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Stefano Omboni,1 Ettore Malacco,2 Jean-Michel Mallion,3 Massimo Volpe4,5 1Clinical Research Unit, Italian Institute of Telemedicine, Solbiate Arno, Varese, Italy; 2Department of Internal Medicine, Ospedale L Sacco, University of Milan, Milan, Italy; 3Cardiology and Arterial Hypertension, CHU de Grenoble, Grenoble, France; 4Division of Cardiology, II Faculty of Medicine, University of Rome “La Sapienza”, Sant’Andrea Hospital, Rome, Italy; 5IRCCS Neuromed, Pozzilli, Isernia, Italy Abstract: In this paper, we present the results of a reanalysis of the data of two large randomized, double-blind, parallel group studies with a similar design, comparing the efficacy of an angiotensin-receptor blocker (olmesartan medoxomil) with that of an angiotensin-converting enzyme inhibitor (ramipril), by applying two different blood pressure targets recently recommended by hypertension guidelines for all patients, irrespective of the presence of diabetes (

Objective: To assess whether nocturnal blood pressure dipping status in type 1 diabetes is correlated with specific sleep characteristics and differences in nocturnal glycemic profiles.Research Design and Methods: Twenty type 1 diabetic adult patients underwent sleep studies with simultaneous 24-h ambulatory blood pressure monitoring and continuous nocturnal glucose monitoring.Results: Altogether, 55% of patients exhibited blunted blood pressure dipping. They did not differ from the dipper group in age, BMI, or systolic (SBP) and diastolic (DBP) blood pressure. Total sleep period (TSP) was higher in the dipper group (497 +/- 30 vs. 407 +/- 44 min for dippers and nondippers, respectively, P < 0.001). TSP was correlated with SBP and DBP day-night differences (r = 0.44 and 0.49, respectively). Periods of nocturnal hypoglycemia (i.e., % of TSP with glycemia <70 mg/dl) were longer in the dipper group (8.1 +/- 10.7 vs. 0.1 +/- 0.4% for dippers and nondippers, respectively, P = 0.02).Conclusions: Dipping status in type 1 diabetes was associated with longer sleep duration and with hypoglycemia unawareness. [ABSTRACT FROM AUTHOR]

Background: Non-invasive methods allow the evaluation of structural and functional arterial abnormalities. So far, no study has focused on the comparison of vascular parameters by type of cardiovascular event., Methods: In this pilot study, cardiovascular risk factors, carotid parameters, carotid-to-femoral pulse wave velocity (PWV), brachial flow-mediated dilation and ambulatory blood pressure were assessed in patients who presented with acute coronary syndromes (ACS) or ischaemic atherothrombotic stroke (IAS). Groups were matched for age and gender., Results: Prevalences of hypertension, diabetes and dyslipidaemia and heredity, smoking and body mass index were similar in the ACS (n=50) and IAS (n=50) groups. Carotid intima-media thickness (IMT) and PWV were significantly higher in the IAS vs. ACS group (769±180 vs. 701±136 μm; P=0.039 and 12.5±3.5 vs. 10.7±2.4 m/s; P=0.006). Carotid distensibility was significantly lower in the IAS vs. ACS group (16.2±3.2 vs. 18.9±7.6 10(-3)/kPa; P=0.02). These differences persisted after adjustment for blood pressure for carotid distensibility but not for PWV. The prevalences of endothelial dysfunction and carotid plaques were not significantly different in the ACS and IAS groups (86% and 74%; 80% and 78%). In a multivariable model, carotid distensibility remained associated with ACS (odds ratio 1.19; 95% confidence interval 1.03-1.38; P=0.016)., Conclusions: Stiffness and carotid wall thickness were higher in IAS than in ACS patients. These differences may support the interest in new therapeutic targets for cardiovascular secondary prevention., Nct No: NCT00926874., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

