Cardiovascular risk and the COVID-19 pandemic: A retrospective observational study in a population of healthcare professionals.

BACKGROUND AND AIM: To contain the spread of COVID-19, many countries imposed several restrictive measures, leading to radical changes in daily life behaviors. Healthcare workers experienced additional stress due to the increased risk of contagion, possibly causing an increase in unhealthy habits. We investigated changes in cardiovascular (CV) risk assessed by the SCORE-2 in a healthy population of healthcare workers during the COVID-19 pandemic; an analysis by subgroups was also conducted (sportspeople vs sedentary subjects). METHODS AND RESULTS: We compared medical examination and blood tests in a population of 264 workers aged over 40, performed yearly before (T0) and during the pandemic (T1, T2). We found a significant increase in the average CV risk, according to SCORE-2, during the follow-up in our healthy population, with a shift from a mean low-moderate risk profile at T0 (2.35%) to a mean high-risk profile at T2 (2.80%). Furthermore, in sedentary subjects was observed a greater and early increase in SCORE-2 compared to sportspeople. CONCLUSIONS: Since 2019, we observed an increase in CV risk profile in a healthy population of healthcare workers, particularly in sedentary subjects, highlighting the need to reassess SCORE-2 every year to promptly treat high-risk subjects, according to the latest Guidelines.

Changes in admissions, and hospitalization outcomes of IBD patients in an Italian tertiary referral center over a 13-year period.

OBJECTIVE: The management of Inflammatory Bowel Disease (IBD) has changed significantly in recent years, mainly due to the introduction of biologic medications, however, other factors may also have a role. The aim of this study was to evaluate the evolution of IBD admissions, including trends, modality of admission and rates of surgical intervention, in a tertiary care center. PATIENTS AND METHODS: Hospitalization of patients with a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) were identified between 2000 and 2013, using ICD-9-CM codes for IBD, from our hospital database. The following parameters were evaluated for each admission: type of admission (ordinary vs. day care service), mode of admission (elective vs. emergency care, for ordinary admissions only), admission code, surgical procedures and complication rates. Comparison between pre- and post-biologic therapy introduction years was also performed. RESULTS: Between 2000 and 2013 a total of 8834 IBD-related admissions were recorded. Hospitalizations increased linearly reaching a peak in 2006, with a downward trend in the following years. The downward trend was especially marked for patients younger than 40 years. No significant differences in hospitalization trends between CD and UC were recorded. Disease flare represented the cause of hospitalization in approximately 50% of cases. Overall, 10.8% of patients underwent surgery with no difference between the two conditions. Complications occurred in 28.7% of admissions. CONCLUSIONS: Hospitalizations for IBD patients have decreased in recent years, especially in younger patients. However, a significant proportion of patients are still admitted to complete diagnostic workup, indicating the need to better implement outpatient services. A clear reduction in surgery occurrence over time could not be observed in our study.

Probabilistic tsunami forecasting for early warning.

Tsunami warning centres face the challenging task of rapidly forecasting tsunami threat immediately after an earthquake, when there is high uncertainty due to data deficiency. Here we introduce Probabilistic Tsunami Forecasting (PTF) for tsunami early warning. PTF explicitly treats data- and forecast-uncertainties, enabling alert level definitions according to any predefined level of conservatism, which is connected to the average balance of missed-vs-false-alarms. Impact forecasts and resulting recommendations become progressively less uncertain as new data become available. Here we report an implementation for near-source early warning and test it systematically by hindcasting the great 2010 M8.8 Maule (Chile) and the well-studied 2003 M6.8 Zemmouri-Boumerdes (Algeria) tsunamis, as well as all the Mediterranean earthquakes that triggered alert messages at the Italian Tsunami Warning Centre since its inception in 2015, demonstrating forecasting accuracy over a wide range of magnitudes and earthquake types.

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 point of uric acid but previous evidence suggests that the negative impact of cardiovascular system could occur also at lower levels. In this context, the Working Group on uric acid and CV risk of the Italian Society of Hypertension has designed the Uric acid Right for heArt Health project. The primary objective of this project is to define the level of uricemia above which the independent risk of CV disease may increase in a significantly manner. In this review we will summarize the first results obtained and describe the further planned analysis.

