key: cord-0013071-2idl8dgx
authors: nan
title: Abstracts from 2020 national congress of the Italian Society of Hypertension (SIIA)
date: 2020-10-01
journal: High Blood Press Cardiovasc Prev
DOI: 10.1007/s40292-020-00410-0
sha: 079ec4e68398ab2239fbb607f318408e89599bfd
doc_id: 13071
cord_uid: 2idl8dgx

nan

INTRODUCTION: Sodium-Glucose Co-Transporter-2 Inhibitors (SGLT2i) act on the proximal renal tubule and have been found to exert relevant cardiovascular benefits beyond the mere glycemic control in patients with diabetes. Their use have been associated to a reduction in both target organ damage and cardiovascular events, mainly heart failure and progression of renal disease. METHODS: We performed an extensive review of the available literature aiming at describing the main pathophysiological mechanisms of SGLT2i that may have led to such positive findings in the randomized clinical trials performed with this drug class. RESULTS: These ''antidiabetic'' drugs act as ''hybrid'' diuretics. Indeed, they promote both natriuresis and osmotic diuresis due to glycosuria, leading to a reduction in blood volume and blood pressure. This peculiar activity, not found in the other classic diuretics, is mainly derived by the stimulation of the renal tubuleglomerular feedback, leading to the release of adenosine by macula densa cells, resulting in a vasoconstriction of the afferent arteriole and a reduction of renin release. These mechanisms lead to lower intraglomerular pressure, preventing the hyperfiltration-mediated organ damage tipically found in diabetes, hypertension and obesity. In the CREDENCE trial, Canagliflozin led to a 30% reduction in both the progression of renal disease and cardiovascular deaths in patients with diabetes (but no renal disease) who were also taking renin-angiotensin-system inhibitors. Natriuresis and glycosuria lead to lower circulating blood volume and pressure, resulting in lower cardiac overload. Indeed, SGLT2i have been found to reduce both hospitalizations and cardiovascular deaths in patients with heart failure, regardless the diabetic condition, also improving both symptoms and cardiac remodeling. CONCLUSIONS: The beneficial effects of SGLT2i, supported by multiple clinical data, suggest a more extensive use of these drugs also by internists, cardiologists and nefrologists.

age, history and state of hypertension, divided in 292 normouricemic (NSUA: \ 5.34 mg/dl), 73 BSUA e 165 (HSUA) underwent ABPM, identification of metabolic syndrome factors (MSn), arterial tonometry for stiffness measurement (PWVcf) and assessment of cognitive impairment (CIS) by multiple choice (1) (2) (3) (4) 18-item questionnaire investigating different neuropsychological functions. RESULTS: Patients showed similar hypertensive state (134 ± 15/80 ± 9 vs 136 ± 14/81 ± 8 vs 136 ± 15/ 81 ± 9;n.s.), confirmed by ABPM, but other significant characteristics. (m ± s:d.*:p \ .05, **:p \ .01, ***:p \ .001 vs NSUA;°:p \ .05,°°:p \ .01,°°°:p \ .001 vs BSUA). INTRODUCTION: Nephrolithiasis (NL) is a common multifactorial disease associated with high morbidity if not correctly diagnosed and treated. NL is characterized by an increasing incidence and prevalence in the adult population of industrialized countries, most evident in the females. For the primary and secondary prevention of NL, it is recommended a normocalcic hyposodic diet associated with hydropinic therapy. AIM: to evaluate the habitual salt intake of subjects with recurrent NL. METHODS: Were evaluated all adult subjects, both sexes, who went to the extracorporeal lithotripsy (ESWL) ambulatory of the Azienda Universitaria Federico II hospital, in the time interval between 1st May 2019 and 1st September 2019 affected by idiopathic NL. The habitual salt intake and the consciousness of its use were evaluated using the MINISAL-SIIA questioner. RESULTS: Were examined 69 male subjects treated with ESWL (mean age 50.3 ± 13.5 yr, BMI: 27.7 ± 4.2 kg/m 2 ) and 68 female subjects treated with ESWL (mean age 55.0 ± 10.8 yr, BMI: 28.0 ± 5.9 kg/m 2 ). The average MINISAL-SIIA score is 9.0 ± 1.2 in male and 9.0 ± 1.5 in female subjects (p \ 0.05). The percentage of subjects with MINISAL-SIIA score that identifies high salt consumption (equal or more than 10) is 30.4% in male and 35.3% in female subjects (p \ 0.05). The percentage of subjects who declare to eat cheese and cured meats 3 or more times a week is significantly higher in males on females (42% vs 26m4%, p = 0.03). The percentage of subjects who correctly indicates the daily salt intake recommended by World Health Organization is 62.3% of male and 69.1% of female subjects. CONCLUSIONS: Despite hyposodic diet is the pivot of primary and secondary prevention of nephrolithiasis, our studies demonstrate a reduced adherence to the hyposodic diet, and a reduced knowledge of the correct daily salt intake recommended by World Health Organization.

(CPAP) is the main therapy for obstructive sleep apnoea (OSA); nevertheless, uncertainty remains about the effectiveness of CPAP not only in controlling OSA-related hypertension, but also in improving the metabolic dysregulation that characterizes OSA patients. AIM: This meta-analysis of randomized controlled trials (RCTs) aimed to investigate whether CPAP therapy, compared to other control treatments (sham CPAP, oral placebo or standard care), could improve glucose metabolism (fasting plasma glucose [FPG] or glycated haemoglobin or fasting plasma insulin [FPI] In subgroups analysis, greater adherence to CPAP therapy along with severe nocturnal oxygen desaturations at baseline (SpO2-nadir \ 77%) was associated with a significant decrease of TC. Furthermore, dividing the primary studies according to the median TC at baseline (198 mg/dL), the positive effects of CPAP were maintained only in those that presented a TC above the median. Conversely, CPAP did not modify triglycerides, HDL-, and LDL-cholesterol. CONCLUSIONS: CPAP treatment significantly improves insulin sensitivity and reduces TC in OSA patients but with a low effect size. The effectiveness of CPAP therapy is higher in patients with greater CPAP usage, and with a greater number of apnoeic events and oxygen desaturations at baseline. Concerning TC, patients presenting higher levels at baseline benefit the most from CPAP.

The relationship between serum uric acid (SUA) and microvascular remodeling in humans remains largely unexplored. AIM: We assessed whether SUA provides additional information on the severity of microvascular remodeling than that obtained from the European Heart Score (HS), the patterns of microvascular remodeling associated with changes in SUA levels and the mediation by endothelial function and NO availability on this relationship. METHODS: A total of 162 patients included in the microvascular dataset of the Italian Society of Hypertension with available information on SUA, media-to-lumen (M/L) ratio, media cross-sectional area (MCSA), endothelial function, NO availability and HS were included in the analysis. The top tertile of M/L ratio and MCSA were used to define severe microvascular remodeling. RESULTS: A U-shaped association was observed between SUA and both M/L ratio and MCSA. Adjustment for HS did not affect these associations. SUA was able to reclassify a significant amount of subjects without and with severe M/L ratio and MCSA remodeling over the HS alone. The microvascular remodeling associated with SUA levels presented a predominant hypertrophic pattern. SUA was inversely associated with endothelialfunction and NO availability. Structural equation modeling analysis controlling for the HS suggested that the association of SUA with M/L ratio and MCSA was mediated through changes in endothelial function and NO availability.

CONCLUSIONS: The addition of SUA to the HS improves the identification of subjects with greater microvascular remodeling. The relationship between SUA and microvascular remodeling is mediated by endothelial function and NO availability. mg/dL, HDL-C = 50.8 ± 12.7 mg/dL, non HDL-C = 118.9 ± 35.9 mg/ dL, TG = 90.3 ± 77.9 mg/dL, LDL-Cd = 106.2 ± 29.9 mg/dL, LDL-Cf = 100.9 ± 33.8 mg/dL, and LDL-Cs = 102.2 ± 33.4 mg/dL. RESULTS: Comparing the distance to the LDL-Cd, Friedewald's formula mildly but significantly underestimated in infants (3.4 ± 5.3 mg/dL), preschoolers (1.5 ± 7.1 mg/dL). Children (1.2 ± 2.2 mg/dL) and adolescents (1.1 ± 5.9 mg/dL) compared to Sampson's formula (all comparisons, p \ 0.001) (see figure-136_20200617133601). CONCLUSIONS: Our analysis, being carried out on a large population sample, shows that Sampson's formula is more reliable than Friedewald's one at each considered age class and even for extreme TG values.

INTRODUCTION: Serum uric acid (SUA) can stratify patients with different cardiovascular risk and has been depicted as a contributory causal factor in metabolic syndrome (MS), which in turn portends an unfavourable prognosis. AIM: We assessed the independent prognostic role of SUA in patients with MS. METHODS: We used data from the multicentre, retrospective, observational URRAH (Uric Acid Right for Heart Health), which recruited subjects from hypertension clinics. The outcome we considered was cardiovascular mortality (CVM), defined as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure. RESULTS: A total of 9589 subjects (median age 58.5 years old, 45% males) were included in the analysis, and 5100 (53%) patients had a final diagnosis of MS. After a median follow-up of 142 months, we observed 558 events. Using a previously validated cardiovascular SUA cut-off to predict CVM ([ 5.1 mg/dL in women and 5.6 mg/dL in men), elevated SUA levels were significantly associated to a worse outcome in patients with and without MS (all p \ 0.0001) and provided a significant net reclassification improvement of 5.1% over the diagnosis of MS for CVM (p = 0.004). Multivariate Cox regression analyses identified an independent association between SUA and CVM ]; p \ 0.001) after the adjustment for MS, its single components and other common CV risk factors. CONCLUSIONS: Increasing SUA levels are associated with a higher risk of CVM irrespective of the presence of the MS. A cardiovascular SUA threshold may improve cardiovascular risk stratification in patients with MS. INTRODUCTION: historically, women have been underrepresented in clinical trials: particularly, only a few studies described gender effect on surgical and non-surgical interventions, with discordant results. AIM: to investigate whether and how gender influences weight loss (WL) in two different populations, after sleeve gastrectomy and Ketogenic diet. METHODS: 125 patients with morbid obesity (BMI 40 kg/m 2 or 35 kg/m 2 ? comorbidity) eligible to sleeve gastrectomy (group1) and a group of 40 patients following a ketogenic diet (group2). We evaluated anthropometric parameters, peripheral BP, biochemical and serum analysis at the enrollment and at twelve months after interventions. RESULTS: in the whole population there was a female prevalence (70% in group1 and 60% in group2). Males presented increased adiposity (measured as VFA and fat mass) in both groups and a worse glyco-metabolic profile in group1. Only after ketogenic diet we observed a significant difference between sexes in total body WL (7.4% in males vs 5.9% in females, p \ 0.05) and excess of body WL (15.7% in males vs 12.1% in females, p \ 0.05) in favour of male population. However, only in group1, we observed a larger and significant improvement in adiposity (VFA, fat mass) and glyco-metabolic (HOMA-IR, HbA1c) parameters in males rather than in females. CONCLUSIONS: male subjects, beyond a higher weight and BMI, had a worse glyco-metabolic pattern. No significant difference between sexes was found in WL in group 1 patients; on the contrary, male patients seemed to have a major benefit in WL from ketogenic diet in comparison to female population. In both groups, male sex was an independent predictor of EBWL. Gender differences in WL intervention could be determined by several factors: hormonal profiles, different body composition or higher initial weight in males. Further studies are necessary to investigate the determinants of these differences.

Francesca Battista 1 , Neunhäuserer Daniel 1 , Quinto Giulia 1 , Frigo Anna Chiara 2 , Bianchi Elia 1 , Gobbo Stefano 1 , Ortolan Sara 1 , Gasperetti Andrea 1 , Ermolao Andrea 1 1-Department of Medicine, Sports and Exercise Medicine Division, University of Padova; Regional Center for Exercise Prescription in Chronic Diseases, Veneto Region, Italy; 2-Department of Cardiac, Thoracic and Vascular Sciences, Biostatistics, Epidemiology and Public Health Unit, University of Padova, Padova, Italy INTRODUCTION: Cardiorespiratory fitness is a strong predictor of morbidity and mortality also in people with obesity. However, no reference values of aerobic capacity are currently available for subjects with severe obesity and comorbidities. AIM: This study describe the distribution of aerobic capacity in a group of patients with severe obesity and its relationship with comorbidities. METHODS: observational study on 542 patients (69% Females) with BMI C 30 kg/m 2 that consecutively performed a Cardiopulmonary Exercise Test (CPET) by using incremental ramp treadmill test (modified Bruce protocol) or bicycle ergometer test (?15 W/minute). Anthropometric and clinical data were recorded simultaneously. RESULTS: The median (IQR) age is 47.0(62) years, mean BMI is 41.7 ± 6.7 kg/m 2 . Normal values curves have been developed for relative VO2peak (VO2peak/Kg) that shows mean value of 20.9 ± 4.8 ml/min/Kg (median/IQR = 20.3/ 37.6 ml/min/Kg). Upper limit of the lower quartile of VO2peak/kg is 17.87 ml/min/Kg. Mean absolute VO2peak is 2.410 ± 6.7 L/min. Analysis of covariance (ANCOVA) displays that VO2peak/kg inversely correlates with age (p 0.0001) and BMI (p 0.0001) and also a significant effect of the interaction term age*BMI (p 0.0001). ANCOVA of absolute VO2peak shows direct correlation with BMI (p 0.0001), inverse correlation with age (p 0.0001) and significant effect of the interaction term age*gender (p 0.0006). Both relative and absolute VO2peak are lower in females than in males (p 0.0001). A multivariate logistic regression model points out that the odds of belonging to the lower quartile of VO2peak/kg is independently determined by age (age 47-54 years OR 2.549 IC 95% 1.205-5.392 p \ 0.0001) and BMI (BMI [ 45 kg/m 2 OR 5.864 IC 95% 2.920-11.778 p \ 0.0001), but not by number of comorbidities. INTRODUCTION: While it is commonly thought that left ventricular (LV) systolic function may insidiously deteriorate in hypertensive patients, few prospective data are available to support this notion. METHODS: We evaluated 680 hypertensive patients (66 ± 7 years; 45% women) with ECG-LV hypertrophy enrolled in the LIFE echo-substudy. Only patients free of prevalent cardiovascular disease and with baseline ejection fraction (EF) C 55% were included. Echocardiographic exams were performed annually for 5 years during antihypertensive treatment. Development of reduced systolic function was defined as incident EF \ 50%. RESULTS: During a mean follow up of 4.8 ± 1 years, 37 patients developed reduced EF without an intercurrent myocardial infarction (5.4%). Patients who developed reduced EF were more often men (p \ 0.05). In analysis of covariance, patients who developed reduced EF had greater baseline LV diameter and LV mass, lower mean EF (all p \ 0.05), and similar diastolic function indices. At last available exam before EF reduction, independently of covariates, patients with reduced EF showed a significant increase in LA size, LV diameter, end-systolic stress and mitral E/A ratio, as compared to those who did not develop reduced EF (all p \ 0.05). In time-varying Cox regression analysis, also controlling for baseline EF, predictors of developing reduced EF were higher in-treatment LV diameter (HR = 5.19 per cm; 95% CI 2.58-10.41) and higher in-treatment mitral E/A ratio (HR = 2.37; 95% CI 1.58-3.56; both p \ 0.0001).

In treated hypertensive patients, incident reduced EF is associated with the development of dilated LV chamber and signs of increased LV filling pressure. Higher in-treatment LV diameter and mitral E/A ratio are the strongest echocardiographic predictors of reduced EF 

GINGIVAL BLEEDING IS ASSOCIATED WITH HIGH BLOOD PRESSURE INTRODUCTION: Cardiovascular disease (CVD) and related risk factors, including hypertension, are characterized by systemic inflammation. Periodontitis, a chronic inflammatory disease of the supporting tissues of the tooth, can impact the systemic inflammatory burden and has recently been associated with hypertension. However, it is not clear whether the risk of hypertension can vary throughout the natural history of periodontal diseases, that is, if it is modified by gingival bleeding, an easily investigable indicator of local pathology. METHODS: Survey-based propensity score matching (PSM) incorporating major confounders shared between hypertension and periodontal diseases (age, gender, ethnicity, poverty, BMI, hypertension diagnosis and treatment, smoking habit, diabetic status, and aspirin use) was applied to cross-sectional NHANES III data from adults C 30 years who underwent BP measurement and periodontal examination, identifying two matched groups with and without gingival bleeding. The association of bleeding gums with systolic blood pressure (BP, mmHg) and high/ uncontrolled BP according to the European Society of Hypertension (ESH) was then assessed with generalized additive models incorporating inflammatory markers (CRP, white blood cells, ferritin). Stratification by periodontal health status (healthy; gingivitis; stable periodontitis; unstable periodontitis) was performed. RESULTS: Gingival bleeding (gingivitis; unstable periodontitis) was independently associated with ?2.6 mmHg (p \ 0.001) systolic BP compared with no bleeding (healthy periodontium; stable periodontitis), and with greater odds (OR 1.42; 95% CI 1.19-1.68; p \ 0.001) of high/uncontrolled BP. Participants with unstable periodontitis had higher systolic BP than those with stable periodontitis (?2.1 mmHg; p \ 0.001) or gingivitis (?5.3 mmHg; p \ 0.001). Unstable periodontitis and gingivitis, but not stable periodontitis, were associated with increased risk of high/uncontrolled BP (OR 1.65, 95% CI 2.14-1.82; OR 1.49, respectively) . CONCLUSIONS: Gingival bleeding contributes to shaping the relationship between periodontal diseases and hypertension. Investigating gingival bleeding status could be of importance in hypertensive patients, especially if poorly controlled by therapy.

