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Clinic-ambulatory blood pressure (BP) difference is influenced by patients- and device-related factors and inadequate clinic-BP measurement. We investigated whether nonadherence to antihypertensive medications may also influence this difference in a post hoc analysis of the DENERHTN trial (Renal Denervation for Hypertension). We pooled the data of 77 out of 106 evaluable patients with apparent resistant hypertension who received a standardized antihypertensive treatment and had both ambulatory BP and drug-screening results available at baseline after 1 month of standardized triple therapy and at 6 months on a median of 5 antihypertensive drugs. After drug assay samplings on study visits, patients took their antihypertensive treatment under supervision immediately after the start of the ambulatory BP recording, and supine clinic BP was measured 24 hours post-dosing; both allowed to calculate the clinic minus daytime ambulatory systolic BP (SBP) difference (clinic-SBP–day-SBP). A total of 29 (37.7%) were found nonadherent to medications at baseline and 38 (49.4%) at 6 months. At baseline, the mean clinic-SBP–day-SBP difference in the nonadherent group was 12.7 mm Hg (95% CI, 7.8–17.7 mm Hg, P P =0.947). Similar observations were made at 6 months. Using receiver operating characteristics curves, we found that a 6 mm Hg cutoff of clinic-SBP–day-SBP difference had 67% sensitivity and 69% specificity to predict nonadherence to the triple therapy at baseline. In conclusion, a large clinic-SBP–day-SBP difference may help discriminating between adherence and nonadherence to treatment in patients with resistant hypertension. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT01570777.

Introduction Les fievres prolongees inexpliquees (FPI) restent un defi diagnostique majeur en medecine interne. En apportant des informations morphologiques et fonctionnelles de maniere non invasive, l’avenement du FDG PET/CT en a modifie la demarche diagnostique. L’objectif de notre etude etait d’evaluer la contribution diagnostique du FDG PET/CT, d’en determiner la place au sein de la demarche diagnostique de la FPI et d’identifier des facteurs clinicobiologiques predictifs d’une meilleure rentabilite. Patients et methodes Il s’agit d’une etude retrospective d’usage du FDG PET/CT dans l’indication FPI, en analysant les donnees des patients adultes ayant realise un FDG PET/CT entre avril 2012 et decembre 2017 au CHU de Montpellier dans l’indication FPI. Les caracteristiques clinicobiologiques des patients ainsi que les examens paracliniques effectues avant et apres le FDG PET/CT etaient releves. Les FDG PET/CT qui mettaient en evidence une anomalie en lien avec le diagnostic final etaient juges contributifs. Resultats 44 patients presentant une FPI ont ete inclus. L’âge median etait de 60 ans. La duree mediane d’hospitalisation avant le FDG PET/CT etait de 13 jours. Pour 70 % des patients, un diagnostic etait pose a l’issue des explorations. On retrouvait une maladie inflammatoire non infectieuse pour 39 % des patients (dont 6 cas d’arterite a cellules geantes et 3 cas de maladie de Still), une pathologie infectieuse pour 20 %, une neoplasie pour 7 %. Le FDG PET/CT etait juge contributif au diagnostic chez 44 % des patients, sa sensibilite evaluee a 85 % et sa specificite a 37 %. Pour un total de 135 examens d’imagerie, d’endoscopie ou prelevements histologiques differents realises avant le FDG PET/CT, le nombre median d’examens paracliniques realises etait de 3, les plus couramment effectues etant le scanner (93 %) principalement thoraco-abdomino-pelvien (TAP, 77 %) et l’echocardiographie transthoracique (ETT, 59 %). Avoir eu un FDG PET/CT ne reduisait pas le nombre d’examens complementaires effectues apres. Pour un total de 108 examens realises apres le FDG PET/CT, le nombre median d’examens paracliniques etait de 2, les plus couramment effectues etant les prelevements histologiques (BAT) et l’IRM. Sur 51 prelevements histologiques realises apres le FDG PET/CT, 35 % ont ete directement guides par les resultats du FDG PET/CT parmi lesquels seulement 22 % ont ete contributifs. Parmi les prelevements non contributifs guides par le FDG PET/CT, 42 % etaient des biopsies digestives. Ces resultats suggerent de reserver l’endoscopie digestive aux seuls cas d’hyperfixations digestives focales intenses suspectes. Le FDG PET/CT etait retrouve superieur au TAP chez 32 % des patients ayant beneficie des 2 examens. Aucun facteur clinique ou biologique n’etait associe a la presence d’un diagnostic final. En revanche, chez les patients pour lesquels le FDG PET/CT etait contributif, le taux d’hemoglobine etait significativement plus bas (OR.0,41, 95 %CI [0,20–0,87], p = 0,019) en analyse multivariee. Le taux de CRP n’etait pas associe a l’interet diagnostique du FDG PET/CT. Discussion Notre etude confirme la rentabilite diagnostique du FDG PET/CT [1] et son utilisation de plus en plus precoce en routine dans un groupe homogene de patients FPI representatif de la pratique clinique. Son accessibilite croissante, son caractere non invasif et sa meilleure contribution diagnostique que le scanner TAP pourraient en faire un examen de premiere ligne. Comme cela avait ete rapporte Crouzet et al. [2] , la presence d’une anemie, et non d’une elevation de la CRP [3] , etait associee a une meilleure rentabilite du FDG PET/CT. Conclusion L’importance de la contribution diagnostique du FDG PET/CT, examen non invasif et d’accessibilite croissante, suggere d’en faire un examen de premiere intention dans l’algorithme diagnostique de la FPI.

Les tumeurs a renine ou tumeurs juxta-glomerulaires sont des tumeurs rares, de decouverte relativement recente, dont le premier cas fut decrit en 1967 par Robertson et al. [1 ]. Une formation tumorale fut decouverte au pole inferieur du rein gauche chez un jeune garcon hypertendu lors d'une intervention pour ablation de la surrenale gauche, l'exerese de cette formation tumorale renale engendra une guerison de l'hypertension arterielle (HTA). Le diagnostic doit etre evoque devant une HTA resistante au traitement habituel chez le patient jeune en association avec des anomalies biologiques evocatrices (hyperaldosteronemie, hypokaliemie, elevation plasmatique de la renine).

Introduction Avec plus d’une centaine de causes possibles, une fievre prolongee inexpliquee (FPI : superieure a 38,3 °C – durant plus de 3 semaines – inexpliquee apres 3 jours d’explorations) est un defi diagnostique frequent pour le medecin interniste, qui peut etre amene a prescrire de multiples examens complementaires. Observation Le cas d’une patiente de 26 ans, sans antecedent hormis une cholecystectomie pour lithiase 5 ans auparavant, souligne l’interet du FDG-TEP scan dans cette demarche diagnostique. Une fievre intermittente (pics quotidiens a 39–40 °C) evoluant pendant un mois, associee a des nodosites cutanees erythemateuses des membres, des arthralgies inflammatoires des chevilles et des poignets sans synovite, une hepatomegalie, des amygdales erythemateuses, mais sans alteration de l’etat general (poids stable, IMC 29 kg/m 2 ) fait evoquer un erytheme noueux post-streptococcique ou une sarcoidose. Le syndrome inflammatoire (CRP 236 mg/L) est aspecifique, les recherches microbiologiques et immunologiques sont negatives, l’echographie cardiaque est sans anomalie, la tomodensitometrie thoraco-abdomino-pelvienne ne met en evidence qu’une hepatomegalie homogene sans anomalie biologique associee. Le FDG-TEP scan de seconde intention montre un hypermetabolisme intense au niveau des lesions dermo-hypodermiques et du colon droit. Les biopsies cutanees montrent un aspect de vascularite atypique, compatible avec une atteinte paraneoplasique. La coloscopie guidee par le FDG-TEP scan trouve une lesion bourgeonnante ulceree, qui s’averera etre un adenocarcinome differencie infiltrant en histologie, sans extension (pT2N0M0), d’allure sporadique sur l’etude genetique. La fievre s’attenue sous ketoprofene, et cede apres l’exerese chirurgicale de la lesion colique. Discussion La fievre serait un mode de revelation du cancer colique dans 7 a 11 % des cas [1] . Il s’agit le plus souvent d’une complication infectieuse, et la presence de symptomes colo-rectaux peut amener rapidement a la realisation d’une coloscopie. Une FPI est plus rare, son origine paraneoplasique exceptionnelle. Si le cancer colique apparait comme une des causes neoplasiques principales de FPI d’allure recurrente, il est interessant de noter qu’il n’a ete rapporte aucun cas de cancer colique diagnostique grâce au FDG-TEP scan. Les recommandations de la SNMMI (Society of Nuclear Medicine and Molecular Imaging) et l’EANM (European Association of Nuclear Medicine) retiennent la FPI comme une indication clinique a realiser un FDG-TEP associe a une imagerie morphologique : la sensibilite (90,6 %) est bonne, la specificite (76,9 %) plus mediocre, coherente avec le large spectre diagnostique possible [2] . L’interet du FDG-TEP scan est d’objectiver un hypermetabolisme dont la localisation permet de cibler les examens complementaires. Pour ce qui concerne les FPI, une meta-analyse recente, portant sur 14 articles et un total de 714 patients [3] , suggere que la mise en evidence d’anomalies par le FGD-TEP ameliore les performances diagnostiques par un facteur 9 (OR 8,94 ; IC 95 [4,18–19,12]). Conclusion La decouverte en FDG-TEP scan d’un hypermetabolisme colique localise a permis le diagnostic de cancer colique dans un cas de fievre prolongee inexpliquee. L’accessibilite croissante et le caractere non invasif de cet examen doivent en faire preciser la place exacte dans la strategie diagnostique de cette presentation.

L’HAP est la principale cause d’hypertension arterielle responsable de complications cardiovasculaire, nephrologique et metabolique. Les objectifs de l’etude etaient de caracteriser une population atteint d’HAP et d’etudier l’interet du catheterisme des veines surrenales (CVS) avant chirurgie. Etude retrospective multicentrique incluant les patients avec un HAP des CHU de Grenoble, Nimes entre 2008 et 2016. Pour etudier le CVS, nous avons inclus egalement des patients avec un HAP traites chirurgicalement au CHU de Montpellier sans CVS initial sur la meme periode. Le diagnostic positif, etiologique, le retentissement et la prise en charge ont ete etudies. Deux criteres etaient retenus pour le second objectif : persistance HTA et persistance de l’hypokaliemie. Sur 56 patients, 53 % avaient une HTA severe et 57 % une hypokaliemie. Aucune correlation n’a ete mise en evidence entre le rapport aldosterone sur renine (RAR) et la severite clinique. Les complications cardiaques etaient presentes dans 46 % et une nephropathie survenait dans 23 % des cas. L’effet tensionnel etait similaire entre les 2 options therapeutiques (antialdosterone et surrenalectomie). Il n’y avait pas de difference statistiquement significative entre groupe sans versus avec CVS concernant les deux criteres (HTA p 0,42 ; hypokaliemie p 0,88). L’HAP doit etre recherche en cas HTA severe ou resistante avec ou sans hypokaliemie, ou lorsque le retentissement cardiorenal est disproportionne. Le RAR reste le test de depistage et doit etre realise dans les conditions standardisees. Le bilan des complications doit etre systematique et exhaustif. La place du CVS avant traitement chirurgical dans le cadre de nodule unilateral reste a definir.

Introduction La lutte contre la iatrogenie et les erreurs medicamenteuses (EM) est une priorite de sante publique en France. Les EM peuvent affecter la qualite de vie du patient hospitalise, prolonger sa duree de sejour, voire mettre en jeu son pronostic vital. La conciliation medicamenteuse permet de securiser la prise en charge medicamenteuse du patient lors de son parcours de soins. A l’admission du patient, la conciliation medicamenteuse d’entree vise a intercepter et a corriger les divergences non intentionnelles (DNI) introduites entre la prescription de ville et l’ordonnance medicale d’admission (OMA). Ces DNI correspondent a des EM potentielles. Determiner les situations a risque de survenue d’EM est indispensable pour promouvoir leur prevention. En vue d’etablir un score de risque de survenue d’EM a l’admission en service de medecine interne, l’objectif de cette etude etait de determiner les variables associees a la survenue d’EM. Patients et methodes Etude prospective chez les patients hospitalises dans un service de medecine interne de notre etablissement de mai 2012 a aout 2014. Pour chaque patient, un bilan medicamenteux optimise (BMO) a ete realise et compare a l’OMA. Les DNI ont ete relevees, et celles corrigees par l’equipe medicale etaient definies comme des EM. L’impact clinique potentiel des EM pour le patient a ete evalue collegialement par deux medecins et deux pharmaciens selon 4 niveaux de gravite : mineur, modere, severe ou tres severe. Seuls les patients concilies pour la premiere fois ont ete inclus dans l’etude. Les groupes avec et sans EM ont ete compares en analyse univariee, puis les variables associees a la survenue d’une EM ont ete mises en evidence en analyse multivariee. Resultats Sur 908 patients concilies inclus, 777 patients ont ete analyses (392 hommes, âge moyen de 75,1 ± 15,4 ans), majoritairement hospitalises via les urgences (69,8 %), pour des pathologies cardiorespiratoires (35,7 %), avec 43,5 % d’admission la nuit ou le week-end. Au total, 6006 lignes de traitements ont ete analysees. L’OMA comportait en moyenne 7,8 ± 3,6 lignes de traitement. Un total de 308 EM a ete identifie chez 168 patients (21,62 %). Les EM etaient majoritairement des omissions (61 %), ou des erreurs de posologie (27 %) et concernaient essentiellement les medicaments cardiovasculaires (28 %) et du systeme nerveux (27 %). Dans 40 % des cas, l’impact clinique potentiel a ete evalue comme mineur, 40 % comme modere et 20 % comme severe ou tres severe. En analyse univariee, les patients avec EM etaient plus âges (p = 0,002), admis via les urgences (p 65 ans (OR = 1,72 ; 95 % CI 1,04-2,83) et le nombre de traitement sur l’OMA > 8 (OR = 1,20 ; 95 % CI 1,01–1,43) etaient significativement associes a un risque d’EM. Seul le passage par les urgences constituait un facteur de risque d’EM severe (OR = 4,69 ; 95 % CI 1,42–15,50). Discussion Dans notre population, 21 % des patients ont eu au moins une EM, majoritairement une omission de medicament, et 20 %, une EM jugee severe ou tres severe, a risque de prolonger leur hospitalisation voire de mettre en jeu leur pronostic vital. Outre le fait de confirmer le role majeur du pharmacien clinicien en service de medecine interne, notre etude a mis en evidence des facteurs de risque d’EM, justifiant la collaboration entre professionnels de sante autour du patient hospitalise, notamment âge, polymedique et admis en urgence, la nuit ou le week-end. A terme, l’elaboration d’un score clinique simple de risque de survenue d’EM permettrait de mieux cibler et prioriser l’attention sur les patients a risque, et donc de tendre a diminuer les EM. C’est pourquoi l’analyse de validation d’un score comportant les items : âge > 65 ans, sexe, admission via les urgences, admission la nuit ou le week-end, > 8 traitements sur l’OMA est en cours, avec validation externe secondaire sur une cohorte de 800 patients inclus dans notre service depuis aout 2014. Conclusion Prevenir la survenue d’EM grâce a la conciliation medicamenteuse permettra de contribuer a une meilleure continuite et qualite de soin des patients hospitalises en service de medecine interne.

The objective of this review is to analyze the relationship between moderate decrease in renal function and cardiovascular (CV) risk and to discuss the potential mechanisms of this association. Prevalence of chronic kidney disease (CKD) is increasing in developed countries. Several studies have shown that a moderate fall in glomerular filtration (GFR) or the presence of microalbuminuria is associated with an increase in CV risk, independently of the traditional CV risk factors. Mechanisms are probably multiple and could include anemia, calcium/phosphate metabolism, inflammation, but also large arteries function. In order to achieve primary or secondary prevention of CV risk, DFG should be estimated from serum creatinine and microalbuminuria should be assessed in every high risk subject. The finding of CKD implies optimal management of all traditional CV risk factors. Future studies are needed in order to evaluate the efficacy and safety of specific therapeutic approach to reduce CV risk in CKD.

International audience

Drug-induced adverse effects are one of the main avoidable causes of hospitalization in older people. Numerous lists of potentially inappropriate medications for older people have been published, as national and international guidelines for appropriate prescribing in numerous diseases and for different age categories. The present review describes the general rules for an appropriate prescribing in older people and summarizes, for the main conditions encountered in older people, medications that are too often under-prescribed, the precautions of use of the main drugs that induce adverse effects, and drugs for which the benefit to risk ratio is unfavourable in older people. All these data are assembled in educational tables designed to be printed in a practical pocket format and used in daily practice by prescribers, whether physicians, surgeons or pharmacists., Les effets indésirables médicamenteux représentent l'une des principales causes évitables d'hospitalisation chez les sujets âgés. Un certain nombre de listes de médicaments potentielle-ment inappropriés chez les sujets âgés a été publié et il existe de nombreuses recommandations internationales pour le bon usage des médicaments par pathologie, et par tranche d'âge. La présente mise au point précise les règles générales de prescription des médicaments chez les sujets âgés et résume, pour les situations cliniques les plus fréquemment rencontrées, les médicaments sous-utilisés à tort et à recommander, les précautions d'emploi à observer pour réduire les effets secondaires des principaux médicaments pourvoyeurs d'effets indésirables et les médicaments dont le rapport bénéfice/risque est défavorable chez les sujets âgés. Ces recommandations sont synthétisées dans des tableaux didactiques conç us pour être imprimés dans un format de poche et être utilisés au quotidien par les prescripteurs quel que soit leur domaine d'activité, médicale, chirurgicale, ou pharmaceutique.

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

Introduction L’hyponatremie, une anomalie hydro-electrolytique frequente, est un predicteur de mortalite et de morbidite ainsi que de surcouts des soins quelle que soit son degre. Divers consensus d’experts ont ete bases sur des etudes observationnelles et des principes physiopathologiques, mais le niveau de preuve des recommandations reste limite. Plusieurs etudes montrent que l’hyponatremie reste mal diagnostiquee et mal traitee. Des donnees de prevalence des formes severes et l’explicitation de la demarche diagnostique devant une forme particuliere d’hyponatremie chronique moderee nous donnent l’occasion de revenir sur les exigences de raisonnement et de decision pour l’interniste. Resultats Sur 71 131 hospitalisations d’adultes en une annee dans un centre hospitalier universitaire, l’incidence d’hyponatremies hypotoniques (osmolalite n = 441, 55 % femmes, âge moyen 68 ± 16 ans ). Un quart des cas concerne les secteurs de medecine interne et geriatrie ( n = 110), autant que ceux d’urgences et reanimation ( n = 105). Seuls 7 % ont des symptomes neurologiques severes sur le moment, sans lien avec le pronostic ulterieur (48 deces pendant l’hospitalisation, 36 dans l’annee qui suit). Le diagnostic reste approximatif : une normo/hypervolemie est affirmee 1×/2, une hypovolemie 1 × 5, le statut volemique est imprecis dans le reste des cas. Sodium et osmolarite urinaires ne sont mesures que 1×/5 et 1×/8 au moment de l’hyponatremie. Une cause formelle n’est etablie que dans 60 % des cas, dont syndrome œdemateux cardiaque ou hepatique 19 %, insuffisance renale 10 %, iatrogenie 10 %, syndrome d’antidiurese inappropriee (SIAD) par probable secretion d’hormone antidiuretique (HAD) 9 %, potomanie 3 %, deficit endocrinien 1 %. Le constat est severe, mais les recommandations de diagnostic et traitement de l’hyponatremie moderee (125–135 mmoL/L), 10 fois plus frequente, sont encore moins bien definies et suivies. Une femme de 65 ans est referee pour hypertension arterielle et hyponatremie moderee (125–130 mmol/L) persistant depuis plusieurs annees. Elle est asymptomatique, cliniquement euvolemique, sans œdemes. Hors tout traitement, l’osmolalite urinaire (335 mOsm/kg) est inappropriee par rapport a la valeur sanguine (262 mOsm/kg). Par ailleurs, la natriurie (102 mmol/L) et l’excretion fractionnelle (EF) de sodium (1,25 %), l’uricemie (153 mcmol/L) mais pas l’EF d’acide urique (9,3 %), l’EF (61 %) mais pas le taux sanguin d’uree (4,1 mmol/L), ainsi que l’absence de correction de la natremie par la restriction hydrique ou la perfusion de serum sale physiologique confirment l’absence d’hypovolemie. Il n’y a pas d’insuffisance renale, surrenale ou thyroidienne. Il pourrait etre conclu a ce stade a un SIAD [1] , mais la caracterisation de son mecanisme [2] demande la realisation d’epreuves dynamiques. Lors d’une charge en eau (20 mL/kg de poids) rapidement eliminee, l’osmolalite urinaire baisse a 88 mOsm/kg a la 3 e heure sans grande variation de l’osmolalite sanguine, demontrant la normalite de la capacite de dilution urinaire. De plus, la copeptinemie, un substitut valide du taux circulant d’HAD, baisse de 7,6 a 4,5 pmol/L pendant la charge en eau, et augmente a 19,1 pmol/L avec une perfusion de serum sale hypertonique a 3 % (0,1 mL/kg/min) pendant laquelle l’osmolalite atteint 283 mOsm/kg. Ces tests permettent de confirmer une relation lineaire entre osmolalite et copeptine, une pente de 1,31, et un seuil de secretion de copeptine a 271 mOsm/kg, tous caracteres correspondant au « reset osmostat » comme defini par Fenske et al. [3] . Il est interessant de noter que la soif (evaluee par echelle analogique) est apparue avec une osmolalite de 279 mOsm/L. La stricte absence de symptome et l’anciennete des signes biologiques font suspecter le caractere « idiopathique » de ce syndrome de « decalage de l’osmostat ». Sa demonstration permet de refuter toute prescription therapeutique, et notamment de restriction hydrique. Conclusion Au-dela d’examens biochimiques simples (sodium, osmolalite, creatinine, uree, urique dans le sang et l’urine) insuffisamment realises, la realisation d’une charge en eau et le dosage de la copeptine (ou de l’HAD) ne sont pas recommandes dans la prise en charge d’une hyponatremie. Il n’est habituellement pas necessaire d’identifier le syndrome de « reset osmostat », car il n’est pas specifique d’une cause (il pourrait representer 15 a 30 % des cas associes aux tumeurs), mais la prevalence des formes idiopathiques notamment chez le sujet âge est inconnue. En outre, doser la copeptine et caracteriser le sous-type de SIAD pourraient etre utiles lorsqu’une prescription de vaptan est envisagee.

Resume Introduction. – Le baroreflexe a haute pression est operant dans les conditions physiologiques et il enclenche des reponses sympathiques ou vagales qui modifient le tonus arteriel et la frequence cardiaque. Ces reponses adaptees font que la pression arterielle est une variable autoregulee, autrement dit qu’elle varie peu puisque ce reflexe la rectifie constamment alors que de nombreux facteurs tendraient a la modifier. Exegese. – L’ablation d’un chemodectome carotidien bilateral genere une instabilite tensionnelle majeure chez le patient faisant l’objet de cet article. Les indices refletant la mise en jeu spontanee du baroreflexe sont fortement alteres. Conclusion. – Cette situation de denervation sinoaortique met en relief l’importance du baroreflexe a haute pression dans la regulation tensionnelle.

Urinary excretion of albumin exceeds normal values in 10 to 25% of patients with essential hypertension. The level of albuminuria is highly correlated with arterial pressure, and more closely with ambulatory arterial pressure. The interaction between albuminuria and arterial pressure is enhanced by overweight, smoking, protein intake, insulin resistance, lipid abnormalities, and possibly genotypes of the components of the renin-angiotensin system. The renal mechanisms of microalbuminuria are not well elucidated. Notably, an increase in filtration fraction suggestive of intraglomerular hypertension was observed in patients with hyperfiltration. Microalbuminuria may be a marker of diffuse vascular abnormalities predisposing to cardiovascular disease and/or hypertensive renal disease heralding future renal failure, but its predictive value needs to be tested in more long-term follow-up studies. Antihypertensive treatment has a varied influence on albuminuria; angiotensin-converting enzyme inhibitors may correct this abnormality (at least partially) better than other agents.

Resume Propos. — Independamment de l’elevation de la pression arterielle, le vieillissement est associe a un remodelage concentrique du ventricule gauche qui pourrait moduler avec le temps l’effet des traitements antihypertenseurs sur le cœur. L’objectif de la presente etude etait de mettre en evidence les facteurs pouvant influencer la regression de l’hypertrophie ventriculaire gauche chez les hypertendus. Methodes. - Il s'agissait d’une etude de suivi, non randomisee, portant sur 60 patients hypertendus, âges de 20 a 75 ans, jamais traites a l’inclusion et presentant une hypertrophie ventriculaire gauche. Resultats. — Apres 5 ans d’evolution sous traitement antihypertenseur, la diminution de la masse ventriculaire gauche de 14% est largement significative. La pression arterielle s'etait normalisee et l’hypertrophie avait regresse chez, respectivement, 50 et 58% des patients. Le groupe de patients qui ne repondaient pas au traitement (44% de la population), dont la diminution de la masse cardiaque, inferieure a 10%, n'etait pas significative, etaient plus âges, la duree d’evolution de l’hypertension arterielle etant plus longue. Dans l’ensemble de la population, il a ete montre l’existence d’une relation positive entre la diminution de la masse cardiaque et l’âge: c'est chez les patients les plus âges que la diminution de la masse ventriculaire gauche est la moins importante. En revanche, il n'a pas ete trouve de relation avec la classe therapeutique utilisee. Conclusions. — La diminution de la masse cardiaque sous traitement antihypertenseur n'est pas seulement le resultat d’une diminution de la pression arterielle, mais fait intervenir d’autres facteurs. Parmi ceux-ci, le vieillissement pourrait etre un facteur de resistance a l’action du traitement sur la diminution de la masse ventriculaire gauche. Ces resultats justifient un depistage et une prise en charge precoce de la maladie hypertensive.

Resume Essentiel veut-il dire ignorance ? A travers la demonstration historique de Jerome Conn, qui decrivit en 1954 pour la premiere fois l'hyperaldosteonisme primaire, l'accent est mis sur la demarche diagnostique remarquable qui permit de devoiler une partie de nos ignorances. A travers l'hyperaldosteronisme et l'hypertension renovasculaire une reflexion est menee pour eveiller notre curiosite. Derriere le mot essentiel, nous devons comprendre qu'il s'agit de causes que nous n'avons pas encore su decouvrir.

Results from the ONTARGET trial remind us that acute haemodynamically mediated renal dysfunction, triggered by low arterial pressure or volume depletion, can occur in high-risk cardiovascular patients (who usually have some degree of diseased intrarenal vessels) treated with renin–angiotensin system (RAS) blockers (especially in combination). However, nephroprotection could not be properly assessed in the trial, as the population was at low renal risk. Although albuminuria remains a useful marker in many patients, it can neither predict acute renal dysfunction nor replace end-stage renal disease (ESRD) as the endpoint in clinical trials. Recent trials using surrogate endpoints suggest that some RAS blockers (ACE inhibitors, angiotensin receptor blockers, the renin inhibitor aliskiren) may be more nephroprotective than others, but proving this requires comparing them (alone or in combination) in populations with identified renal disease (mainly diabetic nephropathy) and the use of hard endpoints. RAS-blocker dosages are critical: as some patients need much larger doses to decrease proteinuria than do others, the efficacy of a high-dose RAS blocker needs to be assessed in patients with persistent proteinuria. In patients with massive proteinuria despite maximum RAS-blocker dosages, combination RAS blockade should be considered by nephrologists, but will require close monitoring of renal function; also, the treatment needs to be withdrawn (at least temporarily) as soon as volume depletion or excessively low arterial pressure arises. In recent trials, lowering blood pressure towards values recommended by the current guidelines (130/80 mmHg) has reduced microvascular (lower levels of urinary albumin excretion) and macrovascular events in diabetic patients.

The only curative treatment of phaeochromocytoma consists in surgical removal. This carries a high risk due to the acute release of catecholamines. General anaesthesia cannot by itself prevent haemodynamic disturbances during surgical manipulation of the tumour. Careful preparation, based on intravascular volume repletion as well as α-, and, if required, β-adrenergic blockade, has been shown to reduce morbidity and mortality. However, this protocol is often cumbersome, and does not prevent totally the haemodynamic instability as a decrease in blood pressure at the start of treatment, or after removal of the tumour. Since voltage-dependent calcium channels are involved in both secretion and action of catecholamines, calcium-channel antagonists might be an interesting therapeutic alternative. In fact, short-term treatment by dihydropyridines may attenuate blood pressure variability during the preoperative period. During surgery, a dose-dependent reduction in systemic vascular resistances has been shown with intravenous nicardipine. However, dihydropyridines do not control cardiac adrenergic stimulation, which causes tachycardia or persistently increased blood pressure in spite of low or normal systemic vascular resistances. Such an acute cardiac hyperactivity, which can only be assessed by continuous haemodynamic monitoring, is electively sensitive to a β-adrenergic blocker rather than a calcium channel antagonist with high cardiac affinity (diltiazem, verapamil). Esmolol is available for intravenous administration. It is an ultra-short acting agent, ensuring a selective dose-related cardiac β1-blockade. Combining esmolol with nicardipine gives control over almost all episodes of haemodynamic worsening during phaeochromocytoma resection. Preoperative medical treatment no longer aims to suppress adrenergic stimulation completely, but to prevent acute haemodynamic changes. During surgery, step-by-step management of haemodynamic alterations will be based on invasive monitoring and such manoeuvers as volume loading and the use of short-acting drugs (sodium nitroprusside, nicardipine, esmolol).

The objective of this review is to analyze the relationship between moderate decrease in renal function and cardiovascular (CV) risk and to discuss the potential mechanisms of this association. Prevalence of chronic kidney disease (CKD) is increasing in developed countries. Several studies have shown that a moderate fall in glomerular filtration (GFR) or the presence of microalbuminuria is associated with an increase in CV risk, independently of the traditional CV risk factors. Mechanisms are probably multiple and could include anemia, calcium/phosphate metabolism, inflammation, but also large arteries function. In order to achieve primary or secondary prevention of CV risk, DFG should be estimated from serum creatinine and microalbuminuria should be assessed in every high risk subject. The finding of CKD implies optimal management of all traditional CV risk factors. Future studies are needed in order to evaluate the efficacy and safety of specific therapeutic approach to reduce CV risk in CKD.