Effects of ventilation mode and manual chest compression on flow bias during the positive end- and zero end-expiratory pressure manoeuvre in mechanically ventilated patients: a randomised crossover trial.

OBJECTIVES: To investigate the effects of ventilation mode and manual chest compression (MCC) application on the flow bias generated during positive end-expiratory pressure-zero end-expiratory pressure (PEEP-ZEEP) in mechanically ventilated patients. PEEP-ZEEP is an airway clearance manoeuvre with the potential to exceed the flow bias required to remove secretions. However, the ventilation mode applied during the manoeuvre has not been standardised. DESIGN: Randomised crossover trial. PARTICIPANTS: Nineteen mechanically ventilated patients. INTERVENTIONS: Patients were randomised to receive PEEP-ZEEP in volume-controlled and pressure-controlled modes, and with or without MCC. MAIN OUTCOME MEASURES: The difference in flow bias - assessed by the peak expiratory flow (PEF) and peak inspiratory flow (PIF) ratio and difference - between PEEP-ZEEP applied in both ventilation modes, and with and without MCC. RESULTS: The expiratory flow bias was significantly higher in the volume-controlled mode than the pressure-controlled mode. This result was caused by a lower PIF in the volume-controlled mode. PEEP-ZEEP applied in the pressure-controlled mode did not achieve the PEF-PIF difference threshold to clear mucus. Moreover, in the majority of cycles of PEEP-ZEEP applied in the pressure-controlled mode, an inspiratory flow bias was generated, which might embed mucus. PEF was 8l/minute higher with MCC compared with without MCC, which increased the PEF-PIF difference by the same amount. No haemodynamic or respiratory adverse effects were found. CONCLUSIONS: If applied in the volume-controlled mode, PEEP-ZEEP can achieve the flow bias needed to expel pulmonary secretions. However, this is not the case in the pressure-controlled mode. MCC can augment the flow bias generated by PEEP-ZEEP, but its application may be dispensable. CLINICAL TRIAL REGISTRATION: http://www.ensaiosclinicos.gov.br/rg/RBR-223xv8/.

Quality improvement of medical records through internal auditing: a comparative analysis.

INTRODUCTION: The systematic evaluation of the quality of medical records is crucial. Nevertheless, even if the improvement of medical records quality represents a priority for every health organization, it might be difficult to realize.This is the first study to assess the efficacy of internal audit as a tool to improve the quality of medical records in hospital setting. METHODS: The program was carried out in a third level teaching hospital. Trained ad hoc evaluation teams carried out two retrospective assessments of quality of medical records using a random sampling strategy. The quality assessment was performed using a 48-items evaluation grid divided into 9 domains: General; Patient Medical History and Physical Examination; Daily Clinical Progress Notes; Daily Nursing Progress Notes; Drug Therapy Chart; Pain Chart; Discharge Summary; Surgery Register; Informed Consent. After the first evaluation of 1.460 medical records, an audit departmental program was set up. The second evaluation was carried out after the internal auditing for 1.402 medical records. RESULTS: Compared to the first analysis, a significant quality amelioration in all the sections of the medical chart was shown with the second analysis, with an increase of all the scores above 50%. The differences found for each section of medical records between the first and second analysis are all significant (p<0.01). CONCLUSIONS: Internal audits are not just measurement activities but a necessary activity to support the organization in achieving its objectives and assessing the quality of clinical care and maintaining high quality professional performance.

Overview on surgical management of papillary thyroid microcarcinoma.

Particular interest is now being given to the best treatment of papillary thyroid microcarcinoma (PTMC) due to its significantly increased incidence. PTMC typically shows indolent organic behavior but, in a low percentage of cases, it can express a relative aggressive behavior. Several risk factors have been shown to negatively influence the rate of regional recurrences and metastases such as tumor diameter, Romaage, sex, multifocality, capsular invasion, extracellular diffusion, lymph node metastases, histological variants, mutated Braf and incidentality. The identification of patients with aggressive PTMCs among the majority with low risk lesions is very important to plan an adequate clinical management, thus the most appropriate surgical treatment. The latter includes thyroid lobectomy and total thyroidectomy with central compartment lymphadenectomy, though several studies did not show statistically significant differences in terms of recurrence and mortality rates between the two techniques. At last, it seems crucial to better define those biological features able to improve selection making process of patients with PTMCs aiming to reserve more radical surgery to those patients carrying more aggressive clinicopathologic features and worse prognosis.