INTRODUCTION: Type 1 diabetes mellitus (T1DM) is characterized by the early development of macrovascular damages in both genders but could manifest earlier in males. Traditional risk factors, along with T1DM per se, are associated with this process in T1DM. If specific differences in early vascular damage are viewable even during childhood in T1DM is unknown. METHODS: Arterial structural changes (carotid intimamedia thickness [cIMT]) and vascular elasticity (carotid coefficient of distensibility [cDC] and Pulse Wave Velocity [PWV]) were measured in 180 children and adolescents with T1DM by carotid ultrasonography and the Sphyg-moCor XCel device. Hemodynamic and metabolic risk factors (peripheral and central systolic/diastolic blood pressure [pSBP/pDBP; cSBP], body mass index (BMI), glycated haemoglobin, triglycerides, total cholesterol, nonHDL/HDL-cholesterol ratio were also assessed. The sample was divided according to Tunner's stages (pre-pubertal-pubertal vs. post-pubertal) and gender: seventy-four subjects were classified as pre-pubertal-pubertal (44 male, mean age ± SD 12 ± 2 years: 30 females, 12 ± 1.5 years) and 106 as post-pubertal (43 males, 16 ± 1 years; 63 females; age: 15.5 ± 1.5 years). Sex-specific linear regression models, adjusted for the pubertal state, BMI, duration of diabetes, glycated haemoglobin, nonHDL/ HDL-cholesterol ratio, were constructed to assess the relation between risk factors and the markers of early vascular damage. RESULTS No differences in cIMT, cDC, PWV and the respective z-score were found between males and females in the pre-pubertal-prepubertal sub-group. In the post-pubertal group, males had higher cIMT (0.05 ± 0.01 mm; p value: 0.001) and Z-score cIMT (0.62 ± 0.02; p value: 0.04) but no differences in cDC and PWV were found. In linear regression models, the only risk factors independently associated with z-cIMT, were the nonHDL/HDLcholesterol ratio (b ± SEM: 0.267 ± 0.30; p value: 0.03) in males and z-cSBP in females (b ± SEM: 0.286 ± 0.13; p value: 0.01). z-PWV and z-cDC showed associations with different types of BP values both in males and females. CONCLUSIONS: Gender-specific differences in cIMT are present early after puberty in adolescents with T1DM but seem associated with different risk factors in males and females. Different preventive strategies could be beneficial in males and females with T1DM, starting during adolescence. STIMULATING THE PRIMING OF ADAPTIVE  IMMUNITY IN THE SPLEEN THROUGH  INCREASED ACTIVITY OF THE SPLENIC  SYMPATHETIC NERVE INTRODUCTION: Angiotensin II (AngII) is an important modulator of the sympathetic nervous system, acting through its neuronal AT1 (AT1R) receptors in the main cardiovascular control centers. The subfornical organ (SFO), located in a ventricular region where the blood brain barrier is permeable to circulating peptides as AngII, and the paraventricular nucleus of the hypothalamus (PVN), to which SFO is closely connected, are densely enriched of AT1R. In the past, we have described a vagussplenic nerve pathway responsible for priming T cells in hypertension, but brain areas have not yet been well identified. METHODS: To study the role of SFO we injected, through stereotaxis apparatus, a recombinant adenovirus, encoding a Cre-recombinase and a GFP (AdCreGFP), or GFP alone as control in SFO of AT1a flox mice (mice with loxP sites upstream and downstream of exon 3 of AT gene type 1a). To study the role of PVN we crossed AT1a flox mice with Sim1Cre mice, since the Sim1 neurons of PVN express AT1aR and Cre-recombinase on the Sim1 promoter. RESULTS: After evaluating the gene deletion by PCR on SFO and PVN samples obtained by laser microdissection, we treated mice of the two genotypes chronically with AngII and vehicle. Boh AT1aR flox ; AdGFPCre mice and AT1aR flox ; Sim1Cre ? mice showed a significant reduction of blood pressure levels, as compared to WT control mice after AngII. Interestingly, SSNA in both KO mice for AT1aR was significantly reduced when compared to WT mice as well as the expression of the placental growth factor (PlGF) in the splenic marginal zone and the activation of T cells from the spleen. To investigate renal organ damage, we observed protection from infiltrating CD4/ CD8 cells in both KO mice for AT1aR after 28 days of AngII. CONCLUSIONS: These data identify a nervous control axis of immunity in hypertension to block splenic sympathetic activation and adaptive immunity. 

We previously described how Angiotensin-II (AngII) recruits T-cells through the spleen, homing them to the cardiovascular system and inducing elevated blood pressure (BP). AngII action is mediated by the central nervous system to enhance the sympathetic tone, in this work we aim at characterize the connection between spleen and brain analysing the activity of cholinergic inflammatory pathway (CIP). METHODS: we recorded splenic and celiac vagus nerve activity, showing how mice infuse with AngII by subcutaneous osmotic pumps show an incremented celiac vagus nerve activity, evidenced by a nervous burst analysis tool. After this, we set up a technique to stimulate the celiac vagus nerve while recording the splenic nerve activity. RESULTS: Mice subjected to vagus nerve stimulation present an incremented splenic nerve activity, with a consequent splenic noradrenergic pathway recruitment shown by an increased noradrenaline and tyroxine hydroxylase expression in the spleen with a subsequent T-cells egression shown with a reduced CD3 ? positive staining in immunofluorescence analysis. Flow cytometry analysis shown a specific reduction in CD8 ? effector cells. CONCLUSIONS: Our experiments shown also that, while not involved in nervous signal transduction to the spleen, the Placental Growth Factor (PlGF) plays a key role in the transduction of the neural signal to an immune response. Supra-aortic trunks echo-colour-Doppler was performed before starting the therapy (time 0), after 6 months and then after 12 months of therapy. For each carotid CIMT, PSV (Peak Systolic Velocity), EDV (End Diastolic Velocity) and ICA/CCA PSV ratio were measured. RESULTS: We observed after 6 months a reduction of right mean CIMT of -0.09 (p = 0.000 vs. baseline) and of-0.14 of left CIMT (p = 0.008 vs. baseline); the reduction was for right CIMT after 12 months of -0.16 (p = 0.006 vs 6 months) and for left CIMT of -0.15 (p = 0.005 vs 6 months). Between 0 time and 12 months of treatment we observed a reduction of-0.16 (p = 0.05) for right CIMT and of-0.18 (p = 0.004) for left CIMT. LDL-C levels were reduced from 134 ± 35.73 mg/dL at baseline to 65.61 ± 41.43 mg/dL after 6 months (p = 0.000) and to 51.50 ± 18.67 mg/dL after 12 months (p = 0.000).Moreover, we observed a progressive ''remodeling'' of the plaques, modifying from a soft/dense composition to a predominantly fibro-calcific composition (p = 0.000 for 0 vs. 12 months). CONCLUSIONS: This is the first study showing that the inhibitors of PCSK9, can decrease or even reverse the progression of carotid atherosclerosis, reducing the intimamedia thickness, the lipid content of atheromatous plaques leading to a reduction of clinical adverse events. 

In this prospective open-label study 54 subjects (mean age 78.6 ± 8.2 years, 75.0% male), with HFrEF (29.8 ± 4.3%) and with a New York Heart Association (NYHA) class II-III symptoms were assigned to receive SV. These patients were gender and age-matched with a control arm of patients with HFrEF receiving the optimal standard therapy for HF before the introduction in the market of SV. The clinic blood pressure (BP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), estimated glomerular filtration rate (eGFR), blood glucose and glycated haemoglobin (HbA1c), uric acid (UA), left ventricular ejection fraction (LVEF) and NYHA class were evaluated at a mean follow-up of 12 months.

: NYHA class significantly improved in the SV compared to the control group (24.9 vs. 6.4%, shifting from class III to II, and 55.4 vs. 25.2%, from class II to I, p \ 0.05 for all). A significant improvement in LVEF and eGFR levels was found in the SV compared to the control group (42.4 vs. 34.2%, 73.8 vs. 61.2 ml/min, respectively; p \ 0.001 for all). NT-proBNP, clinic systolic and diastolic BP, blood glucose, HbA1c and UA values were reduced in both treatment arms, but they were lower in the SV compared to the control group (3107 vs. 4552 pg/mL, 112.2 vs. 120.4 and 68.8 vs. 75.6 mmHg, 108.4 vs. 112.6 mg/dL, 5.4 vs. 5 .9% and 5.9 vs. 6.4 mg/dL, respectively, p \ 0.05). Mortality and re-hospitalization for HF was lower in the SV group (20.1 vs. 33.6% and 27.7 vs. 46.3% respectively; p \ 0.05 for all). No side effects were observed. CONCLUSIONS: In elderly patients with HFrEF and comorbidities, the treatment with SV seems effective and safe. The improvement in LVEF, BP, eGFR, and metabolic profile could be the mechanisms by which SV play their beneficial role on clinical outcomes. AIM: We aimed to investigate myocardial performance using pressure-strain loops in hypertensive patients with and without type 2 diabetes mellitus (DM). METHODS: This cross-sectional study included 135 subjects (45 controls, 50 hypertensive patients without DM and 40 hypertensive with DM patients) who underwent complete two-dimensional echocardiographic examination (2DE) including two-dimensional speckle-tracking echocardiography. Using pressure-strain curve was used to determine global myocardial work, constructive work, wasted work, and work efficiency in all study participants. RESULTS: Left ventricular (LV) longitudinal and circumferential strains gradually reduced from controls throughout hypertensive subjects to patients with DM and hypertension. Radial strain was lower in patients with concomitant hypertension and DM than in healthy controls. Global myocardial work gradually decreased from controls, throughout hypertensive patients to subjects with hypertension and DM (2118 ± 262 vs. 2021 ± 228 vs.

1913 ± 255 mmHg %, p = 0.001). Constructive work also deteriorated in the same direction (2388 ± 386 vs. 2197 ± 326 vs. 2081 ± 347 mmHg %, p \ 0.001). Work efficiency was significantly lower in patients with hypertension and DM in comparison with controls, but there was no difference in comparison to hypertensive patients without DM (97 ± 3 vs. 92 ± 3 vs. 90 ± 3%, p \ 0.001). Wasted work did not differ between three observed groups (95 ± 53 vs. 102 ± 62 vs. 108 ± 58 mmHg %, p = 0.586). Glycosylated hemoglobin and systolic blood pressure were associated with LV longitudinal strain and global myocardial work independently of age, body mass index, LV mass and LV ejection fraction in all study participants. CONCLUSION: Pressure-strain curve showed that myocardial work was significantly affected by hypertension and particularly when hypertension and diabetes were concomitant diseases. Diabetes demonstrated an additional negative effect on myocardial work in hypertensive patients. Glycosylated hemoglobin level and systolic blood pressure were related with myocardial work independently of LV structure and systolic function.

Marijana Tadic 1 , JELENA Suzic-Lazic 1 , VLADAN Vukomanovic 1 , CESARE Cuspidi 2 , SANJA Ilic 1 , VERA Celic 1 AIM: The study sought to evaluate cardiorespiratory fitness in patients with type 2 diabetes mellitus (DM) with different levels of left ventricular (LV) diastolic dysfunction (LVDD). Methods: This investigation included 55 controls and 85 uncomplicated diabetic patients, who underwent laboratory analysis, echocardiographic evaluation and cardiopulmonary exercise testing. All DM subjects were separated into 3 groups using the level of LV diastolic function as main criterion: normal, intermediate and LVDD. RESULTS: Echocardiographic parameters of LV hypertrophy were significantly higher in DM subjects, particularly those with intermediate LV diastolic function and LVDD comparing with controls. The same is valid for parameters of LV diastolic function (E/e', left atrial volume index, and tricuspid regurgitation velocity). Peak oxygen uptake was lower, whereas ventilation/carbon dioxide slope was higher, in DM subjects with intermediate LV diastolic function and LVDD in comparison to controls. In the whole study population HbA1c, LV mass index and mitral E/e' were independently related with peak oxygen uptake and ventilation/carbon dioxide slope. CONCLUSION: LVDD significantly impacted functional capacity in DM patients. Glycemic control, LV mass index and LVDD were independently related with peak oxygen consumption and ventilation/carbon dioxide slope in the study population. These results show that timely diagnosis of LVDD and more intensive antidiabetic treatment could prevent target organ damage in DM patients. INTRODUCTION: Impaired peak oxygen consumption (VO 2 ) during exercise is a typical feature of heart failure (HF). This impairment is usually ascribed to alterations in the components of the Fick principle: VO 2 =cardiac output (stroke volume [SV] 9 heart rate [HR]) 9 arterio-venous oxygen difference. However, these parameters may not allow for a sufficient characterization of the derangement of cardiopulmonary function in HF. AIM: We investigated whether echocardiographic indices of cardiac function may relate to peak VO 2 independently of the components of the Fick principle. METHODS: We enrolled 30 healthy controls and 357 dyspnoeic patients: 113 with dyspnoea of unknown origin (DUO: 92/113, 81% with arterial hypertension and 72/113, 64% with diabetes mellitus), 143 with HF with reduced ejection fraction (HFrEF) and 101 with preserved ejection fraction (HFpEF). All subjects underwent an integrated cardiopulmonary exercise testing-exercise stress echocardiography (CPET-ESE). Echocardiographic image acquisition was performed at rest, at anaerobic threshold (AT, i.e. after reaching a stable respiratory exchange ratio C 1.00) and at peak effort.

The study population consisted of 387 subjects (mean age: 67.9 ± 11.1 years; 68% males). AT and peak VO 2 were significantly impaired in DUO, HFpEF and HFrEF patients. Peak HR was significantly lower in HF patients; rest and peak SV were significantly reduced in HFrEF patients. In addition to HR and SV, peak VO 2 was significantly and independently related to measures of left ventricular systolic function (Tissue-Doppler Imagingderived S') and left atrial function (LA reservoir strain/E/ e') and to right-sided ventricular-arterial coupling (tricuspid annular plane systolic excursion/systolic pulmonary arterial pressure [TAPSE/sPAP] ratio). CONCLUSIONS: CPET-ESE revealed multiple abnormalities in cardiac function could co-exist in dyspnoeic patients with and without a definite diagnosis of HF. A thorough evaluation of the pathophysiological background behind dyspnoea may be useful to identify subjects at higher risk of developing HF and develop a tailored medical treatment. Recently, it has been proposed to reclassify preeclampsia no longer on the basis of gestational age (GA) at which the pressure rise and proteinuria occur, but on the basis of specific maternal hemodynamic parameters in combination with evidence or not of intrauterine growth restriction of the fetus (IUGR). AIM: We compared two clinical cases of preeclampsia late onset (hypertension ? proteinuria [ 34 GA), with and without IUGR. CASE REPORT: (1) HDP-IUGR 39 years, CVRF: obesity, familiarity with CHD and AH, first trimester screening: high risk preeclampsia, prophylaxis with ASA. 34 GA: preeclampsia, IUGR, bilateral notches of the uterine arteries. Recovery, treatment with labetalol 100 mg 9 2. 36 ? 1 GA: urgent cesarean section because of CTG's alterations. During the post-partum oliguria and desaturation: thoracic ecoscopy (increased size and thickness of LV, systolic function preserved); chest CT diagnostic for APO. Furosemide 20 mg x 7 days ? Labetalol 100 mg x3 9 10 weeks. Newborn F, 2080 gr (\ 2,5 pct).

(2) HDP-NIUGR 34 years, no CVRF, no first trimester screening. 34 GA: normal fetal biometry and uterine arteries doppler. 35 GA: preeclampsia, normal fetal growth. Recovery, no therapy. 35 ? 4 GA: urgent cesarean section because of two incoming eclamptic crisis. Brain CT ? MRI diagnostics for PRES, ecoscopy (normal size and thickness of LV, EF 63%). Nifedipine 20 mg x 2 weeks. Newborn F, 2200 gr (25 pct). It almost seems these two patients suffer from two different pathologies:

(1) HDP-IUGR: maternal cardiovascular disease (same RFs, cardiac dysfunction precedes clinical presentation) with secondary placental hypoxia. Until now, there's evidence of altered LV geometry and myocardial activity, sub-optimal plasmatic expansion (lower SV, CO and HR and higher TVR compared to physiological pregnancy).

(2) HDP-NIUGR: placental disease. Current hemodynamics results are inconclusive (CO and TVR similar to physiological pregnancy). CONCLUSIONS: Our experience confirms these observations. The HDP-IUGR/NIUGR classification provides the basis for a more in-depth pathophysiological knowledge of these disorders, with important clinical consequences in terms of obstetrical-neonatal outcome and lifetime cardiovascular risk. AIM: We performed a systematic meta-analysis of these studies in order to offer a comprehensive information on this topic.

The PubMed, OVID-MEDLINE, and Cochrane library databases were analyzed to search English-language articles published from January 1st 1990 up to March 31st 2020. Studies were identified by crossing the following terms ''renal artery stenosis'' ''reno-vascular hypertension'' ''fibromuscular dysplasia'' ''renal artery stenting'' ''renal artery surgery'' with ''cardiac damage'', ''hypertensive heart disease'' ''left ventricular mass'', ''left ventricular hypertrophy'', ''echocardiography'' . RESULTS: A total of 726 hypertensive patients with renal artery stenosis (mean age 61 years, 64% men, 98% treated, 10% with fibromuscular dysplasia) were included in 13 studies. Baseline and post-intervention pooled mean LV mass versus baseline values were 203 ± 19 g and 220 ± 15 g, respectively (SMD -0.24 ± 0.06, CI -0.37/-0.21, p \ 0.0001); corresponding values for LV mass index were 115 ± 7 g/m2 and 129.0 ± 6 g/m2, respectively (SMD -0.28 ? 0.04, CI -0.36-0.21, p \ 0.0001). Renal revascularization was associated with a 40% lower risk of LVH. This trend was accompanied by a reduction in the number of antihypertensive drugs (SMD -0.27 ? 0.04, CI -0.37-0.17, p \ 0.0001). CONCLUSIONS: The present meta-analysis suggests that renal artery revascularization added to anti-hypertensive therapy promotes a favourable effect on LV structure, as reflected by a significant decrease in absolute and indexed LV mass index as well by a lower risk of LVH. Limitations include :I) high prevalence of modest renal artery stenosis ([ 50%); II) small sample of fibromuscular dysplasia; III) lack of randomized design of most studies. AIM: We sought to assess the echocardiographic systodiastolic changes, including global longitudinal strain (GLS), in patients treated with Carfilzomib and to identify predictors of increased risk of cardiovascular adverse events (CVAEs) during therapy. METHODS: 88 patients with MM performed a baseline cardiovascular evaluation comprehensive of transthoracic echocardiogram (TTE) before the start of Carfilzomib therapy and after about 6 months. All patients were followed-up to early identify the occurrence of CVAEs during therapy. RESULTS: After Carfilzomib treatment, mean GLS slightly decreased (-22.2% ± 2.6 vs -21.3% ± 2.5; p \ 0.001). 58% of patients experienced CVAEs during therapy: 71% of them had uncontrolled arterial hypertension, 29% had major CVAEs or CV events not related to arterial hypertension. GLS variation during therapy was not related to an increased risk of CVAEs; however, patients with baseline GLS C -21% and/or left ventricular ejection fraction B 60% had an increased risk of major CVAEs (p = 0.004, OR = 6.2; p = 0.04, OR = 3.7; respectively). Carfilzomib led to an increased risk of diastolic dysfunction (5.6% vs 13.4% p = 0.04) and to a rise in E/e' (8.9 ± 2.7 vs 9.7 ± 3.7; p = 0.006). CONCLUSIONS: Carfilzomib leads to LV function impairment early demonstrated by GLS changes and diastolic dysfunction. Baseline echocardiographic evaluation, through the estimation of GLS and LVEF, might improve cardiovascular risk stratification before treatment. METHODS: C57/Bl6 mice were treated with DOX (10 mg/Kg) by intraperitoneal injection and hearts were collected after 5 days to perform histological analysis. In hearts treated with DOX, the histological analysis showed a significant macrophages infiltration. In order to evaluate whether a crosstalk could exist between macrophages and cardiac cells that could affect cardiac outcomes in response to DOX, we compared the effects of two different treatments in cardiomyoblasts (H9C2): incubation with culture medium from macrophages (RAW 264.7) treated with DOX for 24 h (M-DOX) and direct treatment with DOX (D-DOX). RESULTS: Both conditions induced an increase of Cleaved caspase-3 levels that was higher in response to M-DOX. Since apoptosis in response to DOX is mediated by p53, we evaluated p53 levels by western blot. In response to M-DOX, p53 is accumulated in mitochondria where it induced the release of cytochrome c, suggesting that p53-dependent mitochondrial damage occurs in response to M-DOX. Accordingly, mitochondrial morphology, evaluated by fluorescence microscopy analysis of Mitotracker staining, was altered. This was associated with an impaired autophagic flux, as demonstrated by levels of LC3-II and accumulation of autophagosomes. CONCLUSIONS: All these data clearly indicate that in vivo doxorubicin induces macrophage infiltration that could potentially contribute to cardiac cell damage. In vitro, the conditioned medium from DOX-activated macrophages amplifies cardiomyoblasts damage by inhibiting autophagy and enhancing p53 mediated mitochondrial apoptosis. It is likely that macrophages release cytokines which activate p53 enhancing DOXO dependent cardiac damage.

(LV) which involves immune cells. We previously found that placenta-derived growth factor (P1GF), a growth factor belonging to the VEGF family, is necessary for adaptive remodeling to pressure overload. AIM: we investigate the immuno-modulator role of PlGF in response to pressure overload induced by coarctation of the aorta (TAC) in mice. METHODS: We analyzed cardiac monocyte/macrophage infiltration by flow cytometry to discriminate the resident response from the recruited one using CD11b/CD64/ Timd4/Ly6C markers, in mice PlGF KO and WT at 4 days from TAC/sham procedure. RESULTS: WT mice, but not PlGF KO, showed a significant infiltration of non-resident macrophages after TAC, suggesting that PlGF may influence their recruitment. Given that the expression of PlGF was increased after TAC in the heart and spleen, we generated chimeric mice through spleen transplantation between WT and PlGF KO. PlGF KO mice with WT spleen showed a typical adaptive remodeling to TAC, as evidenced by echocardiographic analysis. In contrast, WT mice with PlGF KO spleen showed an early heart failure (HFrEF) response after TAC. To investigate the potential role of the spleen as a reserve of myeloid cells with adaptive/reparative functions, we splenectomized mice observing an early HFrEF and a reduced monocyte/macrophage recruitment in LV. To study the involvement of a neuroimmune mechanism, we performed a selective denervation of splanchnic district through the surgical removal of the celiac ganglion (CGX). Mice subjected to CGX and TAC showed a HFrEF and a reduced recruitment of monocytes/macrophages in LV similarly to splenectomized and PlGF KO mice. CONCLUSIONS: These data demonstrate that pressure overload activates a neuroimmune mechanism in the spleen that induces the PlGF release as an effective immunomodulator to recruit adaptive/reparative macrophages in the heart promoting LV adaptive remodeling to pressure overload.

INTRODUCTION: Left Atrial enlargement (LAe) is a subclinical marker of hypertensive mediated organ damage, whose identification is important in cardiovascular risk stratification. Recently, LA indexing for height has been suggested as more accurate marker to define LAe. AIM: to test the difference in LAe prevalence using Body surface area (BSA) and height 2 definitions in an essential hypertensive population. METHODS: A total of 441 essential hypertensive patients underwent complete clinical and echocardiographic evaluation. Left Atrial Volume (LAV), left ventricular morphology and sisto-diastolic function were evaluated. RESULTS: LAe was twice as prevalent when defined using height 2 (LAe h2 ) indexation rather than BSA (LAe BSA ) (51%vs.23%, p \ 0.001). LAe h2 , but no LAe BSA , was more prevalent in females (p \ 0.001). Male and female differed also for Left Ventricular Hypertrophy (p = 0.046) and Left Ventricular Diastolic Disfunction (LVDD) indexes (septal Em/Etdi: p = 0.009; lateral Em/ Etdi: p = 0.003; mean Em/Etdi: p \ 0.002). All patients presenting LAe BSA also met criteria for LAe h2 . According to presence-absence of LAe, we created 3 groups (Norm = BSA-/h 2 -; DilH = BSA-/h 2 ? ; DilHB = BSA ?/h 2 ?). Female sex prevalence in DilH group was higher than in both others (Norm: p \ 0.001; DilHB: p = 0.036). LVH and mean and septal Em/Etdi grew from Norm to DilH group and from DilH to DilHB group (p \ 0.05 for all comparisons). CONCLUSIONS: LAe h2 identified twice as many patients as having LAe compared to LAe BSA . Both LAe h2 and LAe BSA definitions are associated with LVH and LVDD. In female patients, LAe h2 definition and its sex-specific threshold seems to be more sensible than LAe BSA in identifying a chamber enlargement. INTRODUCTION: Cardiovascular adverse events (CVAEs) are closely related to Carfilzomib (CFZ) therapy in multiple myeloma (MM), but their prevention is challenging due to lack of validated predictors of cardiovascular events. Moreover, the nature and prevalence of each CVAEs is debated, due to the lack of 'real-life' perspective trials. AIM: We sought to identify predictors for CVAEs in patients ongoing Carfilzomib therapy. For the first time, the nature and the incidence of each CVAEs in a 'real-life' study were assessed. METHODS: MM patients with indication to CFZ therapy were prospectively enrolled. A comprehensive baseline evaluation, previously CFZ beginning, were performed: cardiovascular anamnesis, office blood pressure (BP), ABPM, ECG, trans-thoracic Echocardiography, pulse wave velocity (PWV). After starting the CFZ treatment, the incidence of CVAEs was detected. RESULTS: 116 patients were enrolled, between 2015 and 2020. At basal evaluation, the proportion of target organ damage and uncontrolled hypertension (51.7%) were substantial. Main predictors of CVAEs were: systolic hypertension office (b 4.09; p = 0.001) and day (b 2.27; p = 0.044), blood pressure variability C 10 (b 5.07; p = 0.002), left ventricular hypertrophy (b 3.06; p = 0.021), PWV C 8.75 m/s (b 5.13; p = 0.000) and global longitudinal strain (b 1.19; p = 0.003). During a follow-up of 13.56 ± 9.63 months after CFZ starting, the rate of all-grade CVAEs was 44.8%, distinct in hypertensive events (30.2%) and major (14.7%). The chronic rise/ new onset of arterial hypertension (31.9%) and uncontrolled hypertension pre-CFZ infusion (22.4%) were the most frequent hypertensive events, arrhythmias (41.2%) and acute coronary syndromes (23.5%) the most frequent within the major CVAEs; one patient died of sudden cardiac arrest. CONCLUSIONS: CFZ therapy is linked to high rate of CVAEs, potentially life-threatening. A comprehensive cardiovascular evaluation is effective in CVAEs prediction and need to allow risk mitigation strategies.

Matteo Mazzola1-2, Nicola Riccardo Pugliese2, Nicolò De Biase2, Gennaro D'Angelo1, Cosimo Bruni3, Marco Matucci-Cerinic3, Stefano Masi2, Stefano Taddei2, Luna Gargani1

Systemic Sclerosis (SSc) are responsible for a progressive myocardial involvement leading to cardiac remodeling and diastolic dysfunction. Nevertheless, little is known about how these conditions interact. METHODS: We enrolled 277 SSc patients with (94 pts, SSc/HT) and without (183 pts, SSc) HT. Patients with pulmonary artery hypertension (PAH) were excluded from the study. All patients underwent a complete transthoracic echocardiography comprehensive of diastolic evaluation according to European Recommendations. RESULTS: Patients from the two groups were age-matched and displayed a similar global systolic function in terms of ejection fraction and systolic Tissue Doppler Imaging (TDI). Compared to SSc group all the main diastolic parameters were worse in SSc/HT except for systolic pulmonary arterial pressure which is likely to be elevated in these patients mainly as a result of the increase in pulmonary vascular resistance. Interventricular septum and left ventricular posterior wall thickness of SSc/HT patients were also higher than SSc. Furthermore, patients with SSc/HT were more commonly treated with dihydropiridinic calcium channel blockers (CCB) [CCB SSc: 26 (14.2%) vs CCB SSc/HT: 24 (25.5%) vs, p = 0.031], renin-angiotensin-aldosterone system inhibitors (RAASI)

[RAASI SSc: 7 (3.8%) vs RAASI SSc/HT: 50 (53.2%), p \ 0.0001] and beta-blockers (BB) [BB SSc: 3 (1.6) vs BB SSc/HT: 10 (10,6%), p = 0.001].

CONCLUSIONS: Both SSc and HT can affect left ventricular diastolic function. Patients with SSc and HT display worse echocardiographic parameters of diastolic dysfunction compared to patients with isolated SSc, despite the more frequent treatment with vasoactive drugs. Being a further source of diastolic pattern impairment, the presence of HT should be considered in the echocardiographic evaluation of SSc patients. INTRODUCTION: Uric acid (UA) has been related to inhospital mortality in patients with acute coronary syndromes (ACS), to early relapse, after ACS, of non-fatal cardiovascular events and to negative intermediate outcomes such as use of intra-aortic balloon pump, non-invasive ventilation, longer inward stay, bleeding, clinical presentation with Atrial Fibrillation (AF) or Heart Failure (HF). AIM: to evaluate the role of UA as a possible determinant of primary (in-hospital mortality) and secondary outcomes defined as variables of relapsing ischemia (myocardial reinfarction, in-stent thrombosis, bleeding, stroke), worse clinical presentation (with HF or AF, admission EF, trivasal coronary artery disease (CAD) at the coronary angiography), in-hospital complications (use of inotropes, intra-aortic balloon pump and non-invasive ventilation during hospital stay) and worse recovery (discharge EF). METHODS: 563 patients, admitted for ACS to Cardiological Intensive Care Unit of Niguarda Ca' Granda Hospital, were enrolled for this retrospective cohort study. Cox regression analysis was performed to evaluate the association between UA and primary and secondary outcomes, adjusting for the following covariates: age, gender, previous myocardial infarction, arterial hypertension, Charlson Comorbidity Index and creatinine. RESULTS: mean age was 66.5 ± 12.3 years, 79.2% of the patients were males and 49.9% were ACS-STEMI. Hyperuricemic subjects were older, with more prominent cardiovascular risk factors and history of previous myocardial infarction. They more frequently died during hospital stay, had HF and AF as clinical presentation, more commonly had trivasal CAD and needed intra-aortic balloon pump and non-invasive ventilation. Also EF at admission and discharge were lower in hyperuricemic patients. At multivariate analysis, UA was a significant determinant of primary and secondary outcomes (except for trivasal CAD, bleeding, stroke, re-infaction and in-stent thrombosis). CONCLUSIONS: UA is an independent determinant of in-hospital mortality and a variable suggestive for worse clinical presentation, in-hospital complications and worse recovery. 

We tested the prognostic role of a risk score including bio-humoral evaluation, cardiopulmonaryechocardiographic stress (CPET-ESE) and lung ultrasound, in patients with heart failure (HF) with reduced and preserved ejection fraction (HFrEF and HFpEF), and subjects at risk of developing HF (American College of Cardiology/ American Heart Association Stages A and B). METHODS: We evaluated 318 subjects: 94 in Stages A-B, 194 in Stage C (85 HFpEF and 109 HFrEF), and 30 age and sex-matched controls (Stage 0). During a median follow-up of 18.5 months, we reported 40 urgent HF visits, 31 HF hospitalisations and 10 cardiovascular deaths. Cox proportional-hazards regression for predicting adverse events identified five independent predictors and each was assigned a number of points proportional to its regression coefficient: D stress-rest B-lines [ 10 (3 points), peak oxygen consumption \ 16 mL/kg/min (2 points), minute ventilation/carbon dioxide production slope C 36 (2 points), peak systolic pulmonary artery pressure C 50 mmHg (1 point) and resting N-terminal pro-brain natriuretic peptide (NT-proBNP) [ 900 pg/mL (1 point). We defined three risk categories: low-risk (\ 3 points), intermediate-risk (3-6 points), and high-risk ([ 6 points). RESULTS: The event-free survival probability for these three groups were 93%, 52% and 20%, respectively. Hazard Ratio was 4.55 for each risk category upgrade (95% confidence interval [CI] 3.44-5.93). The area-under-curve for the scoring system to predict events was 0.92 (95% CI 0.88-0.96). CONCLUSIONS: A multiparametric risk score including indices of exercise-induced pulmonary congestion, markers of cardiopulmonary dysfunction and NT-proBNP identifies patients at increased risk for HF events across the HF spectrum. 

The association between atrial fibrillation and cardiovascular death is not yet clear. Moreover, recent meta-analyses on the association between atrial fibrillation and cardiovascular death assessed selected populations and did not exclude stroke death. AIM: to perform a systematic review and meta-analysis on the association between atrial fibrillation and cardiovascular death, including and excluding stroke death, in general populations. METHODS: We identified 11 eligible studies. Separate data for men and women or type of event were reported in some studies, so we could obtain 17 subgroups. Studies included 1408290 subjects experiencing more than 8000 events. Data were pooled together by random effects model. RESULTS: The overall adjusted hazard ratio and 95% confidence interval for cardiovascular death was 2.85 (2.33-3.49) in patients with versus those without atrial fibrillation. Subgroup meta-analysis showed that hazard ratio and 95% confidence interval was 2.37 (1.63-3.47) in men and 3.73 (2.59-5.37 ) in women, 3.18 (2.47-4.10) for cardiovascular death including stroke death and 2.55 (1.94-3.37) for cardiac death (coronary disease, heart failure and sudden cardiac death). Risk was similar by follow-up length, ethnicity and study design. CONCLUSIONS: In general populations, patients with versus those without atrial fibrillation had approximately 3 times higher risk of cardiovascular death and 2.5 times higher risk of cardiac death. Risk tended to be higher in women than in men. 

The 2016 ESC guidelines classify Heart Failure (HF) according to levels of Ejection Fraction (EF) in HF with reduced EF (HFrEF, EF \ 40%), preserved (HFpEF, EF C 50%) and the newborn mid-range (HFmrEF, EF 40-49%). AIM: to analyse clinical and echocardiographic features of patients hospitalized for HF when divided accordingly to their admission EF, focusing on HFmrEF. METHODS: We enrolled 192 patients hospitalized in the Internal Medicine of our hospital between January and September 2017. We collected data on clinical history, P.E., laboratory tests, pharmacological treatment and echocardiography; follow-up for subsequent fatal and nonfatal events ended in May 2018. RESULTS: Prevalence of HFpEF (55.21%) is higher than HFrEF (23.60%) and HFmrEF (17.19%). Mean age is 80.9 ± 8.3 years, and does not differ among groups. HFpEF are more commonly female, show higher SBP at the presentation (p \ 0.001) and have more non-cardiac comorbidities, such as renal dysfunction (p \ 0.001), anemia (p = 0.05), COPD (p = 0.036) and also AF (p = 0.04); in this group hypertensive aetiology is significantly prevailing (p = 0.002). On the contrary previous myocardial ischaemia and higher NT-proBNP levels on the admission (p = 0.038) are typical in HFrEF. Diastolic and systolic dysfunctions co-exist in patients and many candidates show marks of inverse remodelling. HFmrEF carry intermediate attributes (prevalence of CAD and systemic multimorbidities) and exhibit a 'hybrid' US hypertrophy pattern (high RWT, medium LVMi); compared to the other groups, they include the lowest trend on NYHA classification (I-II, p = 0.027), a less aggressive treatment with the shortest number of drugs and dosages (p = 0.04) and show decreased mortality and rehospitalization rates. During the follow-up, patients with HFmrEF experience more longitudinal transition among groups (33% becomes HFpEF and 23% HFrEF). CONCLUSIONS: HFmrEF share features of both HFrEF and HFpEF, with a high prevalence of CAD and non-cardiac comorbidities, and a large longitudinal transition to the other two classes.

