M. Lopez-Sublet

Combinations of inhibitors of the renin–angiotensin system with calcium channel blockers for the treatment of hypertension: focus on perindopril/amlodipine

Abstract Background: Combination antihypertensive therapy with an inhibitor of the renin–angiotensin system (RAS) and a calcium channel blocker (CCB) is a rational approach to achieve blood pressure (BP) goals in patients with hypertension, and may provide additional cardiovascular protection compared to other strategies in special populations. This article reviews the rationale for, and evidence supporting, the use of newer fixed-dose combinations of RAS inhibitors and CCBs, with particular emphasis on perindopril/amlodipine. Methods: A literature search was performed in Medline and EMBASE databases to identify articles published up to May 2010 describing the impact of combination treatment with angiotensin receptor blocker (ARB)/CCB or angiotensin-converting enzyme (ACE) inhibitor/CCB based antihypertensive strategies on BP or clinical outcomes. Findings: A substantial body of evidence supports the BP-lowering efficacy of RAS inhibitor/CCB combination therapy in patients with hypertension. RAS inhibitors and CCBs represent two different and complementary mechanisms of actions; their use in combination is associated with effective BP lowering with favourable tolerability and fewer adverse metabolic effects than some other combination therapies. Currently, intervention studies demonstrating the impact of ARB/CCB combinations on cardiovascular mortality and morbidity are lacking. However, evidence from large outcome trials supports the use of ACE inhibitor/CCB combinations for reducing the risk of cardiovascular and renal events, particularly in high-risk patients. There is also evidence that the benefits of ACE inhibitor/CCB combinations may extend beyond those solely associated with brachial BP lowering, by an additional impact on central BP haemodynamics. Conclusions: RAS inhibitor/CCB combination therapy is an effective antihypertensive therapy. Strong evidence supports the antihypertensive efficacy of ACE inhibitor/CCB combinations with cardioprotective and renoprotective properties. In particular, evidence suggests that fixed-dose perindopril/amlodipine effectively decreases BP and currently is the only RAS inhibitor/CCB combination proven to decrease all-cause and cardiovascular mortality as well as major cardiovascular events, and thus is a valuable option for the management of hypertension, especially in high-risk patients.

Aortic pulse pressure and atherosclerotic structural alterations of coronary arteries

Pulse pressure (PP) is an independent predictor of myocardial infarction, mainly above 50 years of age. In subjects with preserved ejection fraction (EF), aortic PP predicts the severity of coronary atherosclerosis. Comparable findings in subjects with reduced EF have not been evaluated. In 1337 subjects with severe coronary ischaemic disease, intra-aortic and brachial blood pressures were measured together with EF and coronary angiography to evaluate cardiac function, the presence of coronary stenosis and/or occlusions or calcifications. The presence (odds ratio±95% CI) of coronary calcification was marginally but not significantly associated (P=0.06) to increased aortic PP (1.32 (0.97–1.80)), whereas that of coronary occlusion was significantly associated (P<0.01) with decreased aortic PP (0.62 (0.42–0.91)), even after adjustment to EF and heart rate. Increased aortic PP did not correlate with stenosis number. No comparable predictive value was observed using intra-aortic or non-invasive brachial systolic blood pressure (SBP) or diastolic blood pressure (DBP). In high cardiovascular risk populations, even in the presence of reduced EF and high heart rate, intra-aortic PP, but not SBP or DBP, is a significant predictor of coronary occlusions and possibly calcifications, but not stenosis.

Mise au pointPlace des différentes techniques de mesure de la pression artérielle en 2016Usefulness of different techniques of blood pressure measurements in 2016

The management of hypertensive patients is greatly influenced by blood pressure levels and accurate measurement of blood pressure is crucial in this context. Mercury sphygmomanometer has been progressively replaced by more precise oscillometric devices that can be widely used in the clinic and ambulatory setting. The purpose of this review was to detail the different methods for evaluating blood pressure, and to refine their indications and clinical benefit. Office blood pressure measurement has a great variability and should follow a strict protocol to give consistent results. National and international guidelines focus on blood pressure measurement in the ambulatory setting. When used by trained patients, home blood pressure monitoring is reproducible and can provide substantial prognostic information, even if ambulatory blood pressure monitoring remains the gold standard. The role of central blood pressure and pulse wave velocity monitoring in the therapeutic strategy of hypertension needs further assessment.

Place des différentes techniques de mesure de la pression artérielle en 2016

The management of hypertensive patients is greatly influenced by blood pressure levels and accurate measurement of blood pressure is crucial in this context. Mercury sphygmomanometer has been progressively replaced by more precise oscillometric devices that can be widely used in the clinic and ambulatory setting. The purpose of this review was to detail the different methods for evaluating blood pressure, and to refine their indications and clinical benefit. Office blood pressure measurement has a great variability and should follow a strict protocol to give consistent results. National and international guidelines focus on blood pressure measurement in the ambulatory setting. When used by trained patients, home blood pressure monitoring is reproducible and can provide substantial prognostic information, even if ambulatory blood pressure monitoring remains the gold standard. The role of central blood pressure and pulse wave velocity monitoring in the therapeutic strategy of hypertension needs further assessment.

[PP.08.06] IS THE DEVELOPMENT OF TELEMEDICINE IN HYPERTENSION A DIGITAL IMMIGRANT ISSUE ?

Objective: Telemedicine refers to the use of medical information exchanged from one site to another via electronic communication and the role in the management arterial hypertension should strive against uncontrolled patients. Nowadays, patients easily e-transfer their results of home blood pressure measurement (HBPM) and practitioners receive and assess these HBPM results. Young generations, grown with the Internet, have been labelled “digital natives” (born after 1985) in comparison with older generations, labelled “digital immigrants”, who need to learn e-technology. Thus, we aimed to collect data on technical equipment of physicians and patients, on their expectations of use about this way of relationship. Design and method: 116 physicians, hypertension specialists (36 ± 9 y, 50.8% men), mostly hospital practitioners (84.5%) and 322 hypertensive outpatients (61 ± 14.6 y, 60.4% men, SBP/DBP average 143 ± 19/82 ± 13 mmHg, 31.8% with diabetes) completed a self-administered questionnaire. Results: The prevalence of technical equipment in both groups is summarized in Table 1. Figure. No caption available. 68.2% of patients had an HBPM device (51.6% upper arm). From the 69/98 diabetic’ patients used a blood glucose meter. 41% of patients vs 66% of physicians believed that telemedicine could improve the control of hypertension; 25% of patients vs 22% physicians thought that consultations’ frequency could be lightened. 18% of physicians thought that HBPM would fight inertia. 75% of patients vs 84% of physicians would agree for HBPM data being transferred to a non- medical staff. Whilst 89.5% of physicians were supporting the development of telemedicine in their daily practice, 99% of them found many “limits” to this method: budget (49%), difficulties in accessing informatics tools (38%), medical reluctance (35%), lack of legal frame (34%), confidentiality (33%), absence of direct benefit (21%). Conclusions: Although our population has no daily access to the telemedicine, today technical equipment is no longer an obstacle. The majority of patients and medical practitioners agree with e-transfer of HBPM data. However physicians highlight various obstacles to its expansion: financial limits, medical reluctance and lack of legal frame. Telemedicine might take off when the natives will outnumber immigrants. Meanwhile, physicians have a key-role to lead the patients in their e-education.

[PP.09.02] ACCESSORY RENAL ARTERIES IN RESISTANT HYPERTENSION

Objective: Refractory hypertension (RHT) is a major health care concern affecting 20 to 30% of hypertensive patients and increasing cardiovascular risk. Recent renal denervation trials suggest a high prevalence of accessory renal arteries (ARA) in RHT. Previous publications report a putative role of ARA in triggering hypertension through renin secretion in underperfused renal segments. Our objective was to compare the prevalence of ARA in RHT vs non-refractory hypertension (NRHT). Design and method: 86 essential hypertensive patients who benefited from an abdominal CT-scan or MRI during their initial work-up were retrospectively recruited in 6 french hypertension centers. At the end of a minimal 6 months of follow up, patients were classified between RHT or NRHT. RHT was defined as blood pressure that remains above goal in spite of 3 antihypertensive agents at optimal dose including a diuretic, or controlled by more than 3 medications (Calhoun, 2008). Other patients were classified as NRHT. Blinded independant central review of all radiologic renal artery charts was performed. Results: Baseline characteristics were: age 50 ± 15 years, 62% males, BP 145 ± 23 / 87 ± 13 mmHg. 53 (62%) patients had RHT and 25 (29%) had at least one ARA. Prevalence of ARA was comparable between RHT (25%) and NRHT patients (33%, p = 0,62), but there were significantly more ARA per patient in NRHT (2 ± 0,9) vs RHT (1,3 ± 0,5, p = 0,03). ARA were similar in diameter or length between the 2 groups. Patients with ARA had a significative increase in renin plasma levels at baseline (51,6 ± 49,3 mUI/l) versus patients without ARA (20,3 ± 25,1 mUI/l, p = 9x10-3), but this did not translate into a worse blood pressure control or a raise in medication number, especially in renin angiotensin system inhibitors at the end of follow up. Conclusions: In this retrospective series of 86 essential hypertensive patients, we found no difference in the prevalence of ARA in RHT and NRHT, but NRHT patients had significantly more ARA per patients than RHT patients. This study confirms elevated renin plasma levels at baseline in hypertensive patients with ARA, but limits its clinical relevance in terms of blood pressure control.

