Hyperuricemia and Risk of Cardiovascular Outcomes: The Experience of the URRAH (Uric Acid Right for Heart Health) Project

The latest European Guidelines of Arterial Hypertension have officially introduced uric acid evaluation among the cardiovascular risk factors that should be evaluated in order to stratify patient's risk. In fact, it has been extensively evaluated and demonstrated to be an independent predictor not only of all-cause and cardiovascular mortality, but also of myocardial infraction, stroke and heart failure. Despite the large number of studies on this topic, an important open question that still need to be answered is the identification of a cardiovascular uric acid cut-off value. The actual hyperuricemia cut-off (> 6 mg/dL in women and 7 mg/dL in men) is principally based on the saturation …

Within-visit BP variability, cardiovascular risk factors, and BP control in central and eastern Europe: findings from the BP-CARE study.

INTRODUCTION AND OBJECTIVE Blood pressure variability (BPV) within 24 h or between visits has been found to represent an independent risk factor for cardiovascular disease. The present study was aimed at determining whether a clinical significance can be given also to the BP variations occurring within a single clinical visit. METHODS BPV was quantified as coefficient of variation and as standard deviation (SD) of the mean of three systolic SBP values within a visit in the context of a large-cross subclinical survey (BP-CARE) of treated hypertensive patients living in Eastern European countries. The study population was divided into coefficient of variation and SD quartiles and for each qua…

The association of uric acid with mortality modifies at old age: data from the uric acid right for heart health (URRAH) study

Objectives: In older individuals, the role of serum uric acid (SUA) as risk factor for mortality is debated. This study investigated the association of SUA with all-cause and cardiovascular (CV) mortality in older adults participating in the large multicentre observational uric acid right for heart health (URRAH) study. Methods: Eight thousand URRAH participants aged 65+ were included in the analysis. The predictive role of SUA was assessed using Cox regression models stratified according to the cut-off age of 75. SUA was tested as continuous and categorical variable (age-specific quartiles). The prognostic threshold of SUA for mortality was analysed using receiver operating characteristic …

Blood pressure control and cardiovascular risk profile in hypertensive patients from central and eastern European countries: results of the BP-CARE study.

AimsLimited information is available on office and ambulatory blood pressure (BP) control as well as on cardiovascular (CV) risk profile in treated hypertensive patients living in central and eastern European countries.Methods and resultsIn 2008, a survey on 7860 treated hypertensive patients followed by non-specialist or specialist physicians was carried out in nine central and eastern European countries (Albania, Belarus, Bosnia, Czech Republic, Latvia, Romania, Serbia, Slovakia, and Ukraine). Cardiovascular risk assessment was based on personal history, clinic BP values, as well as target organ damage evaluation. Patients had a mean (±SD) age of 60.1 ± 11 years, and the majority of them …

Blood pressure and low-density lipoprotein-cholesterol lowering for prevention of strokes and cognitive decline: a review of available trial evidence.

BACKGROUND AND OBJECTIVES:: It is well established by a large number of randomized controlled trials that lowering blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) by drugs are powerful means to reduce stroke incidence, but the optimal BP and LDL-C levels to be achieved are largely uncertain. Concerning BP targets, two hypotheses are being confronted: first, the lower the BP, the better the treatment outcome, and second, the hypothesis that too low BP values are accompanied by a lower benefit and even higher risk. It is also unknown whether BP lowering and LDL-C lowering have additive beneficial effects for the primary and secondary prevention of stroke, and whether these…

Identification of a plausible serum uric acid cut-off value as prognostic marker of stroke: the Uric Acid Right for Heart Health (URRAH) study

The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad hoc study aimed at searching for prognostic cut-off values of serum uric acid (SUA) in predicting combined (fatal and non-fatal) cerebrovascular (CBV) events in the whole database. The URic acid Right for heArt Health study is a nationwide, multicenter, observational cohort study involving data on subjects aged 18-95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 120.7 ± 61.8 months. A total of 14,588 subjects were included in the analysis. A prognos…

Prevalence and clinical characteristics of patients with true resistant hypertension in central and Eastern Europe

Objective Scanty information is available on the clinical characteristics of resistant hypertension in Central and East European countries. The Blood Pressure (BP) control rate and CArdiovascular Risk profilE (BP-CARE) study allowed us to assess the prevalence and the main clinical features of resistant hypertension in this population. Design and method The study was carried out in 1312 treated hypertensive patients living in nine Central and East European countries. Results Four hundred and twenty-three patients had apparent resistant hypertension, of whom 168 had pseudo-resistant hypertension (noncompliant/white-coat) and 255 were true treatment-resistant hypertension patients (TRH). Clin…