Elena De Angelis, Mariarosaria Rusciano, Maria Grazia Petti, Carmine Vecchione, Gennaro Galasso, Michele Ciccarelli

INTRODUCTION: Cardiac remodeling after an acute myocardial infarct is characterized by molecular, cellular, and interstitial changes leading to changes in size, shape, and function of the heart. Inflammation and immune responses play a crucial role in infarct healing and subsequent LV remodeling. In the setting of heart failure (HF) the observed increased level and activity of GRK2 is correlated to harmful effects on cardiac function and a worse prognosis. GRK2 levels and activity in peripheral blood mononuclear cells (PBMC) are increased in patients with acute myocardial ischemia and associated with a poor prognosis. The possible role of GRK2 in the regulation of the immune system during AMI and involvement in the following cardiac remodeling is not known. METHODS: We enrolled 49 patients with the diagnosis of STEMI. Levels of GRK2 were evaluated in peripheral blood mononuclear cells (lymphocytes, monocytes, and granulocytes), by FACS analysis at hospital admission (time 0) and 24 and 96 h post-admission. RESULTS: At the admission, all patients showed a depressed cardiac systolic function as estimated by an EF \ 40%. After five days post-admission 53.85 (n = 31) displayed a recovering of cardiac systolic function (EF [ 45%) while 46,15% (n = 18) did not show a significant recover of systolic function (EF \ 45%). At time 0, white blood cells (monocytes, lymphocytes, and granulocytes) from patients with EF \ 45% (Fig 1) , showed an increased level of GRK2 expression compared to the EF [ 45% group (lymphocytes: 73.4% vs 11.3%, monocytes: 73.5% vs 3%, granulocytes 9.4% vs 2.3%) (Fig 2) . The levels of GRK2 in EF \ 45% group were persistently higher also at 48 and 96 h post-admission. Interestingly, in the group with EF [ 45%, the level of GRK2 in lymphocytes and monocytes increased at 96 h post-admission respect to 0 and 48 h post-admission. CONCLUSIONS: Our data demonstrate that the different patterns of expression of GRK2 in white blood cells can predict the outcome of the systolic cardiac function in a short time.

Dominioni I 1 , Alessio S 1 , Russo A 2 , Cerasari A 1 , Sanesi L 1 , Filippucci L 2 , Vaudo G 1 , Pucci G 1 1. Department of Medicine, University of Perugia, Unit of Internal Medicine, Terni University Hospital, Terni, Italy; 2. Unit of Rehabilitative and Preventive Cardiology, Grocco Center, Usl Umbria 1, Perugia, Italy INTRODUCTION: HF patients typically show effort intolerance due to a reduction in peak exercise oxygen (peak VO2) consumption, which is related to inability to adapt systolic function to increased demand. Left ventricular ejection fraction (EF) is a surrogate marker of cardiac contractility and a powerful predictor of adverse prognosis in chronic heart failure (HF). AIM: to explore the relationship between EF and other echocardiographic findings with peak VO2 in a population of HF individuals undergoing cardiopulmonary exercise testing (CPX). METHODS: We evaluated 101 patients (61% hypertensives, 74% with documented coronary artery disease) undergoing both resting echocardiography and symptomlimited CPX (COSMED Bike, personalized ramp protocol). The following parameters were evaluated: peak VO2, slope VE/VCO2, oxygen pulse, slope VO2/WR. RESULTS: Mean age was 58 ± 13 years, 83% were males. Mean EF was 55 ± 12%; 20% of the patients showed EF \ 40%. Mean test duration was 9.4 ± 2.2 min. Average peak VO2 was 21 ± 6 mL/kg/min. Peak VO2 showed a robust positive correlation with EF (R = 0.42, P \ 0.001). Other independent predictors of peak VO2 were age, male sex, height and tricuspidal anular plane systolic excursion (TAPSE), this latter reflecting right ventricular dysfunction. When subjects were dichotomized according to predicted peak VO2 values, those with higherthan-predicted peak VO2 showed significantly lower VE/ VCO2 slope, and higher values of both oxygen pulse and VO2/WR slope. CONCLUSIONS: EF and TAPSE are associated with peak VO2 in HF patients independently from age, sex and height. The evaluation of potentially relevant mechanisms affecting exercise capacity in HF patients could have therapeutic implications. INTRODUCTION: Acute dyspnoea is one of the main reason for admission to the Emergency Department (ED). A rapid and accurate diagnosis can be lifesaving for these patients. Particularly, it is important to differentiate between dyspnoea of cardiac origin and dyspnoea of pulmonary origin. AIM: to evaluate the real accuracy of the evaluation of diameter and collapsibility of IVC for the diagnosis of AHF among dyspnoeic patients. METHODS: We analyzed 155 patients admitted for acute dyspnoea to the ED of ''Maurizio Bufalini'' hospital in Cesena (Italy) and ''Antonio Cardarelli'' hospital in Naples (Italy) from November 2014 to April 2017. All patients underwent ultrasound (lung-cardiac-inferior vena cava) examination with a hand-held device in addition to the traditional pathway. Patients were classified into AHF group or non-AHF group according to the current guidelines. RESULTS: The final diagnosis was acute dyspnoea of cardiac origin in 64 patients and dyspnoea of non-cardiac origin in 91 patients. The diameter of IVC and the collapsibility of IVC showed low sensitivity (70.3% and 76.6% respectively) and low specificity (75.8% and 69.2% respectively) for the diagnosis of HF. AUC was 0.729 (0.647-0.811) for IVC collapse and 0.731(0.648-0.813) for IVC dilatation. CONCLUSION: Our study demonstrated that the sonographic assessment of IVC diameter and/or collapsibility is not really accurate for differentiating acute dyspnoea due to AHF or other causes in the emergency setting. METHODS: Random oxygen saturation, glycemia and total cholesterol as well as arterial blood pressure (three times) were measured in every person accessing to our stand. RESULTS: A group of 202 subject were included (112 females and 89 males). Mean age was 68 years, mean weight 72.4 kg (females: 67.4 kg.; men 78.7 kg); mean BMI was 26.3 (females 25.9; men 26.8). Data are summarized in table 1 and 2. Among patients treated for any cause, mean number of pills was 3.3; among hypertensives, mean number of anti-hypertensive drugs was 1.8. Arterial blood pressure (p \ 0.01) and heart rate (p = 0.002) were significantly higher during first measure compared to second and third check, confirming once more the importance of national and international societies indication on blood pressure measurement. During World Hypertension Day we identified 13 newly diagnosed hypertensives, 14 patients with high cholesterol level and one new diabetes.

Patients were addressed to their General Practitioner to undergo proper evaluation. CONCLUSIONS: Our data confirm that adequate blood pressure control is still far from being achieved in a general population and demonstrate once more the importance of World Hypertension Day in screening and in raising awareness of the importance of risk factors in general population RESULTS: A significant increase in mortality was observed in patients with a score higher than or equal to 8 (median value of the population-p = 0.035; Figure 1 ). Results were confirmed and even more consistent when using a more conservative cut-point (10; p = 0.006). A significant correlation (r = -0.41, p = 0.006) between Brixia score and partial oxygen pressure and flow ratio (pO 2 /FiO 2 )-a clinical hallmark of respiratory distress severity-was found. CONCLUSIONS: Brixia score shows a relevant prognostic significance, allowing to detect patients with SARS-CoV-2 at higher risk of poor outcome. A score higher or equal to 8 is related to a greater mortality in COVID-19 patients. The correlation becomes even stronger when choosing 10 as a cutoff. infarction. Data concerning blood pressure control in the previous 12 months was available for 26949 patients (females 51. %). By logistic regression analysis, predictors of inadequate blood pressure control were, not being treated (n = 2013), female sex, heart failure and chronic kidney disease (P \ 0.0001). When only patient that could ben defined as resistant to medication were considered (uncontrolled blood pressure control with 3 drugs or treated with 4 drugs or more, n = 6472), the prevalence of diabetes mellitus (32.8%), atrial fibrillation (20.1%), heart failure (9.1%), chronic kidney disease (7.8%) myocardial infarction (4.4%) was higher than in patients treated (P \ 0.0001). CONCLUSIONS: In a large proportion of the population of hypertensives blood pressure control is not achieved.

Overt cardiovascular diseases or diabetes mellitus in hypertensive patients are associated with poor blood pressure control, independently of the number of prescribed drugs, suggesting a vicious circle that could result in worsening of organ damage. blood pressure values of 1301 high school students aged between 13 and 18 were measured. Two questionnaires were administered, one relating to anamnestic data and anthropometric parameters and a second, aimed at investigating lifestyle. For the diagnosis of increased blood pressure, both ESH and AAP criteria were considered. RESULTS: Applying the LG ESH the prevalence of high blood pressure values was 7.5%, applying the AAP GL the prevalence stood at 14.1%. These difference were not observed only in subjects with short stature, in students aged 15 and in male gender. With regard to the association with risk factors and lifestyle, the ORs are comparable between the two GLs with the exception of overweight, no physical activity and smoking. With regard to the screentime (time spent using a device such as smartphone, tablet or computer), a new emerging risk factor, there are significant differences only in the stratified analysis by gender and age. CONCLUSIONS: Our study is still in progress, but from our results it seems that the use of nomograms based on the exclusion of overweight and fixed thresholds independent of gender or of an anthropometric parameter so changeable in this population such as height can represent a factor of confusion and overestimation, while a potential role of the screen time among the risk factors emerges. (1) Sokolow-Lyon (S v1 ? R v5/v6 C 3.5 mV); (2) Cornell (S v3 ? R avL C 2.8 mV (m), C 2.0 mV (w)); (3) Cornell product (S v3 ? R avL ) 9 qrs (ms) C 2440 mm.ms); (4) R avL C 11 mm; (5) Romhilt-Estes C 5, and the Perugia criterion (S v3 ? R avL C 2.4 mV (m), C 2.0 mV (w) or Romhilt-Estes C 5 or typical LV strain pattern Angiotensin converting enzyme (ACE)2 is the negative regulator of the renin angiotensin system, as it degrades Angiotensin (Ang)II and produces Ang1-7. It has been recently reported that genetic ACE2 deficiency is associated with reduced body weight as well as with impaired gestational weight gain and fetal growth restriction in pregnancy. It has been argued that ACE2 deficiency, which is usually associated with an increase of AngII, could be associated with prenatal as well as postnatal changes leading to reduced growth (such as uterine artery dysfunction and IGF-1 reduction, respectively). AIM: Based on these premises, the aim of our study was to evaluate whether there was a difference of ACE2 expression in children with short stature as compared to age-matched controls.

We designed an exploratory case-control study aiming at recruiting consecutively 40 children with short stature (cases) and 40 controls presenting at the Endocrinology Service, aged 2-13 years, excluding those with acute intercurrent diseases, diabetes, renal insufficiency, syndromes and/or on medications. After signing the informed consent to participating in the study, children underwent a medical visit and a fasting blood sampling. Peripheral blood mononuclear cells (PBMC) were isolated to extract mRNA for gene expression analyses. Sera were collected for protein measurements. RESULTS: Children with short stature (n = 29) presented with lower height and body weight as compared to controls (n = 29). Our preliminary data show that children with short stature exhibited a significant reduction of ACE2 gene expression, and a significant increase of ACE/ACE2 and AngII/Ang1-7 ratio. ACE/ACE2 ratio was inversely associated with weight, height, and BMI. CONCLUSIONS: To our knowledge, this is the first study investigating ACE2 expression in a paediatric population. Consistent with the literature, our preliminary results show that ACE2 expression is significantly reduced in children with short stature. This study could represent the basis for further investigations aiming at establishing the presence of a causal relationship between ACE2 deficiency and growth reduction, with further diagnostic and therapeutic perspectives CASE REPORT: In December 2018 the patient was admitted to hospital for suspected coronary artery disease: the echocardiogram showed regional wall motion abnormalities (dyskinesia of the middle septum and hypokinesia of the lateral wall and of the middle segment of the infero-lateral wall), conditioning mild left ventricle systolic dysfunction (EF 45%); signs of hypertensive cardiopathy were also observed (moderate mitro-aortic regurgitation and dilatation of the ascending aorta). However, coronary angiography did not show any significant coronary artery stenosis. As blood pressure measurements were still uncontrolled, despite optimized polypharmacological therapy, in May 2019 the patient was admitted to hospital for the work up of resistant hypertension. Renin/aldosterone ratio, urinary metanephrines and catecholamines were not indicative of secondary causes. We did not find stenosis of renal arteries or obstructive sleep apneas. Only hyperplasia of left adrenal gland was found (adenomas were absent), therefore an imaging follow up was started, which is currently negative. Cardiac MRI showed a dilated left ventricle, with increased thickness and severely depressed function (EF 30%; 35% according to the echocardiogram). Brain, retina and kidney damage was also found. Multiple attempts to modify medical therapy were made, trying to use many active principles at maximum dose, but they were only partially effective in blood pressure control. In July 2019, because of persisting severe systolic dysfunction after six months of optimized medical therapy (including bisoprolol, valsartan, spironolactone, chlortalidone, furosemide, doxazosin, nifedipine, clonidine), the patient was started on sacubitril-valsartan (titrated up to 97/103 mg). CONCLUSIONS: Since September until today, there has been a progressive improvement in pressure control, so that the therapy was reduced to sacubitril-valsartan, amlodipine, spironolactone, bisoprolol, and in ventricular function (mild diffuse hypokinesis conditioning EF 48%). INTRODUCTION: Hypertension leads to aortic stiffening and dilatation but unexpected data from the Framingham Heart Study showed an inverse relationship between brachial pulse pressure and aortic diameter. Proximal aortic dilatation would be associated with lower pulse pressure, but would also predispose to a worse prognosis (cardiac events, heart failure). AIM: to evaluate the relationship between invasivelymeasured central blood pressure and proximal aortic diameter adjusted for age, gender and body height (Z score).

In 71 consecutive patients referred to invasive hemodynamic study, proximal aortic remodeling was evaluated in terms of Z-score, comparing diameters measured at the Sinus of Valsalva to the diameter expected according to patients' age, gender and body height. Pressures were recorded directly in the proximal aorta by means of a catheter before coronary assessment. RESULTS: In this cohort, aged 67 ± 10 years (77.5% men) mean invasive aortic systolic and diastolic blood pressures were 146 ± 23 and 78 ± 13 mmHg, respectively, giving a central pulse pressure (cPP) of 68 ± 21 mmHg. Proximal aortic diameter was 34.9 ± 19.4 mm, while Z-score was -0.3 ± 1.7. In bivariate analysis, invasive cPP was inversely related to Z-score (R = -0.271, p = 0.022) and positively related to age and mean blood pressure. Subjects with higher cPP showed a significantly lower Z-score (-0.789 vs. 0.155, p = 0.001). In a stepwise multiple regression analysis Z-score at the sinuses of Valsalva was independently and inversely related to invasive aortic pulse pressure (b = -0.241, p = 0.011). CONCLUSIONS: Aortic root Z-score is inversely associated with invasively-measured central pulse pressure in a cohort of subjects undergoing invasive coronary assessment. Remodeling at the sinuses of Valsalva may be a compensatory mechanism to limit pulse pressure. METHODS: we collected data of 267 patients, who presented with ischemic stroke and BP C 180/120 mmHg at the Emergency Department of Niguarda Hospital from 2015 to 2017. In-hospital mortality, hospitalization length and discharge disability (evaluated with modified Rankin score-mRs) were considered as outcomes. RESULTS: Mean age was 75.7 ± 11.7 years with SBP values of 194.9 ± 14.9 mmHg at admission. 34.8% of the patients received anti-hypertensive treatment with those achieving a higher SBP reduction in comparison with the untreated one (DSBP 37.8 ± 26.8 mmHg vs 30.7 ± 20.8 mmHg p = 0.034). At the multivariate analysis in the overall population, no SBP values are related to all causes in-hospital mortality. Instead, higher admission SBP relates to high discharge disability and hospitalization length. Furthermore, BP values at admission in Emergency Department appear as disability determinants in patients who did not receive systemic thrombolysis and in patients who did not receive antihypertensive drugs. In these two subgroups, higher SBP values at department entrance determine a higher in-hospital mortality. CONCLUSIONS: In overall population, no BP values are related to all causes in-hospital mortality while higher admission BP relates to high disability and hospitalization length. (Table 1 ). Asymptomatic patient. No evidence of hypertensive heart disease. Subsequent videolaparoscopic right adrenalectomy with histological confirmation of the presence of adrenal cortical adenoma. Regular post-operative course with normalized blood pressure values. In Table 2 the clinical and laboratory characteristics of the patient before and after the adrenalectomy. The patient was initiated to AVS as young, with a history of short-lived hypertension and with biochemical evidence of primary hyperaldosteronism. In fact, it is known that in these cases the response to surgical therapy is usually complete; in addition, up to 48% of patients with primary hyperaldosteronism have normal adrenals on CT scan and over 32% of these have significant lateralization of aldosterone production, a form potentially correctable with surgery. The patient was therefore sent to surgery despite the discrepancy between AVS and imaging. The AVS is currently the diagnostic gold standard, although it is complicated to perform it and subsequently interpret the data, so the evaluation must be carried out at a dedicated center. CONCLUSIONS: In our case, as a result of further documentation of AVS superiority, complete clinical and biochemical healing was obtained six months after the surrectomy. No genetic abnormalities have been identified. INTRODUCTION: Epigenetic mechanisms may regulate CYP11B2 gene function in primary aldosteronism. It has been hypothesized that aldosterone-producing cell clusters (APCCs) may become a source of autonomous aldosterone production when evolving into aldosterone-producing adenoma (APA). AIM: to determine whether CYP11B2 DNA is differentially methylated in APAs and in their concurrent APCCs. METHOD: Eleven formalin-fixed paraffin-embedded adrenal tissues from patients with APA were studied. Immunohistochemical staining was performed using anti-CYP11B1 and anti-CYP11B2 monoclonal antibodies. Staining was quantified by McCarty's H-score. APAs and satellite APCCs identified by immunohistochemistry were microdissected using manual core drilling, and genomic DNA was extracted for CYP11B2 methylation analysis. CYP11B2 DNA methylation level was measured by quantitative Bisulfite-NGS. Bio-informatic analysis was performed in a GalaxyProject environment and processed by BSPAT. The equation 2^-ddCt was used to calculate the fold changes in gene expression between the different adrenal cell structures. Somatic DNA mutations in aldosterone-driver genes KCNJ5, ATP1A1, ATP2B3 and CACNA1D were analyzed by Sanger sequencing. RESULTS: 8/11 APA specimens showed at least one concurrent APCC and 6/8 were available for molecular study. A wide range of CYP11B2 and CYP11B1 immunohistochemical expression was detected in APAs, while positive CYP11B2 and negative CYP11B1 staining was uniformly found in APCCs. The H-score for CYP11B2 expression was not different in all APCCs compared to APAs (P = 0.078). CYP11B2 DNA methylation levels were lower in APAs than in concurrent APCCs (0.51 ± 0.25 vs 0.82 ± 0.16 as mean ± SD, P \ 0.05). Five KCNJ5 and one ATP2B3 mutations were found overall in 11 APAs, and four KCNJ5 and one ATP2B3 mutations among the 6 APAs with concurrent APCCs. No somatic mutations were found in APCCs. CYP11B2 DNA methylation rate was not different in APAs with and without mutations (P ns). CONCLUSIONS: CYP11B2 DNA methylation levels lower in APAs than in concurrent APCCs may sustain the hypothesis of APCC switching to autonomous aldosterone production via a CYP11B2 demethylation process.

Alessio Balletti 1 , Nicola Riccardo Pugliese 1, Katia Raimo 1, Stefano Taddei 1, Alessandra Violet Bacca 1

Paragangliomas are rare extra-adrenal tumors originating from the neural crest-derived chromaffin cells of the sympathetic or parasympathetic ganglia. Their clinical presentation is variable, depending mainly on tumor location and secretion pattern. Cardiac paragangliomas have relevant mortality due to their localization. CASE REPORT: A 72-year-old man presented to our emergency department for head and thoracic trauma following a witnessed transient loss of consciousness. The ATLS protocol, including a full-body CT scan, was executed and multiple rib fractures and a vascularized mass adjacent to the ascending aorta were found. After partial embolization of arterial branches supplying the mass, the patient was referred to our Internal Medicine Department for further evaluations. Syncope work-up (physical examination, blood tests, ECG, Holter monitoring, echocardiogram, carotid sinus massage) was negative except for the presence of orthostatic hypotension (clinostatic BP 134/82 mmHg HR 74 bpm, orthostatic BP time 0' 112/71 mmHg HR 77 bpm). An MRI revealed a 78x48x63mm vascularized, defined and solid intrapericardial tumor located within the aortopulmonary window, without bleeding signs. Morphological features suggested paraganglioma. Urinary normetanephrines and chromogranin A serum levels were elevated (normetanephrines 697 lg/24 h n.v. \ 600, metanephrines 91 lg/24 h n.v. \ 350, CgA 563 ng/ml n.v. \ 100). The 68 Ga-DOTATOC PET/CT confirmed the involvement of chromaffin tissue. The patient was submitted to alpha-beta blockade therapy (carvedilol 12,5 mg bid), showing a normotensive and dipper pattern on ambulatory blood pressure monitoring. Finally, he was discharged and submitted to surgery. Genetic analysis of the known susceptibility genes was performed (RET, VHL, SDHA, SDHAF2, SDHB, SDHC) and a wild type pattern was found. CONCLUSIONS: This case confirms the challenging paragangliomas diagnosis due to their clinical variability and often intermittent secretive pattern, making them asymptomatic or paucisymptomatic for years. AIM: to evaluate arterial subclinical markers of early renal damage obtained by intrarenal Doppler ultrasonography in patients affected by Essential Arterial hypertension (EH) and PA, without overt organ damage. METHODS: We consecutively enrolled 73 hypertensive subjects [30 with EH (mean age 49.5 ± 18.7 years) and 43 with PA (mean age 57.1 ± 11.6 years)]. PA group included 19 with idiopathic aldosteronism (IHA) and 23 with aldosterone-secreting adrenal adenoma (APA). RESULTS: PA patients showed higher levels of urinary albumin excretion (38.9 ± 16.7 mg/24 h) and lower concentration of plasmatic creatinine (0.80 ± 0.18 mg/24 h) than EH (respectively, 9.2 ± 4.5 mg/24 h; 0.98 ± 0.2 mg/ 24 h; p \ 0.001). Using intrarenal Doppler ultrasonography study, compared to EH group, PA showed increased values of right and left Parietal Thickness (respectively, 18.1 ± 3.5 mm vs 13.6 ± 1.8 mm; 17.98 ± 3,4 mm vs 14.55 ± 1.7; p \ 0.001), increased values of right and left Atrophy Index (AI) (respectively, 1.49 ± 0.13 vs 0.65 ± 0.07; 1.46 ± 0.1 vs 0.662 ± 0.070; p \ 0.001), increased values of right and left Pulsatility Index (PI) (respectively, 1.28 ± 0.28 vs 1.14 ± 0.3 s-d/v; 1.27 ± 0.28 vs 1.12 ± 0.24 s-d/v; p \ 0.03) and higher percentage of patients with altered right and left Resistance Index ([ 0.7 cm/s) (respectively, 12% vs 6%; 10% vs 6%; p \ 0.001). Finally, in overall population, plasmatic aldosterone levels were positively correlated to AI (r = 0.55; p \ 0.05) and PI (r = 0.35; p \ 0.05) (Figure 2 ). CONCLUSIONS: Beyond higher 24-hours urinary albumin excretion, this study showed greater subclinical renal damage in PA patients, characterized by altered arterial Stiffness parameters, assessed through the intrarenal Doppler ultrasonography study; moreover, these alterations were significantly correlated to plasmatic aldosterone levels. 

We consecutively enrolled 82 hypertensive subjects [37 males (mean age 48.9 ± 13.3 years) and 45 women (mean age 48.5 ± 14.8 years)], distinguished in two groups: 60 EH patients and 22 PA patients [5 aldosterone-secreting adrenal adenoma (APA), 17 idiopathic aldosteronism (IHA)]; as control group we enrolled 37 normotensive subjects (NS). RESULTS: PA group showed higher UAE excretion (65.7 ± 11.0 mg/24 h) than EH and NS (21.5 ± 7.0 mg/24 h, 9.2 ± 15.0 mg/24 h, respectively; p \ 0.02); in particular, APA patients showed higher UAE excretion than IHA (111.8 ± 56.0 mg/24 h vs 65.7 ± 11.0 mg/24 h; p \ 0.001). In overall hypertensive population, UAE was positively correlated to PAC (r = 0.25; p \ 0.02) and AUR (r = 0.3; p \ 0.001). APA group showed significant increased values of Arterial Stiffness Index (11.7 ± 4.8 m/s; p \ 0.02) compared to IHA (8.8 ± 2.3 m/s), EH (8.3 ± 3 m/s) NS (7.2 ± 1.7 m/s). Furthermore, APA patients showed significant reduced levels both of Subendocardial Variability Ratio (SEVR) (104.8 ± 25.7%) and Travel Time of reflected waves (83.8 ± 28.3 ms), compared to EH (respectively 120.5 ± 22.4%, 112.9 ± 38.1 ms; p \ 0.05) and NS (respectively 119.8 ± 12%, 131.2 ± 32 ms; p \ 0.05). Using multiple linear regression model, in overall hypertensive patients UAE value has been shown to predict Augmentation Index (ß = 0.025; p \ 0.01), SEVR (ß = -0.067; p \ 0.03) and Arterial Stiffness (ß = 0.021; p \ 0.001); predictors of Travel Time of reflected waves were UAE (ß = -0.178; p \ 0.01), triglycerides (ß = -0.139; p \ 0.05), SBP (ß = -1.001; p \ 0.01), DBP (ß = -1.567; p \ 0.01), age (ß = -1.157; p \ 0.01) and waist circumference (ß = -0.940; p \ 0.03) (Figure 3) . CONCLUSIONS: PA patients showed higher cardiovascular subclinical damage, evaluated by PWV, respect to EH; in overall hypertensive population, UAE excretion had significant correlation with aldosterone behaviors, resulting the best marker of subclinical vascular remodeling. INTRODUCTION: Primary aldosteronism is the most common cause of secondary hypertension. Elevated aldosterone levels have been associated with endothelial proliferation and pathological remodeling of the heart and arteries; however, coronary arterial abnormalities have never been reported in patients with primary aldosteronism. CASE REPORT: We report the case of a 53-year-old obese man (BMI 37 kg/m 2 ) with recent history of hypertension, fatigue and subjective dyspnoea who was admitted to our hospital after performing an echocardiography that showed hypertensive and ischemic heart disease in dilated phase. His laboratory results showed hypokalemia and an elevated aldosterone/renin ratio. After case confirmation, the abdominal CT scan showed a slight thickening of the left adrenal gland and a subcentimeter adenoma in the contralateral gland. Interestingly, that after oral potassium correction, the electrocardiogram revealed a symmetrical T-wave inversion and subsequently a coronary angiography detected a coronary-pulmonary fistula in the absence of significant stenosis. In the Italy's coronavirus pandemic full spread, we preferred to postpone the diagnosis of the lateralization of aldosterone hypersecretion by adrenal venous sampling and we started a mineralocorticoid receptor antagonist with a clinical follow-up of cardiovascular symptoms for the optimal treatment of coronary artery fistula. After about two months of follow-up, the patient remains asymptomatic with good blood pressure control and normal potassium levels. CONCLUSIONS: Our case highlights a possible association between hypertensive patients with coronary artery fistulas and primary aldosteronism. We recommend clinicians and cardiologists to maintain a high level of suspicion of primary aldosteronism in these patients.

Aresta Carmen 1 , Favero Vittoria 1,2 , Ripepi Federica 2 , Giovanelli Luca 1,2 , Bilo Grzegorz Marek 3,4 , Pengo Martino 3 , Parati Gianfranco 3,4 , Persani Luca 1,2 , Chiodini Iacopo 1,2 INTRODUCTION: Apparent mineralocorticoid excess (AME) is an autosomal recessive disorder caused by the 11b-hydroxysteroid dehydrogenase type 2 (11b-HSD2) enzyme deficiency. Traditionally, 11b-HSD2 activity is assessed by measuring the cortisol metabolite ratio (tetrahydrocortisol/tetrahydrocortisone, THF ? 5aTHF/THE) in 24 h urine collection. Urinary exosomes, vesicles derived from the renal tubule, are a useful tool to investigate rare proteins and mRNA in diseases. It is not known whether urinary exosomal expression HSD11B2 is related to THF ? 5aTHF/THE, and to mutation status in patients with AME. AIM: to isolate 11b-HSD2 mRNA from urinary exosomes in a family with AME, and to investigate the relationship with either THF ? 5aTHF/THE ratio and the A221G (662C [ G) variant. METHODS: among the A221G carriers (two homozygous probands, two heterozygous parents, four heterozygous relatives) and four wild-type family members, THF ? 5 aTHF/THE ratio, hormonal and biochemical parameters were measured. Urinary exosomes were extracted from morning urine by precipitant reagent and centrifugation. Exosomal RNAs were isolated and pre-amplified with specific kit and primers. Absolute quantification of HSD11B2 mRNA (copies/ll) was assessed by Droplet Digital PCR (ddPCR) using B2M (microglobulin2-beta) gene as the housekeeping. RESULTS: 11b-HSD2 mRNA was detectable in 9 out of 12 samples. Expression of HSD11B2 mRNA varied according to the 662C [ G genotype so that the two probands showed the highest levels (169 ± 72), the four heterozygous intermediate levels (52.54 ± 53.85), and the three wild-type subjects had the lowest levels (8 ± 5.22). The 11b-HSD2 expression related to the hypertensive status among heterozygous subjects. Among the 9 samples where it was detectable, the HSD11B2mRNA correlated inversely with their renin and aldosterone serum concentrations, and slightly positively with THF ? 5aTHF/THE ratio. CONCLUSIONS: HSD11B2 mRNA is detectable in urinary exosomes and its abundance relates to 11b-HSD2 enzyme activity as estimated by the THF ? 5aTHF/THE ratio. The HSD11B2 exosomal expression is coherent with the different 662C [ G genotypes within AME family members, and clearly paralleled with the hypertensive status among heterozygous subjects. Exosomal HSD11B2 mRNA is a useful tool to investigate 11b-HSD2 deregulation in relation to hypertension.

A. Tagetti 

Obesity is considered a pseudo-Cushing state and often elevated levels of cortisol and its metabolites can be found; however, the relationship between cortisol metabolites and blood pressure (BP) in obese children is understudied. 11-b-hydroxysteroid dehydrogenase type 2 (11b-HSD-2) catalyses the reversible conversion of physiological glucocorticoids (tetrahydrocortisol, THF and allo-tetrahydrocortisol, allo-THF) to inactive products (tetrahydrocortisone, THE). An increase in the THFs/THE ratio reflects 11b-HSD-2 impairment and has been associated with BP elevation. Ambulatory blood pressure monitoring (ABPM) provides an accurate measurement of BP during 24 h. AIM: We aimed to investigate the relationship between BP measured by ABPM, urinary cortisol and its metabolites, in a sample of obese children. METHODS: 50 obese children aged between 8 and 17 years (mean age 11.5 ± 3.3 years, 66% males), were included in the present study. Children underwent ABPM. Cortisol, sodium, THF, allo-THF and THE were measured on urinary 24-hour collection. Cortisol urinary metabolites were quantified by liquid chromatography tandem mass spectrometry (Nexera Shimadzu, 4500 MD Sciex).

TheTHF ? alloTHF/THE ratio negatively correlates with 24-hours urinary sodium excretion (p = -0.346; r = 0.015) and to SBP and DBP load (percentage of measure of PAS [ 130 mmHg or percentage of PAD [ 80 mmHg) (respectively r = 0.283 p = 0.047 and r = 0,284; p = 0.046). No correlation between THFs/THE ratio and daytime or night-time SPB or DBP were found. The sum of urinary cortisol and its metabolites, a gross index of relative excess of cortisol, is directly correlated with SBP load (r = 0.355; p = 0.029). CONCLUSIONS: In our sample of obese children, both the impaired activity of the 11-beta-HSD-2 and the amount of cortisol and its metabolites excreted by urine are associated with an excessive 24-h BP load. Reduced urinary sodium excretion mediated by increasing of THF/THE ratio could be involved.

Piera Altieri 1 , Claudio Borghi 1 , Nicola Rizzo 1 , Eugenio Roberto Cosentino 1 , Crescenzio Bentivenga 1

The HELLP Syndrome (HS) is a serious complication in pregnancy characterized by Hemolysis, Elevated, Liver enzymes, Low Platelets and also by cephalea, visual disturbances, epigastralgia and, in many cases, a risk for impaired renal function. PreEclampsia (PE) is a condition implying hypertension, proteinuria and/or associated alterations. Generally, it occurs after the 20th week of pregnancy in previously normotensive, non proteinuric women and it is reversible in postpartum within 6-12 weeks. AIM: The purposes of this study are: (1) to verify the impact of HS in women affected by the aforementioned syndromes in the areas of Bologna and San Lazzaro di S., and to report a longitudinal survey about the main outcomes of the children born to affected patients in the period between 2004 and 2018; (2) to look for a correlation between mothers afflicted by those syndromes and the development of Metabolic Syndrome (MS), hyperuricemia, or cardiovascular disease (CD) in their children and to ascertain whether the paternal age or potential comorbidities can lead to these pathologies in the partner and to any predispositions and pathologies in the child. METHODS: we have considered all the useful parameters-as well as the bio humoral ones-which can determine the diagnosis of HELLP or PE syndrome, and we have created an appropriate database built on medical records. Furthermore, retrospective research on primary care pediatrician and on all completed pregnancies was carried out using a checklist containing measures of outcomes and of the main cardiovascular risk indicators. During the period considered by this study, the results revealed an distinct increase in the number of women affected by these syndromes. This could be a consequence of a greater accuracy in diagnosis, or because the average age of pregnant women has risen as compared to the past, or because of the increased use of assisted reproductive techniques. RESULTS: According to the available data, it seems that there is no correlation between the mother's pathology and the development of MS in children nor a predisposition to cardiovascular diseases, at least in the period we are considering, which is normally characterized by a low incidence of cardiovascular problems. Lastly, it would seem very suggestive that the fathers' reproductive age can reverberate negatively on the partners who are affected in a tendentially higher degree. Similarly to what emerged from the data of children born to affected mothers, no predisposition to these syndromes appears in children during their infant-youth age. In light of these findings, it is expected that these patients shall have a more extensive and rigorous screening.