Pseudo xanthome élastique péri ombilical et hypertension artérielle : une association fortuite ?

ntroduction.– Le pseudo xanthome élastique péri ombilical PXEP) est une forme rare du pseudo xanthome élastique (PXE) aractérisée par une atteinte cutanée limitée à la région péri mbilicale, l’absence de contexte familial et la rareté des compliations systémiques. Le PXEP s’associe à une prévalence élevée e manifestations cardio-vasculaires, notamment d’hypertension rtérielle (HTA), dont les rapports avec d’éventuelles lésions asculaires liées au PXE restent inconnus. Nous rapportons ici ’observation d’une patiente présentant un PXEP et une HTA évère, dont nous décrivons pour la première fois une exploration xhaustive. atients et méthodes.– Madame D., 66 ans, malienne, est hospitaliée pour une poussée hypertensive sévère dans un contexte d’HTA ncienne. L’examen clinique identifie des papules kératosiques jauâtre confluente péri ombilicale, apparues dans les suites de ses grossesses. La patiente ne présente aucun signe clinique d’atteinte ardio-vasculaire. La biopsie cutanée d’une papule péri ombilicale évèle un aspect de fragmentation et de calcification des fibres élasiques évocateur de PXE. ésultats.– La recherche de manifestations systémiques spécifiques phtalmologiques, cardiaques ou digestives sont négatives. L’écho oppler carotidien identifie un minime athérome sans augmenation de l’épaisseur intima média et l’écho doppler artériel des embres inférieurs ne montre pas de médiacalcose. Concernant e bilan étiologique de l’HTA, il n’existe pas de sténose ou califications artérielles rénales. Il n’y a aucun argument pour une utre forme d’HTA secondaire. Le retentissement sur les organes ibles est marqué par une rétinopathie hypertensive chronique, ne hypertrophie ventriculaire gauche modérée et une élévation e la vitesse de l’onde de pouls carotido-fémorale. Il n’y a pas ’atteinte rénale. Les autres facteurs du risque cardiovasculaire se ésument à une hypercholestérolémie et un âge élevé. La pression rtérielle est finalement contrôlée sous quadrithérapie antihyperensive associant bêtabloquant, diurétique thiazidique, sartan et nhibiteur calcique. iscussion.– Le PXE est une maladie génétique rare du tissu conjoncif liée à une mutation sur le gène ABCC6, responsable d’une égénérescence avec calcification des fibres élastiques. L’atteinte asculaire du PXE se manifeste par des lésions sténosantes calciées prédominant sur les artères de moyen calibre, mimant une thérosclérose précoce avec médiacalcose. L’HTA est fréquente 1/4 des patients) et principalement liée à une calcification des rtères rénales. Le remodelage de la paroi artérielle ne semble pas nduire d’élévation de la rigidité aortique. Le rôle de l’atteinte micro irculatoire occlusif reste méconnu. Le PXEP est l’apanage de la emme noire âgée, obèse et multipare. Certains en font une forme urement cutanée acquise sous l’effet de contraintes mécaniques hez des sujets génétiquement prédisposés, d’autres le considèrent omme une forme limitée du PXE héréditaire, avec possibilité ’atteinte systémique. Une forte prévalence de facteurs de risque t de maladies cardio-vasculaires (dont une HTA dans 3/4 des cas) t rénales est décrite chez ces patients, mais aucune étude n’en recherché de facteurs étiologiques. Notre travail présente pour a première fois un bilan exhaustif de l’HTA d’un sujet porteur de XEP. L’absence d’athérosclérose marquée, de médiacalcose ou de ténose artérielle rénale et l’existence d’une rigidité aortique élevée

Œdèmes pulmonaires « flash » par sténose des artères rénales

Depuis les observations de Pickering et al., il a ete decrit un tableau particulier d’insuffisance cardiaque aigue revelant chez un sujet âge une stenose bilaterale des arteres renales, ou une stenose unilaterale sur rein fonctionnel unique. Ces œdemes aigus pulmonaires (OAP), souvent recidivants, contrastent avec une fonction cardiaque basale conservee. Les rapporter a leur cause permet un traitement endoluminal efficace.