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Showing papers by "Luis M. Ruilope published in 2017"


Journal ArticleDOI
TL;DR: An overview of the diagnosis, epidemiology, pathogenesis and treatment of hypertension in patients on dialysis, aiming to offer the renal physician practical recommendations based on current knowledge and expert opinion and to highlight areas for future research.
Abstract: In patients with end-stage renal disease (ESRD) treated with haemodialysis or peritoneal dialysis, hypertension is common and often poorly controlled. Blood pressure (BP) recordings obtained before or after haemodialysis display a J- or U-shaped association with cardiovascular events and survival, but this most likely reflects the low accuracy of these measurements and the peculiar haemodynamic setting related to dialysis treatment. Elevated BP detected by home or ambulatory BP monitoring is clearly associated with shorter survival. Sodium and volume excess is the prominent mechanism of hypertension in dialysis patients, but other pathways, such as arterial stiffness, activation of the renin-angiotensin-aldosterone and sympathetic nervous systems, endothelial dysfunction, sleep apnoea and the use of erythropoietin-stimulating agents may also be involved. Non-pharmacologic interventions targeting sodium and volume excess are fundamental for hypertension control in this population. If BP remains elevated after appropriate treatment of sodium and volume excess, the use of antihypertensive agents is necessary. Drug treatment in the dialysis population should take into consideration the patient's comorbidities and specific characteristics of each agent, such as dialysability. This document is an overview of the diagnosis, epidemiology, pathogenesis and treatment of hypertension in patients on dialysis, aiming to offer the renal physician practical recommendations based on current knowledge and expert opinion and to highlight areas for future research.

110 citations


Journal ArticleDOI
TL;DR: The European Expert Group pointed out the major unmet need of standardization of measurements, trial design and procedural performance, and the need for high-quality, collaborative research and openness to new methods for recruitment, patient selection, and assessment of outcomes will be able to establish incontrovertibly whether device therapies for hypertension are effective.
Abstract: The interest in RDN for hypertension has fluctuated recently, with a flurry of initial enthusiasm followed by sudden loss of interest by researchers and device manufacturers, with an almost as sudden resurgence in clinical trials activity and device innovation more recently. There is widespread consensus that this therapeutic strategy can be effective, at least for some of the technologies available. Major uncertainties remain as to the clinical role of RDN, and whether any of the emerging technologies such as AV-anastomosis formation, carotid body ablation, carotid bulb expansion, or baroreflex stimulation will have a future as effective treatment options in patients with hypertension. In our first consensus report in 2015, the European Expert Group pointed to the major unmet need of standardization of measurements, trial design and procedural performance.6 With the large number of different technologies currently in the pipeline, this need has even increased. Only through high-quality, collaborative research and openness to new methods for recruitment, patient selection, and assessment of outcomes will it be possible to establish incontrovertibly whether device therapies for hypertension are effective and what are preferred patient populations. Once the proof of concept is established, further studies with a design relevant to clinical reality will be needed to establish the place of new devices in the treatment armoury. The clinical and research community has a large responsibility to prove or disprove the value of new therapies, in order to ensure that antihypertensive devices provide future patients with the greatest benefit and the smallest risk. copy; The Author 2017. Published by Oxford University Press on behalf of the European Society of Cardiology.

96 citations


Journal ArticleDOI
TL;DR: One out of 4 patients with RfH have normal 24‐hour blood pressure and less target organ damage, thus indicating the important role of ambulatory blood pressure monitoring in guiding antihypertensive therapy in difficult‐to‐treat patients.
Abstract: BackgroundWe aimed to estimate the prevalence of refractory hypertension (RfH) and to determine the clinical differences between these patients and resistant hypertensives (RH). Secondly, we assess...

50 citations


Journal ArticleDOI
TL;DR: 2016 ESC Guideline for the diagnosis and treatment of acute and chronic heart failure and the special contribution of the Heart Failure Association is developed.
Abstract: 2016 ESC GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF ACUTE AND CHRONIC HEART FAILURE. The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC.

48 citations


Journal ArticleDOI
TL;DR: Compared with the normotensive group, WCH defined by normal daytime, night-time, and 24-h BP did not significantly differ in terms of other cardiovascular risk factors or organ damage.
Abstract: Background and aim:The prevalence and associated risks of white-coat hypertension (WCH) are still a matter of debate. We aimed to assess differences in prevalence and associated conditions of WCH defined on the basis of the normality of all daytime, night-time, and 24-h blood pressure (BP), only day

39 citations


Journal ArticleDOI
TL;DR: An overview of the diagnosis, epidemiology, pathogenesis and treatment of hypertension in patients on dialysis, aiming to offer the renal physician practical recommendations based on current knowledge and expert opinion and to highlight areas for future research as mentioned in this paper.
Abstract: In patients with end-stage renal disease treated with hemodialysis or peritoneal dialysis, hypertension is very common and often poorly controlled. Blood pressure (BP) recordings obtained before or after hemodialysis display a J-shaped or U-shaped association with cardiovascular events and survival, but this most likely reflects the low accuracy of these measurements and the peculiar hemodynamic setting related with dialysis treatment. Elevated BP by home or ambulatory BP monitoring is clearly associated with shorter survival. Sodium and volume excess is the prominent mechanism of hypertension in dialysis patients, but other pathways, such as arterial stiffness, activation of the renin-angiotensin-aldosterone and sympathetic nervous systems, endothelial dysfunction, sleep apnea and the use of erythropoietin-stimulating agents may also be involved. Nonpharmacologic interventions targeting sodium and volume excess are fundamental for hypertension control in this population. If BP remains elevated after appropriate treatment of sodium-volume excess, the use of antihypertensive agents is necessary. Drug treatment in the dialysis population should take into consideration the patient's comorbidities and specific characteristics of each agent, such as dialysability. This document is an overview of the diagnosis, epidemiology, pathogenesis and treatment of hypertension in patients on dialysis, aiming to offer the renal physician practical recommendations based on current knowledge and expert opinion and to highlight areas for future research.

37 citations


Journal ArticleDOI
TL;DR: In this paper, the potential capacity of metabolites to predict response to spironolactone was investigated, and a metabolic panel showing alteration before and after spironoline treatment and predicting future response of patients was shown.
Abstract: Resistant hypertension (RH) affects 9% to 12% of hypertensive adults. Prolonged exposure to suboptimal blood pressure control results in end-organ damage and cardiovascular risk. Spironolactone is the most effective drug for treatment, but not all patients respond and side effects are not negligible. Little is known on the mechanisms responsible for RH. We aimed to identify metabolic alterations in urine. In addition, a potential capacity of metabolites to predict response to spironolactone was investigated. Urine was collected from 29 patients with RH and from a group of 13 subjects with pseudo-RH. For patients, samples were collected before and after spironolactone administration and were classified in responders (n=19) and nonresponders (n=10). Nuclear magnetic resonance was applied to identify altered metabolites and pathways. Metabolites were confirmed by liquid chromatography-mass spectrometry. Citric acid cycle was the pathway most significantly altered (P<0.0001). Metabolic concentrations were quantified and ranged from ng/mL malate to μg/mL citrate. Citrate and oxaloacetate increased in RH versus pseudoresistant. Together with α-ketoglutarate and malate, they were able to discriminate between responders and nonresponders, being the 4 metabolites increased in nonresponders. Combined as a prediction panel, they showed receiver operating characteristiccurve with area under the curve of 0.96. We show that citric acid cycle and deregulation of reactive oxygen species homeostasis control continue its activation after hypertension was developed. A metabolic panel showing alteration before spironolactone treatment and predicting future response of patients is shown. These molecular indicators will contribute optimizing the rate of control of RH patients with spironolactone.

35 citations


Journal ArticleDOI
TL;DR: Exosomal protein alterations in hypertensive patients with albuminuria in the presence of chronic RAS suppression are examined to find novel clues underlying its development and constitute potential targets for drug development.
Abstract: // Laura Gonzalez-Calero 1 , Paula J. Martinez 1 , Marta Martin-Lorenzo 1 , Montserrat Baldan-Martin 2 , Gema Ruiz-Hurtado 3 , Fernando de la Cuesta 2 , Eva Calvo 4 , Julian Segura 3 , Juan Antonio Lopez 5 , Jesus Vazquez 5 , Maria G. Barderas 2 , Luis M. Ruilope 3 , Fernando Vivanco 1, 6 and Gloria Alvarez-Llamas 1 1 Department of Immunology, IIS-Fundacion Jimenez Diaz, REDinREN, Madrid, Spain 2 Department of Vascular Physiopathology, Hospital Nacional de Paraplejicos SESCAM, Toledo, Spain 3 Hypertension Unit, Instituto de Investigacion Imas12, Hospital Universitario 12 de Octubre, Madrid, Spain 4 Ibermutuamur, Madrid, Spain 5 Laboratory of Cardiovascular Proteomics CNIC, Madrid, Spain 6 Department of Biochemistry and Molecular Biology I, Universidad Complutense, Madrid, Spain Correspondence to: Gloria Alvarez-Llamas, email: galvarez@fjd.es Luis M. Ruilope, email: ruilope@ad-hocbox.com Keywords: exosomes, hypertension, albuminuria, renin-angiotensin system, proteomics Received: March 13, 2017 Accepted: April 20, 2017 Published: May 11, 2017 ABSTRACT Albuminuria is an indicator of cardiovascular risk and renal damage in hypertensive individuals. Chronic renin–angiotensin system (RAS) suppression facilitates blood pressure control and prevents development of new-onset-albuminuria. A significant number of patients, however, develop albuminuria despite chronic RAS blockade, and the physiopathological mechanisms are underexplored. Urinary exosomes reflect pathological changes taking place in the kidney. The objective of this work was to examine exosomal protein alterations in hypertensive patients with albuminuria in the presence of chronic RAS suppression, to find novel clues underlying its development. Patients were followed-up for three years and were classified as: a) patients with persistent normoalbuminuria; b) patients developing de novo albuminuria; and c) patients with maintained albuminuria. Exosomal protein alterations between groups were identified by isobaric tag quantitation (iTRAQ). Confirmation was approached by target analysis (SRM). In total, 487 proteins were identified with high confidence. Specifically, 48 proteins showed an altered pattern in response to hypertension and/or albuminuria. Out of them, 21 proteins interact together in three main functional clusters: glycosaminoglycan degradation, coagulation and complement system, and oxidative stress. The identified proteins constitute potential targets for drug development and may help to define therapeutic strategies to evade albuminuria progression in hypertensive patients chronically treated.

35 citations


Journal ArticleDOI
TL;DR: One in 3 very elderly treated hypertensive patients attended in usual clinical practice were potentially at risk of having hypotension according to daytime ABPM, and ABPM could be especially helpful for identifying ambulatory hypotension and avoiding overtreatment in patients with diabetes, heart disease, or on antihypertensive polytherapy.

31 citations


Journal ArticleDOI
TL;DR: The EMPA-REG OUTCOME study, with impressive cardiovascular mortality reduction with empagliflozin, suggested that reduction of SBP to around 130 mmHg is safe and might explain part of these beneficial results.
Abstract: In patients with diabetes mellitus, the presence of hypertension substantially increases the risk of cardiovascular events, and reductions in blood pressure (BP) can reduce cardiovascular morbidity and mortality. Following evidence from trials randomizing patients to diastolic BP levels, previous guidelines recommended an office BP target of <130/80 mmHg in individuals with diabetes mellitus. However, the evidence for this systolic BP (SBP) target was derived from observational studies. When the results of the ACCORD-BP study showed that those individuals with diabetes mellitus and a target BP of <120 mmHg had a cardiovascular risk that is similar to those with <140 mmHg, all guidelines returned to a recommended SBP of <140 mmHg. However, the ACCORD-BP trial was limited by the low number of cardiovascular events observed, whereas the mean SBP in the 'conventional' arm was 133 mmHg. The SPRINT study, showing cardiovascular benefits in hypertensive patients without diabetes mellitus randomized to SBP <120 mmHg versus those randomized to <140 mmHg, came in contrast with the ACCORD-BP, but a detailed evaluation reveals many similarities between the two trials. Finally, the EMPA-REG OUTCOME study, with impressive cardiovascular mortality reduction with empagliflozin, suggested that reduction of SBP to around 130 mmHg is safe and might explain part of these beneficial results. In this Review, we evaluate the implications of the ACCORD-BP, SPRINT and EMPA-REG OUTCOME trials and previous studies for the optimal BP target in diabetes mellitus.

30 citations


Journal ArticleDOI
TL;DR: The epidemiological and management trends and patterns in hypertension that may be specific or more common to Latin-American populations - what the authors term 'Latin American characteristics' of hypertension - are discussed via a review of the recent literature.

Journal ArticleDOI
TL;DR: BPV is increased in interdialytic Day 2 compared with Day 1 in hemodialysis patients; this could be another mechanism involved in the complex cardiovascular pathophysiology and increased cardiovascular mortality of these individuals.
Abstract: Objectives:Patients with end-stage renal-disease under hemodialysis have increased cardiovascular risk and experience severe blood pressure (BP) fluctuations during the dialysis session and the subsequent interdialytic period. BP variability (BPV) may be an additional risk factor for cardiovascular

Journal ArticleDOI
TL;DR: In this large study in usual clinical practice, clinic BP misclassified hypertension status in >40% of patients, and this misclassification was not importantly influenced by age but was more evident in patients with borderline/grade 1 hypertension.
Abstract: Clinic blood pressure (BP) is usually higher than daytime ambulatory BP in hypertensive patients, but some recent studies have challenged this view, suggesting that this relationship is strongly influenced by age. We used the Spanish ambulatory BP monitoring cohort to examine differences between clinic and daytime BP by age among 104 639 adult hypertensive patients (office systolic/diastolic BP ≥140/90 mm Hg or treated) in usual primary-care practice, across the wide age spectrum. To assess the impact of age, cardiovascular variables, and clinic BP on the clinic–daytime BP differences, we built multivariable regression models of the average BP differences, white-coat hypertension (high clinic BP and normal daytime BP), and masked hypertension (normal clinic BP and high daytime BP). In most patients, mean clinic BP values were higher than daytime BP at all ages. Some 36.7% of patients had white-coat hypertension (amounting to 50% at clinic systolic BP of 140–159 mm Hg) and 3.9% had masked hypertension (amounting to 18% at clinic systolic BP of 130–139 mm Hg). Age explained 0.1% to 1.7% of the variance of quantitative or categorical BP differences ( P P P 40% of patients. This misclassification was not importantly influenced by age but was more evident in patients with borderline/grade 1 hypertension. These findings reinforce the importance of ambulatory BP monitoring for defining BP status in routine clinical practice.

Journal ArticleDOI
TL;DR: In community-dwelling older adults, frailty and disability were independently associated with lower diurnal BP, blunted nocturnal decline of SBP, and higherNocturnal SBP.

Journal ArticleDOI
TL;DR: This analysis of patients with and without OSA evaluated the blood pressure-lowering effect of sympathetic modulation by renal denervation (RDN) in a real-world setting, and found that RDN resulted in significant BP reductions at 6 months in hypertensive patients with a history of hypertension and regardless of continuous positive airway pressure usage in OSA patients.
Abstract: Background:Sleep-disordered breathing, predominantly obstructive sleep apnea (OSA), is highly prevalent in patients with hypertension OSA may underlie the progression to resistant hypertension, partly due to increased activation of the sympathetic nervous system This analysis of patients with and

Journal ArticleDOI
TL;DR: Proteomic analysis of circulating extracellular vesicles showed two proteins, kalirin and chromodomain-helicase-DNA-binding protein 7 (CHD7), increased in albuminuric patients, and they are proposed as novel endothelial dysfunction markers to monitor vascular condition in hypertensive patients with albuminuria.
Abstract: // Fernando de la Cuesta 1, 6 , Montserrat Baldan-Martin 1 , Rafael Moreno-Luna 1 , Gloria Alvarez-Llamas 2 , Laura Gonzalez-Calero 2 , Laura Mourino-Alvarez 1 , Tamara Sastre-Oliva 1 , Juan A. Lopez 3 , Jesus Vazquez 3 , Gema Ruiz-Hurtado 4 , Julian Segura 4 , Fernando Vivanco 2, 5 , Luis M. Ruilope 4 , Maria G. Barderas 1 1 Department of Vascular Physiopathology, Hospital Nacional de Paraplejicos (HNP), SESCAM, Toledo, Spain 2 Department of Immunology, IIS-Fundacion Jimenez Diaz, Madrid, Spain 3 Unidad de Proteomica CNIC, Madrid, Spain 4 Unidad de Hipertension, Instituto de Investigacion i + 12, Hospital Universitario 12 de Octubre, Madrid, Spain 5 Departamento de Bioquimica y Biologia Molecular I, Universidad Complutense, Madrid, Spain 6 Current address: Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK Correspondence to: Maria G. Barderas, email: megonzalezb@sescam.jccm.es Luis M. Ruilope, email: ruilope@ad-hocbox.com Keywords: extracellular vesicles, proteomics, endothelial dysfunction, hypertension, albuminuria Received: August 17, 2016 Accepted: December 05, 2016 Published: February 01, 2017 ABSTRACT Despite of the great advances in anti-hypertensive therapies, many patients under Renin-Angiotensin- System (RAS) suppression develop albuminuria, which is a clear indicator of therapeutic inefficiency. Hence, indicators of vascular function are needed to assess patients’ condition and help deciding future therapies. Proteomic analysis of circulating extracellular vesicles (EVs) showed two proteins, kalirin and chromodomain-helicase-DNA-binding protein 7 (CHD7), increased in albuminuric patients. A positive correlation of both with the expression of the endothelial activation marker E-selectin was found in EVs. In vitro analysis using TNFα-treated adult human endothelial cells proved their involvement in endothelial cell activation. Hence, we propose protein levels of kalirin and CHD7 in circulating EVs as novel endothelial dysfunction markers to monitor vascular condition in hypertensive patients with albuminuria.

Journal ArticleDOI
TL;DR: Results in preclinical studies showed that lower doses of finerenone were needed to achieve similar cardiorenal protective effects compared to both spironolactone and eplerenone, so further, large-scale, long-term phase III trials are needed to confirm whether the greater affinity and selectivity is translated into improved clinical outcomes.
Abstract: Finerenone is a novel selective nonsteroidal mineralocorticoid receptor antagonist Results in preclinical studies showed that lower doses of finerenone were needed to achieve similar cardiorenal protective effects compared to both spironolactone and eplerenone and phase II studies in finerenone in patients with heart failure, type-2 diabetes mellitus and/or chronic kidney disease are encouraging as the drug is effective and safe in patients on renin–angiotensin system inhibitors (significant reduction in albuminuria and a low rate of hyperkalemia), but the primary end points were “soft” end points (serum potassium, estimated glomerular filtration rate, albuminuria, N-terminal prohormone B-type natriuretic peptide levels) Thus, further, large-scale, long-term phase III trials are needed to confirm whether the greater affinity and selectivity is translated into improved clinical outcomes

Journal ArticleDOI
TL;DR: An analysis of the SPRINT data, focusing on patient characteristics, blood-pressure measurement method, and applicability of the findings for future management guidelines, concludes that the results can be applied to other patient populations and geographical areas.
Abstract: SPRINT is the first randomized, controlled trial showing that a systolic blood-pressure goal of <120 mmHg can be attained with cardiovascular benefits in a select group of patients with hypertension and an elevated cardiovascular risk with different origins. Although the patient population with characteristics like those in SPRINT makes up only 20-30% of the total hypertensive population, SPRINT is a landmark study that highlights the need to consider lower blood- pressure goals in the treatment of hypertension. Extending this study to include other patient populations and geographical areas is the next step for evaluating the benefits of strict blood-pressure targets and the generalizability of the SPRINT results. Importantly, the blood-pressure measurement method used in SPRINT differs from previous clinical trials, and raises the issue of whether a more accurate method should be used in clinical trials and if such method is feasible in clinical practice. This Perspectives article provides an analysis of the SPRINT data, focusing on patient characteristics, blood-pressure measurement method, and applicability of the SPRINT findings for future management guidelines.

Journal ArticleDOI
TL;DR: Predictors of new onset microalbuminuria are the classical cardiovascular risk factors, followed by age, weight, glycosylated hemoglobin type A1C, blood glucose, total cholesterol, SBP number of antihypertensive drugs and heart rate.
Abstract: Aim:It is important to know which factors predict the development of microalbuminuria in patients with diabetes mellitus type II.Material:Data from the Randomized Olmesartan and Diabetes Microalbuminuria Prevention Study were used to identify predictors for the new onset of microalbuminuria. Further

Journal ArticleDOI
TL;DR: The MMP-9–TIMP-1 AlphaLISA® assay is quick, highly simplified, and cost-effective and can be completed in less than 3 h and has great potential for use in basic and preclinical research as it allows direct determination of native M MP-9-TIMp-1 complexes in circulating blood as biofluid.
Abstract: The protocol describes a novel, rapid and no-wash one-step immunoassay for highly sensitive and direct detection of the complexes between matrix metalloproteinases (MMPs) and their tissue inhibitor of metalloproteinases (TIMPs) based on AlphaLISA® technology. We describe two procedures: i) one approach is used to analyze MMP-9-TIMP-1 interactions using recombinant human MMP-9 with its corresponding recombinant human TIMP-1 inhibitor; ii) the second approach is used to analyze native or endogenous MMP-9-TIMP-1 protein interactions in samples of human plasma. Evaluating native MMP-9-TIMP-1 complexes using this approach avoids the use of indirect calculations of the MMP-9/TIMP-1 ratio for which independent MMP-9 and TIMP-1 quantifications by two conventional ELISAs are needed. The MMP-9-TIMP-1 AlphaLISA® assay is quick, highly simplified and cost-effective, and can be completed in less than 3 hours. Moreover, the assay has great potential for use in basic and preclinical research as it allows direct determination of native MMP-9–TIMP-1 complexes in circulating blood as biofluid.

Journal ArticleDOI
TL;DR: Central BP raises and BP pulsatility appear and contribute to further damage renal microcirculation by direct transmission of the elevated BP.

Journal ArticleDOI
TL;DR: Specific links between immune response and controlled hypertension in patients who develop albuminuria are revealed, pointing to potential protein targets for novel and future therapeutic interventions.
Abstract: Albuminuria development in hypertensive patients is an indicator of higher cardiovascular (CV) risk and renal damage. Chronic renin-angiotensin system (RAS) suppression facilitates blood pressure control but it does not prevent from albuminuria development. We pursued the identification of protein indicators in urine behind albuminuria development in hypertensive patients under RAS suppression. Urine was collected from 100 patients classified in three groups according to albuminuria development: (a) patients with persistent normoalbuminuria; (b) patients developing de novo albuminuria; (c) patients with maintained albuminuria. Quantitative analysis was performed in a first discovery cohort by isobaric labeling methodology. Alterations of proteins of interest were confirmed by target mass spectrometry analysis in an independent cohort. A total of 2416 proteins and 1223 functional categories (coordinated protein responses) were identified. Immune response, adhesion of immune and blood cells, and phagocytosis were found significantly altered in patients with albuminuria compared to normoalbuminuric individuals. The complement system C3 increases, while Annexin A1, CD44, S100A8 and S100A9 proteins showed significant diminishment in their urinary levels when albuminuria is present. This study reveals specific links between immune response and controlled hypertension in patients who develop albuminuria, pointing to potential protein targets for novel and future therapeutic interventions.

Journal ArticleDOI
TL;DR: The very recent American College of Physicians/American Academy of Family Practitioners guidelines were put together by a set of authors and consultants without any expertise in the topic under discussion, that is, hypertension.
Abstract: Several sets of guidelines have been published recently and more are in the works. The very recent American College of Physicians/American Academy of Family Practitioners guidelines were put together by a set of authors and consultants without any expertise in the topic under discussion, that is, hypertension. Although we are not maintaining that all guidelines should be written exclusively by experts, complete lack of expertise among guideline authors is not acceptable.

Journal ArticleDOI
TL;DR: It is important to examine the practical aspects of treating patients with these new lipid-lowering agents, to ensure they are optimally deployed in everyday clinical practice.
Abstract: Suboptimal drug adherence represents a major challenge to effective primary and secondary prevention of cardiovascular disease. While adherence is influenced by multiple considerations, polypharmacy and dosing frequency appear to be rate-limiting factors in patient satisfaction and subsequent adherence. The cardiovascular and metabolic therapeutic areas have recently benefited from a number of advances in drug therapy, in particular protease proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and incretin-based therapies, respectively. These drugs are administered subcutaneously and offer efficacious treatment options with reduced dosing frequency. Whilst patients with diabetes and diabetologists are well initiated to injectable therapies, the cardiovascular therapeutic arena has traditionally been dominated by oral agents. It is therefore important to examine the practical aspects of treating patients with these new lipid-lowering agents, to ensure they are optimally deployed in everyday clinical practice.

Journal ArticleDOI
TL;DR: The data of the paper indicate that sacubitril/valsartan improves the prognosis of hypertensive patients through an improvement in the heart and big arteries, which could provide a therapeutic advantage.
Abstract: In the current issue of European Heart Journal, Schmieder et al. compare the capacity of sacubitril/valsartan to olmesartan on arterial stiffness and left ventricular (LV) remodelling in a group of 114 hypertensive patients. The dual action drug decreases LV mass index significantly more at 12 and 52 weeks of follow-up. These differences remained after adjusting for changes in systolic blood pressure (BP). This was also accompanied by a larger reduction in central pulse pressure obtained in the sacubitril/valsartan group. The authors consider that these findings indicate that the addition of sacubitril to an angiotensin receptor blocker (ARB), valsartan, has valuable advantages compared with the ARB olmesartan administered alone. Furthermore, these positive changes did not seem to depend on the systolic BP drop and could be considered as independent of the BPlowering capacity of sacubitril/valsartan. Since the publication of the first comparison of sacubitril/valsartan to valsartan in a proof of concept trial, it has been clearly established that compared to monotherapy with other ARBs, fundamentally valsartan and olmesartan and with amlodipine, the dual combination is superior. These results created great expectations on the use of sacubitril/valsartan in arterial hypertension by considering that the combination with amlodipine, and if needed with a diuretic, would significantly improve the percentage of patients attaining an adequate control of BP to values below 140/90 mmHg. In this sense, recent publications in Asian populations have shown the good effect of sacubitril/valsartan in salt-sensitive hypertension, severe hypertension, and hypertension accompanying chronic kidney disease (CKD). More recent data, in the PARAMETER (Comparison of Angiotensin Receptor Neprilysin Inhibitor with Angiotensin Receptor Blocker Measuring Arterial Stiffness in the Elderly) study, investigated the effects on central aortic pressure of sacubitril/valsartan compared to olmesartan in elderly patients with systolic hypertension and pulse pressure above 60 mmHg. The results demonstrated a greater reduction in clinic and ambulatory central aortic and brachial pressure in patients with stiff arteries, which could provide a therapeutic advantage. Regression of different types of target organ damage accompanying arterial hypertension, including LV hypertrophy, albuminuria, carotid plaques, and increased pulse wave velocity, are considered as positive strategies to improve the prognosis of cardiovascular and renal disease in arterial hypertension. Take home figure outlines the effect of sacubitril/valsartan on the four main classes of target organ damage. The data of the paper to which this editorial is dedicated, together with those of Williams et al., indicate that sacubitril/valsartan improves the prognosis of hypertensive patients through an improvement in the heart and big arteries. No data are available with respect to changes in carotid plaques during the administration of sacubitril/valsartan. On the other hand, the potential capacity of sacubitril/valsartan for renal protection has been poorly investigated in humans. Data from a study performed in Japan showed a reduction of urine albumin/creatinine ratio by 15.1%, which is inferior to what is required for renal and cardiovascular protection. A small but significant increase in urine albumin/creatinine ratio with the administration of sacubitril/valsartan in heart failure with preserved ejection fraction (HFpEF) patients has also been described. Ongoing studies will answer the question of the capacity of the dual action drug to diminish albuminuria to an adequate degree while protecting from the progression of CKD. In the meantime, the publication of the PARADIGM (Prospective Comparison of ARNI to Determine Impact of Global Mortality and Morbidity in Heart Failure Trial) study has shown the excellent capacity of sacubitril/valsartan, when compared to enalapril, to very significantly improve the prognosis of patients with heart failure with reduced ejection fraction (HFrEF),

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TL;DR: Several possible pharmacological reasons that may explain the lack of success to develop new drugs and the pharmacological challenges to overcome in the future to developed new more effective and safer drugs for the treatment of AHFS are reviewed.

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TL;DR: This article will discuss chemical therapies for hypertension in patients with diabetes, based on currently available evidence on the effects of antihypertensive treatment on metabolic profile and renal endpoints, and suggests an ACEI or an ARB, if tolerated, should be the first choice in diabetic individuals.
Abstract: Introduction: Hypertension and diabetes are two of the most important modifiable risk factors for cardiovascular and renal disease. The majority of patients with diabetes also have high blood pressure (BP) and the presence of hypertension in these patients dramatically increases cardiovascular and renal risk.Areas covered: This article will discuss chemical therapies for hypertension in patients with diabetes, based on currently available evidence on the effects of antihypertensive treatment on metabolic profile and renal endpoints that are the factors mostly influencing drug choice.Expert opinion: Several lines of evidence suggest that angiotensin-converting-enzyme-inhibitors (ACEIs), angiotensin-receptor-blockers (ARBs) and calcium-channel-blockers (CCBs) have beneficial or neutral effects on carbohydrate metabolism, whereas old β-blockers and thiazide diuretics have not. Renal outcome trials clearly suggest that in proteinuric diabetic CKD ACEIs and ARBs reduce the rate of disease progression. ...