In hypertension and diabetes, early structural changes of the arterial wall precede or support atherosclerosis. There is evidence that some antihypertensive drugs exert an antiathero-sclerotic effect. Over 36 months, we investigated the effect of candesartan cilexetil (CC) on the common carotid intima-media thickness (IMT) vs amlodipine besylate (AML) in patients with type 2 diabetes and mild to moderate essential hypertension. After a 4-week wash-out period, 209 patients were randomized to either CC 8 mg or AML 5 mg once daily for a minimum of 1 month, after which, if BP was not normalized, the dosage was doubled, followed by the addition of hydrochlorothiazide 12.5 mg if necessary. No significant differences were observed between the two groups for change in IMT at M12 (-0.001 vs -0.027 mm/year for CC and AML respectively, p = 0.425), at M24 (-0.033 vs -0.019 mm per year respectively, p = 0.442), and at the last visit (-0.016 vs -0.039 mm per year respectively, p = 0.549). Within the group, comparisons did not show a significant difference in changes in IMT from baseline to the three visits. At the last visit, IMT regression was observed in 52.2% of patients receiving CC and in 51.3% of those receiving AML (p = 0.908). The augmentation in carotid lumen diameter from baseline was statistically greater in the AML group at the last visit (p = 0.034). BP variations during the study were similar in the two groups. The results of this study show that CC and AML treatments may alter identically the natural progression of carotid IMT in hypertensive type 2 diabetic patients.

Objective: To analyse the structural and functional abnormalities in the large arteries in women with the Turner syndrome., Methods: Aortic stiffness (assessed by means of the carotid femoral pulse wave velocity), level of amplification of the carotid pressure wave (by applanation tonometry), and carotid remodelling (by high resolution ultrasound) were studied in women with the Turner syndrome. Clinical and ambulatory blood pressures were taken into account in the analysis. Thus, 24 patients with the Turner syndrome and 25 healthy female subjects matched for age were studied., Results: Women with the Turner syndrome had a higher augmentation index than the controls (Turner, mean (SD) 0.04 (0.14) v controls, -0.14 (0.13), p < 0.001) but a lower peripheral pulse pressure (39 (8) mm Hg v 47 (11) mm Hg, p = 0.010 in the clinic; 44 (5) mm Hg v 47 (6) mm Hg, p = 0.036 during the 24 hour ambulatory recording). The luminal diameter of the common carotid artery and the carotid-femoral pulse wave velocity were similar in the two groups, whereas carotid intima-media thickness tended to be higher in women with the Turner syndrome (0.53 (0.06) mm v 0.50 (0.05) mm, p = 0.06). After correction for body surface area, carotid intima-media thickness and pulse wave velocity were higher in women with the Turner syndrome., Conclusions: Vascular abnormalities observed in the Turner syndrome are implicated in the origin of the cardiovascular complications that occur in this syndrome. These abnormalities are morphological but also functional. An increase in the augmentation index can be explained in part by the short height of these patients.

Cross-sectional studies have shown a positive association between increased pulse pressure (PP) and an increased likelihood of a C-reactive protein (CRP) level >3 mg/L. In a retrospective subgroup analysis of the hypertensive subjects of the multicenter double-blind study, REASON (PREterax in Regression of Arterial Stiffness in a ContrOlled Double-BliNd), in which fixed first-line antihypertensive combination therapy with an angiotensin converting enzyme (ACE) inhibitor, perindopril (2 mg), and a diuretic, indapamide (0.625 mg), proved significantly more effective than atenolol in normalizing PP, we sought to determine whether perindopril plus indapamide was also more effective than atenolol in lowering CRP levels and, if so, whether this effect correlated with a preferential reduction in PP. At the final visit (12 months) in the 269 patients studied, the decrease in PP was greater, and the proportion of patients with CRP >3 mg/L lower (17.9% versus 28. 9%, P=0.03; adjusted odds ratio, 1.02 to 4.08, P=0.01), in the perindopril plus indapamide group than in the atenolol group. After adjustment for confounders, patients with a baseline CRP >3 mg/L displaying the greatest decrease in PP were more likely (P=0.04) to have a CRP < or =3 mg/L at 12 months. No such relationship was found with systolic or diastolic blood pressure. Perindopril-indapamide combination therapy is more effective than beta-blockade in lowering elevated CRP in hypertensive subjects. This effect is significantly associated with a more effective PP reduction in patients with baseline CRP >3 mg/L.

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

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.

In contrast with the huge amount of experimental data available, only few and somewhat unconvincing clinical studies support the hypothesis that oxidative stress is involved in the early stages of essential hypertension in humans. Isoprostanes are chemically stable lipid peroxidation products of arachidonic acid, the quantification of which provides a novel approach to the assessment of oxidative stress in vivo. The main objective of this study was to quantify the urinary levels of 15-F(2t)-IsoP in the early stages of essential hypertension, using gas chromatography/mass spectrometry, by comparing 30 patients with never-treated mild-to-moderate hypertension with 30 gender- and age-paired healthy controls. Urinary 15-F(2t)-IsoP levels were not significantly different in hypertensive patients (69+/-36 pmol/mmol creatinine) compared with controls (75+/-34 pmol/mmol creatinine, 95% confidence intervals on differences: -23 to 13). No significant correlation was found between basal urinary 15-F(2t)-IsoP levels and age, low-density lipoprotein cholesterol, glucose, clinical pulse pressure, carotid intima-media thickness, left ventricular mass index, or aortic pulse wave velocity. In conclusion, this study shows that lipid peroxidation is not increased in never-treated mild-to-moderate hypertension. This suggests that oxidative stress is not implicated in the pathogenesis of human essential hypertension, at least in the early stages.

Elderly patients with isolated systolic hypertension (ISH)--systolic blood pressure (SBP) > or =140 mmHg and diastolic blood pressure (DBP) <90 mmHg--have increased mortality and morbidity. The aim was to study the incidence of ISH in a younger population of between 15 and 60 years of age, and to measure pulse pressure (PP), mean arterial pressure (MAP) and heart rate (HR) in these subjects. The study population consisted of 27 783 subjects, aged 15-60 years, untreated for hypertension (HT) from a cohort of employees formed to study the incidence of HT in the French working population (AIHFP). BP and HR were measured with a validated, automatic device after 5, 6 and 7 min at rest. The prevalence of ISH was 6.9% in men, 2.3% in women. This prevalence was over 5% in young men and increased at 40-44 years; it was negligible in young women, but increased at 50-54 years to about 10% (ie to the same level as in men of the same age): PP in subjects with ISH (46.9 mmHg) was significantly higher than in the normotensive group (NT-40.9 mmHg); it was comparable in both young men (65.5 mmHg) and older men (66 mmHg); it was higher in men (63.1 mmHg) than in women (61.5 mmHg). HR was higher in ISH than in NT and it was higher in women ( approximately 5 bpm) in whom it decreased with age. The prevalence of ISH is not negligible in HT (30% men, 25% women), with a high prevalence in young subjects and elevated PP, MAP and HR values. These data should be taken into account as elevated ISH, PP and HR are considered as cardio-vascular risk factors.

Objective: 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., Research Design and Methods: 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., Results: 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, P < 0.01) 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., Conclusion: 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.

F2-isoprostanes are stable lipid peroxidation products of arachidonic acid and their quantification provides a novel approach to the assessment of oxidative stress in vivo. F2-isoprostanes are present in increased amounts in adult hypercholesterolemia, but no data exist concerning children. We investigated urinary isoprostaglandin F2, type III production as an index of lipid peroxidation in 15 children presenting with type IIa hypercholesterolemia (serum total cholesterol, 290 [SD +/- 70] mg/dl; low-density lipoprotein cholesterol, 210 [SD +/- 90] mg/dl) compared with 15 sex- and age-paired control children (serum total cholesterol, 160 [SD +/- 20] mg/dl). Urinary levels of isoprostaglandin F2alpha type III were measured by gas chromatography mass spectrometry. Urinary concentrations did not differ significantly in hypercholesterolemic children compared with control children (84.7 [SD +/- 37] vs. 96 [SD +/- 35] pmol/mmol creatinine, respectively). No significant correlation was found with total cholesterol, low-density-lipoprotein and high-density-lipoprotein cholesterol, and apolipoprotein B and A1 serum levels. F2-isoprostane urinary levels in children with type IIa hypercholesterolemia do not differ from those of age- and sex-matched control children and are not correlated to blood lipid parameters, suggesting that hypercholesterolemia is not associated with increased lipid peroxidation in childhood.

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.

Enoximone (a type III-selective phosphodiesterase inhibitor) and dobutamine (a beta-receptor agonist) are positive inotropic drugs frequently used in the postoperative management of coronary bypass surgery. The purpose of this study was to characterize their relaxant effects on the human internal mammary artery (IMA) and the gastroepiploic artery (GEA) and to test the hypothesis that their combination may have greater than additive relaxant effects. In organ baths, the relaxant effects of enoximone and dobutamine were tested on rings of IMA (n = 86) precontracted with U46619 (a thromboxane A2 mimetic), norepinephrine (NE), or KCl. The relaxant effects of dobutamine and enoximone also were tested on rings of GEA (n = 42) precontracted with U46619 and NE. The effect of the combination of enoximone and dobutamine were tested on rings of IMA (n = 24) precontracted with U46619 or NE. With respect to maximal relaxations induced by papaverine (10(-4) M), enoximone (< or =10(-3) M) caused full relaxations of IMA precontracted with NE, U46619, or KCI. Dobutamine (< or =10(-3) M) caused full relaxations of IMA precontracted with NE or KCI but only 46% (95% CI, 27-65) relaxation in the rings precontracted with U46619. Similar patterns of relaxation were observed in GEA rings, with dobutamine inducing partial relaxation in GEA precontracted with U46619. The pD2 values of enoximone and dobutamine were both significantly lower in segments precontracted with U46619. The in vitro threshold relaxant concentrations were in the upper limits or over the range of therapeutic plasma concentrations. The relaxant effect of the combination was significantly more important than the theoretic additive effect in IMA contracted with U46619 or NE. Enoximone and dobutamine are potent in vitro vasodilators but exert weak relaxant effects in IMA and GEA at concentrations in the therapeutic range. There is, however, a greater than additive vasorelaxant effect of the combination, suggesting that the vasorelaxant effect of the combination, in addition to the additive inotropic effect, may be beneficial to patients undergoing coronary bypass grafting.

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.)

Thrombolysis may favorably affect the clinical outcome of mobile right atrial thrombus following pulmonary embolism (PE). We report the case of three patients with mobile right atrial thrombus following PE, in whom fibrinolysis was performed. Atrial mass disappeared on the control echocardiogram, but control ventilation perfusion scan showed new perfusion defects in all patients. Thrombolysis seems successful for the treatment of patients with mobile right atrial thrombus following PE; however, recurrent PE may be induced by fibrinolysis. This may affect the benefit of such therapy and should be taken into account when using this therapeutic treatment.

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.

The antihypertensive efficacy of a 1.5-mg sustained-release formulation (SR 1.5) of indapamide, a diuretic related to thiazide, has been pointed out by using conventional sphygmomanometric measurement 24 h after dosing in clinic, in two large European randomized, double-blind, controlled studies (2 and 3 months). One of these studies was then extended to 12 months, as a complementary open study. Quality-controlled ambulatory blood pressure monitoring (ABPM) data for a total of 216 patients from these studies are presented, including subgroups of hypertensives and responders. Indapamide SR 1.5 achieves an adequate 24-h blood pressure control by significantly reducing the 24-h, diurnal, and nocturnal blood pressures versus baseline, confirming the sphygmomanometric data. The benefit at 2 and 3 months is maintained at 1 year, which confirms the long-term efficacy of SR 1.5 mg. The trough-to-peak ratio--not previously calculated for a diuretic according to international guidelines--meets Food and Drug Administration requirements and confirms the 24-h efficacy of indapamide SR 1.5.

Background: Dobutamine (a beta-receptor agonist), enoximone (a type III selective phosphodiesterase inhibitor), and epinephrine (an alpha- and beta-mimetic) frequently are used in the perioperative management of patients undergoing coronary artery bypass grafting., Methods: We performed a double-blind clinical study to compare the effects on internal mammary artery free flow of low doses of these three positive inotropic drugs. Thirty patients in whom the left internal mammary artery was used for coronary artery bypass grafting were randomized into three groups. Internal mammary artery free flow and hemodynamic measurements were evaluated before and 10 minutes after the intravenous infusion of dobutamine (3 microg x kg(-1) x min(-1)), enoximone (200 microg/kg), or epinephrine (0.05 microg x kg(-1) x min(-1))., Results: A significant increase in free flow occurred only in the dobutamine group (33 +/- 7.5 and 42.2 +/- 7.9 mL/min before and after drug infusion, respectively; p = 0.013). Comparison of the increase in flow between the groups, however, showed no difference. These drugs, at doses designed to produce a positive inotropic effect, caused little increase in the free flow of the internal mammary artery., Conclusions: The use of dobutamine, enoximone, and epinephrine as low-dose positive inotropic treatments in the perioperative and postoperative periods of coronary artery bypass grafting should depend on their positive inotropic effects rather than their vasodilative effects on the arterial grafts.

The aim of this study was to evaluate the antihypertensive effect of drugs according to the initial ambulatory blood pressure (BP) level. After a 15-day placebo run-in period, 105 patients with moderate essential hypertension (mean age, 52 years) underwent 24-h BP monitoring (spacelabs: 1 measure/15 min). Patients were subdivided into two groups: the "High" group, with 24-h mean values of systolic BP (SBP) > 137 or diastolic BP (DBP) > 87 mm Hg, and the "Low" group, with SBP < or = 137 and DBP < or = 87 mm Hg. All patients received, in a random and double-blind design, either bisoprolol (10 mg q.d.) or lisinopril (20 mg q.d.) for 8 weeks. At the end of this active treatment period, office and ambulatory BP measurements were performed. Casual measurements revealed similar BP decreases in all subgroups receiving bisoprolol and lisinopril; BP monitoring showed that the antihypertensive effect depended on the baseline mean 24-h value; -15/-12 mm Hg for bisoprolol and -18/-13 mm Hg for lisinopril in the High group; -7/-6 mm Hg for bisoprolol and -6/-6 mm Hg for lisinopril in the Low group. This study shows that the antihypertensive effect depended on initial ambulatory BP values, with a lower BP decrease in the Low group. Assessment of the antihypertensive effect on ambulatory BP is useful in clinical trials.

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.

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.

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)

Variations in blood pressure were investigated by an automatic, non-invasive ambulatory method in 9 subjects with essential hypertension. Recordings were made after 6 week periods during which captopril was taken either once or twice daily, in a double-blind cross-over study. Although the effects of captopril administration either once or twice daily were broadly similar, there was a significant decrease in diastolic blood pressure values on the once-daily regimen. These results suggests that treatment once a day can advantageously replace twice-daily treatment.

Blood pressure and heart rate of 15 male shift workers were measured every 15 minutes for 24 hours during three work shifts: morning, 4:00 AM to noon; afternoon, noon to 8:00 PM; and night, 8:00 PM to 4:00 AM. For each shift, 24-hour systolic and diastolic blood pressure showed a large "trough" (the low pressure span) and a continuous range of elevated pressure (the high pressure span). Fourier series were used to model the 24-hour blood pressure profiles. A careful examination of the residuals (measured minus predicted pressures) showed that four harmonics were necessary to describe the data accurately. The model enabled localization in each blood pressure profile of the high and low pressure spans that did not coincide with the subject's work and rest periods. The time and slope of blood pressure entering and leaving these spans could also be individually determined. Mean blood pressure during the high pressure span was the same for the three shifts, but mean blood pressure during the low pressure span was lower when the subject worked in the afternoon. During that shift, the systolic blood pressure slopes entering and leaving the low pressure span were steeper than during the two other shifts. The high pressure span was longest during the night shift and shortest during the afternoon shift. Therefore, a change in the working time profoundly perturbed the 24-hour blood pressure profile.(ABSTRACT TRUNCATED AT 250 WORDS)