From results of office and home measurements of blood pressure (BP), patients can be classified as "hypertensive (HT)", "normotensive (NT)", "office hypertensive (OH)" or "masked hypertensive (MH)" by crossing the classifications obtained from each method. It seems that 9 to 20% of patients could be MH with a prognosis close to HT (SHEAF study).To test the hypothesis that at least one part of the prevalence of MH would be an artefact due to the difference between the methods of measurements (shygmomanometer vs semi-automatic device) and/or due to different definitions of office hypertension (OHT). To determine the impact of different definitions of OHT on the prevalence of MH.During the course of a phase IV study, BP was measured with the same semi-automatic device (OMRON 705CP) both at doctor's office (3 measurements at 1-minute intervals) and at home, by the patient himself (3 measurements in the morning and in the evening at 1-minute intervals over the 7 days before the visit). Following definitions were used: Office HT: SBPor =140 mmHg, DBPor =90 mmHg, SBPor =140 mmHg or DBPor =90 mmHg; Home HT: SBPor =135 mmHg, DBPor =85 mmHg, SBPor =135 mmHg or DBPor =85 mmHg. Another definition of office HT was used SBPor =135 mmHg, DBPor =85 mmHg SBPor =135 mmHg or DBPor =85 mmHg.575 patients were analysed. Results from the two methods of measurements are closed but significantly different (difference for SBP: 3.2 +/- 16.5 mmHg; p0.0001; difference for DBP: 1.4 +/- 10.3 mmHg; p = 0.002)

The impact of hyperaldosteronism on target organs, and particularly kidney function, is greater than that of essential hypertension. Hyperaldosteronism provokes a glomerular hyperfiltration and hypertension that may cause renal alterations. Those may explain why elevated blood pressure may persist, even after radical treatment of the cause of hyperaldosteronism.

Does "essential" mean "ignorance"? The historical demonstration made by Jerome Conn who was the first to describe primary hyperaldosteronism, back in 1954, shows how an outstanding diagnostic route has enlightened our knowledge. Using the examples of hyperaldosteronism and reno-vascular hypertension, a reflex ion is made to arouse our curiosity. In the end, the term "essential" is only the cover-up of what we yet have to learn.

Calcium channel blockers (CCB) are known to be more efficacious and better tolerated in elderly patients. Lercanidipine is a highly lipophilic CCB with a specific safety profile linked to its pharmacokinetics.To evaluate and compare the efficacy and safety of lercanidipine according to age.Two groups of hypertensive patients (G1: aged65, G2: agedor = 65) entered an open study conducted over 56 days. All received lercanidipine 10 mg/d (monotherapy or add-on), titrated to 20 mg/d if blood pressure (BP) was not controlled at D28. BP was measured using a semi-automatic device at doctor's office (three measurements at 1-min intervals) and at home by the patient himself (three measurements in the morning and in the evening at 1-min intervals over the 7 days before D0 and D56).Seven hundred and fifty-six patients entered the study. Thirty-eight patients dropped out prematurely and 30 were excluded because they were normotensive; 691 patients (G1 n = 375, G2 n = 316) were kept for analysis. At the end of the study, 507 patients were treated with lercanidipine alone (10 mg/d n = 221, 20 mg/d n = 286) and 184 with a combination including lercanidipine (10 mg/d n = 91, 20 mg/d n = 93). Efficacy was not different between the groups excepted home pulse pressure which decreased more in G2. In the office, SBP decreased by 17 and 21 mmHg, respectively, for G1 and G2, and DBP by 9 and 10 mmHg. The prevalence of leg edema was not different between G1 and G2 and was particularly low in both groups (3%).Lercanidipine was as efficacious and well tolerated in younger patients as in elderly patients.

Despite its rare occurrence in Caucasians, thyreotoxic periodic paralysis should be evoked in young male Caucasians presenting with episodes of pseudo-paralytic hypokalemia.A 37 year-old Caucasian was admitted in intensive care for an acute episode of hypotonic tetraplegia and hypokalemia during which laboratory tests revealed hyperthyroidism due to Basedow's disease. The clinical course was rapidly favourable after a small dose of intravenous potassium. Antithyroid treatment avoided any new occurrence of similar episodes.In Caucasians, sporadic acute paralysis with hypokalemia requires testing for hyperthyroidism. Though it is well know that hypokalemia results from potassium intracellular shift, the underlying mechanism remains poorly elucidated. Treatment includes potassium administration with caution and/or beta blockers but the specific treatment is that of hyperthyroidism.

The present study was designed to assess whether the angiotensin-converting enzyme (ACE) gene I/D polymorphism influence the ACE inhibitors effect on the regression of left ventricular hypertrophy.Sixty hypertensive subjects never treated by antihypertensive drugs, aged 46 +/- 11 years, were included in the study. Follow-up with ACE inhibitor treatment was 60 +/- 26 months. Genotypes for ACE I/D polymorphism (DD, ID or II) were determined by PCR. The left ventricular mass index (LVMI) was assessed by two-dimensional directed M-mode echocardiography.ACE genotype distribution was in agreement with the Hardy-Weinberg equilibrium: 21 patients had the DD genotype, 29 were ID, and 10 were II. At baseline, age, systolic arterial pressure and LVMI didn't differ on the basis of genotype. Body mass index was significantly higher in II than in ID and DD groups. Regression of LVMI with ACE inhibitor treatment was similar in the 3 genotypes (-8.9%, -0.6%, -12.1% in DD, ID and II groups respectively). In addition, decrease of systolic arterial pressure was identical in 3 groups.ACE gene I/D polymorphism seems not to influence regression of left ventricular hypertrophy by ACE inhibitors in essential hypertension.

The arterial baroreflex operates in physiological conditions. It induces sympathetic and vagal activity modulation resulting in arterial tone and heart rate changes. These appropriate responses limit blood pressure fluctuations and blood pressure is therefore regulated since the baroreflex constantly buffers the changes.Bilateral carotid body tumor excision resulted in excessive fluctuations of blood pressure. Indices of spontaneous baroreflex activity were markedly altered in the patient described herein.The excessive fluctuations of blood pressure due to the sinoaortic denervation demonstrate how powerful is this negative feedback control mechanism in control conditions.

Renal dysfunction occurring after open heart surgery is multifactorial in origin but activation of the renin-angiotensin system may have a prominent role. Fourteen patients with ischaemic heart dysfunction scheduled for elective coronary artery bypass graft (CABG) surgery were allocated to a treatment group [enalaprilat for 2 days; ACEI (angiotensin-converting enzyme inhibitor) group, n=7] or a control group (n=7). The cardiac index was significantly higher in ACEI-treated patients than in the controls before and after cardiopulmonary bypass (CPB) (P0.05) and on postoperative day 2 (P0.05). The systemic vascular resistance was significantly lower in the ACEI-treated patients than in the controls before and after CPB (P0.05). Renal plasma flow, measured as [131I]orthoiodohippuran clearance (ClH), was higher in the ACEI group than in the control group before CPB, as was endogenous creatinine clearance after CPB (P0.05). On post-operative day 7, ClH was significantly higher in the ACEI group than in the control group (P0.05). Plasma renin activity and vasopressin concentration increased in both groups during CPB (P0.05). The study demonstrates that administration of an i.v. ACEI, enalaprilat, improves cardiac output during CABG surgery in patients with ischaemic heart dysfunction. Moreover, renal perfusion was better maintained during surgery, and this effect was sustained up to post-operative day 7.

Chronic pressure and volume overload result in morphologically and functionally distinct forms of myocardial hypertrophy. In essential hypertension, the respective effect of these factors on the morphology of the left ventricle remains unknown. In the present study, we hypothesised that activity of the renin angiotensin system (assessed by plasma renin activity) may be associated to the variability of the left ventricular adaptation to essential hypertension. To assess this relation, we categorised by echocardiography 333 never-treated hypertensive patients, according to values of left ventricular mass and relative wall thickness. Higher systolic and pulse arterial pressure was strongly associated with concentric left ventricular hypertrophy (27% of hypertensives). When compared to the normal left ventricle group, patients with eccentric left ventricular hypertrophy (15% of hypertensives) had a high cardiac index (5 +/- 1 vs 4 +/- 0.8 L/min/m2; P = 0.0001), a lower basal plasma renin activity (0.81 +/- 0.63 vs 1.45 +/- 1.3 ng/ml/h; P = 0.02) and similar mean values of left ventricular performance and glomerular filtration rate. A tendency for depressed myocardial contractility assessed by the midwall shortening/end-systolic stress was associated with concentric left ventricular remodelling and hypertrophy when compared to hypertensive with a normal left ventricle. In conclusion, at the early phase of essential hypertension, in patients without renal dysfunction, each anatomic pattern of cardiac adaptation to hypertension was associated with a distinct profile of haemodynamics, myocardial function and activity of the renin-angiotensin system. Journal of Human Hypertension (2000) 14, 181-188.

This study investigated the influence of hormone replacement therapy on the variability of the cardiac hypertrophic response to hypertension in postmenopausal women.25 menopausal essential hypertensive women (mean age 54 +/- 0.8 years, range 45 to 70) treated with estrogen (without progestin) for at least 1 year were studied and compared with 25 menopausal age-matched women (55 +/- 1 years old, range 46 to 70) not taking such therapy. No women had ever received antihypertensive therapy. Left ventricular mass corrected by height2.7 and relative wall thickness were assessed by M mode echocardiography.Age, blood pressure, body mass index, 24 h urinary sodium excretion and plasma renin activity were in the 2 groups with and without hormone replacement therapy. Left ventricular mass corrected by height2.7 was significantly higher in the group with without estrogen replacement therapy when compared to menopausal women with estrogen replacement (55 +/- 3 vs 45 +/- 4 g/m2.7 p0.02). In addition the slope of the regression line between LV mass and systolic BP was significantly higher (p0.01) in the group of women without hormonal therapy r = 0.50 p0.001.These results suggest that estrogen therapy of menopause attenuate the cardiac hypertrophic response to hypertension.

To evaluate in a primigravid normotensive population the predictive value of outcome of the ambulatory blood pressure monitoring (ABPM) at the 4th month of pregnancy.A longitudinal observational study was carried out in 174 primigravid normotensives free from proteinuria and glycosuria during the first trimester. These women underwent an ABPM (Spacelabs 90207) at 17 +/- 3 weeks gestation and were then followed up throughout pregnancy for the identification of outcome: gestational hypertension (blood pressureor = 140/80), proteinuria, hyperuricemia, preterm delivery, birth weight10th percentile, need for admission to the special care neonatal unit (SCNU).Non parametric tests, ROC curves.Of the 174 women, 170 had sufficient readings to be considered for analysis. Pre-eclampsia occurred in 5 cases (3%), gestational hypertension in 27 (16%), proteinuria in 20 (12%), hyperuricemia in 2 (1%), preterm delivery in 11 (6%), low birth weight in 9 (5%) and admission to SCNU in 16 (9%). Women with gestational hypertension already exhibited at the 4th month, both ambulatory and clinical blood pressure (BP) higher than did normotensive women (respectively: 117 +/- 7/70 +/- 5 vs 110 +/- 7/65 +/- 6 mmHg, p0.0001 for 24-hour ABPM, and 124 +/- 8/76 +/- 7 vs 117 +/- 10/70 +/- 9 mmHg, p0.005 for clinical BP). There was a non significative trend for both ambulatory and clinical values to be slightly higher in the setting of preterm delivery, proteinuria and admission to SCNU and in contrast to be slightly lower in case of low birth weight. The occurrence of one outcome or more (49 outcomes, low birth weight excepted), was associated with significantly higher ambulatory and clinical BP levels (114 +/- 7/68 +/- 6 vs 111 +/- 7/65 +/- 5 mmHg, p0.009 for ABPM, and 121 +/- 9/74 +/- 8 vs 117 +/- 9/70 +/- 8 mmHg, p0.007 for clinical BP). Positive and negative predictive values for the outcome of gestational hypertension were respectively for systolic ambulatory BP of 28% and 95% using a cut off value of 115 mmHg and for systolic clinical BP of 26% and 97% using a cut-off value of 120 mmHg.ABPM in a normotensive primigravid population at 17 weeks of gestation is not a better predictor of outcome, even of gestational hypertension, than clinical measurement.

