Prise en charge actuelle de l’hypertension artérielle

International audienceHypertension is a common health problem with serious consequences for individuals and a heavy attributable burden for populations. Reducing this burden requires preventive actions at the population level and early diagnosis at the individual level, followed by proactive interventions with proven benefits. Given the variability of blood pressure measurement, diagnosis is established only after repeated measurements under standardized conditions, if possible outside the clinic. Lifestyle changes can modestly reduce blood pressure; their impact is significant if they can be achieved on a large scale. Hypertension treatment requires a rational pharmacological approach, which can reach the target blood pressure within less than 6 months and three pharmacological classes at most in more than 80% of cases. Specialized consultation is required in the remaining 20% to detect secondary hypertensions, to optimize drug therapy and to discuss, in a minority of cases, non-pharmacological treatments. Recommendations are written by experts who select, interpret, and extrapolate the results of clinical research. As a consequence, they are sometimes unsuitable for primary care practice and frequently inconsistent across guidelines. Efforts are currently made to produce less disputable and more usable guidelines.L’hypertension artérielle (HTA) est un problème de santé fréquent dont les conséquences peuvent être graves pour les individus et sont très lourdes pour la population. La réduction de ce fardeau repose sur la prévention à l’échelle de la population et sur le diagnostic précoce à l’échelle des individus, suivis par la mise en œuvre proactive d’interventions dont le bénéfice est démontré. Compte tenu de la variabilité de la mesure de pression artérielle (PA), le diagnostic n’est établi qu’à l’issue de mesures répétées dans des conditions standardisées, si possible en dehors de la consultation. Les mesures hygiéno-diététiques permettent de réduire la PA de façon modeste, leur impact est significatif si elles peuvent être appliquées à grande échelle. La prise en charge des hypertendus repose essentiellement sur une escalade pharmacologique raisonnée et rapide, qui permet d’atteindre les objectifs de PA en moins de six mois avec trois classes pharmacologiques au plus dans plus de 80 % des cas. Une prise en charge spécialisée est requise dans les 20 % restant, pour chercher une cause d’hypertension secondaire, optimiser le traitement pharmacologique et discuter, dans une minorité de cas, de traitements non pharmacologiques. Les recommandations sont rédigées par des experts qui s’appuient sur la sélection, l’interprétation et l’extrapolation de résultats de la recherche clinique. Il en résulte des recommandations parfois inadaptées à la pratique courante et fréquemment contradictoires d’un guide de bonnes pratiques à l’autre. Des réflexions sont en cours pour proposer des guides moins discutables et plus directement applicables

Aldosterone-producing adenoma and other surgically correctable forms of primary aldosteronism

Surgically correctable forms of primary aldosteronism are characterized by unilateral aldosterone hypersecretion and renin suppression, associated with varying degrees of hypertension and hypokalemia. Unilateral aldosterone hypersecretion is caused by an aldosterone-producing adenoma (also known as Conn's adenoma and aldosteronoma), primary unilateral adrenal hyperplasia and rare cases of aldosterone-producing adrenocortical carcinoma. In these forms, unilateral adrenalectomy can cure aldosterone excess and hypokalemia, but not necessarily hypertension. The prevalence of primary aldosteronism in the general population is not known. Its prevalence in referred hypertensive populations is estimated to be between 6 and 13%, of which 1.5 to 5% have an aldosterone-producing adenoma or primary unilateral adrenal hyperplasia. Taking into account referral biases, the prevalence of surgically correctable primary aldosteronism is probably less than 1.5% in the hypertensive population and less than 0.3% in the general adult population. Surgically correctable primary aldosteronism is sought in patients with hypokalemic, severe or resistant forms of hypertension. Recent recommendations suggest screening for primary aldosteronism using the aldosterone to renin ratio. Patients with a raised ratio then undergo confirmatory suppression tests. The differential diagnosis of hypokalemic hypertension with low renin includes mineralocorticoid excess, with the mineralocorticoid being cortisol or 11-deoxycorticosterone, apparent mineralocorticoid excess, pseudo-hypermineralocorticoidism in Liddle syndrome or exposure to glycyrrhizic acid. Once the diagnosis is confirmed, adrenal computed tomography is performed for all patients. If surgery is considered, taking into consideration the clinical context and the desire of the patient, adrenal vein sampling is performed to detect whether or not aldosterone hypersecretion is unilateral. Laparoscopic surgery for unilateral aldosterone hypersecretion is associated with a morbidity of about 8%, with most complications being minor. It generally results in the normalization of aldosterone secretion and kalemia, and in a large decrease in blood pressure, but normotension without treatment is only achieved in half of all cases. Normotension following adrenalectomy is more frequent in young patients with recent hypertension than in patients with long-standing hypertension or a family history of hypertension