Obesity and cardiovascular risk

: Obesity is a key factor for cardiovascular diseases and complications. Obesity is associated with hypertension, dyslipidemia and type II diabetes, which are the major predictors of cardiovascular disease in the future. It predisposes for atrial fibrillation, heart failure, sudden cardiac death, renal disease and ischemic stroke that are the main causes of cardiovascular hospitalization and mortality. As obesity and the cardiovascular effects on the vessels and the heart start early in life, even from childhood, it is important for health policies to prevent obesity very early before the disease manifestation emerge. Key roles in the prevention are strategies to increase physical exercise,…

Serum Uric Acid and Kidney Disease Measures Independently Predict Cardiovascular and Total Mortality: The Uric Acid Right for Heart Health (URRAH) Project

Background: Serum uric acid predicts the onset and progression of kidney disease, and the occurrence of cardiovascular and all-cause mortality. Nevertheless, it is unclear which is the appropriate definition of hyperuricemia in presence of chronic kidney disease (CKD). Our goal was to study the independent impact of uric acid and CKD on mortality.Methods: We retrospectively investigated 21,963 patients from the URRAH study database. Hyperuricemia was defined on the basis of outcome specific cut-offs separately identified by ROC curves according to eGFR strata. The primary endpoints were cardiovascular and all-cause mortality.Results: After a mean follow-up of 9.8 year, there were 1,582 (7.2…

Obesity and cardiovascular risk: a call for action from the European Society of Hypertension Working Group of Obesity, Diabetes and the High-risk Patient and European Association for the Study of Obesity part B obesity-induced cardiovascular disease, early prevention strategies and future research directions

: Obesity predisposes for atrial fibrillation, heart failure, sudden cardiac death, renal disease and ischemic stroke, which are the main causes of cardiovascular hospitalization and mortality. As obesity and the cardiovascular effects on the vessels and the heart start early in life, even from childhood, it is important for health policies to prevent obesity very early before the disease manifestation emerge. Key roles in the prevention are strategies to increase physical exercise, reduce body weight and to prevent or treat hypertension, lipids disorders and diabetes earlier and efficiently to prevent cardiovascular complications.

Age and Multimorbidity Predict Death Among COVID-19 Patients: Results of the SARS-RAS Study of the Italian Society of Hypertension

Several factors have been proposed to explain the high death rate of the coronavirus disease 2019 (COVID-19) outbreak, including hypertension and hypertension-related treatment with Renin Angiotensin System inhibitors. Also, age and multimorbidity might be confounders. No sufficient data are available to demonstrate their independent role. We designed a cross-sectional, observational, multicenter, nationwide survey in Italy to verify whether renin-angiotensin system inhibitors are related to COVID-19 severe outcomes. We analyzed information from Italian patients diagnosed with COVID-19, admitted in 26 hospitals. One thousand five hundred ninety-one charts (male, 64.1%; 66±0.4 years) were r…

Continuation of the ESH-CHL-SHOT trial after publication of the SPRINT: rationale for further study on blood pressure targets of antihypertensive treatment after stroke.

New developments in the pathogenesis of obesity-induced hypertension

Obesity is a disorder that develops from the interaction between genotype and environment involving social, behavioral, cultural, and physiological factors. Obesity increases the risk for type 2 diabetes mellitus, hypertension, cardiovascular disease, cancer, musculoskeletal disorders, chronic kidney and pulmonary disease. Although obesity is clearly associated with an increased prevalence of hypertension, many obese individuals may not develop hypertension. Protecting factors may exist and it is important to understand why obesity is not always related to hypertension. The aim of this review is to highlight the knowledge gap for the association between obesity, hypertension, and potential …

Sympathetic neural activity, metabolic parameters and cardiorespiratory fitness in obese youths.

OBJECTIVE: The main objective of this cross-sectional study is to assess the cardiac autonomic neural activity in the presence of abnormally increased body weight in youths and its relationship to metabolic risk factors and cardiorespiratory fitness (CRF). METHODS: Sixty-four overweight and obese patients, aged 9-17 years, of both sexes, stratified according to the international BMI cut-off, were enrolled. Continuous ECG was recorded during 15 min in resting conditions, and the heart rate variability (HRV) was measured in the time domain, frequency domain and for nonlinear dynamics. In addition, cardiometabolic risk factors and CRF in effort conditions were assessed. RESULTS: Among the over…

European Society of Hypertension Working Group on Obesity Obesity-induced hypertension and target organ damage: current knowledge and future directions.

