[Resistant hypertension by unadvertised non-compliance detected by psychiatric expertise and drug dosages]. / Hypertension artérielle résistante par inobservance non avouée dépistée par expertise psychiatrique et dosages médicamenteux.

The management of patients with resistant hypertension remains a major challenge in daily clinical practice in order to limit macro and microvascular impact. However, lack of compliance often remains one of the main etiologies of resistant hypertension. Through a clinical case of complex therapeutic non-compliance, we will detail the frequency, the screening and the management of therapeutic non-compliance. Finally, we will specify the contribution of drug dosages and psychological expertise in screening non-observant patients with presumed resistant hypertension.

[Renal artery stenosis long time after renal denervation for resistant hypertension]. / Sténose de l'artère rénale à distance d'une dénervation rénale pour HTA résistante.

The onset of renal artery stenosis following a renal denervation is rare and occurs in the first few months after renal denervation. We report the onset of renal artery stenosis a long time after the renal denervation for resistant hypertension. This is a 74 year-old patient who stopped smoking in 1980 and who was treated for dyslipidemia with a revascularized coronary artery disease in 2011, a well-stabilized peripheral arterial disease since 2001, a stable asymptomatic carotid atheroma and a good kidney function. His hypertension known since 1995 became resistant. After the control of renal arteries by angio-CT scan, he had a renal denervation in October 2012. His blood pressure decreased 3 months later confirmed by self-blood pressure monitoring (SBPM) and ambulatory blood pressure monitoring (ABPM) with a CT scan with a non-significant renal artery stenosis in January 2014. He remained normotensive under treatment until July 2015 but his hypertension became uncontrolled at the end of 2015 then resistant and severe confirmed by SBPM in April 2017, despite a 5-drug antihypertensive treatment associated to atorvastatin and clopidogrel confirmed by SBPM in April 2017. A left post-ostial renal artery stenosis with decrease in size of left kidney and cortex as compared to 2011 was detected at CT and treated by angioplasty. It was associated with a rapid decrease in blood pressure but unfortunately a new increase related to a restenosis occurred at the end of 2017, which justified a new angioplasty. Discussion about the etiology and the management of this renal post-denervation late stenosis.

[Control of cardiovascular risk factors in coronary patients one year after cardiac rehabilitation]. / Contrôle des facteurs de risque chez les patients coronariens un an après une réadaptation cardiaque.

OBJECTIVE: To assess risk factors monitoring in coronary patients one year after cardiac rehabilitation. METHOD: From 2015 to 2015, cardiac morbidity, total mortality and risk factors data were collected from a 4-week ambulatory cardiac rehabilitation program with a control one year later and were compared with the results of Euroaspire and Reach studies. RESULTS: Out of 1091 (87%) coronary patients, 746 (68%) were re-examined 12months later (aged 60years (ranging from 20 to 85years), 15% women, 44% hypertensive, 36% smokers, 17% diabetics, 74% with dyslipidemia). At the end of the program, management of CV risk factors was improved (BP ≤ 140/90mmHg and BMI > 30: 80 and 20% vs 65 and 25% at the beginning of the program; LDL < 0.7g/L: 42% and smoking: 4% vs 18% when hospitalized for their cardiac event). Unfortunately, this benefit decreased significantly at one year (BP ≤ 140/90mmHg: 63%, LDL < 0.7g/L: 27%; smoking: 6%) but it remains better than in Euroaspire IV study: 57, 20 et 16% respectively). While 54% had insufficient physical activity before cardiac rehabilitation, they were only 23% at 1-year vs 60% in Euroaspire study. We reported a total mortality of 0.6% vs 2.9% in Reach study and 12% cardiac hospitalization (53% for a new coronary event). CONCLUSION: Participation of coronary patients in a cardiac rehabilitation program significantly improves management of CV risk factors, morbidity and mortality. However, the control obtained at the end of the program decreases at one year.

Management of resistant hypertension: expert consensus statement from the French Society of Hypertension, an affiliate of the French Society of Cardiology.

To improve the management of resistant hypertension, the French Society of Hypertension, an affiliate of the French Society of Cardiology, has published a set of eleven recommendations. The primary objective is to provide the most up-to-date information based on the strongest scientific rationale and that is easily applicable to daily clinical practice. Resistant hypertension is defined as uncontrolled blood pressure on office measurements and confirmed by out-of-office measurements despite a therapeutic strategy comprising appropriate lifestyle and dietary measures and the concurrent use of three antihypertensive agents including a thiazide diuretic, a renin-angiotensin system blocker (ARB or ACEI) and a calcium channel blocker, for at least 4 weeks, at optimal doses. Treatment compliance must be closely monitored, as must factors that are likely to affect treatment resistance (excessive dietary salt intake, alcohol, depression, drug interactions and vasopressor drugs). If the diagnosis of resistant hypertension is confirmed, the patient should be referred to a hypertension specialist to screen for potential target organ damage and secondary causes of hypertension. The recommended treatment regimen is a combination therapy comprising four treatment classes, including spironolactone (12.5-25 mg per day). In the event of a contraindication or a non-response to spironolactone, or if adverse effects occur, a ß-blocker, an α-blocker, or a centrally acting antihypertensive drug should be prescribed. Because renal denervation is still undergoing assessment for the treatment of hypertension, this technique should only be prescribed by a specialist hypertension clinic.

[Itraconazole: a new drug-related cause of hypertension]. / HTA sous itraconazole : une nouvelle cause d'HTA iatrogène.

Itraconazole is a triazole agent used in the treatment of fungal infections and in some metastatic cancers. Its use has been associated with cardiovascular adverse events and particularly heart failure with preserved ejection fraction. We report the case of a 68-year-old male patient with a well-controlled hypertension treated with irbesartan 150mg/day since 2007. He developed a pulmonary aspergillosis on post-tuberculosis cavitary lesions treated in July 2011 with itraconazole 200mg/day. Early 2012, his antihypertensive treatment had to be gradually increased to a quadritherapy and his blood pressure was at 157/78mmHg at home. Hypokalemia was observed on several occasions as well as edema of the lower limbs. Plasma renin and plasma and urine aldosterone concentrations on treatment not interfering with the renin angiotensin system were low, associated with normal serum and urine cortisol, ACTH, SDHA and DOC, BNP and creatinine concentrations. Plasma itraconazole values were much above the therapeutic range. Left ventricular ejection fraction was preserved. There were no adrenal or renal artery abnormalities at the CT scan. Three months after stopping itraconazole, hypokalemia and edema disappeared and blood pressure was normalized with less treatment. Plasma renin and aldosterone concentrations were normalized. He had a pulmonary lobectomy for his pulmonary aspergillosis. Itraconazole may induce a resistant hypertension with low renin. The mechanisms of this adverse effect of itraconazole remain unknown.

[Effectiveness of a health network in secondary prevention among coronary patients]. / Efficacité d'un réseau pour la prévention secondaire chez les patients coronariens.

OBJECTIVE: To improve the secondary prevention, particularly hypertension management among coronary patients. METHODS: In 2004-2005, out of 175 coronary patients having taken part in a cycle of the Educoeur center of the health network Rivarance, 131 (75%) aged between 32-79 years of age (an average of 61 years with 11% women, 52% hypertensive, 24% smokers, 10% diabetics and 72% with unbalanced dyslipidemia (LDL>1g/l)) were re-examined within 12 months and were compared with a French cohort of the EuroAspire II study (365 patients - Lancet 2001). 56% were treated by angioplasty, 24% by coronary bypass and 20% by medical treatment. The 4-week ambulatory educational program consisted of a physical education with 22 meetings of cardiac rehabilitation (ergo cycle, carpet, segmentary muscular work, steps and balneotherapy) and a therapeutic and dietetic education (18 courses and cooking workshops, supermarket visits and self BP measurement). These 131 patients were re-examined 3, 6 and 12 months after by the paramedical team. The GP and nurses were taught recommendations on CV risk factors management. The patients were followed by a computerized medical file. BP (average of 3 measurements by OMRON M4), total cholesterol (CT), weight, physical activity (insufficient if less than 3 walks of 30 min per week), smoking and drugs intake were analyzed on J0 then at one year and were compared with the French results of EuroAspire II. [table: see text] CONCLUSION: The education and the follow-up of the patient in a network of health improve CV risk factors and particularly hypertension management of these coronary patients but this decreases with time.

[MICROALB study: screening for microalbuminuria in type 2 diabetic hypertensive patients by general practitioners in France]. / Enquête MICROALB: dépistage de la microalbuminurie chez l'hypertendu diabétique de type 2 par le médecin généraliste en France métropolitaine.

OBJECTIVE: To determine the prevalence of microalbuminuria (MAU) detected by a specific urinary strip in type 2 diabetic hypertensive patients in metropolitan France. METHOD: Screening for MAU with a semi-quantitative strip measuring the albumin/creatinine ratio was performed by general practitioners (GPs) in 6 type 2 diabetic hypertensive patients. This screening method was considered reliable if a preliminary search for proteinuria was performed with a usual strip and the quality of the MAU reading was good. RESULTS: 3347 GPs screened 19,714 patients (60% M, average age 64 +/- 10 years): 43.3% had MAU. MAU screening was considered reliable for 6679 patients (61.8% M, average age 65 +/- 10 years): 48.5% had MAU (alb/creat ratio between 30 and 300 mg/g), and 10.7% had manifest MAU (alb/creat ratio >300 mg/g). In all cases, the prevalence of MAU increased with the severity of hypertension. In the population with a reliable MAU screen, the analysis of risk factors according to the level of MAU yielded the following results: [table: see text]. In the MAU+ group, the need for multiple antidiabetic (including insulin) and antihypertensive drugs was more frequent. In contrast to current guidelines, only a minority of patients received an antiplatelet agent (approximately 33%). CONCLUSION: Despite recommendations, screening for proteinuria in type 2 diabetic hypertensive patients is seldom performed. However, the prevalence of MAU was high in this patient population. The prevalence of comorbidities and risk factors was significantly higher in the MAU+ group, with less frequent BP control despite a more aggressive antihypertensive treatment.

[Home blood pressure monitoring in addition to office blood pressure determination is useful in patients with systolic hypertension before their inclusion into a drug trial]. / L'automesure tensionnelle en complément de la mesure de consultation est utile pour l'inclusion dans un essai clinique de sujets avec une HTA systolique.

OBJECTIVE: In patients with uncontrolled systolic hypertension, to estimate the value of home blood pressure monitoring in addition to office blood pressure for inclusion in a trial. METHODS: 80 patients with systolic hypertension, defined as SBP > or =140 mmHg and pulse pressure > or =60 mmHg, were treated for 4 weeks with a thiazide diuretic at usual dose (25 mg HCTZ or 1.5 mg indapamide or methyclothiazide 5 mg). Blood pressure was measured using an automatic monitor (Omron M6) at office and at home in the 3 days prior the visit. Subjects with an uncontrolled hypertension were included in the second part of the trial only if there fulfilled inclusion criteria: office SBP > or =140 mmHg and home SBP > or =135 mmHg (mean of 18 measurements obtained on 3 consecutive days) and office pulse pressure > or =60 mmHg. RESULTS: After 4 weeks with diuretic treatment, 62% of patients fulfilled 3 criteria and were included in the second part of the trial. It was observed 76% of patients with office SBP > or =140 mmHg, 72% with office pulse pressure > or =60 mmHg and 70% with both office SBP and PP criteria. However, only 67% of patients had home SBP > or =135 mmHg. Discrepancy between office and home SBP was observed and subjects with a white coat hypertension was noticed in 14% and masked hypertension in 5%. CONCLUSION: If patients with systolic hypertension have to be included into a drug trial because there are uncontrolled, home blood pressure monitoring in addition to office blood pressure is a very useful criteria for inclusion because misclassifications due to white coat or masked hypertension is frequent in these patients.

[District program to improve the cardiovascular risk of resistant hypertensive patients in general medicine]. / Programme régional d'amélioration de la prise en charge en médecine gnérale du patient hypertendu résistant.

PURPOSE: To try to improve the cardiovascular risk of resistant hypertensive patients in general medicine in Brittany after using french hypertension recommendations. METHODS: 581 hypertensive patients under 3 antihypertensive drugs have asked for an exoneration of the patients' social contribution: 297 (51%) were uncontrolled at their general practitioner (GP) among whom 106 (36%) have refused to take part in the program. 191 resistant hypertensive patients followed by 170 different GP have been pre-included. After a meeting between the social security physician, the GP measured blood pressure (BP) with a validated BP device and passed it on to the patient for a self-BP measurement (SBPM). In the case of a confirmed resistance, after specialist opinion, the treatment was then modified and the patient was checked after four months by his GP for a new clinical and self BP measurement. RESULTS: After the initial automated BP measurement by GP, 51 patients (27%) had in fact controlled hypertension. Out of 136 resistant hypertensive patients (mean: 63 ys) during consultation (60% with systolic isolated hypertension), 121 (89%) have been closely followed during the whole study period among who 114 were also resistant with SBPM (94%). Only 8 patients (6%) were controlled at home. A check-up with specialist opinion was conducted: ECG (82%), echocardiography (59%), vascular echography (35%), funduscopy (30%), plasma renin/aldosterone measurement (15%), renal artery exploration (26%). Eight (7%) secondary hypertension have been founded. After 4 months, 32 (26%) obtained controlled hypertension during GP consultation and 15% during SBPM but the 20/32 controlled patients (62%) had a masked hypertension. Cholesterol levels (63% of dyslipidemics) and the body mass index (80% of overweighed patients) have not varied. On the contrary, 12/28 (48%) has stopped smoking. The coronary risk using Anderson's model has only decreased from 16.5% to 13.8%. CONCLUSION: If this health program has shown its feasibility and the good participation of the GPs, treatment of hypertension and others risk factors really remains insufficient. On the contrary, the use of a validated automatic BP device has been really well carried out. Its use has allowed reclassifying as controlled one third of the resistant hypertensive patients and as uncontrolled at home one patient out of two which were controlled with GP. These results prove the necessity to increase this BP measurement technique in this population.

[Treatment decision as a function of cardiovascular risk in isolated systolic hypertension in general medicine. The PREHSI study]. / Décision thérapeutique en fonction du risque cardiovasculaire dans l'HTA systolique isolée en médecine générale. Etude PREHSI.

OBJECTIVE: To analyse the decision of treatment made by the GP, based on the characteristics of patients with isolated systolic hypertension (ISH). METHODS: 11,436 patients with SBP > or = 140 and DBP < 90 mmHg were examined by 1,464 GPs who filled out a questionnaire for each patient, which included the patient's BP, risk factors, the presence of target organ damage (TOD), antihypertensive treatment and the physician's decision of treatment during the visit. Before the visit, 4,378 patients were not treated: 57 +/- 13 years: 53% men: BP: 157/81 mmHg; smokers: 30%; diabetes: 8%; dyslipidemia: 17%; BMI > 25 kg/m2: 54%; TOD: 11%. Thus, according to ISH tables, 15% of the patients who were not treated presented a low cardiovascular risk (LR), 69% a medium risk (MR), and 16% a high risk (HR). After the visit, 2,599 patients (59%) started antihypertensive treatment. [table: see text] CONCLUSION: 78% of the patients with ISH had at least one other risk factor. Three elements (the grade of ISH, the number of risk factors and the level of CV risks) are significantly taken into account in making the decision of treatment. Decision of treatment was in accordance with ISH recommendation in 91% of patients. Nevertheless, while ISH recommendations are life style measures, only when a LR exists, 39% with a LR were treated. On the other hand, 24% with a HR were not treated.

[Characteristics of patients with isolated systolic hypertension in relation to body mass index. The PREHSI study]. / Caractéristiques des patients avec une HTA systolique isolée en fonction de la masse corporelle. Etude PREHSI.

OBJECTIVE: To analyse patient's isolated systolic hypertension (ISH) in relation to the body mass index (BMI). METHODS: 11,436 patients with SBP > or = 140 and DBP < 90 mmHg were examined by 1,464 GPs who filled in a questionnaire for each patient: the patient's BP, risk factors, the presence of target organ damage (TOD) and antihypertensive treatment. 11,100 patients were split into 3 groups depending on their BMI: Gp 1 (BMI < 25 kg/m2: 4,324), 39%; 62 +/- 14 yrs; 44% men; BP: 157/80 mmHg, 55% treated; Gp 2 (BMI 25 and 30 kg/m2: 5,164) 47%; 62 +/- 12 yrs; 61% men; BP: 158/81 mmHg, 63% treated; and Gp 3 (BMI > 30 kg/m2: 1,612) 14%; 62 +/- 12 yrs; 49% men; BP: 159/81 mmHg, 75% treated. 11,085 patients' CV risks were analysed and categorised into high (HR), medium (MR) and low risk (LR). [table: see text] 11,100 patients' CV history (CVH) were analysed: > 1 CVH were 1,056 (24%) into Gp 1; 1,531 (30%) into Gp 2 and 653 (41%) into Gp 3; left ventricular hypertrophy was 454 (10%) into Gp1; 815 (16%) into Gp 2 and 388 (24%) into Gp 3. CONCLUSION: 61% patients with ISH carry excess weight and 14% are obese. In spite of a more frequent antihypertensive treatment which gives comparable BP levels, the higher the BMI, the higher the CV risk and CV history. Treatment of all CV risks is therefore necessary.

Effects of nicardipine and clonidine on cognitive functions and electroencephalography in hypertensive patients.

The aim of this study was to investigate the cognitive and electroencephalography (EEG) short-term effects of a calcium antagonist, nicardipine, compared to placebo and clonidine (which, having known sedative effects, acted as a negative control) for 15 days in elderly hypertensive patients with memory complaints. Nicardipine and clonidine were compared with placebo in a double-blind, randomized, three-way cross-over controlled study after a 2-week placebo run-in period. This was a phase II clinical study carried out on out-patients in a single research centre. Fifteen elderly (63 +/- 10 years) hypertensive patients, without dementia but with memory complaints, were included. Psychomotor performance and cognition were assessed using both an extensive battery of validated psychometric tests (which evaluated attention and vigilance, body sway and memory) and an EEG profile. Cardiovascular parameters measured were blood pressure and heart rate. No detrimental effects of nicardipine were found on attention, vigilance, body sway or memory. Nicardipine produced a significant increase in alpha EEG energies, which may indicate possible alerting effects. In contrast, clonidine induced well-known deleterious sedative effects in psychometric tests and in EEG analysis (decrease in alpha and increase in delta and theta waves). The two drugs produced equivalent decreases in blood pressure at steady state. In conclusion, clonidine induced well-known sedative effects, while nicardipine did not impair central nervous system activity and may have had some short-term alerting effects in elderly hypertensive patients with memory complaints. This study supports the hypothesis of a dissociation between blood pressure and direct drug effects on the central nervous system.

[What tests should be conducted for secondary arterial hypertension in hypertensive patients resistant to treatment?]. / A quoi conduit la recherche d'une HTA secondaire chez des patients hypertendus résistant aux traitements?

UNLABELLED: The aim of this study was to determine the prevalence of secondary hypertension in a population of refractory hypertension without initial clinical or biological findings suggesting identifiable causes of hypertension. METHODS: A survey included 200 consecutive hypertensive patients referred to hypertension specialists for refractory hypertension (BP > 140/90 mmHg on at least two antihypertensive drugs). Prior inclusion, the permanent elevation of blood pressure was confirmed by ambulatory monitoring. In each subject an extensive work-up was performed to detect a secondary cause for hypertension. RESULTS: An essential hypertension was confirmed in 61% of this cohort. A secondary hypertension was detected in 20% of the patients; 8.5% with a primary hyperaldosteronism, 8% with a reno-vascular hypertension and 3% with a nephropathy. Moreover, 18.5% had a low renin hypertension. Thus, 27% of these patients had an abnormality of the renin-aldosterone axis. CONCLUSION: Patients with refractory hypertension should be explored to detect secondary hypertension even without findings suggesting such causes. This additional diagnostic procedure must include at least renovascular investigations and plasma renin/aldosterone level determinations in appropriate conditions.

Self-measurement of blood pressure in clinical trials and therapeutic applications.

Self-measurement of blood pressure (SMBP) is increasingly used to assess blood pressure outside the medical setting. A prerequisite for the wide use of SMBP is the availability of validated devices providing reliable readings when they are handled by patients. This is the case today with a number of fully automated oscillometric apparatuses. A major advantage of SMBP is the great number of readings, which is linked with high reproducibility. Given these advantages, one of the major indications for SMBP is the need for evaluation of antihypertensive treatment, either for individual patients in everyday practice or in clinical trials intended to characterize the effects of blood-pressure-lowering medications. In fact, SMBP is particularly helpful for evaluating resistant hypertension and detecting white-coat effect in patients exhibiting high office blood pressure under antihypertensive therapy. SMBP might also motivate the patient and improve his or her adherence to long-term treatment. Moreover, SMBP can be used as a sensitive technique for evaluating the effect of antihypertensive drugs in clinical trials; it increases the power of comparative trials, allowing one to study fewer patients or to detect smaller differences in blood pressure than would be possible with the office measurement. Therefore, SMBP can be regarded as a valuable technique for the follow-up of treated patients as well as for the assessment of antihypertensive drugs in clinical trials.

Hemodynamic effects of reboxetine in healthy male volunteers.

BACKGROUND: Reboxetine [(R,S)-2[(R,S)-alpha-(2-ethoxyphenoxy)benzyl]morpholine methanesulfonate] is a racemic compound that consists of equal proportions of R,R- and S,S-enantiomers. This study investigated the hemodynamic effects of reboxetine and the R,R-enantiomer compared with placebo in volunteers. The pharmacokinetics of reboxetine and its enantiomers were also investigated in the study. METHODS: Nine healthy, male volunteers received single doses of 4 mg reboxetine, 2 mg R,R-enantiomer, and placebo at weekly intervals. Reboxetine and the R,R-enantiomer were well tolerated in all volunteers. RESULTS: The heart rates of patients in the supine and standing positions were increased after reboxetine administration compared with the R,R-enantiomer (P < .05, except supine heart rate at 6 hours) and placebo (P < .05). Supine systolic and diastolic blood pressure was also increased by 3 +/- 4 and 1 +/- 4 mm Hg, respectively, after reboxetine compared with R,R-enantiomer (-2 +/- 4 and -4 +/- 3 mm Hg) and placebo (-4 +/- 4 and -4 +/- 4 mm Hg) administration. The systolic and diastolic blood pressure measurements for subjects while standing did not differ significantly among treatments. There was no significant difference between the maximum plasma concentration, mean time to maximum plasma concentration, plasma half-life, or area under the plasma concentration-time curve (AUC) of the R,R-enantiomer after reboxetine or R,R-enantiomer administration. The ratio of the mean AUC values for the R,R- and S,S-enantiomers was 2.1. CONCLUSION: These findings suggest that the S,S-enantiomer is responsible for the hemodynamic effects of reboxetine in humans. Increases in supine blood pressure after reboxetine administration may be interpreted as regression to the mean value and not caused by any treatment effect.

Lack of effect of mizolastine on the safety and pharmacokinetics of digoxin administered orally in repeated doses to healthy volunteers.

The effects of mizolatine, a new H1 receptor antagonist, on safety and pharmacokinetics of digoxin were studied in a double-blind placebo-controlled crossover study. After administration of digoxine alone (0.25 mg o.d. for 7 days), 12 healthy young male volunteers (23+/-2 years) received either placebo and digoxin (0.25 mg o.d.) or mizolastine (10 mg o.d.) and digoxin (0.25 mg o.d.) during 7 days. The assessment criteria consisted in hemodynamic and ECG parameters recordings and the pharmacokinetics of digoxin during the last day of coadministration (day 14). No difference between the 2 treatment groups was evidenced on ECG, hemodynamic, and clinical and laboratory safety parameters. No change in AUC and tmax was recorded. No clinically relevant effect of mizolastine on the digoxin pharmacokinetics was found. However, a statistically significant increase in digoxin Cmax (3.03+/-0.18 nmolxl(-1) vs 2.52+/-0.19 nmolxl(-1), p < 0.05) and Cmin (0.99+/-0.08 nmolxl(-1) vs 0.87+/-0.07 nmolxl(-1), p=0.05) occurred after the coadministration vs digoxin alone. It can be concluded that mizolastine and digoxin at therapeutic dosages can be safely coadministered.

[Baseline blood pressure in healthy normotensive volunteers]. / Etat basal de la pression artérielle chez le volontaire sain normotendu.

UNLABELLED: The aim of this study was to define the reproducibility and the time required to obtain a stable baseline level of blood pressure (BP) in normotensive volunteers during a phase I trial. Blood pressure was recorded automatically (Dinamap and Marquette monitors) every 5 min during a 2-hour period and manually (Random zero device) at T20, T60 and T120, twice at a one-week interval, under similar study conditions (6 in the morning, 7 in the afternoon) in supine position in 13 normotensive men (aged 20 to 28). The average BP was compared using a 3-way ANOVA (subject, time, week). 1.SBP/DBP decreased significantly (p < 0.001) from one week to the other and SBP, but not DBP, decreased significantly over time up to T75 (p < 0.001): [table: see text] 2. SBP was significantly higher in the morning than in the afternoon during both weeks (p = 0.001). The decrease in SBP with rest was only observed in the morning (p = 0.00001). 3. Reproducibility and change over time and period did not significantly differ between manual and oscillometric methods. The best reproducibility of T75 was obtained with the mean of 3 automatic values (T70, T75, T80). CONCLUSION: in normotensive subjects, BP decreased from one period to the next and with rest. The baseline value of BP was obtained from T75 with the best reproducibility when baseline BP level is defined by 3 automatic values.

Systemic and regional hemodynamic and biological effects of a new kappa-opioid agonist, niravoline, in healthy volunteers.

We noninvasively investigated the effects of a single 30-min i.v. infusion of a 2-mg dose of niravoline, a new selective kappa-opioid agonist, on systemic and regional (brachial artery) hemodynamics, on plasma levels of the main hormones regulating the cardiovascular system, on diuresis and on plasma and urinary osmolalities and electrolytes. This was a placebo-controlled, randomized, double-blind, crossover study performed in 12 healthy volunteers. Compared with placebo, niravoline induced a significant, early and potent diuresis, which peaked within 2 hr (urine output increased 2.4-fold) and lasted for 4 hr. Niravoline significantly decreased, between 0 and 2 hr, urine osmolality (-71%) and sodium (-38%) and potassium (-29%) excretion and significantly increased plasma osmolality and natremia, without changing kalemia. Niravoline induced a slight, but significant, increase in blood pressure (+8% at 0.5 hr), which disappeared within 2 hr. Because heart rate, stroke volume and cardiac output were not modified, this effect was due to an increase in total peripheral resistance (+22% at 0.5 hr). Niravoline did not modify brachial artery diameter and flow and corresponding vascular resistance. Niravoline tended to decrease plasma vasopressin levels and urinary excretion and significantly increased plasma levels of norepinephrine (+44% at 0.5 hr), active renin (+22% at 1.25 hr), aldosterone (+52% at 1.25 hr) and atrial natriuretic factor (+20% at 2 hr). We conclude that niravoline induces a potent aquaretic effect associated with antinatriuresis and antikaliuresis. These main effects are accompanied by a stimulation of the sympathetic and reninangiotensin systems and a slight and transient increase in blood pressure.

[Comparison and reproducibility of 4 methods of indirect blood pressure measurement in moderate hypertension]. / Comparaison et reproductibilité de 4 méthodes de mesure indirecte de la pression artérielle dans l'hypertension artérielle légère.

UNLABELLED: The measurements and the reproducibility of ambulatory, home, clinic and repeated non ambulatory automatic blood pressure (BP) were compared in 16 patients (45 +/- 11 yrs) with mild untreated hypertension (BP: 164 +/- 12/101 +/- 6 mmHg at the selection visit); 26 +/- 19 days after this visit, each patient had two sets of BP measurements in 4 different ways taken 2 weeks apart under similar study conditions: daily ambulatory recordings (ABP), home self-measurement readings (over 5 days) (HBP), 2-minute repeated automatic BP measurements during the 20 minutes preceding the physician examination (RABP) and clinic BP (CBP) with a standard sphygmomanometer mercury column. The reproducibility was assessed by standard deviation of the differences (SDD). Decisions to treat the patients were made according to the results obtained by CBP (BP > 140/90 mmHg during the selection visit and the 2 study visits), by the first ABP (mean BP > 139/87 mmHg) and by the first week of HBP (mean BP > 127/83 mmHg) were compared; the outcome of these three procedures was then compared. RESULTS: [table: see text] CONCLUSION: Repeated automatic and clinic BP were higher than ambulatory and home BP. Reproducibility of ambulatory and home BP were comparable and better than clinic or repeated automatic BP. The percentage of decision to treat according to the results of clinic, home and ambulatory BP was comparable but they were not the same patients who were treated with the 3 methods.