A Review of Telmisartan in the Treatment of Hypertension: Blood Pressure Control in the Early Morning Hours

Measurement of blood pressure in the clinic may provide a false impression of blood pressure control. Ambulatory blood pressure monitoring (ABPM) allows the automatic recording of the circadian variation in blood pressure and evaluation of the efficacy of antihypertensive medication throughout the dosing interval. Ambulatory blood pressure provides more effective prediction of cardiovascular risk; blood pressure control at the time of heightened risk in the early morning after waking and before taking the next dose of medication is becoming important in order to improve long-term prognosis. To achieve blood pressure control in the early morning, a long-acting antihypertensive agent is essential. Telmisartan, an angiotensin II receptor blocker, as well as having a terminal elimination halflife of 24 h, has a large volume of distribution due to its high lipophilicity. The efficacy of telmisartan 80 mg monotherapy has been demonstrated using ABPM, with superior reduction in mean values for the last 6 h of the dosing interval compared with ramipril 10 mg and valsartan 80 mg. In addition, telmisartan 80 mg provides superior blood pressure control after a missed dose compared with valsartan 160 mg. When combined with hydrochlorothiazide (HCTZ) 12.5 mg, telmisartan 40 mg and 80 mg is more effective than losartan/HCTZ (50/12.5 mg) at the end of the dosing interval. Furthermore, greater reductions in last 6 h mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) are achieved with telmisartan/HCTZ (80/12.5 mg) than with valsartan/HCTZ (160/12.5 mg) in obese patients with type 2 diabetes and hypertension. Recent data from a large group of patients show that telmisartan 80 mg controls the early morning blood pressure surge more effectively than ramipril 5–10 mg and, thus, may have a greater beneficial effect on long-term cardiovascular risk. This supposition is being tested in the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) programm

Ambulatory blood pressure in hypertensive patients with left ventricular hypertrophy: efficacy of first-line combination perindopril/indapamide therapy

Roland Asmar1, Juan Garcia-Puig2, Philippe Gosse3, Yuri A Karpov4, Peter Wilhem De Leeuw5, Dieter Magometschniggs6, Lajos Matos7, Roland Schmieder81Institut Cardiovasculaire, Paris, France; 2Hospital La Paz, Madrid, Spain; 3Hôpital Saint André, Bordeaux, France; 4Russian Academy of Medical Sciences, Moscow, Russia; 5Academisch Ziekenhuis, Maastricht, the Netherlands; 6Institut für Hypertoniker, Vienna, Austria; 7Hungarian Institut of Cardiology, Budapest, Hungary; 8Medizinische FakultÄt, Erlangen GermanyBackground: Ambulatory blood pressure (BP) is more sensitive than office BP and is highly correlated with the left ventricular mass (LVM) of hypertensive patients with left ventricular hypertrophy (LVH). Methods: In this prospectively designed ancillary study of the PICXEL trial, the effects of first-line combination perindopril/indapamide on ambulatory BP were compared with those of monotherapy with enalapril in 127 patients. Hypertensive patients with LVH received once daily either perindopril 2 mg/indapamide 0.625 mg (n = 65) or enalapril 10 mg (n = 62) for 52 weeks. Dose adjustments were allowed for uncontrolled BP. Twenty-four-hour ambulatory BP and echocardiographic parameters were measured at baseline, week 24, and week 52. Results: At study end, both treatments significantly improved ambulatory BP compared with baseline (p ≤ 0.01). Perindopril/indapamide treatment reduced 24-hour and daytime systolic BP (SBP) and pulse pressure (PP) significantly more than enalapril treatment (p < 0.01). No significant between-group differences were noted for diastolic BP (DBP) or for night-time measurements. Trough/peak ratios were higher with perindopril/indapamide than with enalapril (88.5 vs 65.8 for SBP and 86.7 vs 63.9 for DBP, respectively). The global smoothness index was higher with perindopril/indapamide than with enalapril (6.6 vs 5.2 for SBP and 5.6 vs 4.9 for DBP, respectively). With perindopril/indapamide treatment, LVM index was significantly reduced (−9.1 g/m2 from baseline; p vs baseline <0.001). More patients required dose increases with enalapril (87%) than with perindopril/indapamide (71%). No unusual safety elements were noted.Conclusions: First-line perindopril/indapamide combination decreased ambulatory SBP and PP, and LVM more effectively than enalapril.Keywords: left ventricular hypertrophy, ambulatory blood pressure monitoring, perindopril, indapamide, enalapri

