Hypertension Unit

Tel Aviv, Israel

Hypertension Unit

Tel Aviv, Israel
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Azizi M.,University of Paris Descartes | Azizi M.,Hypertension Unit | Azizi M.,French Institute of Health and Medical Research | Sapoval M.,University of Paris Descartes | And 17 more authors.
The Lancet | Year: 2015

Background Conflicting blood pressure-lowering effects of catheter-based renal artery denervation have been reported in patients with resistant hypertension. We compared the ambulatory blood pressure-lowering efficacy and safety of radiofrequency-based renal denervation added to a standardised stepped-care antihypertensive treatment (SSAHT) with the same SSAHT alone in patients with resistant hypertension. Methods The Renal Denervation for Hypertension (DENERHTN) trial was a prospective, open-label randomised controlled trial with blinded endpoint evaluation in patients with resistant hypertension, done in 15 French tertiary care centres specialised in hypertension management. Eligible patients aged 18-75 years received indapamide 1·5 mg, ramipril 10 mg (or irbesartan 300 mg), and amlodipine 10 mg daily for 4 weeks to confirm treatment resistance by ambulatory blood pressure monitoring before randomisation. Patients were then randomly assigned (1:1) to receive either renal denervation plus an SSAHT regimen (renal denervation group) or the same SSAHT alone (control group). The randomisation sequence was generated by computer, and stratified by centres. For SSAHT, after randomisation, spironolactone 25 mg per day, bisoprolol 10 mg per day, prazosin 5 mg per day, and rilmenidine 1 mg per day were sequentially added from months two to five in both groups if home blood pressure was more than or equal to 135/85 mm Hg. The primary endpoint was the mean change in daytime systolic blood pressure from baseline to 6 months as assessed by ambulatory blood pressure monitoring. The primary endpoint was analysed blindly. The safety outcomes were the incidence of acute adverse events of the renal denervation procedure and the change in estimated glomerular filtration rate from baseline to 6 months. This trial is registered with ClinicalTrials.gov, number NCT01570777. Findings Between May 22, 2012, and Oct 14, 2013, 1416 patients were screened for eligibility, 106 of those were randomly assigned to treatment (53 patients in each group, intention-to-treat population) and 101 analysed because of patients with missing endpoints (48 in the renal denervation group, 53 in the control group, modified intention-to-treat population). The mean change in daytime ambulatory systolic blood pressure at 6 months was -15·8 mm Hg (95% CI -19·7 to -11·9) in the renal denervation group and -9·9 mm Hg (-13·6 to -6·2) in the group receiving SSAHT alone, a baseline-adjusted difference of -5·9 mm Hg (-11·3 to -0·5; p=0·0329). The number of antihypertensive drugs and drug-adherence at 6 months were similar between the two groups. Three minor renal denervation-related adverse events were noted (lumbar pain in two patients and mild groin haematoma in one patient). A mild and similar decrease in estimated glomerular filtration rate from baseline to 6 months was observed in both groups. Interpretation In patients with well defined resistant hypertension, renal denervation plus an SSAHT decreases ambulatory blood pressure more than the same SSAHT alone at 6 months. This additional blood pressure lowering effect may contribute to a reduction in cardiovascular morbidity if maintained in the long term after renal denervation. Funding French Ministry of Health. © 2015 Elsevier Ltd.


Savard S.,Hypertension Unit | Jeunemaitre X.,Center for Rare Vascular Diseases | Jeunemaitre X.,University of Paris Descartes | Azizi M.,Assistance Publique Hopitaux de Paris | And 3 more authors.
Hypertension | Year: 2013

The pathogenesis of fibromuscular dysplasia (FMD) remains unclear, but tobacco use is thought to be involved. This retrospective cross-sectional study aimed to evaluate smoking first as a risk factor for renal artery FMD diagnosis and second as a modifier of the clinical and radiological phenotype of this disease. We retrieved 337 adult patients diagnosed with FMD in a referral center for hypertension management, who were first individually matched to controls with essential hypertension for sex, age, systolic blood pressure, number of antihypertensive drugs, and year of visit. Smoking status and other relevant data were collected at first visit. The proportion of current smokers was higher for patients with FMD than for the controls (30% and 18%, respectively, P<0.001; odds ratio, 2.5 [95% confidence interval, 1.6-3.9]). Second, characteristics of FMD were compared between current smokers and other patients. Among patients with multifocal FMD, current smokers experienced an earlier diagnosis of hypertension (36 versus 42 years, respectively; P<0.001) and FMD (43 versus 51 years; P<0.001) than other patients, and a greater likelihood of renal artery interventions (57% versus 31%; P<0.001) and of kidney asymmetry (21% versus 4%; P=0.001). In conclusion, current smoking is associated with a higher likelihood of renal artery FMD diagnosis. Rather than a higher incidence of FMD, this may reflect a more aggressive course in smokers, who have earlier hypertension leading to increased and earlier recognition of the disease. Smoking cessation should be strongly encouraged in patients with FMD. © 2013 American Heart Association, Inc.


