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This double-blind, randomised, controlled study compared the efficacy of candesartan cilexetil 8 mg (n = 87) and losartan 50 mg (n = 89), once daily for 6 weeks, relative to placebo (n = 80) in patients with mild-to-moderate essential hypertension (diastolic blood pressure (DBP): 95-115 mmHg). Ambulatory BP measurements were done every 15 min over 36 h. At the end of the 6-week treatment, the mean change in DBP between the baseline and the 0-24-h period after the last dose of study medication was greater in patients receiving candesartan cilexetil 8 mg (-7.3 mmHg +/- 6.9 mmHg) compared with losartan 50 mg (-5.1 mmHg +/- 4.9 mmHg) (p < 0.05) or placebo (0.3 mmHg +/- 6.5 mmHg) (p < 0.001). The mean change in systolic BP (SBP) during this time was greater in patients receiving candesartan cilexetil 8 mg (-10.8 mmHg +/- 11.3 mmHg), or losartan 50 mg (-8.8 mmHg +/- 8.9 mmHg) than placebo (1.2 mmHg +/- 9.9 mmHg) (p < 0.001). Candesartan cilexetil 8 mg was associated with a greater reduction in DBP and SBP, relative to placebo, when compared with losartan 50 mg, during both daytime and night-time, and between 12 and 24 h after dosing (p < 0.001). Both active treatments were well tolerated. In patients with mild-to-moderate essential hypertension, candesartan cilexetil 8 mg therefore had greater, more consistent antihypertensive efficacy throughout the day and the night, and long-lasting efficacy after the last dose, compared with losartan 50 mg. This greater efficacy is maintained with an excellent tolerability associated with members of the angiotensin Il type 1-receptor blocker class.

Office blood pressure (OBP) and home blood pressure (HBP) enable the identification of patients with masked hypertension. Masked hypertension is defined by normal OBP and high HBP and is known as a pejorative cardiovascular risk factor.The objective was to evaluate in the SHEAF study the influence of the number of office or home blood pressure measurements on the classification of patients as masked hypertensives.Patients with OBP140/90 mmHg (mean of six values: three measurements at two separate visits, V1 and V2) and HBP135/85 mmHg (mean of all valid measurements performed over a 4-day period) were the masked hypertensive reference group. The consistency of the classification was evaluated by using five definitions of HBP values (mean of the 3, 6, 9, 12 and 15 first measurements) and two definitions of OBP values (mean of three measurements at V1 and mean of three measurements at V2).Among the 4939 treated hypertensives included in the SHEAF study, 463 (9.4%) were classified as masked hypertensives (reference group). By decreasing the number of office or home measurements, the prevalence of masked hypertension ranged from 8.9-12.1%. The sensitivity of the classification ranged from 94-69% therefore 6-31% of the masked hypertensives were not detected. The specificity ranged from 98-94% therefore 1-6% of patients were wrongly classified as masked hypertensives.A limited number of home and office BP measurements allowed the detection of masked hypertension with a high specificity and a low sensitivity. A sufficient number of measurements (three measurements at two visits for OBP and three measurements in the morning and in the evening over 2 days for HBP) are required to diagnose masked hypertension.

Decreased baroreflex sensitivity (BRS) is a prognostic marker in essential hypertension. Animal experiments suggest that decreased BRS is related to increased oxidative stress. Our study was aimed at testing whether oxidative stress, estimated by isoprostane 15-F(2t)-IsoP urinary levels, is correlated to BRS variation in healthy subjects as well as in patients suffering from essential hypertension. Urinary 15-F(2t)-IsoP levels and BRS were evaluated in two groups of subjects: healthy volunteers (n=64) and patients with untreated mild-to-moderate hypertension (n=33). Data were analysed in 61 and 31 subjects, respectively, BRS analysis being impossible in three and two subjects, respectively. 15-F(2t)-IsoP levels were measured using gas chromatography/mass spectrometry. BRS was measured using the sequence method [PS+/RR+ and PS-/RR-] and crossspectral analysis (CSP) (MF gain) at rest, lying down. No significant correlation was found between basal urinary 15-F(2t)-IsoP levels and BRS (sequence method and CSP) in either healthy controls or hypertensive patients. Our study shows that oxidative stress is not involved in interindividual variations of BRS in healthy subjects and patients suffering from mild-to-moderate hypertensionJournal of Human Hypertension (2004) 18, 517-521. doi:10.1038/sj.jhh.1001684 Published online 12 February 2004

Resume Propos. – Cet article fait le point sur les donnees passees et actuelles des relations existantes entre syndrome d’apnees obstructives du sommeil et maladies cardiovasculaires. Actualites et points forts. – Le syndrome d’apnees obstructives du sommeil est une pathologie frequente mais sous-estimee qui ne se resume pas a l’association ronflements et obesite. Il est evoque par l’interrogatoire mais son diagnostic de certitude est obtenu par la polysomnographie. De nombreuses etudes ont retrouve des relations significatives entre la presence d’un syndrome d’apnees obstructives du sommeil et la survenue d’evenements cardiovasculaires. Cependant, le lien de causalite n’est etabli de facon formelle que pour l’hypertension arterielle. Les stimuli a l’origine de la reponse cardiovasculaire, aigue et chronique, sont multiples. Les mecanismes physiopathologiques pouvant expliquer l’association morbide entre syndrome d’apnees obstructives du sommeil et maladies cardiovasculaires sont egalement nombreux, en premier lieu l’hyperactivite sympathique. Le pronostic vital de cette pathologie est etroitement lie a la survenue d’accidents cardiovasculaires. Perspectives et projets. – L’existence d’une relation independante entre syndrome d’apnees obstructives du sommeil et atherosclerose n’est pas demontree. L’effet benefique de la pression positive continue nocturne, traitement de reference du syndrome d’apnees obstructives du sommeil, sur l’incidence des maladies cardiovasculaires reste egalement a etablir malgre les resultats des etudes recentes qui suggerent que la prise en charge du syndrome d’apnees obstructives du sommeil par cette therapeutique est a meme de reduire le risque cardiovasculaire, en particulier d’hypertension arterielle.