Italian acacia honey exhibits lytic effects against the crayfish pathogens Aphanomyces astaci and Fusarium avenaceum.

This study purpose was to evaluate the in vitro inhibitory properties of Italian acacia honey extracts against pathogenic aquatic oomycete/fungal isolates that cause different diseases in crayfish, resulting in an elevated mortality rate. The antimycotic activity of acacia honey aqueous extracts was evaluated against the strain UEF88662 of Aphanomyces astaci (oomycete) and the strain SMM2 of Fusarium avenaceum (fungus). The extracts preparation was carried out with water by a cheap, not complex and organic solvent-free procedure, with low environmental impact and the higher possibility of large-scale reproducibility. The anti-oomycete and antifungal activities were quantitatively evaluated by growth, survival and sporulation microbiological assays. The extracts displayed a dose-dependent inhibitory efficacy on oomycete and fungal growth and survival, as well as on the production of oomycete and fungal spores. Supported by future in vivo studies, our results encourage the use of natural extracts like honey as innovative tools to counteract mycotic infections. SIGNIFICANCE AND IMPACT OF THE STUDY: The continuous spread of aquatic fungal disease as the 'crayfish plague' and the 'burn spot disease' has severe ecological and commercial repercussions. Critical factor to prevent further spread is the availability of effective antifungals possibility derived from local natural resources to use in innovative strategies of control and eradication of these diseases. This study provides relevant information about the in vitro anti-oomycete and antifungal activity of Italian acacia honey aqueous extracts against two highly infectious and dangerous pathogenic species, Aphanomyces astaci and Fusarium avenaceum, that are responsible for important crayfish diseases.

Update on sutureless thyroidectomy.

INTRODUCTION: The Harmonic scalpel ("Focus" and the new version "Focus+") is one of the first devices for surgical simultaneous cutting and tissue coagulation which allows to obtain dissection and hemostasis by direct application of ultrasound and allows minimally invasive surgical procedures with minimal lateral thermal spread and, thus, minimal adjacent tissue destruction. The aim of the study is to complete the previous study that we made in 2014, based on the TT performed between January 2008 and December 2013, with new data about TT performed in our Surgical Division between January 2014 and December 2016 and compare the outcome using the Ultrasonic scalpel versus the device Ligasure in term of safety, operative time, overall drainage volume, complications, hospital stay. PATIENTS AND METHODS: 250 patients were randomized into two groups: Group A where Ultracision were used and Group B where the Ligasure device was used. RESULTS: The results of the group A and of the Group B 2014-2016 have been compared with the results of the previous study and we found that they are similar, but asymptomatic hypocalcaemia increased in the patients of the new study. CONCLUSIONS: We found that the use of Ultrasonic scalpel and Ligasure is effective both in the hemostasis of all vessels and in dissection of tissues and confirm the results of our first study without significant difference in the rate of post-operative morbidity with these two different energy based devices used.

Single blind, multicentre, randomized, controlled trial testing the effects of a novel nutraceutical compound on plasma lipid and cardiovascular risk factors: Results of the interim analysis.