A Systematic Approach For Kinematic Design Of Upper Limb Rehabilitation Exoskeletons

Kinematic structure of an exoskeleton is the most fundamental block of its design and is determinant of many functional capabilities of it. Although numerous upper limb rehabilitation devices have been designed in the recent years, there is not a framework that can systematically guide the kinematic design procedure. Additionally, diversity of currently available devices and the many minute details incorporated to address certain design requirements hinders pinpointing the core kinematics of the available devices to compare them against each other. This makes the review of literature for identifying drawbacks of the state of the art systems a challenging and puzzling task. In fact, lack of a unifying framework makes designing rehabilitation devices an intuitive process and prone to biases from currently available designs. This research work proposes a systematic approach for kinematic design of upper limb rehabilitation exoskeletons based on conceptual design techniques. Having defined a solution neutral problem statement based on the characteristics of an ideal device, the main functionality of the system is divided into smaller functional units via the Functional Decomposition Method. Various directions for concept generation are explored and finally, it has been shown that a vast majority of the current exoskeleton designs fit within the proposed design framework and the defined functionalities

Etre parent d'enfant atteint des troubles du spectre de l'autisme : Le stress parental à travers l'analyse interprétative phénoménologique.

International audienceL’objectif de notre étude était de faire partager l’expérience de parents, expériences de vie etd’accompagnement de leur enfant atteint des troubles du spectre de l’autisme, afin decomprendre les facteurs du stress parental tels qu’ils étaient perçus par les parents eux-mêmes.Cette recherche visait à élucider de quels éléments sont constitués le vécu des parents d’enfantsautistes, comment ces parents ont vécu l’expérience de vie suite au diagnostic de leur enfant etcomment ils ont su mettre en place « leur normalité » dans leur vie familiale

A Godunov-type method for the shallow water equations with discontinuous topography in the resonant regime

We investigate the Riemann problem for the shallow water equations with variable and (possibly) discontinuous topography and provide a complete description of the properties of its solutions: existence; uniqueness in the non-resonant regime; multiple solutions in the resonant regime. This analysis leads us to a numerical algorithm that provides one with a Riemann solver. Next, we introduce a Godunov-type scheme based on this Riemann solver, which is well-balanced and of quasi-conservative form. Finally, we present numerical experiments which demonstrate the convergence of the proposed scheme even in the resonance regime, except in the limiting situation when Riemann data precisely belong to the resonance hypersurface.Comment: 39 page

Effects of Renal Denervation vs Sham in Resistant Hypertension after Medication Escalation:Prespecified Analysis at 6 Months of the RADIANCE-HTN TRIO Randomized Clinical Trial