Savard S.,Hypertension Unit | Steichen O.,University Pierre and Marie Curie | Steichen O.,University of Paris Descartes | Azizi M.,Hypertension Unit | And 6 more authors.
Circulation | Year: 2012

BACKGROUND-: Initially based on histology, the diagnosis of renal artery fibromuscular dysplasia (FMD) is now based mostly on angiographic appearance because arterial tissue samples are rarely available. This retrospective cross-sectional study aimed to assess the clinical relevance of a binary angiographic classification of FMD lesions (unifocal or multifocal) based on computed tomographic or magnetic resonance angiography. METHODS AND RESULTS-: Adult patients diagnosed with FMD in a single tertiary care center for hypertension management were identified by screening of electronic files. FMD lesions were reviewed and classified according to computed tomography or magnetic resonance angiography as multifocal if there were at least 2 stenoses in the same arterial segment; otherwise, they were classified as unifocal. Of 337 patients with established renal artery FMD, 276 (82%) were classified as multifocal. Patients with unifocal and multifocal lesions differed significantly in median age at diagnosis of FMD (30 and 49 years) and hypertension (26 and 40 years), sex distribution (female:male ratio, 2:1 and 5:1), initial blood pressure (157/97 and 146/88 mm Hg), current smoking (50% and 26%), prevalence of unilateral renal artery lesions (79% and 38%), presence of kidney asymmetry (33% and 10%), renal revascularization procedures (90% and 35%), and hypertension cure rates in patients who underwent revascularization (54% and 26%). CONCLUSIONS-: A binary angiographic classification into unifocal or multifocal renal artery FMD is straightforward and discriminates 2 groups of patients with different clinical phenotypes. © 2012 American Heart Association, Inc.


Rossi G.P.,University of Padua | Auchus R.J.,University of Michigan | Brown M.,University of Cambridge | Lenders J.W.M.,Radboud University Nijmegen | And 5 more authors.
Hypertension | Year: 2014

Adrenal venous sampling is recommended by current guidelines to identify surgically curable causes of hyperaldosteronism but remains markedly underused. Key factors contributing to the poor use of adrenal venous sampling include the prevailing perceptions that it is a technically challenging procedure, difficult to interpret, and can be complicated by adrenal vein rupture. In addition, the lack of uniformly accepted standards for the performance of adrenal venous sampling contributes to its limited use. Hence, an international panel of experts working at major referral centers was assembled to provide updated advice on how to perform and interpret adrenal venous sampling. To this end, they were asked to use the PICO (Patient or Problem, Intervention, Control or comparison, Outcome) strategy to gather relevant information from the literature and to rely on their own experience. The level of evidence/recommendation was provided according to American Heart Association gradings whenever possible. A consensus was reached on several key issues, including the selection and preparation of the patients for adrenal venous sampling, the procedure for its optimal performance, and the interpretation of its results for diagnostic purposes even in the most challenging cases. © 2013 American Heart Association, Inc.


Kupers E.M.,Hypertension Unit | Amar L.,Hypertension Unit | Raynaud A.,Georges Pompidou European Hospital | Plouin P.-F.,Hypertension Unit | And 4 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2012