BACKGROUND AND AIMS: The clustering of high levels of LDL cholesterol (LDL-C) and other risk factors represents a predisposing condition for atherosclerotic disease development. Cardiovascular prevention is based on effective control of these conditions. In adult subjects with mild hypercholesterolemia we compared in the real life the effects of a new combination of nutraceuticals on lipid and glucose metabolism and blood pressure with those of an established nutraceutical combination. METHOD AND RESULTS: This multicenter, controlled, randomized, single-blind trial was designed to compare the effect of Armolipid Plus® versus that of LopiGLIK® on lipid and glucose levels and blood pressure (BP) in subjects with mild hypercholesterolemia not on statin therapy. Primary outcome was the proportion of subjects achieving therapeutic targets of LDL-C (<130 mg/dl); secondary outcomes were the effects on HDL-C, glycated haemoglobin and insulin levels. Data from an overall sample of 359 adult individuals (age 55.2 ± 11.1 years, women 57.7%, LDL-C 157.3 ± 22.6 mg/dl, HDL-C 50.7 ± 13.0 mg/dl) are reported. 72% of subjects treated with LopiGLIK® and 43% treated with Armolipid Plus® achieved the primary endpoint (p < 0.0001). Both treatments reduced plasma levels of total and LDL-C and triglycerides (p < 0.001 for all comparisons). The treatments also reduced systolic and diastolic blood pressure, plasma levels of glycated haemoglobin, insulin and HOMA index. The changes induced by LopiGLIK® in all these metabolic parameters were greater than those obtained with Armolipid Plus®. CONCLUSIONS: The present analysis shows that LopiGLIK® may represent a more effective tool for clinical management of CV risk factors in subjects with mild hypercholesterolemia.

Sustainability of Endovenous Iron Deficiency Anaemia Treatment: Hospital-Based Health Technology Assessment in IBD Patients.

Iron deficiency anaemia (IDA) is the main extraintestinal manifestation affecting patients with inflammatory bowel disease (IBD). The Health Technology Assessment approach was applied to evaluate the sustainability of intravenous (IV) iron formulations in the Italian hospital setting, with particular focus on ferric carboxymaltose. Data on the epidemiology of IBD and associated IDA, in addition to the efficacy and safety of IV iron formulations currently used in Italy, were retrieved from scientific literature. A hospital-based cost-analysis of the outpatient delivery of IV iron treatments was performed. Organizational and ethical implications were discussed. IDA prevalence in IBD patients varies markedly from 9 to 73%. IV iron preparations were proven to have good efficacy and safety profiles, and ferric carboxymaltose provided a fast correction of haemoglobin and serum ferritin levels in iron-deficient patients. Despite a higher price, ferric carboxymaltose would confer a beneficial effect to the hospital, in terms of reduced cost related to individual patient management and additionally to the patient by reducing the number of infusions and admissions to healthcare facilities. Ethically, the evaluation is appropriate due to its efficacy and compliance. This assessment supports the introduction of ferric carboxymaltose in the Italian outpatient setting.

Temporal correlation between differentiation factor expression and microRNAs in Holstein bovine skeletal muscle.

Satellite cells are adult stem cells located between the basal lamina and sarcolemma of muscle fibers. Under physiological conditions, satellite cells are quiescent, but they maintain a strong proliferative potential and propensity to differentiate, which underlies their critical role in muscle preservation and growth. MicroRNAs (miRNAs) play essential roles during animal development as well as in stem cell self-renewal and differentiation regulation. MiRNA-1, miRNA-133a and miRNA-206 are closely related muscle-specific miRNAs, and are thus defined myomiRNAs. MyomiRNAs are integrated into myogenic regulatory networks. Their expression is under the transcriptional and post-transcriptional control of myogenic factors and, in turn, they exhibit widespread control of muscle gene expression. Very little information is available about the regulation and behavior of satellite cells in large farm animals, in particular during satellite cell differentiation. Here, we study bovine satellite cells (BoSCs) undergoing a differentiation process and report the expression pattern of selected genes and miRNAs involved. Muscle samples of longissimus thoracis from Holstein adult male animals were selected for the collection of satellite cells. All satellite cell preparations demonstrated myotube differentiation. To characterize the dynamics of several transcription factors expressed in BoSCs, we performed real-time PCR on complementary DNA generated from the total RNA extracted from BoSCs cultivated in growth medium (GM) or in differentiation medium (DM) for 4 days. In the GM condition, BoSCs expressed the satellite cell lineage markers as well as transcripts for the myogenic regulatory factors. At the time of isolation from muscle, PAX7 was expressed in nearly 100% of BoSCs; however, its messenger RNA (mRNA) levels dramatically decreased between 3 and 6 days post isolation (P<0.01). MyoD mRNA levels increased during the 1st day of cultivation in DM (day 7; P<0.02), showing a gradual activation of the myogenic gene program. During the subsequent 4 days of culture in DM, several tested genes, including MRF4, MYOG, MEF2C, TMEM8C, DES and MYH1, showed increased expression (P<0.05), and these levels remained high throughout the culture period investigated. Meanwhile, the expression of genes involved in the differentiation process also miRNA-1, miRNA-133a and miRNA-206 were strongly up-regulated on the 1st day in DM (day 7; P<0.05). Analysis revealed highly significant correlations between myomiRNAs expression and MEF2C, MRF4, TMEM8C, DES and MYH1 gene expression (P<0.001). Knowledge about the transcriptional changes correlating with the growth and differentiation of skeletal muscle fibers could be helpful for developing strategies to improve production performance in livestock.