INTRODUCTION: despite current evidences are limited, 2016 Endocrine Society guideline recommends screening for primary aldosteronism (PA) in all individuals with arterial hypertension and obstructive sleep apnoea (OSA). AIM: We performed a multicentre, multi-ethnic, crosssectional study, designed to investigate the prevalence of PA in patients with OSA and the prevalence of OSA in patients with PA. METHODS: we screened 203 patients with OSA (102 of Caucasian and 101 of Chinese ethnicity) for PA. In case of positive screening, patients underwent confirmatory test for PA and subtyping diagnosis. 207 patients with PA (104 Caucasians, 100 Chinese and 3 of African descent) were screened for OSA by cardio-respiratory polygraphy. RESULTS: 8.9% of patients with OSA had confirmed PA diagnosis (11.8% in Caucasian and 5.9% in Chinese patients). The prevalence of PA in patients without other indications for PA screening, other than OSA diagnosis, was very low (1.5%). The prevalence of OSA was 67.6% (64.4% in Caucasian and 70.0% in Chinese patients). OSA was more prevalent in PA patients with idiopathic hyperaldosteronism than aldosterone-producing adenoma (75.8% vs 59.2%, p = 0.031). We observed a significant correlation between aldosterone levels and apnea/hypopnea index in Caucasian group with PA (R 2 = 0.360, p = 0.013), but not in the Chinese group with PA. Similarly, multinomial logistic regression confirmed a significant association between plasma aldosterone and moderate to severe OSA in Caucasian patients (OR 1.002, p = 0.002), independently of the main confounding factors. No association was present in Chinese patients with PA. CONCLUSIONS: patients with OSA do not have an increased risk of PA, challenging the current recommendation of the Endocrine Society guideline for screening all patients with OSA for PA, independently of hypertension severity. However, OSA is frequent in patients with PA and aldosterone level can worsen OSA severity in Caucasian patients. INTRODUCTION: Primary aldosteronism (PA) is a frequent cause of secondary hypertension and its screening is expected to become a routine evaluation in patients with hypertension. The interference of antihypertensive medications with the Aldosterone-to-Renin-Ratio (ARR) is a major confounder during screening testing. Renin-angiotensin-aldosterone-system (RAAS) triple-A analysis is a novel liquid chromatography/tandem mass spectrometry diagnostic assay that allows simultaneous quantification of aldosterone, equilibrium angiotensin I (eqAngI) and angiotensin II (eqAngII). AIM: to assess the reliability of RAAS triple-A analysis for PA screening. METHODS: We evaluated the diagnostic performance of the Aldosterone-to-AngII-Ratio (AA2R) and five renin based diagnostic ratios, differing in methods to determine aldosterone levels and renin activity, either based on chemiluminescence or radioimmunoassay. RESULTS: We enrolled a cohort of 110 patients with hypertension and suspected PA referred to a single hypertension unit (33 patients with confirmed PA and 77 with essential hypertension). All ratios showed comparable areas under the curves ranging between 0.924 and 0.970 without significant differences between each other. The evaluation of the AngII-to-AngI ratio revealed persistent ACE inhibitor intake in some patients as cause for suppressed renin-based diagnostic ratios, while AA2R remained unaffected, allowing a AA2-R-based PA screening in presence of ACE inhibitor. The optimal cutoff value for the AA2R was 6.6 [(pmol/L)/(pmol/L)] with a sensitivity and specificity of 90% and 93%, respectively, non-inferior to the ARR while pointing to the potential for an interference free application in patients under ACE-inhibitor therapy. CONCLUSIONS: This study shows for the first time the accuracy and reliability of RAAS triple-A analysis for the screening of PA, even in the presence of therapy with ACE inhibitors. Combining information on drug efficacy and compliance monitoring with PA screening, this method might have a significant impact on the overall performance of PA screening. INTRODUCTION: Rectangular (cylindrical) cuffs and bladders are currently used for blood pressure (BP) measurement at the upper arm. However, large arms have a conical shape which make cylindrical cuffs potentially unsuitable. AIM: to study the shape of the arm in people with severe obesity and to investigate the effect of the shape of the cuff on BP measurement in these subjects. METHODS: We compared cylindrical and tronco-conical cuffs of appropriate size in 79 obese subjects with upper arm mid-circumference [ 40 cm and 79 subjects of control (arm mid-circumference \ 33 cm). The upper arm was considered either as a single truncated cone (model 1) or as the sum of two tronco-conical shapes, with bases at the proximal and middle arm circumference, respectively (model 2). We measured the frustum slant angle of the proximal (upper a) and distal (middle a) truncated cones, if the difference between ''upper a'' and ''middle a'' was equal to zero, the upper arm can be assimilated to a single truncated cone (Figure 4a ), if the difference was positive, it means that the distal half of the arm was more conical than the proximal half ( Figure 4b) . RESULTS: In the Obese, upper a was greater than middle a, whereas in the Nonobese the two angles were similar (p \ 0.0001 versus Obese for both a). In the Obese, the cylindrical cuff overestimated BP measured with the tronco-conical cuff by 4.3 ± 5.4/3.1 ± 4.7 mmHg, whereas in the Nonobese slight discrepancies were found between the two cuffs (p \ 0.0001/\ 0.0001versus Obese). In the whole study sample, the difference between the ''upper a'' and ''middle a'' was correlated with systolic BP (p = 0.0008) and diastolic (p \ 0.0001) BP discrepancies. In a multivariable linear regression, the difference between the ''upper a'' and ''middle a'' was an independent predictor of the between-cuff BP differences in obese men (p = 0.004/0.0007) but not in obese women. CONCLUSIONS: In very obese people, the tronco-conical shape of the upper-arm is more pronounced on the distal than the proximal half, a feature that amplifies the BP measurement error when cylindrical cuffs are used.

INTRODUCTION: In a previous analysis of the ABP-International study we showed that extreme dipping in the elderly carries an increased risk of cardiovascular events (CVE) similar to that of reverse dipping. However, the reason for this association remained uncertain. AIM: The present analysis was conducted to test the hypothesis that the main factor accounting for the risk associated with extreme dipping is a low night-time blood pressure (BP). METHODS: We included 10,868 participants (53% men) aged 53 ± 15 years (hypertensives, 81%) enrolled in 8 prospective studies in Australia, Italy, Japan, and U.S.A. Using the systolic BP nocturnal decline (in percent) we identified 3 groups: dippers ([ 10-20%), non-dippers (B 10%), and extreme dippers ([ 20%). Extreme dippers were further splitted into two groups, one with low night-time systolic BP (\ 120 mmHg, ED-low-NBP) and one with high night-time BP (C 120 mmHg, ED-high-NBP). The association between dipping category and CVE was estimated as a function of age (B 70 or [ 70 years) using Cox models adjusted for average 24-hour systolic BP and traditional risk factors. RESULTS: During 6.6 ± 4.0 years of follow-up there were a total of 829 CVE (168 fatal). Among the older participants, there was a significant increase in risk for both non-dippers and extreme dippers, compared to dippers. However, among the extreme dippers a significant increase in risk was found only in ED-low-NBP. The HRs (95%CI) were 1.57 (1.13-2.20) in the non-dippers (p = 0.008), 2.59 (1.33-5.09 ) in the ED-low-NPB (p = 0.005), and 1.15(0.49-2.68 ) in the ED-high-NBP (p = 0.75). If the night-time systolic BP cut-off was set at 110 mmHg, the HR in the ED-low-NBP rose to 3.44 (1.20-9.87) . No increase in risk of CVE was observed among the extreme dippers B 70 years for both night-time BP cut-offs irrespective of whether night-time BP was low or high (p [ 0.59 for all groups). CONCLUSIONS: These data confirm that the prognostic value of extreme dipping is heavily dependent on age. However, a key factor in predicting prognosis is the level of night-time BP. Prolonged exposure to low BP during the night may be harmful due to cerebral and cardiac hypoperfusion. INTRODUCTION: Several studies showed that sleep apnoea (SA) independently enhances the cardiovascular risk but very few investigated its impact on blood pressure (BP) reactivity to stressful task in grade 1 hypertensives with increased arterial stiffness. METHODS: After medical visit and detection of risk factors for SA (Lausanne test: LSAs), 110 hypertensives (132 ± 5/82 ± 6), with similar age, office SBP/DBP, BMI and metabolic state, underwent ABPM with actigraphy and skin oximetry to check sleeping time (SleepT), desaturation time (m' \ 90%) and index (ODI).They underwent arterial tonometry (PWVcf) and laboratory stress session composed by Color Word Stroop test (5'), ability to car driving basic (5') and skilful (5') videogame, alternated with baseline-recovery phases (10'). SBP/DBP was taken every min. and total stress response was measured as ''area-under-the-curve'' = value x time (auc). RESULTS: Patients, in monotherapy with ACEi/ARB, in order of SA and arterial stiffness, were divided in 34 controls (SA-PW-), 33 with SA only (SA ? PW-) and 43 with both SA and arterial stiffness (SA ? PW ?). They presented similar diurnal (131 ± 4/78 ± 5 vs 132 ± 4/ 79 ± 6 vs 132 ± 3/79 ± 5) but different nocturnal SBP/ DBP (117 ± 4/69 ± 9 vs 122 ± 2/74 ± 10*** vs 124 ± 7/75 ± 9***) and nocturnal SBP fall (11 ± 2 vs 7 ± 3*** vs 6 ± 6***). 

The findings show that SA is associated to increased functional BP laboratory emotional stress response and that this is magnified in patients with arterial stiffness. Quality of sleep, and its related disturbances, should be a critical part of the exam in hypertensives and amelioration of technology of the ambulatory blood pressure monitoring is expected. We found a significant correlation between the change in systolic blood pressure (SBP) during night time and morning surge (b = 0.40, p \ 0.001; Figure 5 ). Then we estimated a significantly augmented probability to show a blunted-MS in reverse dippers than in dippers (OR = 9.68, IC 95% = 3.52-26.60; p \ 0.001; Table 1) .

CONCLUSIONS: the present study shows that a blunted-MS is more prevalent in reverse dippers. Previous works described a link between blunted-MS and a worse cardiovascular prognosis. Kario K. hypothesized that this evidence could be explained with a pathological alteration of the autonomic nervous system, both in a hyper-or in a hypo-reactivity way, affecting the control of blood pressure. Further study is needed to clarify the pathophysiological mechanisms of this relationship and its prognostic significance. 

The study of hypertension in experimental models requires techniques leveraging the implant of radiotelemetric catheters devices. While this technique is the gold standard, it presents some objective difficulties in the complexity of surgery and the scarce catheter positioning precision due to vascular tree variability of the single samples. AIM: Our approach aims at establishing an ultrasound guided metric to optimize the catheter positioning, ensuring the pressure measurement reliability. METHODS: Thirty anesthetized mice (all of C57BL6/J strain) underwent surgery to implant the HD-X11 (DSI instruments) pressure catheter device. Radio signals were acquired by the Physiotel RPC-1 receiver and analysis were carried on Ponemah 6.33 acquisition and blood pressure analysis platform. Recording were performed in a dedicated room, with 12-12 h light dark cycle. Catheter positioning was evaluated by aortic arch echo, performed on a Vevo2100 (VisualSonics, Fujifilm), extracting two parameters: -distance from the center of the aortic arch lumen expressed in percentage -angle between catheter tip and the lower wall of aortic arch. All measurements were performed on VevoLab analysis platform (VisualSonincs, Fujifilm) . RESULTS: We established the Bad Data Marks (BDM) extracted from Ponemah platform as quality metric for our blood pressure recordings. We found a linear correlation between the Tip Distance from the Center (TDC) and the BDM (r 2 = 0.14, p = 0.039), with better tracks recordings obtained in the proximity of the center of the aortic arch vessel. Moreover, we found a tendency of correlation between the Tip Angle of Incidence (TAI) with the overall BDM percentage (r 2 = 0.11, p = 0.067). We obtained the best tracks in case of near 0 TAI and TDC, with bad tracks concentrated in regions with more than 10% of deviation from the center or more than 10 degrees from the optimal direction. CONCLUSIONS: Our work establish a new protocol to optimize the implant of radiotelemetric devices in the small animal. This approach is fundamental to improve the reliability of the measurement and the fidelity of the blood pressure wave across days of registration. Moreover, with our approach we can maximize the number of optimal track to lower the impact of animal usage in respect of the 3Rs principles. correlation and regression coefficients between LTL and cIMT or PWV were retrieved from the papers. Collected data was analysed using a random-effect meta-analysis model. RESULTS: 21 studies were selected for a total of 10306 patients. A reverse association between LTL and cIMT was found (pooled r = -0.249, 95% CI -0.37/-0.128, P \ 0.001), and between LTL and PWV (pooled r = -0.194, 95% CI -0.290/-0.100, P \ 0.001) ( Figure 6 ). CONCLUSIONS: PWV and cIMT are inversely associated with LTL and therefore can be considered reliable markers of vascular ageing. inflammation and atherosclerosis in mice due to increased mitochondrial reactive oxygen species (ROS). We, therefore, hypothesized that GRK2 could be involved in the process of aortic valve calcification (AVC). AIM: To evaluate the role of GRK2 in AVC implementing in vivo and in vitro models. METHODS: We used 12 months old mice with selective endothelial knock-out of GRK2 (Tie2CRE-GRK2fl/fl) in EC compared to control (GRK2fl/fl) to evaluate the presence of microcalcification in the aortic valve leaflets by histological analysis. We also employed isolated human valve endothelial cells (VEC) from control and calcified (CAVS) aortic valve leaflets to assess GRK2 expression and subcellular compartmentalization. RESULTS: As previously demonstrated, GRK2 removal from EC induces early atherosclerotic lesions. Here, we observed that GRK2fl/fl mice of 12 months-old display presence of microcalcification, as expected. However, this phenotype is significantly more pronounced in the Tie2CRE-GRK2fl/fl, demonstrating that the lack of GRK2 in the EC accelerates the calcific degeneration of the aortic valve in mice (Figure 7) . In vitro, we observed a significant downregulation of GRK2 expression into the mitochondria of CAVS VECs than control VECs ( Figure 8A ), which associates to an increased ROS production. A previous report demonstrated that ßARKct transfection in macrophage increases mitochondrial biogenesis and reduces ROS production. Here, using the cloning strategy depicted in Figure 8B , we cloned several small sequences of the PH domain of GRK2 into the pcDNA3.1 plasmid, named as PH#1-4. We found that the transfection into HEK293 of the PH#3 potently increased GRK2 localization into the mitochondria as compared to ßARKct, PH4, and pcDNA3.1 as control ( Figure 8C ). PH3 also determined increased biogenesis ( Figure 8D ) and reduced ROS production stimulation ( Figure 8E ). These data support the concept that a smaller portion of the PH domain of ßARKct can reproduce its biological effect. CONCLUSIONS: Our data suggest a direct involvement and a casual role of GRK2 expression/localization in the pathogenesis of CAVS. The GRK2 re-localization into mitochondria is a potential novel strategy to counteract ROS production and the process of AVC.

INTRODUCTION: Development of hypertension as well as alterations in microcirculation (decreased capillary density) have been recently reported to be associated with tyrosine kinase inhibitor (TKI) treatment in cancer patients (Dalbeni A, et al. Cancers 2019). An increased blood pressure has also been demonstrated with direct anti-VEGF inhibitor. AIM: to evaluate whether TKI and direct anti-VEGF agents may affect also the structure of retinal arterioles which seems to have prognostic significance in term of cardiovascular events. METHODS: For this purpose, we included 14 patients with a diagnosis of cancer (renal n = 8, lung n = 2, gastrointestinal n = 2, tyroid n = 1, breast n = 1) underwent a treatment neither with a TKI (n = 11: sunitimib n = 5, pazopanib n = 4, nintedanib n = 1, lenvatinib n = 1) or with an anti-VEGF antibody (n = 3: bevacizumab n = 2, ramucirumab n = 1). All patients were submitted to ambulatory monitoring blood pressure for blood pressure evaluation. Basal and total (after venous congestion) capillary density were assessed by capillaroscopy whereas retinal arteriole morphology was obtained by Adaptive Optic in order to evaluate microcirculation. Patients were evaluated before starting the antiangiogenic therapy (T0) and re-evaluated after three (T3) and six (T6) months after treatment. Changes in antihypertensive treatment was also assessed. RESULTS: Result are reported in the Table. Systolic and diastolic blood pressure values were similar in all patients at T3 and T6 compared to T0. However, during the study antihypertensive treatment was optimized (increased dose and/or added additional agents) in 57% of patients (n = 8).

No differences were observed in retinal arteriole structural parameters. Basal capillary density resulted reduced by antiangiogenic drugs after three or six months (Table) . CONCLUSIONS: Our preliminary data suggest that an increase of antihypertensive treatment is necessary in patients treated with a tyrosine kinase inhibitor (TKI) or a direct VEGF inhibitor, confirming a pro-hypertensive effects of these drugs. However, under adequate blood pressure control, a worsening of basal capillary density but no changes in retinal arteriole morphology might be observed. , and 20 patients receiving monthly Levosimendan infusions (median time on treatment 28 months) were enrolled and compared to a group of 20 healthy subjects. ED was evaluated with ultrasound assessment of the diameter before and after ischemic stress at the brachial artery level. The difference between the two diameters normalized for the baseline value (Flow Mediated Dilation -FMD) has been used for the analysis. All the patients were stable at the time of FMD assessment, with those on r-LEVO being evaluated prior to infusion. RESULTS: FMD was significantly lower in HTX and LVAD groups with respect to controls (9.8 ± 7.4, 9.3 ± 5.7, and 15.6 ± 6.4% respectively, p = 0.01), but not in r-LEVO group (12.5 ± 6.9%). When patients were analyzed according to time from the operation or on treatment, (\ versus [ of the median value), no differences were seen in HTX and r-LEVO group, while in LVAD group FMD was borderline significantly higher in patients with longer follow-up (8.4 ± 6.4% versus 10.2 ± 5.2%, p = 0.05). CONCLUSIONS: Based on this preliminary data we can inference the following: 1-FMD is abnormal in HTX recipients, despite their good functional status, probably due to factors unrelated to CHF (e.g. hypertension, renal insufficiency, denervation, and drug effects); 2-LVAD patients also show ED, with possible better adaptation in very long-term survivors; 3-Near-normal FMD values in CHF patients who remain stable with r-LEVO suggest that pulsed treatment may obtain favourable effects at peripheral level, persisting after clearance of the drug and its metabolites.

G. Mule' (1), C.Carollo (1) AIM: to evaluate, in a group of hypertensive patients, the relationships between choroidal thickness and stiffness of the large arteries, a powerful independent predictor of CV events. METHODS: 158 hypertensive patients belonging to our Regional Referral Centre for Arterial Hypertension were enrolled. All underwent evaluation of the retino-choroidal district by OCT Swept-Source and oscillometric assessment (BpLab) of the aPWV at rest (static) and during 24 h blood pressure monitoring (dynamic).

The choroidal thickness of the outer, inner and central rings and the total average of the thicknesses were reduced in subjects with aPWV [ 10 m/s compared to those who had a lower aortic stiffness, and these differences remained significant even after correction for age and other confounding factors (Figure 9 ). The average choroidal thickness showed close inverse correlations with the aPWV, both static and dynamic, in the simple linear regression analyses. Among these correlations, that between the static aPWV and the overall average of the choroidal thicknesses (r = 0.498; p \ 0.001) is the most significant and remains as such even after correction for various covariates in multiple stepwise regression models. CONCLUSIONS: Our results seem to support the role of choroid thickness as an integrated marker of cardiovascular risk and seem to confirm the theory of a cross-talk between micro-and macrocirculation in hypertensive patients.