Context: Adrenal venous sampling is recommended to assess whether aldosterone hypersecretion is lateralized in patients with primary aldosteronism. However, this procedure is invasive, poorly standardized, and not widely available. Objective: Our goal was to identify patients' characteristics that can predict unilateral aldosterone hypersecretion in some patients who could hence bypass adrenal venous sampling before surgery. Design and Setting: A cross-sectional diagnostic study was performed from February 2009 to July 2010 at a single center specialized in hypertension care. Patients: A total of 101 consecutive patients with primary aldosteronism who underwent adrenal venous sampling participated in the study. The autonomy of aldosterone hypersecretion was assessed with the saline infusion test. Intervention: Adrenal venous sampling was performed without ACTH infusion but with simultaneous bilateral sampling. Main Outcome Measures: Variables independently associated with a lateralized adrenal venous sampling in multivariate logistic regression were used to derive a clinical prediction rule. Results: Adrenal venous sampling was successful in 87 patients and lateralized in 49. All 26 patients with a typical Conn's adenoma plus serum potassium of less than 3.5 mmol/liter or estimated glomerular filtration rate of at least 100 ml/min/1.73 m2 (or both) had unilateral primary aldosteronism; this rule had 100% specificity (95% confidence interval, 91-100) and 53% sensitivity (95% confidence interval, 38-68). Conclusions: If our results are validated on an independent sample, adrenal venous sampling could be omitted before surgery in patients with a typical Conn's adenoma if they meet at least one of two supplementary biochemical characteristics (serum potassium <3.5 mmol/liter or estimated glomerular filtration rate ≥100 ml/min/1.73 m2). Copyright © 2012 by The Endocrine Society.


Solini A.,University of Pisa | Grossman E.,Hypertension Unit | Grossman E.,Tel Aviv University
Diabetes Care | Year: 2016

Hypertension is very common in elderly subjects with type 2 diabetes. The coexistence of hypertension and diabetes can be devastating to the cardiovascular system, and in these patients, tight blood pressure (BP) control is particularly beneficial. Little information is available regarding the target BP levels in elderly hypertensive patientswith type 2 diabetes, and therefore extrapolation fromdata in the general population should be done. However, it is difficult to extrapolate from the general population to these frail individuals, who usually have isolated systolic hypertension, comorbidities, organ damage, cardiovascular disease, and renal failure and have a high rate of orthostatic and postprandial hypotension. On the basis of the available evidence, we provide arguments supporting the individualized approach in these patients. Target BP should be based on concomitant diseases, orthostatic BP changes, and the general condition of the patients. It is recommended to lower BP in the elderly patient with diabetes to <140-150/90 mmHg, providing the patient is in good condition. In patients with isolated systolic hypertension, the same target is reasonable providing the diastolic BP is >60 mmHg. In patients with coronary artery disease and in patients with orthostatic hypotension, excessive BP lowering should be avoided. In elderly hypertensive patients with diabetes, BP levels should be monitored closely in the sitting and the standing position, and the treatment should be tailored to prevent excessive fall in BP.


De Giorgi A.,Clinica Medica | Mallozzi Menegatti A.,Clinica Medica | Fabbian F.,Clinica Medica | Portaluppi F.,Hypertension Unit | Manfredini R.,Clinica Medica
European Journal of Internal Medicine | Year: 2013

Background Chronobiology is devoted to the study of biological rhythms. It is possible that a given medication may be therapeutic and safe when administered at some time, but subtherapeutic or poorly tolerated at another. Methods We focused on some classes of drugs, widely used by the internists, performing a PubMed search with the single drugs associated with the MeSH terms "Chronotherapy", "Circadian rhythm", and "Chronobiology, phenomena". Among the studies found, we considered only those provided with discrete numerosity or clearly stated methodological characteristics. Results The results of available studies were given, along with a series of short take-home messages at the end of each mini-chapter devoted to: antihypertensives, statins, anticoagulants, analgesics, drugs for acid-related disorders, and anti-asthmatic drugs. In particular, evidence of morning vs. evening administration, when applicable, was given for each medication. Conclusions Adequate evidence seems to support that at least ACE-inhibitors or angiotensin receptor blockers, simvastatin, corticosteroids (slow-release formulation) for arthritic patients, and ranitidine should preferably be administered in the evening. Morning dosing could be better for proton pump inhibitors, whereas time of administration is not crucial for asthma inhalation drugs. Studies are available for other drugs, but not so strong enough to draw definite conclusions. For now, we need prospective intervention trials specifically designed to investigate the long-term effects of a temporal approach to medical therapy. However, since switching to morning-evening administration or vice versa is simple and inexpensive, in some cases it could be considered, remembering that, in any case, adherence remains the crucial point. © 2013 European Federation of Internal Medicine.