Prevalence and control of hypertension in the general practice in Italy: updated analysis of a large database.

Systematic assessment of blood pressure (BP) control rates may help to improve the clinical management of hypertension in clinical practice. This approach had limited application in Europe over the last three decades and only recently has been implemented in some countries. The present study is aimed at evaluating hypertension prevalence and control among adult outpatients followed by a large, representative sample of general practitioners (GPs) in Italy. We retrospectively analysed the data derived from the GP Health Search-CSD database in 2013. Hypertension prevalence and control were estimated within the overall population sample and in hypertensive outpatients, respectively, according to age and gender. Hypertension diagnosis was defined according to the International Classification of Diseases 9. Clinic BP levels were measured according to the European guidelines. BP control was defined as systolic/diastolic BP <140/90 mm Hg. Data from 911 753 individuals (52.2% females) were scrutinized. Hypertension was diagnosed in 236 377 (25.9%) patients, being higher in male aged <70 years than age-matched female. Hypertension control was recorded in 60.6% of hypertensive patients, being higher in female than male individuals aged <70 years. Our current analysis demonstrates that about 26% of adult outpatients followed in the GP setting had hypertension and that about 61% had controlled BP levels. Both prevalence and control of hypertension appear to be higher when compared with the data reported from the analysis of the same database in 2005, thus confirming a positive trend in BP control in the GP clinical setting in Italy.

Novel antidiabetic drugs and cardiovascular risk: Primum non nocere.

AIMS: Diabetes treatments aim at preventing undesirable metabolic effects of hyperglycemia and at preventing/reducing tissue damage, including cardiovascular (CV) events. For approval, novel diabetes drugs undergo early systematic investigation to assess CV safety. This review provides an updated analysis of the results of recent studies examining novel diabetes medications and CV outcomes. DATA SYNTHESIS: The new regulatory guidelines enforce adjudication of all CV events when testing novel diabetes drugs. Endpoints of CV mortality, myocardial infarction (MI), stroke and hospitalization for heart failure (HF) were included in the most recent clinical studies on novel antihyperglycemics. These are: the incretin mimetics glucagon-like peptide 1 (GLP-1) receptor agonists (GLP1-RA), the incretin enhancers dipeptidylpeptidase-4 (DPP-4) inhibitors (DPP4-I or gliptins), and the sodium-glucose cotransporter (SGLT2) inhibitors (SGLT2-I or gliflozins). The studies ELIXA and EXAMINE, testing lixisenatide and alogliptin, respectively, revealed non-inferiority versus placebo in terms of CV safety. The SAVOR-TIMI 53 results confirmed overall CV safety of saxagliptin, but raised a warning related to the increase in the risk of hospitalization for HF in the saxagliptin group. Recently, TECOS revealed a particularly favorable CV profile for sitagliptin while EMPA-REG showed a significant CV risk reduction in empagliflozin treated subjects. Ongoing studies will provide additional data on CV safety for other GLP1-RAs, DPP4-I and SGLT2-I. CONCLUSIONS: Results of safety outcome studies focused on CV events, including HF and mortality for CV causes, are not homogeneous. A critical analysis of these studies may help cardiologists and diabetes specialists to adapt their therapeutic choices to individual patients.

Differential expression of living mammary epithelial cell subpopulations in milk during lactation in dairy cows.