Proceedings from the European clinical consensus conference for renal denervation: considerations on future clinical trial design: Figure 1

Approximately 8–18% of all patients with high blood pressure (BP) are apparently resistant to drug treatment.1,2 In this situation, new strategies to help reduce BP are urgently needed but the complex pathophysiology of resistant hypertension makes this search difficult. Not surprisingly in this context, the latest non-drug treatment which triggered controversy is catheter-based renal denervation (RDN).3,4 The method uses radiofrequency energy, or alternatively ultrasound or chemical denervation, to disrupt renal nerves within the renal artery wall, thereby reducing sympathetic efferent and sensory afferent signalling to and from the kidneys.5,6 Various experimental models of hypertension s…

Identification of the Uric Acid Thresholds Predicting an Increased Total and Cardiovascular Mortality Over 20 Years

Serum uric acid (SUA) levels discriminating across the different strata of cardiovascular risk is still unknown. By utilizing a large population-based database, we assessed the threshold of SUA that increases the risk of total mortality and cardiovascular mortality (CVM). The URRAH study (Uric Acid Right for Heart Health) is a multicentre retrospective, observational study, which collected data from several large population-based longitudinal studies in Italy and subjects recruited in the hypertension clinics of the Italian Society of Hypertension. Total mortality was defined as mortality for any cause, CVM as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart…

World Hypertension Day 2021 in Italy: Results of a Nationwide Survey

Introduction: Hypertension is the biggest contributor to the global burden of cardiovascular diseases and related death, but the rates of hypertension awareness, treatment, and control remain largely perfectible. Methods: During the XVII World Hypertension Day (May 17th, 2021), a nationwide cross-sectional opportunistic study endorsed by the Italian Society of Hypertension was conducted on volunteer adults ≥ 18 years to raise awareness of high blood pressure (BP). A questionnaire on major demographic/clinical features (sex, age, employment, education, BP status awareness, hypertension family/personal history, antihypertensive medications use) and BP measurement habits (≥1 BP measurement in …

Blood pressure and LDL-cholesterol targets for prevention of recurrent strokes and cognitive decline in the hypertensive patient : design of the European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment randomized trial

BACKGROUND AND OBJECTIVES:: The SBP values to be achieved by antihypertensive therapy in order to maximize reduction of cardiovascular outcomes are unknown; neither is it clear whether in patients with a previous cardiovascular event, the optimal values are lower than in the low-to-moderate risk hypertensive patients, or a more cautious blood pressure (BP) reduction should be obtained. Because of the uncertainty whether 'the lower the better' or the 'J-curve' hypothesis is correct, the European Society of Hypertension and the Chinese Hypertension League have promoted a randomized trial comparing antihypertensive treatment strategies aiming at three different SBP targets in hypertensive pati…

Diagnostic and Therapeutic Approach to Sleep Disorders, High Blood Pressure and Cardiovascular Diseases. A Consensus Document by the Italian Society of Hypertension (SIIA)

Hypertension is a major contributor to fatal/nonfatal cardiovascular diseases, and timely identification and appropriate management of factors affecting hypertension and its control are mandatory public health issues. By inducing neurohormonal alterations and metabolic impairment, sleep disorders have an impact on a variety of cardiovascular risk factors, including hypertension, and ultimately increase the risk of cardiovascular events. There is evidence that qualitative and quantitative sleep disorders are associated with resistant hypertension and with impaired circadian blood pressure variations. However, sleep disturbances are often unrecognized, or heterogeneity exists in their managem…

Renin-Angiotensin System Inhibition in Cardiovascular Patients at the Time of COVID19: Much Ado for Nothing? A Statement of Activity from the Directors of the Board and the Scientific Directors of the Italian Society of Hypertension

Cardiovascular diseases, in particular hypertension, as well as the cardiovascular treatment with Renin-Angiotensin System inhibitors such as Angiotensin Converting Enzyme (ACE) inhibitors and Angiotensin Receptor Blockers (ARBs), are claimed once again as mechanisms of Severe Acute Respiratory Syndrome (SARS) during the COVID-19 outbreak due to Cov-2 epidemics. In vitro studies are available to support the eventual role of ACE inhibitors and ARBs in both the promotion and antagonism of the disease. The available literature, indeed, presents contrasting results, all concentrated in experimental models. Evidence in humans is lacking that those mechanisms are actually occurring in the present…

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, …

ESH position paper: renal denervation - an interventional therapy of resistant hypertension

Experts from the European Society of Hypertension prepared this position paper in order to summarize current evidence, unmet needs and practical recommendations on the application of percutaneous transluminal ablation of renal nerves [renal denervation (RDN)] as a novel therapeutic strategy for the treatment of resistant hypertension. The sympathetic nervous activation to the kidney and the sensory afferent signals to the central nervous system represent the targets of RND. Clinical studies have documented that catheter-based RDN decreases both efferent sympathetic and afferent sensory nerve traffic leading to clinically meaningful systolic and diastolic blood pressure (BP) reductions in pa…

Drug Prescription and Delirium in Older Inpatients: Results From the Nationwide Multicenter Italian Delirium Day 2015-2016

Objective This study aimed to evaluate the association between polypharmacy and delirium, the association of specific drug categories with delirium, and the differences in drug-delirium association between medical and surgical units and according to dementia diagnosis. Methods Data were collected during 2 waves of Delirium Day, a multicenter delirium prevalence study including patients (aged 65 years or older) admitted to acute and long-term care wards in Italy (2015-2016); in this study, only patients enrolled in acute hospital wards were selected (n = 4,133). Delirium was assessed according to score on the 4 "A's" Test. Prescriptions were classified by main drug categories; polypharmacy w…

European Society of Hypertension Working Group on Obesity: background, aims and perspectives.

Clinica Medica, University ofMilano-Bicocca, Ospedale San Gerardo, Monza, Milan, ItalyCorrespondence and requests for reprints to Professor Jens Jordan, ChairmanWorking Group on Obesity, Franz Volhard Clinical Research Center, HELIOSKlinikum Berlin and Medical Faculty of the Charite´, Wiltbergstrase 50, 13125Berlin, GermanyTel: +49 30 9417 2220; fax: +49 30 9417 2265; e-mail: jens.jordan@charite.de

Uncertainty in the assessment of trends in childhood blood pressure.

May Measurement Month 2018: an analysis of blood pressure screening results from Italy

Abstract Cardiovascular (CV) diseases are burdened by high mortality and morbidity, being responsible for half of the deaths in Europe. Although hypertension is recognized as the most important CV risk factor, hypertension awareness and blood pressure (BP) control are still unsatisfactory. In 2017, 30.6% of a >10 000 individual sample who took part in the May Measurement Month (MMM) campaign in Italy was found to have high BP. To raise awareness on the hypertension issue and to report BP data on a nation-wide scale in Italy. In the frame of the MMM campaign, an opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in May 2018. Blood pressure measurement, the def…

High heart rate amplifies the risk of cardiovascular mortality associated with elevated uric acid.

Abstract Aims  Whether the association between uric acid (UA) and cardiovascular disease is influenced by some facilitating factors is unclear. The aim of this study was to investigate whether the risk of cardiovascular mortality (CVM) associated with elevated UA was modulated by the level of resting heart rate (HR). Methods and results  Multivariable Cox analyses were made in 19 128 participants from the multicentre Uric acid Right for heArt Health study. During a median follow-up of 11.2 years, there were 1381 cases of CVM. In multivariable Cox models both UA and HR, either considered as continuous or categorical variables were independent predictors of CVM both improving risk discriminat…

Prospective appraisal of the prevalence of primary aldosteronism in hypertensive patients presenting with atrial flutter or fibrillation (PAPPHY Study): rationale and study design

Primary aldosteronism (PA) is the most common endocrine form of hypertension and may carry an increased risk of atrial flutter or fibrillation (AFF). The primary goal of this multicentre cohort study is thus to prospectively establish the prevalence of PA in consecutive hypertensive patients referred for lone (non-valvular), paroxysmal or permanent AFF. Secondary objectives are to determine: (1) the predictors of AFF in patients with PA; (2) the rate of AFF recurrence at follow-up after specific treatment in the patients with PA; (3) the effect of AFF that can increase atrial natriuretic peptide via the atrial stretch and thereby blunt aldosterone secretion, on the aldosterone-to-renin rati…

Clinical Characteristics and Outcomes of Patients with COVID-19 Infection: The Results of the SARS-RAS Study of the Italian Society of Hypertension

: The COVID-19 infection has rapidly spread around the world and a second wave is sweeping in many countries. Different clinical and epidemiological aspects characterize the disease and their understanding is necessary to better face the management of the pandemic in progress. The Italian society of arterial hypertension with the SARS-RAS study has contributed significantly to the knowledge of the interaction between inhibition of the renin-angiotensin system and COVID-19 infection. Furthermore, the study results help to understand some of the main aspects related to mortality and morbidity deriving from the infection through a multicentre analysis throughout the national territory.

Identifying poor cardiorespiratory fitness in overweight and obese children and adolescents by using heart rate variability analysis under resting conditions.

Background: Childhood obesity, including overweight, continues increasing worldwide affecting health expectancy, quality of life and healthcare expenditure. These subjects have higher probability of suffering or developing cardio metabolic risk factors. Recent studies have revealed cardiorespiratory fitness (CRF) as a valuable clinical parameter to identify these subjects and have even suggested cut-off values. However, evaluating CRF in overweight and obese youth can be difficult to implement, unfriendly and expensive. Objective: Develop a screening tool to identify high-risk subjects in a representative population of those attending overweight/obesity assessment programmes without prior i…

May Measurement Month 2019: an analysis of blood pressure screening results from Italy.

Abstract Cardiovascular (CV) diseases are burdened by high mortality and morbidity, being responsible for half of the deaths in Europe. Although hypertension is recognized as the most important CV risk factor, hypertension awareness, and blood pressure (BP) control are still unsatisfactory. In 2017 and 2018, respectively >10 000 and >5000 individuals took part in the May Measurement Month (MMM) campaign in Italy, of whom 30.6% and 26.3% were found to have high BP, respectively. To raise public awareness on the importance of hypertension and to collect BP data on a nation-wide scale in Italy. In the frame of the MMM campaign, an opportunistic cross-sectional survey of volunteer…

Gender-related differences in serum uric acid in treated hypertensive patients from central and east European countries: findings from the Blood Pressure control rate and CArdiovascular Risk profilE study.

OBJECTIVE: Hyperuricemia has been associated with high blood pressure (BP) values, diabetes mellitus, metabolic syndrome and chronic kidney disease (CKD). In the present study, we assessed the gender-related relationships between serum uric acid (SUA) and cardionephrometabolic variables in central and east European hypertensive patients. METHODS: A total of 3206 treated hypertensive patients with available SUA levels from the BP-CARE study was analyzed. Correlations among SUA, BP values, BP control, diabetes mellitus, metabolic syndrome and CKD were performed according to gender. RESULTS: Twenty-five percent of the whole population showed hyperuricemia (28% in women and 23% in men). These p…

Blood pressure variability and cardiovascular risk in 9 eastern european countries: data from the BP-Care study

Methods: Total 327 patients were enrolled from 2008 to 2011 in the Korean registry program. They met the criteria of PAH and we investigated the clinical data, the medication prescribed and survival status et al. Results: Their mean age was 40.8 15.8years with female /male patient ratio of 2.7:1. The patients in WHO I/II were 32.4% and WHO III/IV were 67.6%. The peak/mean pulmonary arterial pressure was 86.3/ 56.6 mmHg. Idiopathic PAH (22%), connective tissue disease (24%) and congenital heart disease (46%) were predominant. Small number of patients with familial PAH, portal hypertension, HIV infection, pulmonary capillary hemangiomatosis (PCH) existed. The patients described bosentan were …

Serum uric acid levels threshold for mortality in diabetic individuals: The URic acid Right for heArt Health (URRAH) project

Background and aim: The URRAH (URic acid Right for heArt Health) Study has identified cut-off values of serum uric acid (SUA) predictive of total mortality at 4.7 mg/dl, and cardiovascular (CV) mortality at 5.6 mg/dl. Our aim was to validate these SUA thresholds in people with diabetes. Methods and results: The URRAH subpopulation of people with diabetes was studied. All-cause and CV deaths were evaluated at the end of follow-up. A total of 2570 diabetic subjects were studied. During a median follow-up of 107 months, 744 deaths occurred. In the multivariate Cox regression analyses adjusted for several confounders, subjects with SUA ≥5.6 mg/dl had higher risk of total (HR: 1.23, 95%CI: 1.04-…

Serum uric acid, predicts heart failure in a large Italian cohort: search for a cut-off value the URic acid Right for heArt Health study

Objective: To assess the prognostic cut-off values of serum uric acid (SUA) in predicting fatal and morbid heart failure in a large Italian cohort in the frame of the Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension. Methods: The URic acid Right for heArt Health (URRAH) study is a nationwide, multicentre, cohort study involving data on individuals aged 18-95 years, recruited on a community basis from all regions of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 128 ± 65 months. Incident heart failure was defined on the basis of International Classification of Diseases Tenth Revision codes and double-c…

Reappraisal of European guidelines on hypertension management: A European Society of Hypertension Task Force document

Abbreviations ACE: angiotensin-converting enzyme; BP: blood pressure; DBP: diastolic blood pressure; eGFR: estimated glomerular filtration rate; ESC: European Society of Cardiology; ESH: European Society of Hypertension; ET: endothelin; IMT: carotid intima-media thickness; JNC: Joint National Commit