0272: True antihypertensive efficacy of sequential nephron blockade in patients with resistant hypertension and confirmed medication adherence

ObjectiveWe previously showed (Bobrie et al. J Hypertens 2012) that sequential-nephron blockade (SNB) was more effective than combined renin angiotensin system blockade (RB) for controlling BP in patients with resistant hypertension (RH). In this post-hoc analysis, we assessed medication adherence (MA) and its influence on the antihypertensive response to SNB/RB with a new combined scoring system.Design and MethodPts with daytime ambulatory SBP/DBP (dASBP/dADBP) >135 and/or 85mmHg, despite 4 week-treatment with irbesartan 300mg+HCTZ 12.5mg+amlodipine 5mg, were randomised either to SNB (i.e.+spironolactone 25mg, then +furosemide 20-40mg, then +amiloride 5mg, n=82) or RB (ramipril 5-10mg, then bisoprolol 5-10mg, RB group, n=82) for 12 weeks. MA was scored according to 4 criteria: (i) trough/peak plasma irbesartan (Irb) concentration (HPLC); (ii) urinary AcSDKP/creatinine ratio (UR) to evaluate ramipril intake; (iii) delay of last medication intake before visit (LMI); and (iv) pill counting (PC, %). One point of MA score was attributed to trough Irb >20ng/ml, UR >4nmol/mmol, LMI <24h and PC >80%. MA was defined as low (LMA, score <2), intermediate (IMA, score=3), and optimal (OMA, score=4).Results82 pts among 164 had OMA (46 SNB and 36 RB); 52 pts had IMA (23 SNB and 29 RB); and 30 pts had LMA (13 SNB and 17 RB) (inter-groups difference: NS). LMA pts were younger than SMA pts (50±11 vs. 56±10 yrs, p<0.011). In OMA pts, the difference in dASBP/dADBP between SNB vs RB was significant (–11 [–17;–6]/–6 [–9;–2] mmHg, p<0.0001/p=0.0025), favoring SNB, whereas in LMA pts the significant difference between the two groups was no more observed (–6 [–19;7]/–1 [–10;7] mmHg, p=0.352/p=0.7096).ConclusionThe major BP lowering effect of SNB vs. RB observed in pts with OMA is lost in pts LMA. Combined methods for assessing MA allow determining the true efficacy of antihypertensive strategies in patients with RH. Reinforcement of MA in RH pts is deemed necessary

Gene expression profiling of human adrenocortical tumors using complementary deoxyribonucleic Acid microarrays identifies several candidate genes as markers of malignancy.

International audienceThe aim of this study was to identify predictor sets of genes whose over- or underexpression in human sporadic adrenocortical tumors would help to identify malignant vs. benign tumors and to predict postsurgical metastatic recurrence. For this, we analyzed the expression of 230 candidate genes using cDNA microarrays in a series of 57 well-characterized human sporadic adrenocortical tumors (33 adenomas and 24 carcinomas). We identified two clusters of genes (the IGF-II cluster containing eight genes, including IGF-II, and the steroidogenesis cluster containing six genes encoding steroidogenic enzymes plus eight other genes) whose combined levels of expression appeared to be good predictors of malignancy. This predictive value was as strong as that of the pathological score of Weiss. The analysis of the population of carcinomas (13 tumors) for genes whose expression would be strongly different between recurring and nonrecurring tumors allowed identification of 14 genes meeting these criteria. Among these genes, there are probably new markers of tumor evolution that will deserve additional validation on a larger scale. Taken together, these results show that the parallel analysis of the expression levels of a selected group of genes on microgram quantities of tumor RNA (a quantity that can be obtained from fine needle aspirations) appears as a complementary method to histopathology for the diagnosis and prognosis of evolution of adrenocortical carcinomas