Epithelial cells are shed into milk during lactation, and although they generally reflect the cellular characteristics of terminally differentiated luminal cells, previously the detection of more primitive cells was described in human milk where a cell population of epithelial lineage was detected expressing markers typical of progenitor cells. In this investigation, we report the development of flow cytometry analysis to allow multiparametric assessment of mammary epithelial cells observed in milk. Cells collected from milk samples of 10 healthy dairy cows were directly analyzed for 6 different markers: CD45, CD49f, cytokeratin 14, cytokeratin 18, presence of nucleus, and cell viability. Milk samples were collected in 3 different periods of lactation: early lactation (EL=d 0-30), mid-lactation (ML=d 90-120), and late lactation (LL=210-250). Here we identify the differential expression of precursor or differentiated cell markers (or both) in mammary epithelial cells present in bovine milk. Myoepithelial cells, as indicated by cells staining positively for cytokeratin 14(+)/cytokeratin 18(-), were observed to increase from EL to LL with a high correlation with nuclear staining inferring potential proliferative activity. Furthermore, a significant increase in CD49f(+) and cytokeratin 14(+)/cytokeratin 18(+) positive cells was observed in LL. This assay is a sensitive approach for evaluating the variations in the frequency and features of living epithelial cells, whose reciprocal balance may be significant in understanding mammary gland cellular function throughout lactation. These observations suggest that mammary epithelial cell immunophenotypes could be investigated as biomarkers for mammary gland function in dairy cows.

Clinical management of patients with hypertension and high cardiovascular risk in specialised centers and in general practice. Analysis from an Italian Survey Questionnaire.

BACKGROUND AND AIM: Hypertension control remains poorly achieved worldwide, despite the use of modern diagnostic tools and advanced therapeutic strategies. We aimed to evaluate the preferences expressed by either specialised physicians (SPs) or general practitioners (GPs) for the clinical management of hypertension and high cardiovascular risk in Italy. METHODS AND RESULTS: A predefined questionnaire was anonymously administered to a large community sample of physicians, stratified according to clinical expertise. From a total of 64 questions, 557 physicians (478 male, mean age 54.2 ± 7.1 years, average age of medical activity 28.0 ± 8.1 years), including 261 (46.9%) SPs and 296 (53.1%) GPs, provided 9564 answers to the survey questionnaire. Involved clinicians spent the majority of their time and practice for hypertension management and control. SPs aimed to achieve the recommended BP targets (<140/90 mmHg), whereas GPs tended to achieve more rigorous BP goals (<130/80 mmHg); nonetheless, they both reported a very high rate of BP control (about 70%). Concomitant presence of diabetes, organ damage, as well as comorbidities, was reported to be relatively frequent (26-50%), mostly by SPs. ESH/ESC 2007 risk score stratification was preferred by SPs compared to GPs, who favored a comprehensive clinical evaluation. ACE inhibitors or ARBs were considered the best pharmacological option to start antihypertensive treatment, thus adding diuretics or calcium-channel blockers, if needed. CONCLUSIONS: This predefined analysis of a survey questionnaire showed relatively different opinions with respect to recommended BP targets and distributions of cardiovascular risk profile, and similar diagnostic and therapeutic choices between GPs and SPs.

Angiotensin II Receptor Blocker Neprilysin Inhibitor (ARNI): New Avenues in Cardiovascular Therapy.

The burden of cardiovascular disease (CVD) is continuously and progressively raising worldwide. Essential hypertension is a major driver of cardiovascular events, including coronary artery disease, myocardial infarction, ischemic stroke and congestive heart failure. This latter may represent the final common pathway of different cardiovascular diseases, and it is often mediated by progressive uncontrolled hypertension. Despite solid advantages derived from effective and sustained blood pressure control, and the widespread availability of effective antihypertensive medications, the vast majority of the more than 1 billion hypertensive patients worldwide continue to have uncontrolled hypertension. Among various factors that may be involved, the abnormal activation of neurohormonal systems is one consistent feature throughout the continuum of cardiovascular diseases. These systems may initiate biologically meaningful "injury responses". However, their sustained chronic overactivity often may induce and maintain the progression from hypertension towards congestive heart failure. The renin-angiotensin-aldosteron system, the sympathetic nervous system and the endothelin system are major neurohormonal stressor systems that are not only able to elevate blood pressure levels by retaining water and sodium, but also to play a role in the pathophysiology of cardiovascular diseases. More recently, the angiotensin receptor neprilysin inhibitor (ARNI) represents a favourable approach to inhibit neutral endopeptidase (NEP) and suppress the RAAS via blockade of the AT1 receptors, without the increased risk of angioedema. LCZ696, the first-in-class ARNI, has already demonstrated BP lowering efficacy in patients with hypertension, in particular with respect to systolic blood pressure levels, improved cardiac biomarkers, cardiac remodelling and prognosis in patients with heart failure. This manuscript will briefly overview the main pathophysiological and therapeutic aspects of ARNI in the clinical management of hypertension and heart failure.

Blood pressure levels and control in Italy: comprehensive analysis of clinical data from 2000-2005 and 2005-2011 hypertension surveys.

This analysis is aimed to determine blood pressure (BP) levels and BP control rates in a large population of hypertensive patients in Italy. Data were taken from two large and inclusive cross-sectional surveys, which covered two distinct and subsequent time periods (2000-2005 and 2005-2011, respectively). Observational clinical studies and surveys, which reported average systolic/diastolic clinic BP levels, proportions of treated/untreated and controlled/uncontrolled patients, and prevalence of cardiovascular risk factors in hypertensive patients followed in either outpatient clinics, hypertension centres or general practice, were considered for the analyses. The overall sample included 211 591 hypertensive patients (119 997 (56.7%) women, age 57.0±10.0 years, body mass index 26.9±4.0 kg m(-2), BP levels 146.9±16.7/88.7±9.6 mm Hg). BP levels were 148.2±15.4/87.5±9.3 mm Hg in patients followed by general practitioners (n=168 313, 79.5%), 148.1±17.3/90.1±9.7 mm Hg in those followed by hypertension centres (n=28 180, 13.3%), and 142.4±17.6/86.6±9.8 mm Hg in those followed by outpatient clinics and hospital divisions (n=15 098, 7.1%). Among treated hypertensive patients (n=128 079; 60.5%), 43 008 (33.6%) were reported to have controlled BP levels. Over one decade of observation, we reported that ~60% of hypertensive patients were treated and among these only 33% achieved effective BP control. These findings highlight the need for more effective interventions to improve management of hypertension in Italy.

C2238/αANP modulates apolipoprotein E through Egr-1/miR199a in vascular smooth muscle cells in vitro.

Subjects carrying the T2238C ANP gene variant have a higher risk to suffer a stroke or myocardial infarction. The mechanisms through which T2238C/αANP exerts detrimental vascular effects need to be fully clarified. In the present work we aimed at exploring the impact of C2238/αANP (mutant form) on atherosclerosis-related pathways. As a first step, an atherosclerosis gene expression macroarray analysis was performed in vascular smooth muscle cells (VSMCs) exposed to either T2238/αANP (wild type) or C2238/αANP. The major finding was that apolipoprotein E (ApoE) gene expression was significantly downregulated by C2238/αANP and it was upregulated by T2238/αANP. We subsequently found that C2238/αANP induces ApoE downregulation through type C natriuretic peptide receptor (NPR-C)-dependent mechanisms involving the upregulation of miR199a-3p and miR199a-5p and the downregulation of DNAJA4. In fact, NPR-C knockdown rescued ApoE level. Upregulation of miR199a by NPR-C was mediated by a reactive oxygen species-dependent increase of the early growth response protein-1 (Egr-1) transcription factor. In fact, Egr-1 knockdown abolished the impact of C2238/αANP on ApoE and miR199a. Of note, downregulation of ApoE by C2238/αANP was associated with a significant increase in inflammation, apoptosis and necrosis that was completely rescued by the exogenous administration of recombinant ApoE. In conclusion, our study dissected a novel mechanism of vascular damage exerted by C2238/αANP that is mediated by ApoE downregulation. We provide the first demonstration that C2238/αANP downregulates ApoE in VSMCs through NPR-C-dependent activation of Egr-1 and the consequent upregulation of miR199a. Restoring ApoE levels could represent a potential therapeutic strategy to counteract the harmful effects of C2238/αANP.