Local carotid stiffness (Carotid PWV) is an independent predictor of cardiovascular events but few data are available on the progression of Carotid stiffness over time.

AIM: The aim of the present longitudinal study was to analyze the progression of local carotid stiffness over a 6-year period in a general population in Northern Italy (Vobarno Study). METHODS: 123 subjects, age 55 ± 4 years (42% males, hypertension in 43% at baseline visit), underwent a baseline (BL) and a follow up (FU) visit, 6.2 ± 0.5 years apart. In all subjects laboratory examinations, measurements of blood pressure (BP) and of Carotid PWV (using an echotracking approach) were performed at BL and at FU. The vasculature of the eye and of the heart share several common characteristics. Therefore, the easily accessible vessels of the eye may be considered, to some extent, a ''window'' to the heart. AIM: to evaluate retinal arterioles morphological changes in patients with angina and nonobstructive coronary artery disease. METHODS: In 19 patients (M:W 11:8, mean age 71 ? 6 years) with microvascular angina (MA), confirmed by normal coronary angiography and SPECT stress hypoperfusion and in 18 controls (C) (M:W 10:8, mean age 69 ± 6 years) with normal SPECT response, direct measurement of wall to lumen of retinal arterioles (W/L) using an adaptive optics (AO) imaging system (Imagine Eyes, Orsay, France) was performed. All subjects also underwent BP measurement with an automated oscillometric device (Omron HEM 9000Ai, mean of 3 measurements). RESULTS: No differences in demographic and hemodynamic characteristics were observed between MA patients and C, except for BMI (BMI 30 ± 4.2 vs 24 ± 4 kg/m 2 , in MA and C respectively, p = 0.001). Retinal arterioles wall thickness (11.75 ± 1.45 vs 13.9 ± 1.53 lm), W/L ratio (0.29 ± 0.05 vs 0.25 ± 0.03 in MA and C respectively, p = 0.008) and wall cross sectional area (WCSA) (4876 ± 976 vs 4004 ± 872 lm 2 , respectively in MA and C, p = 0.012) were higher in MA patients as compared with C. Differences were confirmed after adjustment for BMI. CONCLUSIONS: Our findings suggest that in patients with angina and normal coronary arteries retinal structural changes may be observed. AIM: To assess mechanical properties of aA by aortic strain in terms of b 2 -Stiffness index (Beta-SI) analysis in hypertensive patients with different severity of aA dilatation and to evaluate the association between mechanical properties of aA and cardiovascular damage. METHODS: 100 hypertensive outpatients underwent clinical evaluation, transthoracic echocardiography (TTE) and assessment of pulse wave velocity (PWV). Strain analysis of aA was performed with speckle-tracking TTE software. Beta-SI was defined as: 100*Ln(systolic blood pressure/diastolic blood pressure)/maximal transversal deformation of aA. Hypertensive patients were divided in three groups based on aA diameter: \ 40 mm, 40-45 mm and C 45 mm. RESULTS: Beta-SI resulted to rise exponentially with aA dimensions (p \ 0.001) with especially in patients having aA [ 45 mm. A progressively greater proportion of patient with impaired (i.e. elevated) Beta-SI was present in groups identified by progressively dilated aA (18.2% vs 48.4% vs 80% respectively, p \ 0.05). On multivariate logistic regression only an impaired Beta-SI predicted aA dilatation (p \ 0.001). Beta-SI was also related to cardiovascular organ damage in terms of left ventricular mass (LVMi, p = 0.030) and PWV (p = 0.028). Patients with high Beta-SI had grater LVMi (94 ± 24 vs. 117 ± 47 g/m 2 ; p = 0.010) and PWV (8.63 ± 1.88 vs. 10.20 ± 2.99 m/s; p = 0.013). CONCLUSIONS: A dilatation in hypertensive subjects is associated with increased local aortic stiffness. Strain analysis adds functional information to the mere morphological evaluation of aortic dimension and it could be an useful tool to better stratify cardiovascular risk in this specific population. (54 males and 24 females, aged 69 ± 13 years) was included in the present study. In 75 patients, high-flow oxygen was required (Venturi mask), 6 patients needed orotracheal intubation and 10 were given continuous positive pressure oxygen therapy (CPAP). Till June 10th, 17 deaths had been observed. Survival curves were calculated according to Kaplan-Meier method. Comparison between groups was performed with Breslow and Mantel-Cox test. RESULTS: A significant reduction in survival was observed in patients under treatment with oral anticoagulant drugs (vitamin K antagonists or new oral anticoagulants) prior to hospital admission (p-0.024), probably as an expression of increased comorbidity and/or more severe cardiovascular disease. On the contrary, the administration of LMWH at a higher dose than usual prophylactic dose (enoxaparin [ 4000 U.C.) was associated with lower mortality (p-0.044, see figure -12_20200610145550): none of the patients treated died. Administration of LMWH at prophylactic dose was not associated with reduction of fatal events (p-NS). CONCLUSIONS: The subcutaneous administration of LMWH at a higher dose than that indicated for deep vein thrombosis prophylaxis is associated with a better outcome in patients with SARS-CoV-2 pneumonia, confirming some emerging evidence.

INTRODUCTION: Hypertension (HT) seems to increase the severity and the risk of mortality from SARS-Coronavirus-2 (COVID-19 infection). This latter presents few symptoms (fever, cough, diarrhoea), but rarely is aggressive and may lead to interstitial pneumonia and septic shock. A case of COVID-19 infection with multi-organ dysfunction is described. CASE REPORT: A 53-year-old male was hospitalized in the Infectious Diseases-Unit for fever (38.8°C), dyspnoea and oxygen (O2) desaturation (87% in ambient air); blood pressure (BP) and heart-rate values were high (148/92 mmHg and 110 bpm). He has a history of HT treated with valsartan 80 mg/daily and hypothyroidism post-thyroidectomy treated with levothyroxine 125 mcg/daily. The nasopharyngeal swab test was positive for COVID-19 virus and the chest CT-scan ( Figure -23_20200604195113) showed lung interstitial disease, bronchiectasis, emphysema and segmental pulmonary embolism of the lower lobes arising from right popliteal venous thrombosis. Despite antibiotic therapy with Piperacillin-Tazobactam 4.5 mg three-a-day and non-invasive C-PAP ventilation with O2 at 14 L/min the patient was transferred to intensive care unit for respiratory distress requiring invasive mechanical ventilation associated with hypotension (84/50 mmHg), renal failure acute, critical illness neuropathy and jaundice. After therapy with sympathomimetic amines, methyl-prednisolone 40 mg/daily, tocilizumab 640 mg for two days, lopinavir/ritonavir 200 ? 50 mg twice-a-day, hydroxychloroquine 200 mg twice-a-day, azithromycin 500 mg/daily and enoxaparin 8000UI twice-a-day, clinical picture improved as well as blood examinations (leukocytes 16.970?6.200, lymphocytes 1.640?3.200, Prothrombin-time 1.34?1.0, activated partial thromboplastin-time 45?29, D-Dimer 20 ± 3.68, Troponin-I 227 ± 20, creatinine 1.54 ± 0.87, urea 56 ± 38, ALT 154 ± 31, bilirubin 20 ± 39). The echocardiogram revealed a basal hypokinesia of the lower wall and of septum suggestive of myocarditis; an abdominal ultrasound documented lithiasic cholecystitis. The patient was discharged after 40 days with BP levels controlled (124/80 mmHg) by a fixed-combination therapy with perindoprilamlodipine 5/5 mg/daily, anti-thrombotic treatment with DOAC Edoxaban 60 mg/daily and hypolipidemic therapy with atorvastatin 20 mg/daily. CONCLUSIONS: In HT, the severity of COVID-19 infection seems due to a pro-thrombotic activation of the coagulation cascade rather than the modulation of the renin-angiotensin system. However, further researches investigating the impact of HT and BP lowering drugs on the clinical course of COVID-19 infections are mandatory. March 2020 compared with March 2019 (11.9% versus 6.1%, p = 0.048). CONCLUSIONS: It is possible that late hospital presentations and consequent greater disease severity affected eligibility and outcome of cardiovascular procedures, thus justifying the disproportion in cardiovascular deaths during the national lockdown period. This evidence advances recent concerns regarding the impact of the pandemic on cardiovascular diseases and related deaths. show cardiovascular complications, including elevated troponin levels and ischemic electrocardiographic changes, which are associated with a worse overall prognosis. To date, the pathophysiology of these complications is unclear. The Buckberg index or Subendocardial Viability Ratio (SEVR), measured by arterial tonometry and possibly corrected for the blood oxygen content (SEVR-O2) is a useful tool for the evaluation of cardiac ischemia caused by an altered balance between oxygen demand and supply to the subendocardium. METHODS: Patients admitted to the medical ward for acute COVID-19 infection were evaluated by carotidfemoral arterial tonometry (PulsePen, Diatecne, Milan), arterial blood gas analysis and high sensitivity troponin measurement (hsTnI). RESULTS: Eight patients (M: F 4: 4) were enrolled, with an average age of 66.7 ± 15.5 years, systolic blood pressure 121.5 ± 10.2 mmHg, diastolic 67.6 ± 10.3 mmHg, heart rate 70 ± 18 bpm, arterial oxygen pressure 100 ± 30 mmHg and inspired oxygen fraction 32 ± 28%; of these, subjects with positive troponin were two (hsTnI peak 227 and 394 ng/L). The SEVR showed an average value of 109 ± 30% (65-139), which was 19.9 ± 9.7 (8. 6-34.6) after the correction for oxyhemia (SEVR-O2). In particular, in the two subjects with troponin increase the SEVR was particularly reduced (SEVR 65% and 81%, SEVR-O2 9.1 and 8.6), confirming a positive correlation between the alteration of the SEVR and myocardial injury.

CONCLUSIONS: Acute COVID-19 infection has high mortality partly mediated by cardiovascular complications. From present data, the increase in troponin, which was found to be a predictor of mortality, is correlated with a significant imbalance between the demand and supply of oxygen to the myocardium. Further and larger studies are needed to confirm the ischemic origin of the rise in troponins and the usefulness of SEVR-O2 as a clinical and prognostic index in patients with COVID-19. INTRODUCTION: COVID-19 epidemia has severely hit North-Italy, and this induced the Italian government to adopt severely restrictive measures to reduce the contagion risk, forcing the most part of the population to stop working and leisure activities and to remain at home for several weeks. Beyond the expected decrease in physical activity, it is yet to know how this quarantine affects dietary habits of isolated people. AIM: To evaluate the effect of COVID-related quarantine on the smoking and dietary habits of a well-characterized northern Italian rural population METHODS: For the purpose of this study, we selected a subpopulation sample from the database of the Brisighella citizens enrolled in the last population survey to be interviewed on its life-style habit changes during quarantine. The first questions were oriented to exclude those subjects not strictly in quarantine because work-wise active (for instance, farmers or nurses), those respecting quarantine from less than 4 weeks, those affected by COVID-19 infection or by other severe diseases diagnosed after the last population survey, those unable to understand or answer the questions related to the life-style, and those not willing to answer to personal questions by phone. Then, the questionnaire usually administered during the population survey has been telephonically administered to 359 adultelderly subjects by trained personnel (M: 156, W: 203; mean age: 64.6 ± 13.3 years old). RESULTS: Smoking habit were nearly unmodified by the quarantine. Body Mass Index did not modifies during quarantine (26.7 ± 4.7 vs. 26.7 ± 4.5 kg/m 2 ). The selfperceived dietary changes reported by the interviewed subjects are the following ones: no change (50%), increased quantity (32%), decreased quantity (6.4%), selective increase in sweets (4.2%), improved quality (3.4%), selective increase in charbohydrates (2.2%), and decreased quality (0.9%). During quarantine, the daily consumption of bread and substitute, pasta and rice, green vegetable and other vegetables, healthy vegetable oils, fruits, milk and yogurt, alcoholic drinks, sugars and sweets, and coffee significantly increased. Among foods classified as never consumed, consumed less than 4 times per week, between 4 and 6 times per weeks, or more than 6, during quarantine the consumption of lean meat, salamis other than ham, cheeses, eggs, and mixed seed oils significantly increased. On the contrary, the intake of fat meat and ham. Among food classified as never consumed, consumed less than 2 times per week, between 2 and 3 times per weeks, or more than 3, during quarantine the consumption of fish, mussels, and legumes, significantly decreased, while the one of nuts slightly increased. The Dietary Quality Index decreased from 42.4 ± 4.1 to 37.8 ± 4.7 (p \ 0.03). CONCLUSIONS: The COVID associated quarantine could worsen the quality of diet, in particular being associated with an increased intake of almost all categories of food.

may result. Health system should address events that may be regarded as another consequence of COVID-19 pandemic.

Coronavirus Infection pneumonia such as that caused by the Severe-Acute-Respiratory-Syndrome-Coronavirus-2 (SARS-CoV-2) infection (COVID-19). METHODS: We performed an accurate revision of the available literature regarding both preclinical and clinical studies on the association between RAS imbalance and the onset of acute lung damage, which is the main clinical feature of COVID-19, assuming a possible beneficial role of RAS-modulating drugs. RESULTS: The respiratory symptoms of COVID-19 are caused by the SARS-CoV-2 infection of the pneumocytes, with subsequent involvement of both alveolar interstitium and vascular endothelial cells, mediated by the binding of the virus to its receptor: the Angiotensin-Converting-Enzyme-2 (ACE2). The binding of the viral spike protein to ACE2 leads to its down-regulation. ACE2 plays a key role in preserving the equilibrium of the two main RAS arms: the ACE/angiotensin (Ang) II/Ang II type 1 receptor (AT1R) axis (''classic RAS'') and the ACE2/Ang 1-7/ MasR axis (''anti-RAS''). Following the down-regulation of ACE2 due to the viral binding, there is an hyperactivation of the ''classic RAS'', with attenuation of the lung and cardiovascular protective roles of the ''anti-RAS'', resulting in endothelial disfunction and microvascular damage with increased permeability, leaky vessels and secondary release of proinflammatory cytokines, leading to alveolar epithelium dysruption and fibrosis. The evidence of a more aggressive COVID-19 evolution in obese males, in whom the ''classic RAS'' is already hyperactivated due to adiposity, support this hypothesis. Both AT1R-blockers (ARB) and ACE-inhibitors (ACEi) are likely to reduce both lung damage and fibrosis by modulating the activity of the ''classic RAS'' and inducing ACE2, thus rebalancing the two opposing arms. Indeed, several animal models and preclinical studies support this hypothesis. CONCLUSIONS: Clinical randomized controlled trials are needed to confirm the protective role of RAS-modulating drugs, such as ARB and ACEi, on lung and cardiovascular damage caused by SARS-CoV-2 infection, that are supported by strong pathophysiological basis and both preclinical and clinical evidences.

Aspidistria Laura (3), Viviani Filippo (4), Di Nuzzo Mariachiara

INTRODUCTION: ACE2, entry point of SARS-CoV-2, has a protective role in SARS-CoV-2-induced Acute Dystress Syndrome (ARDS) and there is a relationship between Rho kinase (ROCK), ARDS and increased ACE2 levels induced by ROCK inhibitors. ACE2 glycosylation, essential for viral binding, is driven by the acidic pH of intracellular endosomes/lysosomes/Golgi vesicles. The prophylactic/therapeutic use of hydroxychloroquine/ chloroquine finds rationale in its effect of increasing endosomal/Golgi pH, leading to production of non-glycosylated ACE2 and therefore reduction/inhibition of viral binding

COVID-19 prevalence in general population was obtained from Civil Protection's official data, the estimated prevalence from recently published data. 95% CI values processed with Clopper-Pearson method using R software. RESULTS: None of GS/BS reported infection/symptoms of COVID-19, which was statistically not significant vs the prevalence of COVID-19 in the general population in the Italian hotspots due to the low prevalence of GS/BS (rare diseases

INTRODUCTION: Preliminary data indicate a reduction in hospitalizations for acute coronary syndromes during the Covid-19 outbreak in Northern Italy. The province of L'Aquila, in Central Italy, was marginally affected by the pandemic, but changes in healthcare seeking behaviours were noticed. AIM: We investigated whether the albeit marginal Covid-19 burden in the area of L'Aquila had an impact on cardiovascular hospitalizations and outcomes. METHODS: We retrospectively analyzed de-identified data from all patients admitted to the five hospitals located in the province of L'Aquila for all-cause and cardiovascular hospitalizations, cardiovascular acute phase treatments (coronary angioplasty, systemic fibrinolysis, endovascular procedures), and in-hospital cardiovascular deaths in the time window from

RESULTS: A total of 5908 patients were hospitalized in the first quarter of 2020 (52.9% women, mean age 59.2 ± 24.9 years), with a mean daily admission rate of 64.9

As of June 10th, 17 deaths had been observed. Survival curves were calculated according to Kaplan-Meier method. Comparison between groups was performed with Breslow and Mantel-Cox test RESULTS: A significant raise in mortality was observed in hypertensive patients (p = 0.008-see figure -12_20200610140123) at standard follow-up (from admission to 10th June); the result was confirmed even after reducing follow-up period to hospitalization time. Ongoing therapy with ACE-inhibitors at the time of admission was associated with a worse prognosis (p = 0.083), while no difference in survival was observed in patients under treatment with ARBs (p = 0.68), statins (p = 0.33) or antiplatelets (p = 0.095). A trend to significance was detected between COPD and mortality (p = 0.059)

HOME BLOOD PRESSURE DURING CORONAVIRUS PANDEMIC PHASE 1: PHONE INTERVIEWS AND WELL-BEING

INTRODUCTION: Endocrine causes are involved in arterial hypertension (AH) pathogenesis in 5-10% of cases. AIM: The aims of the present study are to evaluate in a hypertensive population at higher risk of secondary causes: (i) prevalence of endocrine hypertension (EH) and subclinical hypercortisolism (SH) (ii) clinical predictors of EH (iii) IS-correlated clinical parameters METHODS: 47 patients (age 25-84 years) were selected on the basis of inclusion criteria (grade 3/resistant AH; sudden new onset or unexpected worsening AH; onset of AH \ 30 years without risk factors; organ damage disproportionate to the grade/length of AH) and exclusion criteria (specific signs/symptoms of endocrinopathy). In all patients we assessed blood pressure levels (systolic blood pressure SBP, diastolic blood pressure DBP, mean arterial pressure MAP, ambulatory blood pressure monitoring ABPM), cortisol after 1 mg-overnight-dexamethasone, ACTH, 24-hour urinary free cortisol, 24-hour urinary fractionated metanephrines, aldosterone, renin, IGF1, TSH, calcium, albumin, PTH. RESULTS: EH was diagnosed in 51% of patients (primary aldosteronism 19%, SH 17%, pheochromocytoma 6%, acromegaly 2%, hyperthyroidism 2%, hyperparathyroidism 2%). SBP, DBP, MAP levels and prevalence of non-dippers were higher in EH patients (146 ± 20 mmHg, 93 ± 14 mmHg, 111 ± 15 mmHg, 60.0%) than in the remaining patients (135 ± 12 mmHg, 84 ± 7 mmHg, 101 ± 7 mmHg, 9.1%, p \ 0.05). EH diagnosis was independently associated with older age and non-dipping pattern (OR IC 95%: 1.15, 1.013-1.302, p = 0.031; 28.98, 1.259-667.119, p = 0.035) . SH patients showed higher levels of DBP and MAP (89 ± 5 mmHg, 108 ± 6 mmHg) compared with the essential AH patients (84 ± 7 mmHg, 101 ± 7 mmHg, p \ 0.05).CONCLUSIONS: In a hypertensive population at higher risk of secondary causes, prevalence of EH was 51%; nondipping pattern and older age were clinical predictors of EH; prevalence of SH was 17%; blood pressure levels were higher in SH patients compared with essential AH patients. It is pivotal to distinguish bilateral idiopathic hyperaldosteronism (IHA) from aldosterone-producing adenoma (APA) because surgical removal of the latter can effectively treat PA. Current international guidelines consider adrenal venous sampling (AVS) as the gold standard for diagnosing APA. Pre-test adequate imaging reconstruction of adrenal vein drainage by computed tomography (CT) angiography can improve AVS success. AIM: to evaluate the AVS performance comparing the selectivity Index of patients who underwent pre-test Angio-CT versus a traditional AVS approach with basal CT. METHODS: This was a retrospective observational study. We included all patients who underwent AVS in the Department of Internal Medicine at Pisa University Hospital between January 2010 and February 2020. We reviewed the medical records to obtain information regarding clinical characteristics, laboratory findings for the case detection and diagnosis of PA, computed imaging scans, AVS results and surgical data. Successful AVS was defined as an adrenal vein to inferior vena cava cortisol ratio [ 2 (selectivity index). RESULTS: We collected data of 124 AVS and analyzed complete records of 97 patients (59 males and 38 females, median age 48.3 yrs): 37.1% (36/97) executed pre-test Angio CT scan and 62.8% (61/97) only basal CT. Right AVS failed in 53.6% (52/97) of cases with pre-test angioCT in 32% (17/52, P = 0.3 NS). Likewise, left AVS failed in 10.3% (11/97) of cases with pre-test angioTC in 54% (6/11, P = 0.2 NS); CONCLUSIONS: The difficulty of recognizing or cannulating the right adrenal vein is the most frequent cause of AVS failure, due to small length and/or anatomic variations. The pre-test Angio-CT allows an accurate reconstruction of the right adrenal vein before AVS and may help to improve the success rate of the invasive procedure.AIM: This study attempted to evaluating the effectiveness and safety of a novel nutraceutical compound (NC) associated with EZE on the modulation of blood lipids profile in statin-intolerant patients with moderate-to-high CV risk. METHODS: Ninety-six statin-intolerant hypertensive and hyper-cholesterolemic subjects treated pharmacologically with EZE 10 mg daily, were randomised in open label (n = 48) to take for 3 months a NC containing Monacolin-K 5 mg, Berberine Hydrochloride, t-Resveratrol, Quercetin and Chromium. The control group (n = 48), assumed only EZE in monotherapy at the same dosage; both groups followed a standardised lipid-lowering diet. The total serum cholesterol (TC), low density lipoprotein cholesterol (LDLC), high density lipoprotein cholesterol (HDLC), triglycerides (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatinine phosphokinase (CPK) levels were compared at the follow-up in both groups using Student's t-test. RESULTS: TC and LDL levels reduced in both groups, but were lower in the group treated with EZE ? NC (-25.9% vs -15%, p \ 0.05 and -38.7% vs -21.0%, p \ 0.05, respectively). No significant changes were observed in both groups about TG decrease (-9.4% vs. -11.7%, NS) and HDLC increase (?4.2% vs. ?1.1%, NS). The AST, ALT and CPK levels increased in the group treated with the EZE ? NC compared to the control group, but overall remained within the acceptability range. There was no difference concerning the efficacy of lipid-lowering treatment depending on gender and no patients dropped out of the study. CONCLUSIONS: In the short-term, the EZE ? NC combination therapy is well-tolerated and effective in improving TC and LDLC levels in statin-intolerant patients with moderate-to-high cardiovascular risk.

Gino Seravalle 1 , Fosca Quarti Trevano 2 , Raffaella Dell'oro 2 , Silvio Bertoli 2 , Giuseppe Mancia 2 , Guido Grassi 2 INTRODUCTION: Microneurographic recording of sympathetic nerve traffic (MSNA) have shown that sympathetic activation may occur in chronic kidney disease (CKD). However, the small sample size of the available studies, presence of comorbidities, heterogeneity of the patients examined represented major weaknesses not allowing to draw definite conclusions, particularly for early phases of CKD. METHODS: The present meta-analysis evaluated 1020 subjects recruited in 29 microneurographic studies, assessing MSNA quantification in different CKD stages, excluding comorbidities. Assessment was also extended to the relationships of MSNA with other neuroadrenergic markers, such as plasma norepinephrine and heart rate, anthropometric variables, and markers of renal function. RESULTS: CKD patients stratified by stage coherently showed higher average MSNA values, about 22% in stage 1-2 and 80% in hemodyalisis (P \ 0.001) as compared to controls. MSNA when expressed as bursts/min was significantly related to plasma creatinine in CKD patients (r = 0.70, P \ 0.01). When combined data of patients and controls were analyzed across the various glomerular filtration rate classes MSNA values were progressively higher across classes denoting renal dysfunction of increasing severity reaching a maximum in hemodialysis patients (P value for trend \ 0.01). In the CKD population MSNA was significantly and directly related to age (r = 0.57, b = 0.74, P = 0.02), body mass index (r = 0.75, b = 3.17, P = 0.001), but not to albuminuria. No significant correlation was found between MSNA, heart rate, and norepinephrine. CONCLUSIONS: Thus MSNA is markedly increased in CKD and this increase is (1) independent on comorbidities, (2) not restricted to ESKD patients maintained on chronic dialysis but clearly detectable in mild and moderate, (3) related to the severity of renal dysfunction being an early phenomenon which worsens gradually when the degree of renal dysfunction worsens.

Elisa Russo 1 , Stefania Drovandi 1 , Gennaro Salvidio 1 , Daniela Verzola 1 , Pasquale Esposito 1 , Giacomo Garibotto 1 , Francesca Viazzi 1 INTRODUCTION: Polipharmacy is common in older people, thus increasing the risk of adverse drufg reactrions. AIM: This study aimed to analyse prevalence and predictors of the most relevant adverse drug reactions in older hypertensive adults. METHODS: We retrospectively analysed data on antihypertensive-and statin-related adverse drug reactions in adults aged 65 or older evaluated at the Hypertension Clinic of Careggi Hospital, Florance, Italy, between January 2018 and December 2019. Predictors were investigated using multivariate logistic regression. RESULTS: Of 262 participants (mean age 75.9 years, 55.3% female), the 19% of the patients taking ACE-inhibitors reported cough while 33.6% of the patients taking calcium channel blockers (CCB) reported peripheral edema, occuring more frequently of amlodipine. The prevalence of statin-related myalgia was 23.5%. At multivariate analysis SNRI antidepressants and gastroesophageal reflux disease (GERD) were predictive of ACE-inibitors induced cough (OR 16.220, 95% CI 1.243-211.621; OR 4.207, 95% CI 1.249-4.171, respectively) and angiotensin-receptor antagonists were associated with an increased risk of peripheral edema on CCB (OR 2.500, 95% CI 1.095-5.710). GERD was predictive for statin-induced myalgia (OR 6.737, 95% CI 1.530-29.662). CONCLUSIONS: ACE inhibitor-induced cough, CCBrelated peripheral edema and statin-induced myalgia are common in older hypertensive adults. SNRI antidepressants and GERD are independently associated with ACE inhibitor-induced cough, while angiotensin-receptor antagonists are predictive of CCB-related peripheral edema. GERD is also associated with statin myalgia. The association between Serum Uric Acid (SUA) and Pulse Wave Velocity (PWV), has been extensively evaluated but with some discrepancies in results. A further limitation refers to the fact that only few data were analyzed taking into account the possible effects of gender. AIM: to estimate the association between SUA and arterial stiffness in general population and hypertensive patients, as a whole population and as divided by gender, by pooling results from existing studies. METHODS: Carotid-femoral and brachial-ankle PWV (cf-and ba-PWV) have been analysed separately and subgroup analyses by gender are reported. RESULTS: Among 692 potentially relevant works, 24 paper were analysed. 7 studies referred to cf-PWV in the general population with an overall positive association at adjusted analysis for both males and females (0.07-95%CI: 0.03; 0.11 and 0.06-95%CI: 0.03; 0.09, respectively). 12 studies referred to ba-PWV in the general population with the finding of a positive association at adjusted analysis for females (0.04 -95%CI: 0.01; 0.07), but not for males (0.13-95%CI -0.09;0.34). In hypertensive patients only 4 studies evaluated cf-PWV and 1 ba-PWV with only one study (with cf-PWV) finding positive association. CONCLUSIONS: The association between SUA and cf-PWV resulted significant in general population in both males and females while it was only significant for female regarding ba-PWV. Furthermore, the few available studies found no significant relationship between SUA and both cfand ba-PWV in hypertensive subjects.

Giovambattista Desideri 1 , Claudio Borghi 2 INTRODUCTION: hyperuricemia and gout are strongly related with traditional cardiovascular risk factors and vascular damage. AIM: to assess whether febuxostat is better than allopurinol in ameliorating pulse wave velocity in patients with hyperuricemia and gout.Chirurgia e Odontoiatria ''Scuola Medica Salernitana''/ DIPMED, Universita`degli Studi di Salerno

We recently showed that the endothelium can synthesize and release catecholamines in response to hypoxia. Catecholamines play a key role in regulating vascular tone especially in response to vascular damage, therefore the ability of endothelial cells to produce them autonomously could represent a self-defense mechanism to protect cells from vascular damage and ischemia. It is therefore essential to clarify the pathophysiological function of endothelial catecholamine production and its effect in response to vascular damage. To date, no mouse model allows to achieve this goal, therefore the aim of the study is the generation and characterization of a transgenic mouse model in which the tyrosine hydroxylase (TH) gene, the rate-limiting enzyme in the synthesis of catecholamines, is selectively deleted in the endothelium by the CRE-LOX system with specific tissue expression of the CRE recombinase. METHODS: we crossed TH-FLOX mice and Tie2-CRE mice to obtain mice with endothelial knock-out of the TH gene in heterozygosity (TH ±) and the latter were crossed with each other to obtain the knock-out of the TH gene in homozygosity (TH-/-). RESULTS: The first interesting finding of the study derives from the results of these crossings. In fact, in all the crossings between TH ± we have never obtained pups with the TH-/-genotype suggesting that the total TH deletion in the endothelium could be lethal and that the endothelial production of catecholamines would play an important role in embryonic development. We then evaluated the production of total catecholamines in blood samples of TH ± mice compared to the relative controls by ELISA and showed a significant reduction (Norepinephrine: -22 ± 6.4%; Epinephrine: -56 ± 3.1%, p \ 0.05). CONCLUSIONS: TH ± mice represent a useful model for the study of endothelial catecholamines. Also, the data obtained so far indicate that the catecholamines produced by the endothelium represent a significant rate and that they play a key role in embryonic development.

Bortolazzi E, Macchi F, Amadio G, Franconi A., Trentin M, Rossi A, Zamboni M and Fantin F University of Verona, Verona, Italy INTRODUCTION: Orthostatic hypotension (OH) is an independent risk factor for cardiovascular morbidity and mortality. Arterial stiffness, typical of cardiovascular aging, has been shown to be a pathophysiological mechanism linking OH and increased CV risk. AIM: to evaluate the relationship between OH and arterial stiffness and SubEndocardial Viability Ratio (SEVR) and moreover to identify the main predictors of orthostatic hypotension, Carotid-Femoral Pulse Wave Velocity (PWVcf) and SEVR. METHODS: Eighty-five patients were enrolled (average age 83.45 ± 6.38) in Verona's AOUI Geriatric ward. They underwent blood pressure, heart rate, body weight measurements. In addition, comorbidity, arterial stiffness (PWVcf measured by applanation tonometry), SEVR and biochemical indexes (haemoglobin, creatinine, electrolytes, lipids). RESULTS: Prevalence of orthostatic hypotension was 46.6%. The SEVR values corrected for arterial oxygen and hemoglobin content were statistically lower in OH patients (p = 0.039); PWVcf values were statistically higher in OH subjects (p = 0.041). In a binary logistic regression, PWVcf was the only significant predictor of OH (OR 1.123; p = 0.039; IC = 1.006-1.17). In a backward logistic regression model gender, creatinine clearance and OH were significant predictors of SEVR corrected for O2 content. Mean arterial pressure, creatinine clearance and OH were significant predictors of PWV. CONCLUSIONS: In conclusion, the data collected within this study show that OH is related to increased arterial stiffness, justifying its higher prevalence rate in elderly patients. OH was also associated with reduced values of corrected SEVR, suggesting a possible role of reduced subendocardial vascularization in rising cardiovascular morbidity and mortality in patient with OH. 

With head-up body tilting, a pressure gradient is generated along the aortic pathway. Aortic stiffness as measured by carotid-femoral pulse wave velocity (cfPWV) is known to depend on blood pressure (BP), and this dependency may change with age. Therefore, the hydrostatic BP gradient resulting from a change in body posture may elicit a cfPWV change that is agedependent. AIM: to analyze the relationship between BP gradientinduced by head-up body tilting-and related changes in cfPWV in individuals of varying age. METHODS: cfPWV and other hemodynamic parameters were measured in 30 healthy individuals at head-up tilt of angles of 0°(supine), 30°, and 60°. At each angle, the PWV gradient and resulting cfPWV were also estimated (predicted) by assuming a global non-linear, exponential, pressure-diameter relationship characterized by a constant b0, and taking into account that (diastolic) foot-to-foot cfPWV acutely depends on diastolic BP (DBP). RESULTS: cfPWV significantly increased upon body tilting (8.0 ± 2.0 m/s supine, 9.1 ± 2.6 m/s at 30°, 9.5 ± 3.2 m/s at 60°, p for trend \ 0.01); a positive trend was also observed for heart rate (HR). When observed, tiltinduced, cfPWV change measured by applanation tonometry was compared with that predicted from the estimated BP hydrostatic gradient, the difference in observed-vs.predicted PWV change increased non-linearly as a function of age (R2 for quadratic trend = 0.38, p \ 0.01, p vs. linear = 0.04) (Figure 10 ). This result was unaffected by HR tilt-related variations (R2 for quadratic trend = 0.37, p \ 0.01, p vs. linear = 0.04). CONCLUSIONS: Under a hydrostatic pressure gradient, the pulse wave traveling along the aorta undergoes agerelated, BP-independent, PWV non-linear increases. 

In the beginning of 2020, an unexpected outbreak due to a new COVID-19 corona virus made the headlines all over the world. Exponential growth in the number of those affected makes this virus such a threat. AIM: to investigate determinants of healing among COVID-19 patients. METHODS: We designed a cross-sectional observational multicenter nationwide survey in Italy to understand demographic and clinical characteristics of patients with confirmed COVID-19 infection. We analyzed information from 2446 charts of Italian patients certified for COVID-19 admitted in 26 hospitals. Healing from COVID-19 infection, defined has two negative consecutive swab, was reported in 544 patients (22.2%), 95% of them were hospitalized. RESULTS: Age and Charlson Comorbidity Index were significantly lower in patients experienced healing compare to non-healing (63 ± 15 vs 69 ± 15 and 2 ± 2 vs 3 ± 2). Among antihypertensive medications Ace-inhibitors and Diuretic were less frequently prescribed among patients experiencing healing (p \ 0.01). In multivariable regression model main predictors of healing were younger age (OR: 0.99; 95%, 0.98-0.99, p = 0.0001), being not affected by Chronic kidney disease (OR: 0.35; 95%, 0.17-0.70, p = 0.003) or heart failure (OR: 0.44; 95%, 0.28-0.70, p = 0.001). Non-use ACE inhibitors and diuretics was not significant associated with healing (OR: 0.88; 95%, 0.67-0.1.17, p = 0.377 and OR: 0.77; 95%, 0.56-1.07, p = 0.127). CONCLUSIONS: Our study demonstrated that age and comorbidities plays a major role in determining healing in patients with COVID-19. Antihypertensive therapy is not associated with less chance of healing. -19) . We also evaluated the relevance of these pathways in defining the risk of mortality and complications during hospitalization and the capacity of the treatment to attenuate such a risk.

METHODS: 266 patients hospitalized for SARS-CoV-2 related pneumonia were included in the study. