problems to predict what happens on daily life ambulatory conditions.

Objective: To determine how much of the variations of blood pressure during a 24 hour period could be accounted for by a change in activity and establish a predictive model., Materials and Methods: Twenty three healthy subjects (mean age 25 +/- 2 years) were studied. The BP, heart rate (HR), and time of measure (T) were recorded by ambulatory BP monitoring using Spacelabs (4 measures per hour). At each measure the subject noted in a diary the degree of activity on a six level semi-quantitative scale., Data Analysis: A model was constructed using an analysis of covariance. Different parameters were added in succession to reach a model of the type P: P0 + A + beta + (HR-HR0) + H, were P = predicted systolic pressure, P0 = mean systolic BP over the 24 hours. A variation in systolic BP for activity level, beta = the slope of the regression between systolic BP and HR during activity A, and HR0 the mean HR during this activity., Results: 1) In order to test the model, the values measured in one subject were compared to the predicted values from the model in 22 others. The procedure was then repeated for the other subjects. This common model predicted 41 +/- 21% of fluctuations in BP of the subject analysed with a range of 0 to 66%. 2) In order to refine the individual model two subjects were explored 7 times over 24 h of non consecutive days. The measures of the last recording were compared to the predicted values from the application of the model to the six preceding recordings. The model then predicted 81% and 66% of the BP values of the test day. The mean of the 24 hour individual difference over a one hour period between the measures and its predicted value by the model was 0.13 +/- 4.8 mmHg, and -0.75 +/- 7.7 mmHg., Conclusion: This study expresses in a quantitative fashion the importance of the level of activity in the evaluation of the level of ambulatory BP. The introduction of this method of quantification and analysis seems logical in therapeutic trial. The difference in the predictions by the model for some subjects poses the problem of uniform coding of activities and that of the recognition of other events such as stress and dreaming in sleep.

In the most recent WHO recommendations of 1996 it was reiterated that the classification of HT still remains based on the actual BP figures but also on the importance of target organ lesions. Thus the study of cardiac and vascular function and in particular the presence of hypertrophy or remodeling is of importance. A limited number of studies have examined the prevalence, the association and the correlation between modifications and remodeling in the heart and in the vasculature. It is important to distinguish compliance vessels such as the carotid from resistance vessels such as the radial. For compliance vessels the prevalence of cardiac and vascular hypertrophy are nearly identical being around 5% for normotensive subjects and around 12% for hypertensive subjects. This prevalence of thickening in the intima-media is more evident in subjects with left ventricular hypertrophy (LVH). The left ventricular geometric pattern is also an element to take into account. The presence of concentric remodeling of the left ventricle without LVH has already been associated with an increase in intima-media thickness (IMT). When there is an LVH this IMT is similar in severity to the LVH and in particular concentric. For resistance vessels such as the radial artery the number of studies is limited but a significant correlation between left ventricular mean wall thickness and common carotid artery distensibility and compliance has been found. There is also a significant correlation between the radial median lumen ratio and the relative wall thickness but this correlation disappears when age and systolic BP are taken into account. Thus for this type of vessel it is too early to conclude the elements contributing to structural changes. The determinant factors for these structural changes in the heart and the carotid arteries associated with hypertension are certainly multiple be they haemodynamic, hormonal or genetic. The observation establishing an association between anomalies at cardiac and vascular level may have undoubted diagnostic, prognostic and therapeutic implications which are all intimately related and which require refinement and confirmation.

Aim of the Study: To compare heart rate (HR) and blood pressure (BP) variability in hypertensive patients with or without a fall in BP during the night., Methods: 33 mild to moderato hypertensive patients, mean age 45 +/- 15 years, underwent an echocardiogram, a 24-hr ambultory BP monitoring (ABPM), and a 24-hr ECG monitoring. In addition, a continuous BP recording over 15 minutes was performed between 9 and 11 a.m. both in supine and standing positions, by using digital plethysmography (Finapres device)., Statistical Analysis: non parametric tests., Results: [table: see text], Conclusion: In non dippers, morning BP and HR low-frequency oscillations are shifted to a lower level, as compared to dippers. This characteristic is associated with a reversed circadian pattern of sympathetic activity.

