Treatment strategies of the thromboembolic risk in kidney failure patients with atrial fibrillation.

The incidence and prevalence of atrial fibrillation (AF) in patients affected by kidney failure, i.e. glomerular filtration rate <15 ml/min/1.73 m2, is high and probably underestimated. Numerous uncertainties remain regarding how to prevent thromboembolic events in this population because both cardiology and nephrology guidelines do not provide clear recommendations. The efficacy and safety of oral anticoagulant therapy (OAC) in preventing thromboembolism in patients with kidney failure and AF has not been demonstrated for either vitamin K antagonists (VKA) or direct anticoagulants (DOAC). Moreover, it remains unclear which is more effective and safer between them, because estimated creatinine clearance < 25-30 ml/min was an exclusion criterion of the randomized control trials (RCTs). Three RCTs comparing DOACs and VKAs in kidney failure failed to reach the primary endpoint because they were underpowered. The left atrial appendage is the main source of thromboembolism in the presence of AF. Left atrial appendage closure (LAAC) has recently been proposed as an alternative to OAC. RCTs comparing the efficacy and safety of LAAC vs. OAC in kidney failure were terminated prematurely due to recruitment failure. A recent prospective study showed a reduction in thromboembolic events in hemodialysis patients with AF and undergoing LAAC compared to patients taking or not taking OAC. We review current treatment standards and discuss recent developments in managing the thromboembolic risk in kidney failure patients with AF. The importance of shared decision-making with the multidisciplinary team and the patient, to consider individual risks and benefits of each treatment option is underlined.

Practical guide on left atrial appendage closure for the non-implanting physician: an international consensus paper.

A significant proportion of patients who suffer from atrial fibrillation (AF) and are in need of thromboembolic protection are not treated with oral anticoagulation or discontinue this treatment shortly after its initiation. This undertreatment has not improved sufficiently despite the availability of direct oral anticoagulants which are associated with less major bleeding than vitamin K antagonists. Multiple reasons account for this, including bleeding events or ischaemic strokes whilst on anticoagulation, a serious risk of bleeding events, poor treatment compliance despite best educational attempts, or aversion to drug therapy. An alternative interventional therapy, which is not associated with long-term bleeding and is as effective as vitamin K anticoagulation, was introduced over 20 years ago. Because of significant improvements in procedural safety over the years, left atrial appendage closure, predominantly achieved using a catheter-based, device implantation approach, is increasingly favoured for the prevention of thromboembolic events in patients who cannot achieve effective anticoagulation. This management strategy is well known to the interventional cardiologist/electrophysiologist but is not more widely appreciated within cardiology or internal medicine. This article introduces the devices and briefly explains the implantation technique. The indications and device follow-up are more comprehensively described. Almost all physicians who care for adult patients will have many with AF. This practical guide, written within guideline/guidance boundaries, is aimed at those non-implanting physicians who may need to refer patients for consideration of this new therapy, which is becoming increasingly popular.

Long-term safety and efficacy of left atrial appendage occlusion in dialysis patients with atrial fibrillation: a multi-center, prospective, open label, observational study.

Background: The prevalence of atrial fibrillation (AF) in end stage kidney disease (ESKD) patients undergoing dialysis is high, however, the high risk of bleeding often hampers with a correct anticoagulation in ESKD patients with AF, despite high thromboembolic risk. Left atrial appendage (LAA) occlusion is a anticoagulation (OAT) for thromboembolism prevention in AF populations with high hemorrhagic risk. Methods and Results: The purpose of the study was to evaluate the efficacy and safety of LAA occlusion in a cohort of dialysis patients undergoing the procedure (LAA occlusion cohort, n = 106), in comparison with two other ESKD cohorts, one taking warfarin (Warfarin cohort, n = 114) and the other without anticoagulation therapy (No-OAT cohort, n = 148). After a median follow-up of 4 years, a Cox regression model, adjusted for possible confounding factors, showed that the hazard ratios (HRs) of thromboembolic events in the LAA occlusion cohort were 0.19 (95%CI 0.04-0.96; p = 0.045) and 0.16 (95%CI 0.04-0.66; p = 0.011) as compared with Warfarin and No-OAT cohorts, respectively. The HR of bleeding in the LAA occlusion cohort was 0.37 (95%CI 0.16-0.83; p = 0.017) compared to Warfarin cohort, while there were no significant differences between the LAA occlusion and the No-OAT cohort (HR 0.51; 95%CI 0.23-1.12; p = 0.094). Adjusted Cox regression models showed lower mortality in patients undergoing LAA occlusion as compared with both the Warfarin cohort (HR 0.60; 95%CI 0.38-0.94; p = 0.027) and no-OAT cohort (HR 0.52; 95%CI 0.34-0.78; p = 0.002). Thromboembolic events in the LAA occlusion cohort were lower than expected according to the CHA2DS2VASc score (1.7 [95%CI 0.3-3.0] vs 6.7 events per 100 person/years, p < 0.001). Conclusion: In ESKD patients with AF, LAA occlusion is safe and effective and is associated with reduced mortality compared with OAT or no therapy.

Wall Properties of Elastic and Muscular Arteries in Children and Adolescents at Increased Cardiovascular Risk.

BACKGROUND: Pulse wave velocity (PWV) assessment represents a simple method to estimate arterial distensibility. At present, carotid-femoral PWV (cf-PWV) is considered the gold standard method in the non-invasive evaluation of the elastic properties of the aorta. On the other hand, the mechanical properties of muscular arteries can be evaluated on the axillo-brachial-radia axis by estimating the carotid-radial PWV (cr-PWV). While a number of studies have addressed these issues in adults, limited information is available on the respective features of cf-PWV and cr-PWV and on their modulating factors in children and adolescents at increased cardiovascular risk. METHODS: The mechanical properties of the predominantly elastic (aorta) and muscular (axillo-brachial-radial axis) arteries were evaluated in a pediatric population characterized by either elevated blood pressure (BP) or excess body weight, and the main factors affecting cf-PWV and cr-PWV values in these individuals were investigated. RESULTS: 443 children and adolescents (median age 11.5 years, 43.3% females) were enrolled; 25% had BP values >90th percentile and 81% were excess weight. The cf-PWV values were significantly lower than the cr-PWV values: median (Q1-Q3) = 4.8 m/s (4.3-5.5) and 5.8 m/s (5.0-6.5), respectively (p < 0.001). The pubertal development (p < 0.03), systolic BP and diastolic BP z-scores (p = 0.002), heart rate (p < 0.001), and waist-to-height ratio (p < 0.005) were significantly associated with cf-PWV values. No significant association was found between BMI z-score and cf-PWV. Predictors of high cf-PWV (>95th percentile) were the heart rate (OR 1.07, 95%CI 1.04-1.10, p < 0.001) and waist-to-height ratio (OR 1.06, 95%CI 1.0-1.13, p = 0.04). The variables significantly related with cr-PWV values were diastolic BP z-score (p = 0.001), heart rate (p < 0.01), and HOMA index (p < 0.02). No significant association was found between the cr-PWV and BMI z-score or waist-to-height ratio. CONCLUSIONS: Systolic and diastolic BP values and central obesity are associated with aortic stiffness in a population of children and adolescents at increased cardiovascular risk. In contrast, diastolic BP, heart rate, and levels of insulin resistance appear to be related to distensibility of the upper limb vascular district.

Clinical Approach in the Management of Paediatric Patients with Familial Hypercholesterolemia: A National Survey Conducted by the LIPIGEN Paediatric Group.

Detection and treatment of patients with familial hypercholesterolemia (FH) starting from childhood is fundamental to reduce morbidity and mortality. The activity of National realities such as the LIPIGEN (LIpid transPort disorders Italian GEnetic Network) Paediatric Group, founded in 2018, is a milestone in this context. The aim of this exploratory survey, conducted in October 2021 among Italian lipid clinics included in the LIPIGEN Paediatric Group, was to investigate the current clinical approach in the management and treatment of paediatric patients with suspected FH. A digital questionnaire composed of 20 questions investigating nutritional treatment and nutraceutical and pharmacological therapy for children and adolescents with FH was proposed to the principal investigators of 30 LIPIGEN centres. Twenty-four centres responded to the section referring to children aged < 10 years and 30 to that referring to adolescents. Overall, 66.7% of children and 73.3% of adolescents were given lipid-lowering nutritional treatment as the first intervention level for at least 3-4 months (29.2% and 23.3%) or 6-12 months (58.3% and 53.3%). Nutraceuticals were considered in 41.7% (regarding children) and 50.0% (regarding adolescents) of the centres as a supplementary approach to diet. Lipid-lowering drug therapy initiation was mainly recommended (91.7% and 80.0%). In 83.3% of children and 96.7% of adolescents, statins were the most frequently prescribed drug. We highlighted several differences in the treatment of paediatric patients with suspected FH among Italian centres; however, the overall approach is in line with the European Atherosclerosis Society (EAS) recommendations for FH children and adolescents. We consider this survey as a starting point to reinforce collaboration between LIPIGEN centres and to elaborate in the near future a consensus document on the management of paediatric patients with suspected FH so as to improve and uniform detection, management, and treatment of these patients in our country.

Elevated Serum Urea-to-Creatinine Ratio and In-Hospital Death in Patients with Hyponatremia Hospitalized for COVID-19.

Hyponatremia is associated with adverse outcomes in hospitalized patients. An elevated value of the serum urea-to-creatinine ratio (UCR) has been proposed as a proxy of hypovolemia. The aim of this study was to investigate the relationship between the UCR and in-hospital death in patients hospitalized with COVID-19 and hyponatremia. We studied 258 patients admitted for COVID-19 between January 2020 and May 2021 with serum sodium at < 135 mmol/L. The primary end-point was all-cause mortality. A 5-unit increase in the serum UCR during hospital stays was associated with an 8% increase in the hazard of all-cause death (HR = 1.08, 95% CI: 1.03-1.14, p = 0.001) after adjusting for potential confounders. In patients with a UCR > 40 at baseline, a > 10 mmol/L increase in serum sodium values within the first week of hospitalization was associated with higher odds of in-hospital death (OR = 2.93, 95% CI: 1.03-8.36, p = 0.044) compared to patients who experienced a < 10 mmol/L change. This was not observed in patients with a UCR < 40. Hypovolemia developing during hospital stays in COVID-19 patients with hyponatremia detected at hospital admission bears an adverse prognostic impact. Moreover, in hypovolemic patients, a > 10 mmol/L increase in serum sodium within the first week of hospital stays may further worsen the in-hospital prognosis.

Evidence and Uncertainties on Lipoprotein(a) as a Marker of Cardiovascular Health Risk in Children and Adolescents.

Lipoprotein(a) (Lp(a)) is made up of apoprotein(a) (apo(a)) and an LDL-like particle. The LPA gene encodes apo(a) and thus determines the characteristics and amount of apo(a) and Lp(a). The proportion of Lp(a) in each individual is genetically determined and is only minimally modifiable by the environment or diet. Lp(a) has important pro-atherosclerotic and pro-inflammatory effects. It has been hypothesized that Lp(a) also has pro-coagulant and antifibrinolytic actions. For these reasons, high Lp(a) values are an important independent risk factor for cardiovascular disease and calcific aortic valve stenosis. Numerous studies have been performed in adults about the pathophysiology and epidemiology of Lp(a) and research is under way for the development of drugs capable of reducing Lp(a) plasma values. Much less information is available regarding Lp(a) in children and adolescents. The present article reviews the evidence on this topic. The review addresses the issues of Lp(a) changes during growth, the correlation between Lp(a) values in children and those in their parents, and between Lp(a) levels in children, and the presence of cardiovascular disease in the family. Gaining information on these points is particularly important for deciding whether Lp(a) assay may be useful for defining the cardiovascular risk in children, in order to plan a prevention program early.

Association between lifestyle modifications and improvement of early cardiac damage in children and adolescents with excess weight and/or high blood pressure.

BACKGROUND: It is not known whether, in children and adolescents with alterations in weight and/or blood pressure (BP), lifestyle modifications are associated with an improvement of early cardiac damage. METHODS: In a pediatric population referred for excess weight, high BP, or both (n = 278, 10.6 (2.3) years), echocardiography was performed at enrollment and after 15 months of follow-up, during which participants received nonpharmacological treatment, based on correcting unhealthy lifestyles and improving dietary habits. Left ventricular mass was indexed for height (g/m2.7, LVMI), and an LVMI value higher than or equal to age- and gender-specific 95th percentile was the criterion for defining left ventricular hypertrophy (LVH). Multiple linear and logistic regression analyses were carried out to determine associations between changes in BMI and BP z-scores and changes of LVMI values and LVH prevalence, from baseline to follow-up. RESULTS: At baseline, 33.1% of study participants were hypertensive, 52.9% obese, and 36.3% had LVH. At follow-up, the prevalence of hypertension, obesity, and LVH was 18.7%, 30.2%, and 22.3%, respectively (p < 0.001 for all). A decrease in LVMI from 37.1 to 35.2 g/m2.7 (p < 0.001) was observed. Only delta BMI z-score positively related to an improvement of LVMI. Reductions of BMI (OR = 0.22, 95% CI 0.07-0.64) and diastolic BP (OR = 0.64, 95% CI 0.42-0.93) z-scores from baseline to follow-up and family history of hypertension (OR = 0.36, 95% CI 0.16-0.78) were associated with a lower prevalence of LVH. CONCLUSIONS: In a pediatric population at cardiovascular risk, changing incorrect lifestyle and dietary habits is associated with both reduction of BMI and BP values and regression of early cardiac damage. A higher resolution version of the Graphical abstract is available as Supplementary information.

Role of Insulin Resistance as a Mediator of the Relationship between Body Weight, Waist Circumference, and Systolic Blood Pressure in a Pediatric Population.

Excess weight and high waist circumference (WC) are associated with increased blood pressure (BP), starting from the pediatric age. Insulin resistance is associated with elevated BP in childhood. The aim of the study was to assess the role of insulin resistance in mediating the relationship between body mass index (BMI), WC, and BP values in a pediatric population referred to a cardio-pediatric center for the presence of one or more cardiovascular risk factors. In 419 children (mean age 10.7 [standard deviation, SD 2.5] years), the following parameters were collected both in basal conditions and after 18.6 (SD 9.3) months of follow-up during which a treatment based on lifestyle and dietary modifications was given: systolic and diastolic BP (SBP and DBP), WC, plasma glucose, and insulin values. The HOMA (Homeostasis Model Assessment)-index was considered as an expression of insulin resistance. At baseline there was a significant correlation between HOMA-index and SBP z-score (ß = 0.081, p = 0.003), and insulin resistance was a mediator of the relationship between BMI and SBP z-score (p = 0.015), and between waist circumference to height (WtHr) and SBP z-score (p = 0.008). The effect of BMI z-score modifications on SBP z-score changes from baseline to follow-up was totally mediated by HOMA-index changes (p = 0.008), while HOMA-index only partially mediated the effect of WtHr modifications on SBP z-score changes (p = 0.060). Our study strongly suggests that, in a pediatric population at cardiovascular risk, the HOMA-index is an important mediator of the relationship between BMI, WC and SBP.

The conundrum of the complex relationship between acute kidney injury and cardiac arrhythmias.

Acute kidney injury (AKI) is defined by a rapid increase in serum creatinine levels, reduced urine output or both. Death may occur in 16-49% of patients admitted to an intensive care unit with severe AKI. Complex arrhythmias are a potentially serious complication in AKI patients with pre-existing or AKI-induced heart damage and myocardial dysfunction, with fluid overload, especially electrolyte and acid-base disorders, representing the pathogenetic mechanisms of arrhythmogenesis. Cardiac arrhythmias, in turn, increase the risk of poor renal outcomes, including AKI. Arrhythmic risk in AKI patients receiving kidney replacement treatment may be reduced by modifying dialysis/replacement fluid composition. The most common arrhythmia observed in AKI patients is atrial fibrillation. Severe hyperkalaemia, sometimes combined with hypocalcaemia, causes severe bradyarrhythmias in this clinical setting. Although the likelihood of life-threatening ventricular arrhythmias is reportedly low, the combination of cardiac ischaemia and specific electrolyte or acid-base abnormalities may increase this risk, particularly in AKI patients who require kidney replacement treatment. The purpose of this review is to summarize the available epidemiological, pathophysiological and prognostic evidence aiming to clarify the complex relationships between AKI and cardiac arrhythmias.

Negative prognostic impact of electrolyte disorders in patients hospitalized for Covid-19 in a large multicenter study.

BACKGROUND: The prognostic impact of electrolyte disorders in hospitalized COVID-19 patients is unclear. METHODS: The study included all adult patients hospitalized for COVID-19 in four hospitals in Northern Italy between January 2020 and May 2021 with at least one serum potassium and sodium measurement performed within 3 days since admission. Primary outcome was in-hospital death; secondary outcome was Intensive Care Unit (ICU) admission. A cause-specific Cox proportional-hazards regression model was used for investigating the association between potassium and sodium (as either categorical or continuous variables) and mortality or admission to ICU. RESULTS: Analyses included 3,418 adult hospitalized COVID-19 patients. At multivariable analysis, both hyperkalemia (Hazard Ratio, [HR] 1.833, 95% Confidence Interval [CI] 1.371-2.450) and sK above the median (K 5.1 vs 4.1 mmol/L: HR 1.523, 95% CI 1.295-1.798), and hypernatremia (HR 2.313, 95%CI 1.772-3.018) and sNa above the median (Na 149 vs 139 mmol/L: HR 1.442, 95% CI 1.234-1.686), were associated with in-hospital death, whereas hypokalemia and hyponatremia were not. Hyponatremia was associated with increased hazard of ICU admission (HR 1.884, 95%CI 1.389-2.556). CONCLUSIONS: Electrolyte disorders detected at hospital admission may allow early identification of COVID-19 patients at increased risk of adverse outcomes.

Association of obesity phenotypes with left ventricular mass index and left ventricular hypertrophy in children and adolescents.

It has been argued that metabolically healthy obesity (MHO) does not increase the risk of cardiovascular disease. The aim of this study is to evaluate whether, in a population of obese children/adolescents, the metabolically unhealthy obesity (MUO) phenotype is associated with higher left ventricular mass index and/or higher prevalence of left ventricular hypertrophy than the MHO phenotype. We also tested whether the addition of an insulin resistance index (HOMA-index >90th percentile by sex and age) and the presence of hyperuricemia (serum uric acid >90th percentile by sex and age) to the definition of MUO better identified obese children with early cardiac damage. Left ventricular hypertrophy was defined as the presence of left ventricular mass index greater than or equal to the age- and sex-specific 95th percentile. The study population included 459 obese children (males 53.2%, mean age 10.6 [standard deviation, 2.6] years), of whom 268 (58.4%) were MUO. The left ventricular mass index was higher in MUO children than in MHO children (37.8 vs 36.3 g/m2.7, p=0.015), whereas the percentage of MUO children presenting left ventricular hypertrophy was only slightly higher in MUO children (31.1 vs 40%, p=0.06). Multiple linear regression analyses showed that the variables significantly associated with higher left ventricular mass index were male gender (p<0.01), Body Mass Index z-score (p<0.001) and Waist-to-Height-ratio (p<0.001). Multiple logistic regression analyses showed that the presence of left ventricular hypertrophy was only significantly associated with higher Body Mass Index z-score (p<0.05) and Waist-to-Height-ratio (p<0.05). In spite of the higher left ventricular mass index of MUO as compared to MHO children, the MUO phenotype was not a significant predictor of either higher left ventricular mass index or higher left ventricular hypertrophy prevalence. The MUO phenotype had a low predictive ability on the presence of left ventricular hypertrophy. The area under the receiver operating characteristic curve was 0.57 (sensitivity 0.64, 1-specificity 0.55). The addition of insulin resistance and hyperuricemia to the definition of MUO did not change the results observed with the standard definition of MUO at multivariable analysis. The MUO phenotype appears to be of little usefulness in identifying the early presence of cardiac damage in a large population of obese children and adolescents. Excess weight and abdominal obesity are confirmed as an important determinant of early organ damage in obese children.

Uric acid and arterial stiffness in children and adolescents: Role of insulin resistance and blood pressure.

Several studies describe the association between serum uric acid (SUA) and arterial stiffness in adults. Uric acid contributes through several mechanisms to the increase in blood pressure (BP) and adversely affects the insulin signaling pathway. Moreover, SUA predict the development of hypertension and insulin resistance up to type 2 diabetes. Early arterial stiffening, estimated by carotid-femoral pulse wave velocity (PWV), may already be present in pediatric age. Aim of our study was to investigate the relationship between SUA and PWV in a pediatric population and its interaction with insulin resistance and BP. In 322 children and adolescents (56.2% male, mean age 11.3 [SD 2.8] years), we measured weight, height, waist circumference, BP and PWV. We also assayed SUA and estimated glomerular filtration rate (eGFR) and calculated HOMA-index as a marker of insulin resistance. Simple and multiple regression analyses were performed to assess variables associated with PWV. Mediation models were applied to identify the direct and indirect effects of individual variables on PWV. On univariate analysis, age (p < 0.001), waist circumference-to-height ratio (p = 0.036), systolic and diastolic BP (SBP and DBP) z-score (p < 0.001), heart rate (p = 0.028), SUA (p = 0.002), HOMA-index (p < 0.001), and eGFR (p = 0.014) were significantly associated with PWV. The multiple regression model showed that only age (p = 0.028), SBP z-score (p = 0.006), and heart rate (p = 0.001) were significantly associated with PWV. The results were superimposable when the DBP z-score replaced the SBP z-score in the model. Mediation models showed that the effect of eGFR on PWV was fully mediated by SUA (p = 0.015) and that the effect of SUA on PWV was totally mediated by HOMA-index (p < 0.001). Both SUA (p < 0.01) and HOMA-index (p < 0.01) had a significant association with higher SBP (DBP) z-scores. The double mediation model including both BP and HOMA-index showed that the SUA effect on PWV was totally mediated by both variables (p = 0.005, for HOMA-index, p = 0.004, for SBP z-score and p = 0.007, for combined effect). The results were superimposable when the DBP z-score replaced the SBP z-score in the model. In conclusion, insulin resistance and BP are both important mediators of the association between SUA and vascular stiffness in pediatric age.

Incident Atrial Fibrillation and In-Hospital Mortality in SARS-CoV-2 Patients.

(1) Background: Among the different cardiovascular (CV) manifestations of the coronavirus disease 2019 (COVID-19), arrhythmia and atrial fibrillation (AF) in particular have recently received special attention. The aims of our study were to estimate the incidence of AF in patients hospitalized for COVID-19, and to evaluate its role as a possible predictor of in-hospital all-cause mortality. (2) Methods: We enrolled 3435 people with SARS-CoV2 infection admitted to three hospitals in Northern Italy from February 2020 to May 2021. We collected data on their clinical history, laboratory tests, pharmacological treatment and intensive care unit (ICU) admission. Incident AF and all-cause in-hospital mortality were considered as outcomes. (3) Results: 145 (4.2%) patients developed AF during hospitalization, with a median time since admission of 3 days (I-III quartile: 0, 12). Patients with incident AF were admitted more frequently to the ICU (39.3 vs. 12.4%, p < 0.001), and more frequently died (37.2 vs. 16.9%, p < 0.001). In the Cox regression model, the significant determinants of incident AF were age (HR: 1.041; 95% CI: 1.022, 1.060 per year), a history of AF (HR: 2.720; 95% CI: 1.508, 4.907), lymphocyte count (HR: 0.584; 95% CI: 0.384, 0.888 per 103/µL), estimated glomerular filtration rate (eGFR, HR: 0.988; 95% CI: 0.980, 0.996 per mL/min) and ICU admission (HR: 5.311; 95% CI: 3.397, 8.302). Incident AF was a predictor of all-cause mortality (HR: 1.405; 95% CI: 1.027, 1.992) along with age (HR: 1.057; 95% CI: 1.047, 1.067), male gender (HR: 1.315; 95% CI: 1.064; 1.626), dementia (HR: 1.373; 95% CI: 1.045, 1.803), lower platelet (HR: 0.997; 95% CI: 0.996, 0.998 per 103/µL) and lymphocyte counts (HR: 0.843; 95% CI: 0.725, 0.982 per 103/µL), C-Reactive protein values (HR: 1.004; 95% CI: 1.003, 1.005 per mg/L), eGFR (HR: 0.990; 95% CI: 0.986, 0.994 per mL/min), and ICU admission (HR: 1.759; 95% CI: 1.292, 2.395). (4) Conclusions: Incident AF is a common complication in COVID-19 patients during hospitalization, and its occurrence strongly predicts in-hospital mortality.

