Strategies de traitement dans l'hypertension arterielle essentielle. [Treatment strategies in essential arterial hypertension]

Essential hypertension is a very heterogeneous disease. The availability of antihypertensive drugs lowering blood pressure by various mechanisms allows most often to tailor the treatment, i.e. to find for each patient a drug regimen that is both efficient and well tolerated. Frequently medications given as monotherapy are not effective enough so that the use of drug combinations is required. When combined, low doses of antihypertensive agents are generally sufficient, so that tolerability is optimally preserved. Unfortunately many patients do not have their blood pressure controlled during antihypertensive therapy. These patients therefore do not benefit maximally from the cardiovascular protection afforded by blood pressure lowering. It is also imperative to correct all cardiovascular risk factors in each hypertensive patient. Such a multifactorial approach is known to improve effectively the prevention of cardiovascular diseases.

Mesure de la pression artérielle et dépistage de l'hypertension chez l'enfant. [Blood pressure measurement and screening of hypertension in children].

Children with elevated blood pressure are at risk of being hypertensive in adulthood and of developing complications such as ventricular hypertrophy. Obesity is a cause of hypertension. Because the prevalence of obesity is increasing, some authors argue that the systematic screening for hypertension in children and adolescents is justified for early prevention and treatment. Sex, age and height all influence children's blood pressure. When elevated blood pressure is identified, complementary investigations and treatment might be necessary. However, due to the difficulties of obtaining a valid estimate of blood pressure, to the moderate tracking of blood pressure from childhood to adulthood, and the rarity of hypertension cases in childhood, the usefulness of systematic screening of hypertension during childhood is still controversial. Un enfant dont la pression artérielle est élevée a un risque accru d'être hypertendu à l'âge adulte et de présenter des complications telles que l'hypertrophie ventriculaire gauche. L'augmentation de la prévalence de l'obésité justifierait selon certains auteurs le dépistage systématique de l'hypertension dès le plus jeune âge afin d'instaurer des mesures préventives ou curatives précoces. Les normes de pression dépendent du sexe, de l'âge et de la taille de l'enfant. En cas de pression élevée, des investigations complémentaires, voire un traitement, peuvent être indiqués. Au vu des difficultés pour obtenir une mesure fiable, des incertitudes entachant la valeur pronostique d'une pression artérielle élevée et de la rareté des cas d'hypertension, il n'y a pas de consensus sur l'utilité du dépistage systématique de l'hypertension durant l'enfance.

Physiopathologie de l'hypertrophie ventriculaire gauche. [Physiopathology of left ventricular hypertrophy]

Left ventricular hypertrophy (LVH) is an early complication of hypertension. To a certain degree, this process counteracts the parietal stress induced by high blood pressure. Genetic factors, obesity, high salt diet and different growth factors, notably angiotensin II and noradrenaline, can also predispose to hypertrophic cardiomyopathy. Left ventricular mass is increased on echocardiography in about 20% of hypertensive subjects. LVH is initially associated with a change in myocardial diastolic function and later with abnormal systolic function. It is a major risk factor, a cause of cardiac failure, reduction in coronary reserve and of ventricular arrhythmias. Treatment of hypertension is associated with regression of LVH and preservation or improvement in myocardial diastolic and systolic functions. The decrease in left ventricular mass could reduce the incidence of cardiovascular complications in hypertension.

Diabète et insuffisance rénate terminate. Evolution en huit ans dans le canton de Vaud [Diabetes and end stage renal disease. Eight year progression in the Canton de Vaud, Switzerland].

Diabetic nephropathy is the first cause of endstage renal disease. The demographic expansion, the increase in the incidence of diabetes and the prolonged survival rates explain the steep increase observed these last 30 years. In the United States, improved treatment has brought to a decline in the incidence of end-stage renal disease in the diabetic population since the mid nineties. We examined the change in prevalence of diabetics on dialysis from 2001 and 2009 in the Canton de Vaud, Switzerland. The prevalence of diabetics on dialysis increased from 18% to 31% in dialysis centers and increased from 1.1/1000 to 1.9/1000 in the diabetic population. These are strong indicators that efforts are needed to improve the renal outcome of patients with diabetic nephropathy.

Neutral endopeptidase versus angiotensin converting enzyme inhibition in essential hypertension.

OBJECTIVE: To evaluate the antihypertensive efficacy of sinorphan, an orally active inhibitor of neutral endopeptidase EC 3.4.24.11. DESIGN: The ability of sinorphan (100 mg twice a day) to lower blood pressure was compared with that of the angiotensin converting enzyme (ACE) inhibitor captopril (25 mg twice a day) using a randomized-sequence, double-blind crossover design in 16 patients with essential hypertension. Each treatment was administered for 4 weeks and treatments were separated by a 3-week placebo period. At the end of the last phase of treatment sinorphan was combined with captopril for a further 4-week period. The changes in systolic (SBP) and diastolic blood pressure (DBP) were monitored using repeated ambulatory blood pressure monitoring. RESULTS: When given as monotherapy for 4 weeks, neither sinorphan nor captopril significantly reduced the 24-h or the 14-h daytime mean SBP or DBP. However, a significant decrease in DBP was observed during the first 6 h after the morning administration of captopril. With sinorphan only a significant decrease in night-time SBP was found. With the combined therapy of sinorphan and captopril, significant decreases both in SBP and in DBP were observed, which were sustained over 24 h. After 4 weeks of sinorphan alone or in combination with captopril, no change in plasma atrial natriuretic peptide level was found. However, urinary cyclic GMP excretion increased transiently after administration of the neutral endopeptidase inhibitor. CONCLUSIONS: Neutral endopeptidase inhibition with sinorphan has a limited effect on blood pressure in hypertensive patients when given alone. However, simultaneous neutral endopeptidase and ACE inhibition induces a synergistic effect, and might therefore represent an interesting new therapeutic approach to the treatment of essential hypertension.

Pharmacokinetic-pharmacodynamic profile of angiotensin II receptor antagonists.

The pharmacokinetic and pharmacodynamic properties of nonpeptide angiotensin antagonists in humans are reviewed in this paper. Representatives of this new therapeutic class share common features: lipophilia, intermediate bioavailability, high affinity for plasma proteins and liver metabolism; some have active metabolites. Angiotensin II antagonists block the blood pressure response to exogenous angiotensin II in healthy volunteers, decrease baseline blood pressure in both normal and hypertensive patients, produce a marked rise in plasma renin activity and endogenous angiotensin II and increase renal blood flow without altering glomerular filtration rate. These effects are dose-dependent, but their time course varies between the drugs owing to pharmacokinetic and pharmacodynamic differences. Additionally, the extent of blood pressure reduction is dependent on physiological factors such as sodium and water balance. The characterisation of their pharmacokinetic-pharmacodynamic relationships deserves further refinement for designing optimal therapeutic regimens and proposing dosage adaptations in specific conditions.

Genome-wide association study of blood pressure extremes identifies variant near UMOD associated with hypertension.

Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%-2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 5' region of Uromodulin (UMOD; rs13333226, combined P value of 3.6×10(-11)). The minor G allele is associated with a lower risk of hypertension (OR [95%CI]: 0.87 [0.84-0.91]), reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860-0.991; p = 0.027). In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR) measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83-0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83-0.96], p = 0.003). In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.

The Relevance of Long-Term Adherence to Non Pharmacological and Pharmacological Treatment of Hypertension

Current hypertension guidelines point to the necessity of achieving sustained and strict blood pressure control in every hypertensive patient. To reach this goal the patient should comply both with hygienic measures and pharmacologic treatment. This remains a difficult task, particularly since hypertension is generally asymptomatic and since any therapeutic intervention might adversely alter the patient's quality of life. Long-term persistence with antihypertensive therapy is facilated when the treatment is initiated with well tolerated antihypertensive agents, especially blockers of the renin-angiotensin system. Having a normal blood pressure during treatment is also an important determinant of persistence. This explains the growing interest for fixed-dose combinations, which have the main advantage to be at the same time efficient and well tolerated. These simple to use preparations have even gained acceptance as first-line drug regimen.

Chest pulse-wave velocity: a novel approach to assess arterial stiffness.

Pulse-wave velocity (PWV) is considered as the gold-standard method to assess arterial stiffness, an independent predictor of cardiovascular morbidity and mortality. Current available devices that measure PWV need to be operated by skilled medical staff, thus, reducing the potential use of PWV in the ambulatory setting. In this paper, we present a new technique allowing continuous, unsupervised measurements of pulse transit times (PTT) in central arteries by means of a chest sensor. This technique relies on measuring the propagation time of pressure pulses from their genesis in the left ventricle to their later arrival at the cutaneous vasculature on the sternum. Combined thoracic impedance cardiography and phonocardiography are used to detect the opening of the aortic valve, from which a pre-ejection period (PEP) value is estimated. Multichannel reflective photoplethysmography at the sternum is used to detect the distal pulse-arrival time (PAT). A PTT value is then calculated as PTT = PAT - PEP. After optimizing the parameters of the chest PTT calculation algorithm on a nine-subject cohort, a prospective validation study involving 31 normo- and hypertensive subjects was performed. 1/chest PTT correlated very well with the COMPLIOR carotid to femoral PWV (r = 0.88, p < 10 (-9)). Finally, an empirical method to map chest PTT values onto chest PWV values is explored.

Why Objective Monitoring of Compliance is Important in the Management of Hypertension.

Hypertensive patients often experience poor adherence to treatment, a frequent cause of uncontrolled blood pressure. In this study, we have evaluated whether or not the use of electronic monitoring for drug adherence is a useful approach to identify and correct compliance problems in hypertensive patients, which may ultimately enhance the effect of antihypertensive therapy. Sixty-nine treated patients with an office blood pressure greater than 140/90 mm Hg were enrolled in this study. With patient consent, current antihypertensive therapy was dispensed in electronic pillboxes that record the time and date of each opening without changing the drug regimen. The intention was to provide physicians with objective measurements of drug compliance. The monitoring of compliance per se without any other intervention induced a marked decrease of blood pressure in the whole group (from 159/104Â+/-23/12 mm Hg to 143/92Â+/-20/15, meansÂ+/-standard deviation, p less than 0.001). A complete normalization of blood pressure (less than 140/90 mm Hg) was obtained in one third of the patients (group 1, n=23) during the monitoring period. A significant improvement of blood pressure control was found in another third (group 2, n=23), whereas in the remaining patients (group 3, n=23) no change in blood pressure was observed. The distribution of individual compliance values, as well as the mean compliances was comparable in the three subgroups. Conversely, the compliance reports have identified several potentially overtreated patients in group 1, a large number of patients with a poor adherence to the prescribed therapy in all groups, and patients who clearly needed a change in pharmacotherapy mainly in group 3. Thus, our results suggest that electronic monitoring of compliance can considerably enhance the efficacy of antihypertensive therapy in patients with uncontrolled hypertension. This procedure should be used more extensively in clinical practice whenever the blood pressure response to therapy appears insufficient. (c)2000 by Le Jacq Communications, Inc.

The Macrocirculation and Microcirculation of Hypertension.

Changes in vascular structure that accompany hypertension may contribute to hypertensive end-organ damage. Both the macrovascular and microvascular levels should be considered, as interactions between them are believed to be critically important. Regarding the macrocirculation, the article first reviews basic concepts of vascular biomechanics, such as arterial compliance, arterial distensibility, and stress-strain relationships of arterial wall material, and then reviews how hypertension affects the properties of conduit arteries, particularly examining evidence that it accelerates the progressive stiffening that normally occurs with advancing age. High arterial stiffness may increase central systolic and pulse pressure by two different mechanisms: 1) Abnormally high pulse wave velocity may cause pressure waves reflected in the periphery to reach the central aorta in systole, thus augmenting systolic pressure; 2) In the elderly, the interaction of the forward pressure wave with high arterial stiffness is mostly responsible for abnormally high pulse pressure. At the microvascular level, hypertensive disease is characterized by inward eutrophic or hypertrophic arteriolar remodeling and capillary rarefaction. These abnormalities may depend in part on the abnormal transmission of highly pulsatile blood pressure into microvascular networks, especially in highly perfused organs with low vascular resistance, such as the kidney, heart, and brain, where it contributes to hypertensive end-organ damage.

Therapeutic strategies to improve control of hypertension.

Blood pressure is poorly controlled in most European countries and the control rate is even lower in high-risk patients such as patients with chronic kidney disease, diabetic patients or previous coronary heart disease. Several factors have been associated with poor control, some of which involve the characteristic of the patients themselves, such as socioeconomic factors, or unsuitable life-styles, other factors related to hypertension or to associated comorbidity, but there are also factors directly associated with antihypertensive therapy, mainly involving adherence problems, therapeutic inertia and therapeutic strategies unsuited to difficult-to-control hypertensive patients.It is common knowledge that only 30% of hypertensive patients can be controlled using monotherapy; all the rest require a combination of two or more antihypertensive drugs, and this can be a barrier to good adherence and log-term persistence in patients who also often need to use other drugs, such as antidiabetic agents, statins or antiplatelet agents. The fixed combinations of three antihypertensive agents currently available can facilitate long-term control of these patients in clinical practice. If well tolerated, a long-term therapeutic regimen that includes a diuretic, an ACE inhibitor or an angiotensin receptor blocker, and a calcium channel blocker is the recommended optimal triple therapy.

Glomerular hyperfiltration and increased proximal sodium reabsorption in subjects with type 2 diabetes or impaired fasting glucose in a population of the African region.

BACKGROUND. Glomerular hyperfiltration (GHF) is a well-recognized early renal alteration in diabetic patients. As the prevalence of GHF is largely unknown in populations in the African region with respect to normal fasting glucose (NFG), impaired fasting glucose (IFG) and type 2 diabetes [diabetes mellitus (DM)], we conducted a cross-sectional study in the Seychelles islands among families including at least one member with hypertension. METHODS. The glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and proximal tubular sodium reabsorption were measured using inulin, p-aminohippurate (PAH) and endogenous lithium clearance, respectively. Twenty-four-hour urine was collected on the preceding day. RESULTS. Of the 363 participants (mean age 44.7 years), 6.6% had IFG, 9.9% had DM and 63.3% had hypertension. The prevalence of GHF, defined as a GFR >140 ml/min, was 17.2%, 29.2% and 52.8% in NFG, IFG and DM, respectively (P trend <0.001). Compared to NFG, the adjusted odds ratio for GHF was 1.99 [95% confidence interval (CI) 0.73-5.44] for IFG and 5.88 (2.39-14.45) for DM. Lithium clearance and fractional excretion of lithium were lower in DM and IFG than NFG (P < 0.001). CONCLUSION. In this population of African descent, subjects with impaired fasting glucose or type 2 diabetes had a high prevalence of GHF and enhanced proximal sodium reabsorption. These findings provide further insight on the elevated incidence of nephropathy reported among African diabetic individuals.

Arterial hypertension after surgical closure of omphalocele and gastroschisis.

Arterial hypertension has been reported as a complication of surgical closure of an abdominal wall defect. No report studying the incidence, the characteristics and the clinical significance of hypertension after surgical correction of an omphalocele or gastroschisis has been published so far. The medical records of all newborns with surgically corrected gastroschisis or omphalocele identified in two centers were retrospectively evaluated. Arterial hypertension was defined as a mean daily systolic and/or diastolic blood pressure value higher than the 95 percentile for age and/or weight, according to literature data. The timing of surgery, weight gain, plasma creatinine and the use of diuretics or vasoactive drugs were compared between the groups with and without hypertension. Seventy-two patients were identified and included in the study, 29 with omphalocele and 43 with gastroschisis. Those with omphalocele were born at a mean age of 37.3+/-2.6 weeks with a mean birth weight of 2,971+/-715 g, and those with gastroschisis were born at 36.1+/-2.0 weeks with a mean birth weight of 2,527+/-498 g. Blood pressure values of 66 patients were available for analysis. Of the omphalocele patients, 46.2% (12/26) developed systolic hypertension, compared to 17.5% (7/40) of the patients with gastroschisis (P =0.024). Hypertension was always transient, lasting an average of 4 and 1 day in the omphalocele and gastroschisis groups, respectively. Two patients with omphalocele were given anti-hypertensive therapy. There was no difference between patients with or without hypertension regarding weight gain, use of vasoactive drugs or diuretics, mean weekly creatinine values or the timing of surgery. Newborns with an abdominal wall defect frequently present with transient arterial hypertension. Hypertension occurs significantly more often, is more severe and lasts longer in patients with omphalocele than in patients with gastroschisis. In both groups, hypertension is transient and rarely requires therapy. The cause of hypertension remains unclear.

Comparaison des réponses hémodynamiques d'un repas modérément salé et d'un repas riche en sel : une hypothèse pour expliquer l'hypertrophie ventriculaire gauche des régimes hypersodés

De nombreuses études cliniques ont révélé une corrélation étroite entre un régime alimentaire riche en sel et le développement d'une hypertrophie ventriculaire gauche. Cette association a été classiquement attribuée aux effets hypertensifs à long terme d'une alimentation riche en sel. Toutefois, les études épidémiologiques ont également démontré que l'hypertrophie ventriculaire gauche peut survenir indépendamment de changements de pression artérielle.¦L'ingestion de sel n'étant pas distribuée de manière homogène durant la journée mais ayant lieu principalement durant les repas, nous émettons l'hypothèse que chaque repas riche en sel induit une augmentation aiguë de la pression artérielle, des pressions de remplissage cardiaque, du volume d'éjection systolique et du débit cardiaque. L'augmentation résultante du travail cardiaque pourrait ainsi à la longue entraîner une hypertrophie cardiaque.¦Pour tester si un repas riche en sel conduit à des modifications hémodynamiques favorisant l'hypertrophie cardiaque, nous avons comparé chez la même personne jeune et en bonne santé la réponse hémodynamique à un repas modérément salé (45 mmol) à celle d'un repas riche en sel (165 mmol de sodium). Les repas ont été pris de manière randomisée à 7 jours d'intervalle. Divers paramètres hémodynamiques ont été mesurés en continu avant et jusqu'à 140 minutes après chaque repas. Nos résultats montrent que les augmentations post-prandiales du volume d'éjection systolique et du travail cardiaque ont été plus prononcées après un repas à haute teneur en sel par rapport à un repas modérément salé.¦Nous spéculons que des apports chroniques en sel induisent des charges hémodynamiques répétées. Etant donné que la concentration plasmatique de sodium, qui est augmentée après un repas salé, est également capable de stimuler la croissance des myocytes cardiaques, il est possible que la combinaison sur des mois ou des années de pics hypernatrémiques post-prandiaux et de charges cardiaques soit responsable de l'hypertrophie cardiaque souvent observée avec une alimentation riche en sel.¦-¦Many clinical studies have shown a close correlation between a chronic high salt diet and the development of left ventricular hypertrophy. This association has been classically attributed to the long-term hypertensive effects of a high salt diet. However, epidemiological studies have also shown that left ventricular hypertrophy may occur independently of changes in arterial pressure.¦Since salt ingestion during a high salt diet is not distributed evenly over a 24-hr period, but occurs essentially during meal periods, we speculate that each acute salt load could lead to greater acute increases in blood pressure, heart filling pressure, stroke volume and cardiac output, putting an additional work load on the heart, promoting in the long run cardiac hypertrophy.¦To test whether a high salt meal leads to hemodynamic changes that may favor cardiac hypertrophy, we compared in the same healthy young individual the response to a moderately salted meal (45 mmol) and to a high-salt meal (165 mmol sodium), given in a random order on separate days, on various cardiovascular parameters that were continuously monitored before and up to 140 minutes after the meal. Our results show that the post-prandial increases in stroke volume, and cardiac work were more pronounced after a high-salt meal than after a low-salt meal.¦We speculate that repetitive salt loads associated with a high salt diet may lead to repetitive hemodynamic loads. Since plasma sodium concentration, which is increased after a salty meal, is also capable to stimulate myocyte growth, it is possible that the combination of post-prandial hypernatremic peaks and of cardiac loads may be responsible, when repeated many times over period of months, of the cardiac hypertrophy often seen with a high salt diet.