The Warburg Effect Is Genetically Determined in Inherited Pheochromocytomas

The Warburg effect describes how cancer cells down-regulate their aerobic respiration and preferentially use glycolysis to generate energy. To evaluate the link between hypoxia and Warburg effect, we studied mitochondrial electron transport, angiogenesis and glycolysis in pheochromocytomas induced by germ-line mutations in VHL, RET, NF1 and SDH genes. SDH and VHL gene mutations have been shown to lead to the activation of hypoxic response, even in normoxic conditions, a process now referred to as pseudohypoxia. We observed a decrease in electron transport protein expression and activity, associated with increased angiogenesis in SDH- and VHL-related, pseudohypoxic tumors, while stimulation of glycolysis was solely observed in VHL tumors. Moreover, microarray analyses revealed that expression of genes involved in these metabolic pathways is an efficient tool for classification of pheochromocytomas in accordance with the predisposition gene mutated. Our data suggest an unexpected association between pseudohypoxia and loss of p53, which leads to a distinct Warburg effect in VHL-related pheochromocytomas

PROTEINURIE ET HYPERTENSION ARTERIELLE RENOVASCULAIRE

PARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

Traitement antihypertenseur prescrit aux patients avant leur première consultation dans un service spécialisé : comparaison entre 2001 et 2006

International audiencePurpose : To determine if trends in antihypertensive drug prescriptions by non-specialist physicians reflect evidence from clinical research.Methods : Comparison of antihypertensive drugs prescribed to patients before they attended a hypertension clinic in 2001 and 2006, with a special consideration for thiazide diuretics in drug combinations and angiotensin converting enzyme inhibitors (ACEI) in hypertensive patients at high cardiovascular risk (diabetes or secondary prevention).Results : Overall, 1072 hypertensive patients attended the hypertension clinic in 2001 (mean age 53.9 years) and 1040 in 2006 (mean age 55.6 years); both genders were equally represented. Patients already treated when they came at the consultation received a mean number of 2.24 antihypertensive drug classes in 2001 and 2.44 in 2006 (p = 0.002). The prescription of three antihypertensive drug classes increased between 2001 and 2006: Calcium channel blockers from 49 % of treated patients in 2001 to 56 % in 2006 (p = 0.007), angiotensin receptor antagonists from 28 to 42 % (p < 0.001) and thiazide diuretics from 31 to 39 % (p = 0.001). Thiazide diuretics were included in 48 % of the antihypertensive combinations in 2001 and 55 % in 2006 (p = 0.02). The prescription of ACEI in patients at high cardiovascular risk remained stable around 31 %.ConclusionAntihypertensive treatments were more intensive in 2006 than 2001, but thiazide diuretics remained underused in drug combinations. The prescription of ACEI did not increase in patients at high cardiovascular risk despite convincing evidence of their benefit.Propos : Étudier l’évolution de la prescription des antihypertenseurs par des médecins non-spécialistes, au regard des bonnes pratiques établies par la recherche clinique.Méthodes : Comparaison des traitements prescrits aux patients avant leur première consultation dans un service d’hypertension artérielle en 2001 et 2006, avec une attention particulière pour les diurétiques thiazidiques dans les associations antihypertensives et les inhibiteurs de l’enzyme de conversion (IEC) chez les hypertendus à haut risque cardiovasculaire (diabète ou prévention secondaire).Résultats : La population comportait 1072 hypertendus de 53,9 ans d’âge moyen en 2001 et 1040 hypertendus de 55,6 ans d’âge moyen en 2006, avec une représentation égale des deux sexes. Les patients sous traitement antihypertenseur recevaient en moyenne 2,24 classes thérapeutiques en 2001 et 2,44 en 2006 (p = 0,002). Trois classes ont progressé entre 2001 et 2006 : les inhibiteurs calciques étaient compris dans 49 % des traitements antihypertenseurs en 2001 et 56 % en 2006 (p = 0,007), les antagonistes de récepteurs de l’angiotensine dans 28 et 42 % (p < 0,001) et les thiazidiques dans 31 et 39 % (p = 0,001). En 2006, 55 % des associations antihypertensives comportaient un thiazidique contre 48 % en 2001 (p = 0,02). Les IEC faisaient partie de 31 % des traitements prescrits aux patients à haut risque cardiovasculaire, de façon stable.Conclusion : Malgré une majoration de l’intensité des traitements, les thiazidiques restent sous-utilisés dans les associations antihypertensives. Les IEC ne progressent pas chez les patients à haut risque cardiovasculaire, en dépit des données probantes acquises en leur faveur

Génétique de la maladie de Hirschsprung (étude de mutations du récepteur de type B aux endothélines)

PARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF