Influence of Perivascular Adipose Tissue on Microcirculation: A Link Between Hypertension and Obesity.

Alterations in microcirculation play a crucial role in the pathogenesis of cardiovascular and metabolic disorders such as obesity and hypertension. The small resistance arteries of these patients show a typical remodeling, as indicated by an increase of media or total wall thickness to lumen diameter ratio that impairs organ flow reserve. The majority of blood vessels are surrounded by a fat depot which is termed perivascular adipose tissue (PVAT). In recent years, data from several studies have indicated that PVAT is an endocrine organ that can produce a variety of adipokines and cytokines, which may participate in the regulation of vascular tone, and the secretory profile varies with adipocyte phenotype and disease status. The PVAT of lean humans largely secretes the vasodilator adiponectin, which will act in a paracrine fashion to reduce peripheral resistance and improve nutrient uptake into tissues, thereby protecting against the development of hypertension and diabetes. In obesity, PVAT becomes enlarged and inflamed, and the bioavailability of adiponectin is reduced. The inevitable consequence is a rise in peripheral resistance with higher blood pressure. The interrelationship between obesity and hypertension could be explained, at least in part, by a cross-talk between microcirculation and PVAT. In this article, we propose an integrated pathophysiological approach of this relationship, in order to better clarify its role in obesity and hypertension, as the basis for effective and specific prevention and treatment.

The Results of the URRAH (Uric Acid Right for Heart Health) Project: A Focus on Hyperuricemia in Relation to Cardiovascular and Kidney Disease and its Role in Metabolic Dysregulation.

The relationship between Serum Uric Acid (UA) and Cardiovascular (CV) diseases has already been extensively evaluated, and it was found to be an independent predictor of all-cause and cardiovascular mortality but also acute coronary syndrome, stroke and heart failure. Similarly, also many papers have been published on the association between UA and kidney function, while less is known on the role of UA in metabolic derangement and, particularly, in metabolic syndrome. Despite the substantial number of publications on the topic, there are still some elements of doubt: (1) the better cut-off to be used to refine CV risk (also called CV cut-off); (2) the needing for a correction of UA values for kidney function; and (3) the better definition of its role in metabolic syndrome: is UA simply a marker, a bystander or a key pathological element of metabolic dysregulation?. The Uric acid Right for heArt Health (URRAH) project was designed by the Working Group on uric acid and CV risk of the Italian Society of Hypertension to answer the first question. After the first papers that individuates specific cut-off for different CV disease, subsequent articles have been published responding to the other relevant questions. This review will summarise most of the results obtained so far from the URRAH research project.

Patient phenotype profiling in heart failure with preserved ejection fraction to guide therapeutic decision making. A scientific statement of the Heart Failure Association, the European Heart Rhythm Association of the European Society of Cardiology, and the European Society of Hypertension.

Heart failure with preserved ejection fraction (HFpEF) represents a highly heterogeneous clinical syndrome affected in its development and progression by many comorbidities. The left ventricular diastolic dysfunction may be a manifestation of various combinations of cardiovascular, metabolic, pulmonary, renal, and geriatric conditions. Thus, in addition to treatment with sodium-glucose cotransporter 2 inhibitors in all patients, the most effective method of improving clinical outcomes may be therapy tailored to each patient's clinical profile. To better outline a phenotype-based approach for the treatment of HFpEF, in this joint position paper, the Heart Failure Association of the European Society of Cardiology, the European Heart Rhythm Association and the European Hypertension Society, have developed an algorithm to identify the most common HFpEF phenotypes and identify the evidence-based treatment strategy for each, while taking into account the complexities of multiple comorbidities and polypharmacy.

2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA).

DOCUMENT REVIEWERS: Luis Alcocer (Mexico), Christina Antza (Greece), Mustafa Arici (Turkey), Eduardo Barbosa (Brazil), Adel Berbari (Lebanon), Luís Bronze (Portugal), John Chalmers (Australia), Tine De Backer (Belgium), Alejandro de la Sierra (Spain), Kyriakos Dimitriadis (Greece), Dorota Drozdz (Poland), Béatrice Duly-Bouhanick (France), Brent M. Egan (USA), Serap Erdine (Turkey), Claudio Ferri (Italy), Slavomira Filipova (Slovak Republic), Anthony Heagerty (UK), Michael Hecht Olsen (Denmark), Dagmara Hering (Poland), Sang Hyun Ihm (South Korea), Uday Jadhav (India), Manolis Kallistratos (Greece), Kazuomi Kario (Japan), Vasilios Kotsis (Greece), Adi Leiba (Israel), Patricio López-Jaramillo (Colombia), Hans-Peter Marti (Norway), Terry McCormack (UK), Paolo Mulatero (Italy), Dike B. Ojji (Nigeria), Sungha Park (South Korea), Priit Pauklin (Estonia), Sabine Perl (Austria), Arman Postadzhian (Bulgaria), Aleksander Prejbisz (Poland), Venkata Ram (India), Ramiro Sanchez (Argentina), Markus Schlaich (Australia), Alta Schutte (Australia), Cristina Sierra (Spain), Sekib Sokolovic (Bosnia and Herzegovina), Jonas Spaak (Sweden), Dimitrios Terentes-Printzios (Greece), Bruno Trimarco (Italy), Thomas Unger (The Netherlands), Bert-Jan van den Born (The Netherlands), Anna Vachulova (Slovak Republic), Agostino Virdis (Italy), Jiguang Wang (China), Ulrich Wenzel (Germany), Paul Whelton (USA), Jiri Widimsky (Czech Republic), Jacek Wolf (Poland), Grégoire Wuerzner (Switzerland), Eugene Yang (USA), Yuqing Zhang (China).

Cardiac Phenotypes in Secondary Hypertension: JACC State-of-the-Art Review.

Several forms of secondary hypertension carry a high risk of cardiac morbidity and mortality. Evaluation of cardiac phenotypes in secondary hypertension provides a unique opportunity to study underlying hormonal and biochemical mechanisms affecting the heart. We review the characteristics of cardiac dysfunction in different forms of secondary hypertension and clarify the mechanisms behind the higher prevalence of heart damage in these patients than in those with primary hypertension. Attention to the specific clinical/biochemical phenotypes of these conditions may assist clinicians to screen for and confirm secondary forms of hypertension. Thereby, early signs of heart damage can be recognized and monitored, allowing individualized treatment to delay or prevent evolution toward more advanced disease.

Real-world Antihypertensive Treatment Patterns, Treatment Adherence, and Blood Pressure Control in the Elderly: An Italian Awareness-raising Campaign on Hypertension by Senior Italia FederAnziani, the Italian Society of Hypertension and the Italian Federation of General Practitioners.

INTRODUCTION: Achieving hypertension control is beneficial regardless of age. Fixed-combination pills have the potential of increasing adherence to treatment, improving the benefit/risk ratio, and simplifying therapy, with resulting convenience especially in the elderly. AIM: We examined real-world antihypertensive treatment adherence and hypertension control rates in a cohort of Italian elderly individuals, enrolled in a prospective, pragmatic awareness-raising campaign on blood pressure (BP). METHODS: 13196 treated hypertensive elderly (mean age 73.2±7.5 years, 55.5% women) were recruited through opportunistic sampling, answered a brief questionnaire on antihypertensive therapy, and were followed-up for 6 months, when BP was measured as per routine care. Controlled hypertension was defined as BP < 140/90 mmHg. Real-world treatment adherence and hypertension control rates were evaluated at 6 months according to different treatment patterns (fixed-dose versus free combinations), using Yates correction for continuity to assess likelihood estimates for differences between treatments. RESULTS: 10551 participants (80%) were on a single-pill therapy and 3445 were on a fixed combination therapy of two (24.8%) or three (1.3%) drugs. Individuals on a fixed combination therapy were more adherent to treatment than the counterparts (p < 0.001). Full adherence increased with the number of drugs/pill among single-pill users (47.5%, 68.5%, and 100% with 1, 2, or 3 drugs/pill; p < 0.001). Hypertension control rates were 70% and 65.2% (p = 0.001) according to fixed or free combinations of two drugs and 71% and 63.9% (p = 0.321) for fixed or free combinations of three drugs. CONCLUSIONS: Real-world data suggest that simplified treatment strategies and use of fixed combinations improve adherence to antihypertensive therapy and BP control in the elderly.

The Vobarno Study.

The Vobarno Study represents the first observational study aimed to assess in a general population sample the relationship between parameters of cardiac and vascular structure (and function) and blood pressure values, measured in the clinic and during the 24 hours. In the frame of The Vobarno Study blood samples for hematochemistry and DNA extraction, clinic and 24-hour blood pressure measurements, cardiac and carotid ultrasound, and aortic stiffness were measured in all subjects, living in a small town (Vobarno) between Brescia and the Garda Lake (Italy), and randomly selected from electoral roles. In this sample of a general population an extensive evaluation of organ damage, including left ventricular (LV) mass and hypertrophy, LV systolic function, left atrial dimensions and aortic root diameters, carotid intima media thickness (IMT) and carotid plaques, carotid and aortic stiffness were performed. In this study subjects were included in a long follow-up, lasting 25 years, and cardiovascular morbility and mortality were assessed up to 2019. This will allow to update the information related to cardiovascular morbidity and mortality in the study cohort. The present paper will report the results of some analyses performed, exploring epidemiological and clinical aspects of target organ damage.

Chronic kidney disease and cardiovascular mortality in patients with atrial fibrillation: European Society of Hypertension project - ESH A Fib.

ABSTRACT: Our aim was to analyze characteristics of atrial fibrillation (AF) patients with chronic kidney disease (CKD) from the Croatian cohort of the ESH A Fib survey and to determine the association of estimated glomerular filtration rate (eGFR) with cardiovascular (CV) mortality after 24 months of follow-up.Consecutive sample of 301 patients with AF were enrolled in the period 2014 to 2018. Hypertension was defined as BP > 140/90 mm Hg and/or antihypertensive drugs treatment, CKD was defined as eGFR (CKD Epi) < 60 ml/min/1.73 m2 which was confirmed after 3 months.CKD was diagnosed in 45.2% of patients (13.3% in CKD stage > 3b). CKD patients were older than non-CKD and had significantly more frequent coronary heart disease, heart failure and valvular disease. CKD patients had significantly higher CHA2DS2-VASc score and more CKD than non-CKD patients had CHA2DS2-VASc > 2. Crude CV mortality rate per 1000 population at the end of the first year of the follow-up was significantly higher in CKD vs non-CKD group who had shorter mean survival time. CV mortality was independently associated with eGFR, male gender, CHA2DS2VASc and R2CHA2DS2VASc scores.Prevalence of CKD, particularly more advanced stages of CKD, is very high in patients with AF. Observed higher CV mortality and shorter mean survival time in CKD patients could be explained with higher CHA2DS2VASc score which is a consequence of clustering of all score components in CKD patients. However, eGFR was independently associated with CV mortality. In our cohort, R2CHA2DS2VASc score was not associated significantly more with CV mortality than CHA2DS2VASc score.

Effect of direct renin inhibition on vascular function after long-term treatment with aliskiren in hypertensive and diabetic patients.

OBJECTIVE: We tested the hypothesis that chronic treatment with the direct renin inhibitor aliskiren improves vascular function in resistance and conduit arteries of type two diabetic and hypertensive patients. METHOD: Sixteen patients with mild essential hypertension and with a previous diagnosis of noninsulin-dependent diabetes mellitus were included in the study. Patients were then randomized to aliskiren (150 mg once daily, n = 9), or ramipril (5 mg once daily, n = 7). Each patient underwent a biopsy of the subcutaneous tissue and small arteries were dissected and mounted on a pressurized micromyograph to evaluate endothelium dependent vasorelaxation in response to acetylcholine ±â€ŠN omega-nitro-L-arginine methyl ester hydrochloride in vessels precontracted with norepinephrine. Endothelial function has been quantified also in large conduit arteries by flow-mediated dilation. RESULTS: A similar office blood pressure-lowering effect was observed with the two drugs, although changes in DBP were not statistically significant in the ramipril group. Aliskiren significantly improved endothelium-dependent relaxation in subcutaneous resistance arteries, as well as increased flow-mediated dilation in conduit arteries, whereas the effects induced by ramipril did not reach statistical significance. Only aliskiren significantly increased the expression of p1177-endothelial nitric oxide synthase in the endothelium. Both aliskiren and ramipril had a negligible effect on markers of oxidative stress. CONCLUSION: Aliskiren restored endothelial function and induced a more prompt peripheral vasodilation in hypertensive and diabetic patients possibly through the increased production of nitric oxide via the enhanced expression and function of the active phosphorylated form of endothelial nitric oxide synthase.

Hyperuricaemia and gout in cardiovascular, metabolic and kidney disease.

During the last century, there has been an increasing prevalence of hyperuricaemia noted in many populations. While uric acid is usually discussed in the context of gout, hyperuricaemia is also associated with hypertension, chronic kidney disease, hypertriglyceridaemia, obesity, atherosclerotic heart disease, metabolic syndrome, and type 2 diabetes. Here we review the connection between hyperuricaemia and cardiovascular, kidney and metabolic diseases. Contrary to the popular view that uric acid is an inert metabolite of purine metabolism, recent studies suggest serum uric acid may have a variety of pro-inflammatory, pro-oxidative and vasoconstrictive actions that may contribute to cardiometabolic diseases. Hyperuricaemia is a predictive factor for the development of hypertension, metabolic syndrome, type 2 diabetes, coronary artery disease, left ventricular hypertrophy, atrial fibrillation, myocardial infarction, stroke, heart failure and chronic kidney disease. Treatment with uric acid-lowering therapies has also been found to improve outcomes in patients with hypertension and kidney disease, in some but not all studies. In conclusion, uric acid is emerging as a potentially treatable risk factor for cardiometabolic diseases, and more clinical trials investigating the potential benefit of lowering serum uric acid are recommended in individuals with hyperuricaemia with and without deposition and concomitant hypertension, metabolic syndrome or chronic kidney disease.

Nutraceuticals and blood pressure control: a European Society of Hypertension position document.

: High-normal blood pressure (BP) is associated with an increased risk of cardiovascular disease, however the cost-benefit ratio of the use of antihypertensive treatment in these patients is not yet clear. Some dietary components and natural products seems to be able to significantly lower BP without significant side effects. The aim of this position document is to highlight which of these products have the most clinically significant antihypertensive action and wheter they could be suggested to patients with high-normal BP. Among foods, beetroot juice has the most covincing evidence of antihypertensive effect. Antioxidant-rich beverages (teas, coffee) could be considered. Among nutrients, magnesium, potassium and vitamin C supplements could improve BP. Among nonnutrient-nutraceuticals, soy isoflavones could be suggested in perimenopausal women, resveratrol in insulin-resistant patients, melatonin in study participants with night hypertension. In any case, the nutracutical approach has never to substitute the drug treatment, when needed.

Unattended Versus Attended Blood Pressure Measurement.

It has been suggested that measurement of unattended or automated oscillatory blood pressure (BP) values may provide advantages over conventional BP measurement. Some international guidelines now suggest automated oscillatory BP as the preferred approach for measuring BP. Data on the relationship between automated oscillatory BP and cardiovascular events are much less solid as compared to those obtained with the standard approach; preliminary data suggested that automated oscillatory BP might be more strictly correlated with organ damage. The aim of our study was to evaluate the relationship between attended or unattended BP and organ damage in 564 subjects undergoing an echocardiogram and carotid ultrasound at an European Society of Hypertension Excellence Center.Both unattended BP (patient alone in the room, an oscillometric device programmed to perform 3 BP measurements, at 1-minute intervals, after 5 minutes) and attended BP were measured with the same device, on the same day of the ultrasonographic examination, in random order. In 564 patients (age 61±15 years, 41% female 78% hypertensives) systolic unattended BP was lower as compared with attended BP (128.0±15.5 versus 134.5±19.9 mm Hg). Left ventricular mass index was similarly correlated with attended and unattended systolic BP ( r=0.205 and r=0.194, respectively). Carotid intima-media thickness was also significantly correlated with both attended and unattended systolic BP (mean max intima-media thickness: r=0.206 and r=0.194, respectively, P<0.0001). The differences between correlations were not statistically significant. Our results suggest that attended and unattended BP values are similarly related with hypertensive organ damage.