Journal ArticleDOI
TL;DR: In a large clinical sample of older hypertensive patients, the cutoff point of 24-h PP that best predicts office PP at least 60 mmHg is 55 mmHg, which is slightly higher than the European Guidelines on Hypertension target.
Abstract: OBJECTIVE The European Guidelines on Hypertension define an office pulse pressure (PP) at least 60 mmHg in the elderly patient as asymptomatic organ damage. Our objective was to estimate the cutoff point of 24-h PP that best predicts office PP associated with higher cardiovascular risk (≥60 mmHg) in hypertensive older patients. METHODS We studied all hypertensive patients at least 60 years with a first valid ambulatory blood pressure monitoring drawn from the Spanish ambulatory blood pressure monitoring registry. Receiver operating characteristic curves were used to estimate the best 24-h PP cutoff predictor of office PP at least 60 mmHg that maximized the sum of sensitivity and specificity. RESULTS We included 52 246 hypertensive patients [52.4%, female; mean age (SD) 69.0 (7.0) years]. From these, 34 530 (66.1%) patients had an office PP at least 60 mmHg. The value of 24-h PP that best predicts higher risk clinic PP is 54.9 mmHg [sensitivity: 69.2%; specificity: 70.3%; area under the receiver operating characteristic curve of 0.761 (95% confidence interval 0.756-0.765)]. Mean clinic and 24-h PPs were progressively higher as the study participants were classified at higher cardiovascular risk group. Some 20.5% of patients presented isolated office high PP and 10% a masked high 24-h PP. CONCLUSION In a large clinical sample of older hypertensive patients, the cutoff point of 24-h PP that best predicts office PP at least 60 mmHg is 55 mmHg. In 30.5% of cases, there is a discrepancy between office PP and ambulatory 24-h PP.

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TL;DR: Strict BP control to values of systolic BP around 120 mmHg was recently shown to be safe in CKD according to data from the SPRINT trial, albeit more data confirming this benefit are required.
Abstract: Arterial hypertension and chronic kidney disease (CKD) are intimately related. The control of blood pressure (BP) levels is strongly recommended in patients with CKD in order to protect the kidney against the accompanying elevation in global cardiovascular (CV) risk. Actually, the goal BP in patients with CKD involves attaining values <140/90 mmHg except if albuminuria is present. In this case, it is often recommended to attain values <130/80 mmHg, although some guidelines still recommend <140/90 mmHg. Strict BP control to values of systolic BP around 120 mmHg was recently shown to be safe in CKD according to data from the SPRINT trial, albeit more data confirming this benefit are required. Usually, combination therapy initiated with an angiotensin receptor blocker (ARB) or angiotensin-converting enzyme inhibitor (ACEi) and commonly followed by the addition of a calcium channel blocker and a diuretic is needed. Further studies are required as well as new drugs in particular after the positive data obtained from new oral anti-diabetic drugs.

Journal ArticleDOI
TL;DR: The Free Dictionary defines expertise as "special skills or knowledge acquired by a person through education, training, or experience" as mentioned in this paper, which can be used to assess the quality and quantity of expertise of a guideline author.
Abstract: See Related Editorial, pp 238–239 > Quis custodiet ipsos custodes?—Who will guard the guards themselves? > > —Decimus Iunius Iuvenalis (Juvenal), 1st–2nd century AD, Satire VI, lines 347–348 Guidelines are traditionally scripted by a panel of experts who are intimately familiar with the topic in question. Practicing physicians inherently trust guideline authors and rarely ever question their expertise, especially when guidelines are endorsed by such venerable societies as the American College of Physicians (ACP) and the American Academy of Family Practitioners (AAFP) and are published in high-impact journals, such as the Annals of Internal Medicine . The >250 000 members of the ACP and AAFP have come to expect that any set of clinically meaningful guidelines has been put together by authors who were selected because of their outstanding skills and expertise pertaining to the topic in question. Thus, there is little if any reason to voice doubt as to the validity of published guidelines The Free Dictionary defines expertise as special skills or knowledge acquired by a person through education, training, or experience. For a physician unfamiliar with the experts, there are several simple ways to get a grasp on the quality and quantity of expertise: 1. One can scrutinize the publication list of the experts to assess how often they have been involved with the guideline topic. Any expert is expected to be well published in the specific area of the expertise. 2. One may take into account an expert’s membership in professional organizations pertaining to the subject matter. Obviously, membership and participation in annual meetings demonstrates an ongoing interest in the guideline topic. 3. One may examine whether the physician/scientist has been invited to serve on editorial boards of journals dealing with the topic in question. Being a member of an editorial board and peer reviewing submissions attest to some expertise pertaining to the …