Unlabelled: Angiography still remains the first line investigation to demonstrate a renal artery stenosis. We have evaluated the sensitivity and the specificity of renal scintigraphy in the diagnosis of renal artery stenosis using two technetium markers, MAG 3 and DTPA., Patients: 45 hypertensive (HT) patients (WHO criteria) referred for investigation of renovascular hypertension according to the criteria of the AHA Scientific Council and were found to have a unilateral renal artery stenosis of varying severity. Age was 61 > +/- 13 years; sex-ratio F/M 21/24; creatinine < 150 mumol/l. There were non insulin dependent diabetics, and none had been treated with ACE inhibitors or diuretics for 15 days. Bilateral arterial stenosis was excluded a posteriori., Methods: MAG3 and DTPA scintigraphy were performed one hour after a dose of 25 mg of captopril plus hydration with 500 ml of intravenous saline. Blood pressure was measured by dynamap every 15 min from minus one hour to the end of the study. The principle outcome measure was nephorgram phase and the secondary measure was the angiographic phase (two images per second). The two scintigraphy techniques were performed at a mean interval of 2.9 +/- 2.1 days. Digitized angiography via the arterial route was performed using left anterior oblique and right anterior oblique images., Results: [table: see text], Conclusion: There was only one false positive scintigraphy result with a polar artery. In contrast 45% of unilateral stenoses were not diagnosed by scintigraphy. Both markers gave similar results even if subjectively the MAG3 images were of better quality. Analysis of the angiographic phase and of the size of the kidneys did not improve the diagnostic accuracy and could lead to false positive results.

Aim of the Study: To compare heart rate (HR) and blood pressure (BP) variability in hypertensives with or without left ventricular hypertrophy (LVH)., Methods: Thirty-three mild to moderate hypertensive patients, mean age 45 +/- 15 years, underwent an echocardiogram, a 24 hr ambulatory BP monitoring (ABPM), a 24 hr ECG monitoring and a continuous BP recording over 15 minutes both in supine and standing positions, by using digital plethysmography (Finapres device)., Statistical Analysis: non parametric tests., Results: [table: see text], Conclusion: LVH is associated with a reduction in the markers of sympathetic activity and a decreased baroreflex sensitivity.

OBJECTIVE: To establish the acceptability and tolerance of ambulatory blood pressure monitoring (ABPM). METHODS: A two-part questionnaire was completed by the doctor; one part before ABPM and the second after the recording. The pre-recording data concern the demographic data of the patient: previous illness, symptoms, reaction of the patient, anthropometric data, treatment details and the reason for ABPM. The second part of the questionnaire records the type of monitor used, the conditions of the recording and any difficulties for, or adverse effects on, the patient. SUBJECTS: Six hundred and seventy-two patients considered hypertension by World Health Organization criteria (diastolic blood blood pressure >/=90 mmHg, systolic blood pressure >/=140 mmHg), were considered for the first descriptive part of the study; a total of 654 patients were considered for the second part related to tolerance; 18 patients refused to reply to the questions concerning the second questionnaire. The general characteristics of the population were as follows: 345 men (51.5%), 327 women (48.5%) and mean age 54+/- 15 years. RESULTS: The devices used were SpaceLabs (63%), Novacor (19.3%), Nippon Collin (6.3%) and other machines (11.2%). The difficulties caused by the machine were classified as 'nul', 'moderate' or 'important'. The levels of difficulty defined as 'important' were 32% related to the cuff, 14% to the awkwardness of the machine and 6% to the noise of the monitor. Difficulty in driving was reported in 9% of cases and difficulty related to comments by colleagues in 6%. Analysis during sleep hindered sleep in 55%, with a very disturbed sleep pattern (more than three reported awakenings) in 14% of cases. Regression analysis allowed examination of the links among the different variables, taking into account the type of machine or the profile of the subject. Thus, it was possible to differentiate among the elements that could influence or predict intolerance. CONCLUSION: Recording-related problems are not negligible but can be reduced by an approach oriented towards each individual patients, taking into account specific information for particular circumstances.

OBJECTIVE: To compare different methods of individual therapyh efficacy assessment in order to define responding subjects. METHODS: Hypertensive patients were included in three double-blind clinical trials (placebo versus bisoprolol, lisinopril and amlodipine) and ambulatory blood pressure measurements (four per hour) were performed at the end of each month. We analysed the effect of therapy (placebo minus treatment) according to the following criteria: type of model (hourly mean, moving average, fast Fourier analysis), determination of the time to the peak effect (the lowest value of the modelled blood pressure) and the sampling time around this peak (1, 2,., 24 h). RESULTS: Regardless of the type of model, the level of individual therapy efficacy is significantly higher than that of the overall subjects (group efficiency), when the sampling time around this peak decreases. The proportion of responders decreases as the sampling time used to calculate the drop in blood pressure increases, whatever the kind of model and the threshold used to define responders (5 or 10 mmHg in systolic blood pressure). CONCLUSION: By this method, it is possible to appreciate the percentage of subjects considered individuallyas responders according to the time around the peak. This evaluation complements information given by the trough: peak ratio.

While measurement of blood pressure in the doctor's office remains the method of reference of the WHO, self-measurement yields complementary information, namely: measures outside the surgery, good estimation of the level of blood pressure at home from several day's data, better reproducibility related to standardized conditions of measurement imposed by the constraints of immobility and manoeuvre of the machine. The modalities of variation of BP by automeasure are known: diminution in the BP by automeasure of about 2 to 4 mm Hg between the first and the third measure performed at 1-min intervals, no significant evolution over 3 days and BP more elevated in the evening than in the morning. In comparison with the WHO data, the BP is significantly lower. Recently reference values have been proposed, giving as the upper threshold of normotension = 127/ 83 mm Hg and hypertension = 147/ 86 mm Hg. As regards diagnosis SM allows the identification of "white coat hypertension", and thus avoids treating these patients. The indirect prognostic value via target organ effect is under evaluation, and may be at the same level as ambulatory blood pressure measurement (ABPM). Given the utilisation of validated automatic machines and a rigorous methodology SM is beginning to be used satisfactorily in clinical trials. Numerous studies are still necessary in order to clearly define the place of SM in comparison to WHO and AMBP in the management of hypertension.

The advent of new techniques has greatly contributed to the development of ambulatory measurement as a noninvasive method for evaluating blood pressure. The technique implies use of a validated and reliable standardized apparatus. The operator must strictly comply with operating procedures, which must also be explained to the patient. Ambulatory measurement can be meaningful only if the results are compatible with reference values, which have now been established, and if the causes of possible error can be recognized and interpreted. Ambulatory blood pressure measurement has greatly improved our knowledge of physiological and pathological variations over the circadian cycle including day/night variability and the effects of psychosensorial stimulation. Diagnostic indications are clearly identified and include borderline hypertension suspected but not identified after about 3 months, the white coat effect, severe hypertension when modifications in the circadian cycle are suspected, paroxysmal hypertension, suspected pheochromocytoma, and gravid hypertension or an inversion of the circadian cycle possibly preceding an episode of eclampsia. There are also a certain number of particular indications in patients with degenerative or primary conditions affecting their autonomy. The true prognostic value of these recordings was recognized several years ago and has been confirmed by clinical trials. For example, the white blouse effect has no significant implication in terms or predicting less favourable morbidity or mortality. Finally, ambulatory blood pressure measurement has been definitively shown to be a valid method for evaluating the therapeutic effect of an anti-hypertensive drug in a given patient, especially when resting levels are questioned. For therapeutic trials, ambulatory measurements serve as a reference to evaluate the effect of treatment on the circadian cycle. Peak/dip levels can thus be determined in comparison with the residual effect of the drug. A large number of studies remain to done to identify the full potential of this method.