ESC Council on hypertension position document on the management of hypertensive emergencies.

Hypertensive emergencies are those situations where very high blood pressure (BP) values are associated with acute organ damage, and therefore, require immediate, but careful, BP reduction. The type of acute organ damage is the principal determinant of: (i) the drug of choice, (ii) the target BP, and (iii) the timeframe in which BP should be lowered. Key target organs are the heart, retina, brain, kidneys, and large arteries. Patients who lack acute hypertension-mediated end organ damage do not have a hypertensive emergency and can usually be treated with oral BP-lowering agents and usually discharged after a brief period of observation.

MASked-unconTrolled hypERtension management based on office BP or on ambulatory blood pressure measurement (MASTER) Study: a randomised controlled trial protocol.

INTRODUCTION: Masked uncontrolled hypertension (MUCH) carries an increased risk of cardiovascular (CV) complications and can be identified through combined use of office (O) and ambulatory (A) blood pressure (BP) monitoring (M) in treated patients. However, it is still debated whether the information carried by ABPM should be considered for MUCH management. Aim of the MASked-unconTrolled hypERtension management based on OBP or on ambulatory blood pressure measurement (MASTER) Study is to assess the impact on outcome of MUCH management based on OBPM or ABPM. METHODS AND ANALYSIS: MASTER is a 4-year prospective, randomised, open-label, blinded-endpoint investigation. A total of 1240 treated hypertensive patients from about 40 secondary care clinical centres worldwide will be included -upon confirming presence of MUCH (repeated on treatment OBP <140/90 mm Hg, and at least one of the following: daytime ABP ≥135/85 mm Hg; night-time ABP ≥120/70 mm Hg; 24 hour ABP ≥130/80 mm Hg), and will be randomised to a management strategy based on OBPM (group 1) or on ABPM (group 2). Patients in group 1 will have OBP measured at 0, 3, 6, 12, 18, 24, 30, 36, 42 and 48 months and taken as a guide for treatment; ABPM will be performed at randomisation and at 12, 24, 36 and 48 months but will not be used to take treatment decisions. Patients randomised to group 2 will have ABPM performed at randomisation and all scheduled visits as a guide to antihypertensive treatment. The effects of MUCH management strategy based on ABPM or on OBPM on CV and renal intermediate outcomes (changing left ventricular mass and microalbuminuria, coprimary outcomes) at 1 year and on CV events at 4 years and on changes in BP-related variables will be assessed. ETHICS AND DISSEMINATION: MASTER study protocol has received approval by the ethical review board of Istituto Auxologico Italiano. The procedures set out in this protocol are in accordance with principles of Declaration of Helsinki and Good Clinical Practice guidelines. Results will be published in accordance with the CONSORT statement in a peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: NCT02804074; Pre-results.

2018 Practice Guidelines for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension.

These practice guidelines on the management of arterial hypertension are a concise summary of the more extensive ones prepared by the Task Force jointly appointed by the European Society of Hypertension and the European Society of Cardiology. These guidelines have been prepared on the basis of the best available evidence on all issues deserving recommendations; their role must be educational and not prescriptive or coercive for the management of individual subjects who may differ widely in their personal, medical and cultural characteristics. The members of the Task Force have participated independently in the preparation of these guidelines, drawing on their academic and clinical experience and by objective examination and interpretation of all available literature. A disclosure of their potential conflict of interest is reported on the websites of the ESH and the ESC.

Efficacy and safety of azilsartan medoxomil/chlortalidone fixed-dose combination in hypertensive patients uncontrolled on azilsartan medoxomil alone: A randomized trial.

Patients with grade 2-3 essential hypertension and postplacebo mean clinic systolic blood pressure (SBP) 160-190 mm Hg and 24-hour SBP 140-175 mm Hg by ambulatory blood pressure monitoring (ABPM) received 40 mg azilsartan medoxomil (AZL-M) monotherapy for 4 weeks. "Nonresponders" were then randomized to 8 weeks of double-blind treatment with AZL-M 40 mg, AZL-M/chlortalidone (CLD) 40/25, or AZL-M/CLD 40/12.5 mg. After 8 weeks, mean clinic SBP change was -21.1 (±1.04) mm Hg for AZL-M/CLD 40/25 mg, -15.8 (±1.08) mm Hg for AZL-M/CLD 40/12.5 mg, and -6.4 (±1.05) mm Hg for AZL-M 40 mg (P < 0.001 for both AZL-M/CLD vs AZL-M, ANCOVA). Drug discontinuation rates were 8.9% (AZL-M/CLD 40/25 mg), 7.5% (AZL-M 40 mg), and 3.9% (AZL-M/CLD 40/12.5 mg). Creatinine increased in 8.1% (AZL-M/CLD 40/25), 3.1% (AZL-M/CLD 40/12.5 mg), and 3.0% (AZL-M 40 mg) of patients. AZL-M/CLD was effective and well tolerated in patients not achieving blood pressure targets with AZL-M.

2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension.

: Document reviewers: Guy De Backer (ESC Review Co-ordinator) (Belgium), Anthony M. Heagerty (ESH Review Co-ordinator) (UK), Stefan Agewall (Norway), Murielle Bochud (Switzerland), Claudio Borghi (Italy), Pierre Boutouyrie (France), Jana Brguljan (Slovenia), Héctor Bueno (Spain), Enrico G. Caiani (Italy), Bo Carlberg (Sweden), Neil Chapman (UK), Renata Cifkova (Czech Republic), John G. F. Cleland (UK), Jean-Philippe Collet (France), Ioan Mircea Coman (Romania), Peter W. de Leeuw (The Netherlands), Victoria Delgado (The Netherlands), Paul Dendale (Belgium), Hans-Christoph Diener (Germany), Maria Dorobantu (Romania), Robert Fagard (Belgium), Csaba Farsang (Hungary), Marc Ferrini (France), Ian M. Graham (Ireland), Guido Grassi (Italy), Hermann Haller (Germany), F. D. Richard Hobbs (UK), Bojan Jelakovic (Croatia), Catriona Jennings (UK), Hugo A. Katus (Germany), Abraham A. Kroon (The Netherlands), Christophe Leclercq (France), Dragan Lovic (Serbia), Empar Lurbe (Spain), Athanasios J. Manolis (Greece), Theresa A. McDonagh (UK), Franz Messerli (Switzerland), Maria Lorenza Muiesan (Italy), Uwe Nixdorff (Germany), Michael Hecht Olsen (Denmark), Gianfranco Parati (Italy), Joep Perk (Sweden), Massimo Francesco Piepoli (Italy), Jorge Polonia (Portugal), Piotr Ponikowski (Poland), Dimitrios J. Richter (Greece), Stefano F. Rimoldi (Switzerland), Marco Roffi (Switzerland), Naveed Sattar (UK), Petar M. Seferovic (Serbia), Iain A. Simpson (UK), Miguel Sousa-Uva (Portugal), Alice V. Stanton (Ireland), Philippe van de Borne (Belgium), Panos Vardas (Greece), Massimo Volpe (Italy), Sven Wassmann (Germany), Stephan Windecker (Switzerland), Jose Luis Zamorano (Spain).The disclosure forms of all experts involved in the development of these Guidelines are available on the ESC website www.escardio.org/guidelines.