Correspondance : Jacques Blacher Unite hypertension arterielle, prevention et therapeutique cardiovasculaire Centre de diagnostic et de therapeutique Hotel-Dieu, AP-HP 1, place du Parvis Notre-Dame 75181 Paris cedex 4 jacques.blacher@htd.aphp.fr Membres du groupe de travail : Jacques Amar, Athanase Benetos, Jacques Blacher (redacteur), Guillaume Bobrie, Bernard Chamontin, Xavier Girerd, Jean-Michel Halimi, Daniel Herpin, Claire Mounier-Vehier, Jean-Jacques Mourad, Jean Ribstein, Bruno Schnebert, Bernard Vaisse.

Objective To evaluate the physiological variations in arterial blood pressure in normotensive subjects during activity and in relation to the sitting or lying position. Methods The subjects were 30 healthy volunteers who were normotensive and receiving no treatment. Blood pressure was measured using the validated monitor Diasys Integra (NOVACOR SA, Rueil-Malmaison, France) with an integral position sensor. Blood pressure was recorded every 15min over a 24h period, additional measurements being made in the first, third and sixth minutes after standing up. Results During the active period (1000-2000h), 53% of the measures were made in the standing position. Over this period, the values of systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate were significantly elevated in the standing position in comparison to the sitting position. The difference was of the order of 5mmHg for the SBP, 3.5mmHg for the DBP and 9beats/min for the heart rate. The SBP, DBP and heart rate measured in the first, third and sixth minutes after standing up were not significantly different. Conclusion When measuring the blood pressure and heart rate in ambulatory patients, it seems justified to evaluate the patient's position during monitoring in order to achieve a better reproducibility and also to uncover any problems of blood pressure control with positional change, as could exist in patients with autonomic dysfunction. This might also aid in evaluating antihypertensive treatment and also any deleterious hypotensive effects.

The 1996 World Health Organization (WHO) recommendations for mild hypertension stressed the need to evaluate target-organ lesions as treatment criteria. The effects of both vascular and heart remodelling on hypertension must to be taken into account, as they adversely influence the prognosis of patients with hypertension. It was previously demonstrated that at least three classes of antihypertensive agents were able to decrease morbidity and mortality in patients with hypertension. Meta-analyses have shown that angiotensin-converting enzyme inhibitors seem to have a marked effect on regression of left ventricular hypertrophy (LVH). However, the relationship between drug-induced LVH regression and reduced morbidity and mortality remains to be confirmed. The effect of antihypertensive agents on vascular hypertrophy, as assessed by intima-media thickness, and their involvement in reducing morbid events, also have to be determined at the vascular level. As experimental data have highlighted the involvement of angiotensin II in animal models of LVH and vascular hypertrophy development, the role of angiotensin II AT1 receptor blockers should also be assessed in this indication.

Hypertensive patients with altered circadian blood pressure (BP) profile experience greater repercussion of hypertension on target organs and a higher risk of cardiovascular events, compared with those with physiological variations in BP. It has been demonstrated in animal models, that circadian variations in BP depend on several regulatory systems, in particular the nitric oxide-cGMP pathway. eNOS298 Glu/Asp polymorphism is a functional variant and may alter the amount of NO generated or eNOS activity. The objective of the present study was to find out whether eNOS298 gene polymorphism affects circadian BP regulation in 110 healthy subjects and 155 never-treated hypertensive patients recruited at Hypertension Units in Grenoble, Toulouse and Lille (France).

The occupational exposure of 19 men to hexamethylene diisocyanate (HDI) vapour was monitored during one 8-h shift. It ranged from 0.30 to 97.7 micrograms/m3. This was compared with the urinary output of hexane diamine (HDA) liberated by acid hydrolysis from its conjugates in post-shift samples. The excretion varied from 1.36 to 27.7 micrograms g creatinine, and there was a linear association of HDI air concentration with urinary HDA excretion. The validity of the urinary analysis was confirmed by simultaneous blind analysis in another laboratory. The results had an excellent linear concordance. Thus, it seems that while the gas chromatographic-mass spectrometric detection method requires sophisticated apparatus, the results are very useful to occupational health practices. A biological exposure index limit of 19 micrograms HDA/g creatinine in a post-shift urine specimen is proposed as an occupational limit level of HDI monomer (time-weighted average = 75 micrograms/m3). Most importantly, biological monitoring of HDA is sensitive enough to be used at and below the current allowable exposure limit levels.

Ambulatory blood pressure monitoring (ABPM) is a particularly useful method for evaluating the effects of antihypertensive drugs. ABPM allows the therapeutic effect of an agent to be assessed continually by a large number of measurements, and the greater number of readings contributes to the higher degree of reproducibility associated with ABPM compared to other methods for measuring blood pressure. ABPM also enable measurements to be taken in "real-life" situations and removes the problem of observer bias. The number of patients required for clinical studies can be significantly reduced by using ABPM. It is still essential, however, to identify "white coat" subjects, placebo responders, and patients who do not respond to the treatment. ABPM studies have demonstrated that the novel dihydropyridine calcium antagonist, lacidipine, significantly reduces both systolic and diastolic blood pressures over a 24-h period, both during the day and at night. Furthermore, although the trough-to-peak ratios of many calcium antagonists have been shown to fall below the recommended level of 50%, lacidipine has a ratio above 60%. Other ABPM studies have also shown that lacidipine can correct the 'early morning increase' in blood pressure without effecting the 24-h nycthemeral profile.

Objective This pilot study aimed to compare metabolic disturbances, particularly insulin resistance (IR) and cardiovascular risk factors (CRFs), following two types of acute vascular atherothrombotic disease events: ischaemic atherothrombotic stroke (AS); and acute coronary syndrome (ACS). Design and methods A total of 110 non-diabetic patients presenting with either AS ( n =55) or ACS ( n =55) were included in our prospective comparative study, and matched for age and gender. IR was determined using the homoeostasis model assessment of insulin resistance (HOMA-IR) method, and each patient's personal and family history were also recorded. Results IR was significantly higher in the ACS vs AS group (HOMA-IR index 2.17±1.90 vs 1.50±0.81, respectively; P =0.03). The AS group had a significantly higher prevalence of personal history of hypertension (51% vs 31%; P =0.03), while current smoking was more prevalent in the ACS group (30% vs 18%; P =0.04). There were no significant differences between the two groups as regards any other CRFs. Conclusion The distribution of CRFs varied depending on the vascular event, and metabolic disturbances differed according to the atherothrombotic disease. IR was greater after ACS than AS.

A 62-year-old man had an acute episode of hypertension 72 h after fine needle aspiration biopsy of an intra- hepatic nodule. The patient had been operated 3 years previously for a right adrenal phaeochromocytoma with no evidence of metastases at that time. Thus, a relapse of the tumour was postulated and confirmed by raised levels of urinary metanephrines. The extent of the metastases precluded surgical intervention and thus localised embolisation was proposed and permitted a clinical stabilisation over 8 months. This case indicates the necessity of long-term post-operative follow-up of phaeochromocytoma as well as the dangers of fine needle aspiration biopsy of metastases from this kind of tumour. Treatment of malignant phaeochromocytoma is difficult and embolisation was a useful therapeutic alternative in this case where the metastases were well defined.

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OBJECTIVE To compare 24-h ABP in normotensive type 1 diabetic patients with and without microalbuminuria. RESEARCH DESIGN AND METHODS The study was a retrospective comparison of cases and matched control subjects. The first phase included 35 type 1 diabetic patients, normotensive by OMS criteria. The 23 patients with normoalbuminuria (< 15 μg/min) were compared with 12 patients with microalbuminuria (≥ 15 μg/min). In the second phase, the 12 microalbuminuric patients were paired by sex- and age-matched with 12 normoalbuminuric patients and 12 nondiabetic healthy control subjects. We measured casual systolic and diastolic BP and HR, 24-h ABP and AHR (recorded with a Spacelabs automatic recorder), and microalbuminuria. RESULTS No correlation between microalbuminuria and casual BP was observed. Microalbuminuria was correlated significantly with diastolic 24-h APR and nocturnal systolic and diastolic ABP (r = 0.35, 0.38, and 0.33, respectively; P < 0.05) and with AHR during all time periods (24-h, r = 0.46; day, r = 0.39; night, r = 0.39; P < 0.05). Normo- and microalbuminuric patients did not differ in casual BP and HR. However, microalbuminuric patients had a significant increase in systolic 24-h ABP (119.1 ± 8.2 vs. 113.1 ± 8.1, P = 0.05), diastolic 24-h ABP (74.9 ± 7.5 vs. 70.2 ± 5.7, P = 0.04), nocturnal systolic ABP (112.8 ± 7.1 vs. 105.8 ± 7.9, P = 0.01), and AHR during all time periods. The same results were observed when patients were paired by age and sex. CONCLUSIONS Normotensive microalbuminuric type 1 patients, although strictly comparable with normoalbuminuric patients for casual BP and HR, have an increased ABP and HR, especially during the night. This difference might reflect dysautonomia. Ambulatory measurement of BP and HR is more appropriate than casual measurements in hemodynamic studies of incipient diabetic nephropathies and could be proposed as an interesting tool for an early prediction of diabetic nephropathy.

Compliance with antihypertensive therapy is usually monitored by questionnaire, tablet counts, or estimation of drug levels in blood or in urine. The aim of this study was to examine patient compliance by means of an "electronic monitor." After 2 weeks of run-in on placebo, 34 moderately hypertensive patients were included in an open, randomized, crossover trial examining the efficacy and tolerance of nitrendipine, 20 mg as a single daily dose (morning or evening) for 1 month. We analyzed the results in 26 patients. Patients were supplied with tablet boxes equipped with a microprocessor (MENS) that registered the timing and duration of opening of the box over both the placebo and nitrendipine periods. Compliance (%) was calculated as the ratio of the number of days that the pill box was opened to the number of days between visits. The compliance was analyzed for each treatment group, namely placebo and nitrendipine morning and evening, over 1 month. Compliance (mean + SD) was 96.5 +/- 7.4% on placebo and 94.4 +/- 10.7% in the morning and 90.6 +/- 15.4% in the evening. Nitrendipine was taken in the morning at 0700 h +/- 2 h and in the evening at 1859 h +/- 2 h 12 min. The frequency of 24 h +/- 1 h intervals between medication was 83.5% on placebo. This frequency was 72.6% for morning dosage and 71.8% for evening dosage on nitrendipine. There were no differences in compliance between the morning and evening groups when analyzed according to age and sex. There was a negative correlation with time (r = -0.57, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

This double-blind, randomised, controlled study compared the efficacy of candesartan cilexetil 8 mg (n = 87) and losartan 50 mg (n = 89), once daily for 6 weeks, relative to placebo (n = 80) in patients with mild-to-moderate essential hypertension (diastolic blood pressure (DBP): 95-115 mmHg). Ambulatory BP measurements were done every 15 min over 36 h. At the end of the 6-week treatment, the mean change in DBP between the baseline and the 0-24-h period after the last dose of study medication was greater in patients receiving candesartan cilexetil 8 mg (-7.3 mmHg +/- 6.9 mmHg) compared with losartan 50 mg (-5.1 mmHg +/- 4.9 mmHg) (p0.05) or placebo (0.3 mmHg +/- 6.5 mmHg) (p0.001). The mean change in systolic BP (SBP) during this time was greater in patients receiving candesartan cilexetil 8 mg (-10.8 mmHg +/- 11.3 mmHg), or losartan 50 mg (-8.8 mmHg +/- 8.9 mmHg) than placebo (1.2 mmHg +/- 9.9 mmHg) (p0.001). Candesartan cilexetil 8 mg was associated with a greater reduction in DBP and SBP, relative to placebo, when compared with losartan 50 mg, during both daytime and night-time, and between 12 and 24 h after dosing (p0.001). Both active treatments were well tolerated. In patients with mild-to-moderate essential hypertension, candesartan cilexetil 8 mg therefore had greater, more consistent antihypertensive efficacy throughout the day and the night, and long-lasting efficacy after the last dose, compared with losartan 50 mg. This greater efficacy is maintained with an excellent tolerability associated with members of the angiotensin Il type 1-receptor blocker class.

The presence of hypertension is responsible for an increase in cardiovascular morbidity and mortality. The significance of evaluating variations of blood pressure on exercise in actual or potential hypertensives warrants further consideration. The modes of physiological blood pressure variation on effort and the practical methods of performing an exercise test are well documented and have been the subject of guidelines. Within this framework must be included dynamic exercise tests on ergometric bicycles or with treadmills. From numerous studies it is now possible to better define the predictive and prognostic values of the various modes of blood pressure changes with exercise. Blood pressure measurement on exercise represents an additional investigation in cardiovascular morbidity and mortality (coronary or cerebrovascular events). The diagnostic applications of this exercise measurement reveal these prognostic data, and exercise blood pressure measurement is to be recommended in subjects who experience regular significant physical effort.

Among the major developments of the year 2004 in the knowledge of hypertension, a special part should be dedicated to the venue in Paris of the Fourteenth meeting of the European Society of Hypertension last June. Beside major progress observed in basic science, namely signaling pathways involved in the regulation of smooth muscle tone, growth and inflammation, at the cross-road of hypertension, diabetes, and metabolic syndrome, large clinical trials have afforded strong evidence for the usefulness of lowering blood pressure in various diseases associated with hypertension. Despite these advances, the percentage of treated hypertensive patients who reach the BP goal (140/90 mmHg) is too low (about 30%). Thus urges the need for adapting therapeutic strategies. The ESH meeting gave the opportunity to gather a large body of evidence for a better therapeutic approach, in order to control BP in a larger number of hypertensive patients.

This article is an update of past and current data on the relationship between obstructive sleep apnea syndrome and cardiovascular diseases.Obstructive sleep apnea syndrome is a common, but under-recognised, condition and should not be considered simplistically as the association of snoring and obesity. It may be suspected by the clinical history but a definite diagnosis requires the practice of polysomnography. Numerous studies have found a significant relationship between the presence of obstructive sleep apnea syndrome and the occurrence of cardiovascular events. Nonetheless, a definite causal relationship has only been established for the occurrence of hypertension. There are multiple immediate and delayed cardiovascular responses to the apneic events and thus there are many possible physiopathological mechanisms to explain the association of obstructive sleep apnea and cardiac and vascular events, the primary one being sympathetic hyperactivity. The prognosis of obstructive sleep apnea syndrome is closely related to the incidence of cardiovascular events. FUTURE PROSPECTS AND PROJECS: The existence of an independent relationship between obstructive sleep apnea syndrome and atherosclerosis is not yet demonstrated. The beneficial effects of continuous positive airway pressure, the treatment of choice for this condition, on the incidence of cardiovascular diseases remains to be confirmed although recent studies suggest that correct treatment of obstructive sleep apnea syndrome by continuous positive airway pressure may reduce the cardiovascular risk and in particular that of hypertension.