Unlabelled: Relationships between baroreflex sensitivity (BRS) and arterial distensibility are evaluated by continuous measurement of blood pressure (Finapres) and carotid-femoral pulse wave velocity measurement (PWV); 73 subjects are recruited on WHO criteria (age: 48 +/- 13). An ambulatory measurement of BP is also performed to evaluate the mean BP 24 level. The BRS is evaluated at rest during 20 min of acquisition data in a lying position, using a dedicated software [(automatic detection by of BP sequences were 3 or more systolic BP and RR interval increased of 1 mmHg for SBP and 4 ms for RR (PS+/RR+) or decreased (PS-/RR-)]. The BRS is the slope of the regression line between SBP and RR interval of each sequences (if correlation coefficient > 0.95)., Results: resting BP: SBP/DBP = 170 +/- 12 mmHg. HR 72 +/- 15 batt/min, PWV = 10.8 +/- 3.2 m/s. Mean BRS is 8.2 +/- 3.8 for PS+/RR+ and 8.7 +/- 3.8 ms/mmHg PS-/RR-. The coefficient of correlation (Pearson) between PWV and BRS is -0.59* for PS+/RR+ and -0.41* for PS-/RR- (*: p < 0.01). In multivariate analyses, these relations were statistically independent of age and BP for the sequences PS+/RR+ but not for the sequences PS-/RR- suggesting a predominant vagal alteration in hypertensive subjects associated with the alteration of carotido-femoral pulse wave velocity.

This study aimed at comparing estimations of spontaneous cardiac baroreflex sensitivity (BRS) obtained with 3 different methods from continuous non-invasive blood pressure recordings in humans. A new method, allowing the quantification of the statistical dependence between values of 2 parameters (Z coefficient), was applied to beat-to-beat systolic blood pressure (SBP) and heart period (HP) values. SBP and HP values with positive Z coefficient and corresponding to baroreflex activity (SBP and HP values both lower or higher than the modal values) were submitted to a linear regression and the regression coefficient (Zgain) was taken as an index of BRS. Second, cross-spectral analysis of SBP and HP gave a BRS value (Csgain) computed as the average value of transfer function moduli for frequencies between 0.07 and 0.14 Hz, with coherence between SBP and HP greater than 0.5. The third method relies on the analysis of linear sequences (r > 0.97) containing at least 3 values of SBP and HP varying in the same direction. The average regression coefficient obtained from all selected SBP and HP sequences is the index of BRS (Seqgain). SBP and HR were recorded during 1 hour with a Finapres in 10 healthy male volunteers (NT), 23 to 32 year-old (SBP: 123 +/- 2 mmHg) and 10 recent and untreated hypertensive subjects (HT) (SBP: 152 +/- 6 mmHg). [table: see text] These results show that, in both groups, Zgain and Seqgain correlated with Csgain. No correlation was found between Zgain and Seqgain in healthy volunteers whereas the correlation was strong in hypertensives probably due to more heterogeneous SBP levels and BRS values in these subjects. This suggests that these methods are sensitive to different ways of response of the baroreflex.

The reproducibility of automatic outline detection is a echocardiographic reproducibility which has been poorly evaluated in patients with cardiomyopathy. Two independent observers identified the systolic surface and mid and end diastolic surfaces of 27 hypertensive patients, who had been referred to the laboratory for the measurement of left ventricular mass. Each observer examined on two occasions all parameters and all parameters were measured at least 2 hours apart. The coefficient of variation (CV) expresses the reproducibility of each measurement. The intra observer was 10 to 15% and the inter observer 15 to 22% for the measurement of surface area. The coefficient of variation is regularly greater than 20% for measures of maximum speed, which characterise surface changes in diastole. The automatic detection of contours is a echocardiographic tool whose potential is great for evaluating left ventricular function but the current versions can only be applied to very selective group of patients depending on the quality of their echographic window for acoustic quantitation. This technique is very operator dependent, in particular as regards setting the gains and this explains its poor reproducibility and its limited interest in daily clinical practice.

Measuring blood pressure during exercise under a standard protocol could be a useful diagnostic method in high-risk patients and in borderline hypertensive subjects. It may also serve as an adapted test for hypertensive subjects undergoing physical activity at work or at leisure time with a particular cardiovascular work load. It can be used as a method of assessment to confirm the efficacy of an antihypertensive drug, and for prognostic evaluation of cardiovascular risk in terms of morbidity and mortality. An exercise blood pressure profile does not provide information about blood pressure during activities of daily living. For this purpose, ambulatory blood pressure measurement appears to be more relevant.