Goldstein D.S.,U.S. National Institutes of Health | Sewell L.,U.S. National Institutes of Health | Sharabi Y.,Hypertension Unit
Journal of the Neurological Sciences | Year: 2011

It has been suggested that autonomic dysfunction constitutes a biomarker for early detection of the disease process in Parkinson disease (PD). Recent findings based on cardiac sympathetic and striatal dopaminergic imaging in the same patients indicate that this view is overly simple. Although evidence of cardiac sympathetic denervation is associated with other non-motor manifestations such as anosmia, REM behavior disorder, dementia, baroreflex failure, and orthostatic hypotension (OH), across individual patients the severities of OH and of the cardiac sympathetic lesion (indicated by thoracic 6-[ 18F]fluorodopamine PET scanning) are unrelated to the severity of the putamen dopaminergic lesion (indicated by brain 6-[ 18F]fluorodopa PET scanning). Moreover, whereas cases have been reported with neuroimaging evidence of cardiac sympathetic denervation several years before motor onset of PD, in other cases loss of cardiac sympathetic innervation progresses approximately concurrently with the movement disorder or can even occur as a late finding. Bases for independent sympathetic noradrenergic and striatal dopaminergic lesions in Lewy body diseases remain poorly understood. In elderly patients with unexplained OH or other evidence of autonomic failure, it is reasonable for clinicians to look for subtle signs of parkinsonism, such as masked facies, cogwheel rigidity, and shuffling gate. © 2011 Elsevier B.V.


Cohen Y.,Tel Aviv University | Peleg E.,Hypertension Unit | Belkin M.,Tel Aviv University | Polat U.,Tel Aviv University | Solomon A.S.,Tel Aviv University
Experimental Eye Research | Year: 2012

Form deprivation and low illuminance of ambient light are known to induce myopia in chicks. Low concentrations of retinal dopamine, a light-driven neurohormone, was previously shown to be associated with form deprivation myopia. In the present study we examined the dependence of retinal dopamine release in chicks on illuminance during light-dark cycles and in continuous light, and the role of retinal dopamine release in illuminance dependent refractive development. Newly hatched chicks (n = 166) were divided into two experimental groups, a dopamine (n = 88) and a refraction group (n = 78). Both groups were further divided into six illumination groups for exposure of chicks to illuminances of 50, 500 or 10,000 lux of incandescent illumination (referred to throughout as low, medium, and high illuminance, respectively), either under a light-dark cycle with lights on between 7 AM and 7 PM or under continuous illumination. For the dopamine experiment, chicks were euthanized and vitreous was extracted on day 14 post-hatching at 7, 8 AM and 1 PM. Vitreal dihydroxyphenylacetic acid (DOPAC) and dopamine concentrations were quantified by high-performance liquid chromatography coupled to electrochemical detection. For the refraction experiment, chicks underwent refraction, keratometry and A-scan ultrasonography on days 30, 60 and 90 post-hatching, and each of those measurements was correlated with vitreal DOPAC concentration measured at 1 PM (representing the index of retinal dopamine release). The results showed that under light-dark cycles, vitreal DOPAC concentration was strongly correlated with log illuminance, and was significantly correlated with the developing refraction, corneal radius of curvature, and axial length values. On day 90, low vitreal DOPAC concentrations were associated with myopia (-2.41 ± 1.23 D), flat cornea, deep anterior and vitreous chambers, and thin lens. Under continuous light, vitreal DOPAC concentrations measured at 1 PM in the low, medium, and high illuminance groups did not differ from the concentrations measured at 8 AM. On day 90, low DOPAC concentrations were associated with emmetropia (+0.63 ± 3.61), steep cornea, and shallow vitreous chamber. We concluded that ambient light over a log illuminance range of 1.69-4 is linearly related to vitreal DOPAC concentration. Under both light-dark cycles and continuous light, the intensity of ambient light regulates the release of retinal dopamine. Refractive development is associated with illuminance dependent dopamine release. © 2012 Elsevier Ltd.


Milan A.,Hypertension Unit | Magnino C.,Hypertension Unit | Veglio F.,Hypertension Unit
Journal of the American Society of Echocardiography | Year: 2010

Ultrasound imaging has continuously developed over recent years, leading to the development of several novel echocardiographic indexes. Among these, of particular interest are those that focus on pulmonary hemodynamics, because they not only improve both sensitivity and specificity in the echocardiographic evaluation of pulmonary pressures (systolic, mean, and diastolic), but can also be used to estimate other pulmonary hemodynamic parameters, such as pulmonary vascular resistance, pulmonary capillary wedge pressure, and pulmonary capacitance and impedance. Such parameters can provide important diagnostic and prognostic information in patients with heart failure, chronic obstructive pulmonary disease, and pulmonary arterial hypertension and in every patient with suspected pulmonary impairment. In this review, the authors present a comprehensive overview of the echocardiographic indexes involved in pulmonary hemodynamic evaluation and discuss the applications of these indexes in the clinical setting. © 2010 American Society of Echocardiography.

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