A 74-year-old man had a resistant hypertension with an increase in plasma aldosterone and active plasma renin levels, and an irregular appearance of the left kidney outline by ultrasound. The CT scan showed a stenosis of the left renal artery, which was pushed against the aorta by the left crus of the diaphragm. An angioplasty with placement of an autoexpansible stent was carried out with a good result on the arterial pressure level. After 3 years, the patient was re-hospitalised with severe hypertension. The CT scan demonstrated a compression of the stent by the left crus of the diaphragm, with good permeability of the artery downstream from the stent, and radiographic examination showed a fracture of the left renal artery stent. Thus, a reimplantation of the left renal artery in the aorta was carried out. Stenosis of the renal artery by fibres from a crus of the diaphragm is a rare cause of renovascular hypertension. Helicoidal angioscanner imaging is particularly useful to do the diagnosis. In the present case, renal angioplasty with stenting was complicated by a fracture of the stent that led to the surgery. Thus, when renal artery stenosis by a crus of the diaphragm is diagnosed, surgical treatment needs to be considered on a case-by-case basis in relation to the anatomy and the biological and functional data.

Elderly patients with isolated systolic hypertension (ISH)--systolic blood pressure (SBP) > or =140 mmHg and diastolic blood pressure (DBP)

Epidemiological studies have shown that increased arterial stiffness and wave reflections, major determinants of systolic and pulse pressure, are associated with morbidity and mortality. Therapeutic trials based on cardiovascular mortality have recently shown that reduction of systolic blood pressure (SBP) requires normalization of both large-artery stiffness and wave reflections.To compare the antihypertensive effects of the very-low-dose combination of perindopril (2 mg) and indapamide (0.625 mg) (one or two tablets per day) with the beta-blocking agent atenolol (50 mg; one or two tablets per day) in order to determine whether the combination decreased SBP and pulse pressure more than did atenolol, and whether this decrease occurred in relation to a reduction in arterial stiffness [aortic pulse wave velocity (PWV)] or a decrease in the intensity of, or delay in, wave reflections (augmentation index, measured by applanation tonometry) or a combination of both.This was a double-blind randomized study in 471 individuals with essential hypertension followed for 12 months. Arterial pressure was measured in the brachial artery (mercury sphygmomanometer) and in the carotid artery (applanation tonometry).For the same reduction in diastolic blood pressure (DBP), the combination of perindopril and indapamide decreased brachial SBP and pulse pressure significantly more than did atenolol (adjusted differences between groups -6.2 +/- 1.5 and -5.5 +/- 1.0 mmHg, respectively; P0.001). This difference was even more pronounced for the carotid than for the brachial artery. Whereas both antihypertensive agents similarly decreased PWV, only the combination significantly attenuated wave reflections.Normalization of SBP, pulse pressure and arterial function--a haemodynamic profile known to improve survival significantly in hypertensive populations at high cardiovascular risk--was achieved to a greater extent with a very-low-dose combination of perindopril and indapamide than with atenolol.

The aim of the study was to evaluate by ambulatory blood pressure measurement (ABPM) the 24 hours antihypertensive efficacy of the fixed combination therapy, valsartan 80 mg + hydrochlorothiazide 12.5 mg (V + H), once daily, after 6 weeks of treatment, in patients with mild to moderate hypertension.It was a French, multicenter, double blind, randomized trial in parallel groups comparing V + H and placebo. After an initial two weeks placebo period, patients were assigned to receive either V + H or placebo for six weeks. Were eligible those with clinical arterial blood pressure, measured by sphygmomanometer, between 160/95 and 209/114 mmHg after monotherapy. A 26 hours ABPM, with Spacelabs 90,207, was done at J0 and J42 (one measurement every 15 minutes, in day time and at night). Responders were defined as a fall in day diastolic blood pressureor = 5 mmHg and/or day diastolic blood pressure90 mmHg with ABPM.123 of the 138 randomized patients had two interpretative measurements. Their average age was 59 + 10 years. 57% (78) of them were males and their average ABPM before treatment was 143 +/- 15/88 +/- 11 mmHg. With V + H, the reduction of the systolic and the diastolic blood pressure measured by ABPM, was significantly more important than with placebo (SBP: -15.4 +/- 10.9 mmHg versus -0.6 +/- 7.7 mmHg, p0.001; DBP: -9.1 +/- 7 mmHg versus -0.4 +/- 5.4 mmHg, p0.001). Pulse pressure (PP) was also significantly reduced with the combination therapy V + H, but it was not modified with placebo (-6.3 + 5.5 mmHg versus -0.2 + 4.1 mmHg, p0.001). ABPM responder rate was 73% with V + H versus 24% with placebo (p0.001). Trough/peak ratio was 80.3% for systolic blood pressure and 57.3% for diastolic blood pressure. The combination V + H was as well tolerated as placebo.The fixed combination V + H used for treatment of hypertension, after failure of monotherapy, is very effective in reducing pulse pressure, systolic and diastolic blood pressure, over 24 hours, homogeneously, and is as well tolerated as placebo.

Taking into account all the risk factors and blood pressure levels, as indicated by several American and European recommendations available since 1997, is a leading strategy to reduce mortality and morbidity of hypertensive patients. The aim of this study was to quantify how, in 1999. French practitioners applied recommendations on hypertension (HTN), diabetes and hypercholesterolemia in recently diagnosed hypertensive patients and to evaluate whether or not the recommended targets were met. 1639 French GPs and cardiologists included 5831 recently diagnosed (7.5 +/- 3.6 months) hypertensives (57 +/- 12 years of age, M/F = 55/45%). Initial BP was 173 +/- 15/99 +/- 9 mmHg. 56% had no concomitant disease, 36% had either diabetes, dyslipidemia or coronary heart disease, 8% had at least two concomitant diseases. At the time of the study corresponding to 6.3 +/- 3.8 months after initiation of diet and/or medical treatment, their BP was 148 +/- 17/86 +/- 11 mmHg (-25/-19 mmHg). At that time only 37% of patients with stage 2 HTN were encouraged to adopt lifestyle modifications without any medical treatment as recommended by the JNC VI. Among these hypertensives, measurement of plasma cholesterol was performed in only 61%, HDL-C/LDL-C in 26% and blood glucose in 51%. In the patients with dyslipidemia, LDL-C was measured in only 47%. In the 677 diabetic patients only 27% had a glycated hemoglobin measurement. The percentage of patients reaching target BP was 59% as regard DBP90 mmHg, 25% as regard SBP140 mmHg, and 23% reached both target values of BP. In addition, 30% of patients with dyslipidemia reached the target LDL-C as defined by French recommendations (ANAES 1996) and 30% of the diabetic patients reached the target value for glycemia recommended by ADA (1997). In 1999 in France, a minority of patients reaches the national or international recommended target values for blood pressure, glycemia and plasma LDL-cholesterol. In spite of that, French practitioners do not implement all the available diagnostic tools to improve the treatment of metabolic disorders in hypertensive patients. As a conclusion, to improve the prognosis of hypertensive patients, it is mandatory to raise the awareness of physicians about multiple risk factor management and help them implement the recommendations in their daily practice.

To study the influence of position changes on 24-h ambulatory blood pressure (ABP) in normotensive or mildly hypertensive normoalbuminuric patients with type 1 diabetes.A cross-sectional evaluation of patients was staged according to the duration of diabetes (DD) and the presence of microangiopathy. We recruited 37 patients (30 men and 7 women), aged 38 +/- 12 years, who were normotensive or mildly hypertensive (diastolic blood pressure [DBP]105 mmHg) and free of antihypertensive treatment and microalbuminuria. They were included according to DD (group 1,5 years; group 2,or =10 years). An additional group of seven diabetic patients with microalbuminuria and mild untreated hypertension was also investigated. We recorded 24-h ambulatory blood pressure every 15 min with a position sensor, which allowed for the discrimination between standing or supine/sitting position in the patient.Mean daytime (10:00 A.M. to 8:00 P.M.) ABP in supine/sitting position did not significantly differ between groups 1 and 2. However, standing ambulatory systolic blood pressure (ASBP) and ambulatory DBP (ADBP) were significantly higher than supine/sitting ASBP and ADBP in group 1 (DeltaSBP 4 +/- 5, DeltaDPB 4 +/- 6 mmHg, P0.01) but not in group 2 (DeltaSBP 2 +/- 8, DeltaDBP 2 +/- 4 mmHg, P = NS). Patients free of microangiopathy presented with significantly higher ABP in standing position than in sitting/lying position, whereas patients with retinopathy and/or nephropathy exhibited no significant increase of ABP during standing.The monitoring of position during ambulatory measurement of blood pressure in type 1 diabetic patients shows different patterns in relation to disease duration and the presence of microangiopathy.

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.

This study was designed to analyse the relationship between the different blood pressure (BP) variabilities obtained in a non-invasive way and to determine the potential contribution of aging, severity of hypertension and increased ventricular mass to these different BP variabilities. Two hundred and six hypertensive patients underwent a 24-h ambulatory BP measurement (ABPM) as well as a photoplethysmographic BP recording and a standard echocardiography. Nocturnal BP fall and standard deviations of hourly mean BP levels as well as post-prandial fall in BP were calculated from the 24-h ABPM and were considered as indexes of long-term variability. Baroreflex sensitivity (BRS) and spectral powers of systolic BP, diastolic BP and heart rate (HR) over the low frequency band (LF: 0.05--0.14 Hz) were obtained from photoplethysmographic recording and were used as indexes of short-term variability. Short-term variability indexes were shown to be significantly related to those of long-term variability. A decrease in LF spectral powers was associated with a particular profile characterised by an attenuation of nocturnal BP fall, an increase of daytime BP standard deviations, an increase in post-prandial BP fall, a decrease in BRS and to a lesser extent, a diminution in night-time HR standard deviation. Moreover, a negative significant relationship was found between standard deviation of daytime systolic BP and both night systolic BP fall and BRS. Age and nocturnal BP level were associated with all BP variability disorders, whereas left ventricular hypertrophy was associated only with a decrease in LF spectral powers and in night BP fall, and an increase in standard deviation of daytime BP. Finally, LF spectral power of SBP was identified as independently predicted by age and night SBP fall. Journal of Human Hypertension (2001) 15, 41-48

Objectives: The SHEAF study (Self measurement of blood pressure at Home in the Elderly: Assessment and Follow-up) is a 3-year prospective cohort study of French elderly (⩾60 years) hypertensive patients designed to assess whether home blood pressure (HBP) measurement provides additional prognostic information over office blood pressure (OBP) in terms of cardiovascular mortality and morbidity. The objective of the present work is to describe the baseline data of the population enrolled in the SHEAF study with special emphasis on blood pressure control in treated hypertensives. Methods:During the 2-week initial inclusion phase, baseline demographics, cardiovascular risk factors, antihypertensive treatments as well as office and home blood pressure were recorded. Baseline OBP was assessed using a mercury sphygmomanometer (three consecutive measurements during two visits performed 2 weeks apart). HBP was performed over a 4-day period (three consecutive measurements in the morning and in the evening). Results:A total of 4939 (95%) of the 5211 patients included in the SHEAF study were treated with at least one antihypertensive drug. Their ages ranged from 60 to 99 years (mean age 70 ± 7 years); 49% were men, 12% had a previous history of coronary artery disease, 14% diabetes and 43% a treated dyslipidaemia. A total of 45% of the treated patients received a single antihypertensive drug, 34% two drugs, 21% three drugs or more. Overall 23% of treated hypertensives were normalised at the doctor’s office (systolic BP

Candesartan is one of the first angiotensin II receptor antagonists (AIIRAs) to be developed. It binds tightly to and dissociates slowly from the angiotensin subtype 1 (AT1) receptor in vitro. These binding characteristics differ from those of losartan, which demonstrates lower affinity and faster dissociation from the AT1 receptor. Candesartan causes long-lasting antagonism of the vascular contractile response to angiotensin II compared with irbesartan, losartan or the active metabolite of losartan - EXP-3174. While there are relatively few distinctions that can be made between the AIIRAs in terms of their pharmacokinetic profiles, the antagonistic potency of candesartan cilexetil at the AT1 receptor over 24 h clearly differentiates it from other members of its class. These differences are reflected in the antihypertensive efficacy and duration of action of candesartan in clinical trials.

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.

The goal of the SHEAF study is to determine whether self blood pressure measurement (SBPM) has a better cardiovascular prognostic value than office blood pressure (OBP) among French elderly (or = 60 y) hypertensive patients (pts) followed-up by general practitioners. Baseline SBPM was performed over a 4-day period: every day a series of 3 consecutive measurements was requested in the morning (8:00 am) and in the evening (8:00 pm), using a validated device OMRON 705 CP. Measurements performed out of predefined morning and evening time (outside the 4:00-12:00 am range or the 4:00-12:00 pm range) were discarded as well as aberrant values. Pts were included in the study only if they exhibited at least 15 valid measurements with at least 6 in the morning and 6 in the evening. 5,649 pts were selected. 186 pts were excluded for age60 years. Thus SBPM analysis was performed for 5,463 pts: 2,687 men (49%) and 2,776 women (51%) aged 70 +/- 7 years. Only 252 pts (5%) were excluded for non valid SBPM (207 pts15 measurements, 106 pts6 measurements in the morning and 205 pts6 measurements in the evening). 5,211 pts (95%) with valid SBPM were included. The distribution of pts according to the number of measurements performed is the following: [table: see text] The number of measurements performed in the morning is highly related to the number of measurements performed in the evening. None of the following variables is significantly associated with the poor compliance of measurement protocol: age, gender, CV history, CV risk factors, hypertension duration. In a large cohort of elderly hypertensive living in the community, SBPM is easily performed both in the morning and in the evening by most of the pts. If the SHEAF study demonstrates the prognostic value of SBPM, this would provide the basis for the use of this measurement method by a majority of elderly hypertensives.

Validation of automatic devices for self blood pressure measurement is a necessity, as the mercury columns are no longer available. The European consensus meeting organized by the Group for blood pressure measurement and evaluation (GEM), from French Society of Hypertension held last June 1999 has defined a new international protocol for clinical validation of these devices. The main parts of this protocol are the following: the blood pressure is measured at the same arm with two observers simultaneously and then with the automatic device sequentially seven times among 38 patients. The evaluation is interrupted after the 15th patient if the pre-analysis fails defined criteria. Technical supports are available: A CD-rom from French society of HTA for the training and certification of observers, a special kit for the evaluation (2 mercury column's and a double stethoscope) and a specific software for data analysis created by the GEM.

We have assessed the influence of gender and age on the main outcome results of the Hypertension Optimal Treatment (HOT) study.The aims of the HOT study were to study the relationship between three levels of target office diastolic blood pressure (BP) (or = 90,or = 85 oror = 80 mmHg) and cardiovascular (CV) events in hypertensive patients, and to examine the effects of 75 mg acetylsalicylic acid (ASA) daily versus placebo.Outpatient clinical trial in 26 countries.A total of 18790 patients (mean age 61.5 years, range 50-80) were randomized and followed for an average of 3.8 years until 71051 patient-years and 683 events had occurred.CV death, myocardial infarction (MI) and stroke.There were significantly fewer MIs in those in the lower diastolic BP target groups (3.0 versus 1.2 and 1.7 MIs/1000 patient-years, P for trend = 0.034) in women (n = 8883), whereas the similar but smaller trend (4.1 versus 4.1 and 3.4 MIs/1000 patient-years) was not statistically significant in men nor in the subgroup analysis of younger and older subjects. The effect of ASA on preventing MI was not influenced by age65 years (P= 0.02) or ageor = 65 years (P = 0.04) but was influenced by gender (P = 0.38 in women and P = 0.001 in men, lowered by 42% corresponding to a reduction from 5.0 to 2.9 MIs/1000 patient-years).The data of this HOT study sub-analysis suggest somewhat differentiated optimal gender- and age-dependent effects of anti-hypertensive and anti-platelet therapies; lowering of diastolic BP to about 80 mmHg in hypertensive women and, in addition, the administration of 75 mg of ASA to well-treated hypertensive men appear to effectively reduce the most common cardiovascular complication, i.e. myocardial infarction, in patients with essential hypertension.

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.

Stenosis of a renal artery by extrinsic compression is an uncommon cause of renovascular hypertension. In rare cases, this compression is due to the presence of fibres from the diaphragm or the psoas muscle. This aetiology should be considered when renal artery stenosis is observed in a young hypertensive patient without cardiovascular risk factors. Spiral CT scan is particularly useful for studying the relationship between the diaphragm and arterial structures. Once the diagnosis has been made, the treatment is surgical section of the fibrous tissues responsible for the compression.

First-line treatment of hypertension: from monotherapy to fixed low-dose combination therapy

Two terms are in current use to describe patients whose blood pressures are high only in a medical setting (white-coat hypertension and isolated office or clinic hypertension). The term white-coat effect is also commonly used to describe the pressor response to the clinic setting.White-coat hypertension is generally defined as a persistently elevated clinic blood pressure in combination with a normal ambulatory blood pressure (ABP). There is disagreement regarding the optimal cutoff point for ABP. The white-coat effect is operationally defined as the difference between the clinic blood pressure and daytime ABP. PREVALENCE OF WHITE-COAT HYPERTENSION: This varies according to the definition of white-coat hypertension and the population studied, but is approximately 20% among mild hypertensives, and increases with age.Authors of some studies have suggested that white-coat hypertension is associated with metabolic abnormalities such as hyperlipidemia that lead to an increase in cardiovascular risk, but most have not found this. TARGET-ORGAN DAMAGE: Several measures of target-organ damage have been compared among normotensives, white-coat hypertensives, and sustained hypertensives; these include left ventricular mass, microalbuminuria, and carotid atherosclerosis. In general, target-organ damage in white-coat hypertension is less than that in sustained hypertension, but in some studies it has been found to be more prevalent than in normotensives.Authors of a relatively small number of prospective studies have concluded that white-coat hypertensives have a lower risk of morbidity than do sustained hypertensives, but a larger number have drawn the more general conclusion that, when there is a discrepancy between the clinic blood pressure and ABP, the prognosis is more closely related to the ABP.When white-coat hypertensives are prescribed antihypertensive medication there is usually a decrease in clinic blood pressure, but little or no change in ABP. Thus drug treatment is not necessarily indicated. Another issue is the follow-up of white-coat hypertensives; there is general agreement that blood pressure outside the office should be monitored indefinitely. Some patient may have been wrongly classified as white-coat hypertensives, and others may progress to develop sustained hypertension.

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).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).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 (p0.001).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.

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.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.This device, in the tested configuration, agrees the B grade of BHS and can be recommended for ambulatory blood pressure measurement.

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.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) was10% 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.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; p0.01 for SBP and p0.05 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%; p0.01) for DBP (respectively 35 +/- 14% vs 41 +/- 15%; p0.01) 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, p0.001 for SBP and DBP spectral powers, r = 0.19; p0.005 for HR spectral power) and with the nocturnal DBP fall, too (r = 0.19; p0.005 for SBP spectral power, r = 0.20; p0.002 for DBP spectral power, r = 0.19; p0.005 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.1) The greater the nocturnal BP fall, the higher the sympathetic activity indexes. 2) This relationship was found both in males and females.

The aim of the HOT Study (Hypertension Optimal Treatment) was to determine the optimal diastolic blood pressure decrease and to assess the effect of the acetyl salicylic acid as a primary prevention on the cardiovascular morbidity and mortality in hypertensive patients. The HOT Study is an open, prospective, randomised, international trial with blinded end points. This study included 18,790 patients, 50 to 80 years old (mean 61.5 years) in 26 countries (1,574 patients in France) with a primary hypertension (100or = PADor = 115 mmHg). The patients were randomised in 3 target diastolic blood pressure:or = 80 mmHg (n = 6,262),or = 85 mmHg (n = 6,264),or = 90 mmHg (n = 6,264). The felodipine LP, a long acting dihydropyridine, was selected as a first line therapy, other hypertension drugs combined if necessary. The lowest incidence of cardiovascular events was observed at a diastolic blood pressure level of 82.6 mmHg. There was no increased risk below this level even in the hypertensive patients with medical history of coronary heart disease or stroke. In the diabetic population, the diastolic blood pressure decrease from 90 to 80 reduced the incidence of the major cardiovascular events by 51%. The acetyl salicylic acid reduced the myocardial infarction risk in the blood pressure well-controlled population.

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 o2measurements 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.m−2and 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.h−1of 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 co2than those with obstructive sleep apnoea (33 (5) vs 37 (5) mmHg, P