Hypertension in children and adolescents.

Definition and management of arterial hypertension in children and adolescents are uncertain, due to different positions of current guidelines. The European Society of Cardiology task-force, constituted by Associations and Councils with interest in arterial hypertension, has reviewed current literature and evidence, to produce a Consensus Document focused on aspects of hypertension in the age range of 6-16 years, including definition, methods of measurement of blood pressure, clinical evaluation, assessment of hypertension-mediated target organ damage, evaluation of possible vascular, renal and hormonal causes, assessment and management of concomitant risk factors with specific attention for obesity, and anti-hypertensive strategies, especially focused on life-style modifications. The Consensus Panel also suggests aspects that should be studied with high priority, including generation of multi-ethnic sex, age and height specific European normative tables, implementation of randomized clinical trials on different diagnostic and therapeutic aspects, and long-term cohort studies to link with adult cardiovascular risk. Finally, suggestions for the successful implementation of the contents of the present Consensus document are also given.

Can SGLT2 inhibitors answer unmet therapeutic needs in chronic kidney disease?

Chronic kidney disease (CKD) is a global health problem, affecting more than 850 million people worldwide. The number of patients receiving renal replacement therapy (dialysis or renal transplantation) has increased over the years, and it has been estimated that the number of people receiving renal replacement therapy will more than double from 2.618 million in 2010 to 5.439 million in 2030, with wide differences among countries. The main focus of CKD treatment has now become preserving renal function rather than replacing it. This is possible, at least to some extent, through the optimal use of multifactorial therapy aimed at preventing end-stage kidney disease and cardiovascular events. Sodium/glucose cotransporter 2 inhibitors (SGLT2i) reduce glomerular hypertension and albuminuria with beneficial effects on progression of renal damage in both diabetic and non-diabetic CKD. SGLT2 inhibitors also show great benefits in cardiovascular protection, irrespective of diabetes. Therefore, the use of these drugs will likely be extended to the whole CKD population as a new standard of care.

Fructose Intake, Hypertension and Cardiometabolic Risk Factors in Children and Adolescents: From Pathophysiology to Clinical Aspects. A Narrative Review.

Arterial hypertension, dyslipidemia, alterations in glucose metabolism and fatty liver, either alone or in association, are frequently observed in obese children and may seriously jeopardize their health. For obesity to develop, an excessive intake of energy-bearing macronutrients is required; however, ample evidence suggests that fructose may promote the development of obesity and/or metabolic alterations, independently of its energy intake. Fructose consumption is particularly high among children, because they do not have the perception, and more importantly, neither do their parents, that high fructose intake is potentially dangerous. In fact, while this sugar is erroneously viewed favorably as a natural nutrient, its excessive intake can actually cause adverse cardio-metabolic alterations. Fructose induces the release of pro-inflammatory cytokines, and reduces the production of anti-atherosclerotic cytokines, such as adiponectin. Furthermore, by interacting with hunger and satiety control systems, particularly by inducing leptin resistance, it leads to increased caloric intake. Fructose, directly or through its metabolites, promotes the development of obesity, arterial hypertension, dyslipidemia, glucose intolerance and fatty liver. This review aims to highlight the mechanisms by which the early and excessive consumption of fructose may contribute to the development of a variety of cardiometabolic risk factors in children, thus representing a potential danger to their health. It will also describe the main clinical trials performed in children and adolescents that have evaluated the clinical effects of excessive intake of fructose-containing drinks and food, with particular attention to the effects on blood pressure. Finally, we will discuss the effectiveness of measures that can be taken to reduce the intake of this sugar.