IMPORTANCE: Although early trials of endovascular renal denervation (RDN) for patients with resistant hypertension (RHTN) reported inconsistent results, ultrasound RDN (uRDN) was found to decrease blood pressure (BP) vs sham at 2 months in patients with RHTN taking stable background medications in the Study of the ReCor Medical Paradise System in Clinical Hypertension (RADIANCE-HTN TRIO) trial. OBJECTIVES: To report the prespecified analysis of the persistence of the BP effects and safety of uRDN vs sham at 6 months in conjunction with escalating antihypertensive medications. DESIGN, SETTING, AND PARTICIPANTS: This randomized, sham-controlled, clinical trial with outcome assessors and patients blinded to treatment assignment, enrolled patients from March 11, 2016, to March 13, 2020. This was an international, multicenter study conducted in the US and Europe. Participants with daytime ambulatory BP of 135/85 mm Hg or higher after 4 weeks of single-pill triple-combination treatment (angiotensin-receptor blocker, calcium channel blocker, and thiazide diuretic) with estimated glomerular filtration rate (eGFR) of 40 mL/min/1.73 m(2 )or greater were randomly assigned to uRDN or sham with medications unchanged through 2 months. From 2 to 5 months, if monthly home BP was 135/85 mm Hg or higher, standardized stepped-care antihypertensive treatment starting with aldosterone antagonists was initiated under blinding to treatment assignment. INTERVENTIONS: uRDN vs sham procedure in conjunction with added medications to target BP control. MAIN OUTCOMES AND MEASURES: Six-month change in medications, change in daytime ambulatory systolic BP, change in home systolic BP adjusted for baseline BP and medications, and safety. RESULTS: A total of 65 of 69 participants in the uRDN group and 64 of 67 participants in the sham group (mean [SD] age, 52.4 [8.3] years; 104 male [80.6%]) with a mean (SD) eGFR of 81.5 (22.8) mL/min/1.73 m(2) had 6-month daytime ambulatory BP measurements. Fewer medications were added in the uRDN group (mean [SD], 0.7 [1.0] medications) vs sham (mean [SD], 1.1 [1.1] medications; P = .045) and fewer patients in the uRDN group received aldosterone antagonists at 6 months (26 of 65 [40.0%] vs 39 of 64 [60.9%]; P = .02). Despite less intensive standardized stepped-care antihypertensive treatment, mean (SD) daytime ambulatory BP at 6 months was 138.3 (15.1) mm Hg with uRDN vs 139.0 (14.3) mm Hg with sham (additional decreases of −2.4 [16.6] vs −7.0 [16.7] mm Hg from month 2, respectively), whereas home SBP was lowered to a greater extent with uRDN by 4.3 mm Hg (95% CI, 0.5-8.1 mm Hg; P = .03) in a mixed model adjusting for baseline and number of medications. Adverse events were infrequent and similar between groups. CONCLUSIONS AND RELEVANCE: In this study, in patients with RHTN initially randomly assigned to uRDN or a sham procedure and who had persistent elevation of BP at 2 months after the procedure, standardized stepped-care antihypertensive treatment escalation resulted in similar BP reduction in both groups at 6 months, with fewer additional medications required in the uRDN group. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT0264942

Doppler ultrasound in the measurement of pulse wave velocity: agreement with the Complior method

Aortic stiffness is an independent predictor factor for cardiovascular risk. Different methods for determining pulse wave velocity (PWV) are used, among which the most common are mechanical methods such as SphygmoCor or Complior, which require specific devices and are limited by technical difficulty in obtaining measurements. Doppler guided by 2D ultrasound is a good alternative to these methods. We studied 40 patients (29 male, aged 21 to 82 years) comparing the Complior method with Doppler. Agreement of both devices was high (R = 0.91, 0.84-0.95, 95% CI). The reproducibility analysis revealed no intra-nor interobserver differences. Based on these results, we conclude that Doppler ultrasound is a reliable and reproducible alternative to other established methods for the measurement of aortic PWV

Denudation outpaced by crustal thickening in the eastern Tianshan

The modern high topography of the Tianshan resulted from the reactivation of a Paleozoic orogenic belt by the India/Asia collision. Today, the range exhibits tectonically active forelands and intermontane basins. Based on quantitative morphotectonic observations and age constraints derived from cosmogenic 10Be dating, single-grain post-infrared infrared stimulated luminescence (p-IR IRSL) dating and modeling of fault scarp degradation, we quantify the deformation in the Nalati and Bayanbulak intermontane basins in the central Eastern Tianshan. Our results indicate that at least 1.4 mm/yr of horizontal crustal shortening is accommodated within these two basins. This shortening represents over 15% of the 8.5 ± 0.5 mm/yr total shortening rate across the entire range at this longitude. This shortening rate implies that the Eastern Central Tianshan is thickening at a mean rate of ∼1.4 mm/yr, a rate that is significantly higher than the average denudation rate of 0.14 mm/yr derived from our cosmogenic analysis. This discrepancy suggests that the Tianshan range has not yet reached a steady-state topography and remains in a transient state of topographic growth, most likely due to limited denudation rates driven by the arid climate of Central Asia

Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D