Ambulatory blood pressure monitoring allows characterization of the circadian variations in blood pressure.In order to investigate the diagnostic value of circadian variations in blood pressure in the elderly, 11 patients with autonomic failure and 11 control subjects paired on age, blood pressure level and daily life activity range were studied.Periodic postural disorders, positive response to passive tilt-test and alpha denervation supersensitivity to noradrenaline were found in all patients with autonomic failure. In control subjects, blood pressure levels assessed by ambulatory monitoring were lower at night. Conversely, circadian variations in blood pressure were higher at night and lower in the morning in patients with autonomic failure. The nadir of blood pressure measurement was related with the reported time of peak incidence of orthostatic symptoms.Ambulatory 24-hour blood pressure monitoring may therefore be of value in the diagnosis and management of patients with autonomic failure.

Several imidazole derivatives that bind specifically to the angiotensin II type 1 receptor (the angiotensin receptor blockers, or ARB), have been developed in recent years and made available to clinicians. Preclinical studies revealed some differences in pharmacokinetic parameters and in vitro effects. However, most of the reported physiologic effects associated with ARB administration are similar to those of angiotensin-converting enzyme inhibitors (ACEI). In short-term clinical studies, the efficacy of ARB in reducing BP (BP) was similar to that of the ACEI, whereas (with a few exceptions) the side-effect profile was comparable to that of placebo. Whether targeting antihypertensive treatment with such a high specificity within the renin cascade carries major clinical advantages over inhibiting angiotensin-converting enzyme remains to be demonstrated.

This study was aimed at determining factors acting on the regression of left ventricular hypertrophy due to essential hypertension.It was a non-randomized, echocardiographic study of 60 previously untreated hypertensive subjects (20 to 75 years of age).Following a 5-year therapy, the decrease in the left ventricular mass was 14%. Normalization of blood pressure and reversal of left ventricular hypertrophy were obtained in 50% and 58% of patients, respectively. Patients of the non-responder group (non-response being defined as a less than 10% decrease in the left ventricular mass) were older and had a longer history of high blood pressure. A positive correlation was observed between age and decrease in the left ventricular mass, the latter being less marked in older patients. Antihypertensive drugs classes had no influence on reversal of left ventricular hypertrophy.Ageing may be a factor of resistance to the decrease in left ventricular mass with therapy. These results suggest that early screening and management of hypertension are essential.

Background: Favourable outcome of phaeochromocytoma surgery requires that paroxysmal hypertension and arrhythmia be controlled, and that hypotension be prevented. Is nicardipine, a calcium channel blocking drug, always adequate? Methods: Nineteen consecutive patients underwent surgery for phaeochromocytoma. Management was standardised with regards to anaesthesia and antihypertensive treatment. Nicardipine was used as a vasodilator and was given in order to maintain systemic vascular resistance lower than 1600 dyn · s · cm−5. Results: Hypertension did not occur at any time during surgery in 6/19 patients. Blood pressure rose acutely in 3/19 patients at the time of tracheal intubation or surgical approach to the tumour, and was controlled by increased depth of anaesthesia. Hypertensive episodes occurred in 11/19 patients during tumour manipulation. Nicardipine always succeeded in maintaining low systemic vascular resistance but its dosage varied widely between patients (0.5 to 70 mg), a fact that may be accounted for by the striking intersubject variability of haemodynamic behaviour during surgery. In 7/11 patients, despite nicardipine treatment, sustained increase in blood pressure persisted with increased cardiac index, but low systemic vascular resistance. Following tumour removal, transient serious hypotension (MAP

The prognosis of cholesterol embolism is often poor, and no treatment is presently available. We report the use of a stable prostacyclin analogue in treating cholesterol embolism in a diabetic patient with arteriopathy. As a sole therapy, it improved cutaneous manifestations and pain, in parallel with an increased transcutaneous oxymetry. We think that prostacyclin analogues are novel candidates for the treatment of cholesterol embolism.

Systolic blood pressure and body mass index (BMI) are the main determinants of the left ventricular mass (LVM). The mechanism of this cardiac hypertrophy in the obese individual is multifactorial and involves hemodynamic as well as metabolic factors. The association of LVM with the morphologic features of the individual are well known. The aim of this study was to assess the influence of the morphologic and metabolic features of obese women on LVM. 2D echocardiography evaluation of LVM was done in 24 normotensive, normoglycemic obese women (BMI [27.5-52.2 Kg/m2). Lean and fat body mass were determined by bio-impedancemetry, insulin sensitivity (Si) by the minimal model (Bergman), and basal metabolism by using indirect calorimetry. There was a positive correlation between LVM and BMI (r = 0.61; p = 0.001), waist to hip ratio (r = 0.45; p = 0.03), basal metabolism (r = 0.61, p = 0.001), lean (r = 0.74, p = 0.0002) and fat (r = 0.49; p = 0.01) body mass. Fasting glycemia was positively correlated with LVM (r = 0.62; p = 0.001), but not Si. LVM was also positively correlated to the triglyceride level. No relations were found with systolic or diastolic blood pressure. Multivariate regression analysis was performed to determine the relative contribution of lean body mass (the morphologic variable with the best association to LVM in univariate analysis), blood glucose, waist to hip ratio, age and triglycerides. The multiple r for the model was 0.87 (p0.001). Lean body mass and blood glucose were found to be the only significant and independent predictors of LVM (p = 0.001 and p = 0.03 respectively). We conclude that: 1) lean body mass is an important determinant of LVM in obese normotensive individuals. Hence, in obese women, correcting LVM for lean body mass might be more accurate than correcting it for body surface area or height. 2) There is no relationship between LVM and insulin sensitivity. The link between blood glucose and LVM needs to be studied further.

The prevalence of microalbuminuria in patients with essential hypertension ranges between 10 and 25%. The level of albuminuria is highly correlated with arterial pressure and more closely ambulatory arterial pressure. The interaction between albuminuria and arterial pressure is clearly enhanced by overweight and smoking. The renal mechanisms of microalbuminuria are not well elucidated; an increase in filtration fraction suggestive of intraglomerular hypertension was observed in patients with hyperfiltration. The significance of micro-albuminuria as a marker of cardiovascular risk or hypertensive renal disease needs to be confirmed through long-term follow-up studies. Antihypertensive treatment has variable influence on albuminuria; angiotensin-converting enzyme inhibitors, in contrast to other agents, tend to partially correct this abnormality.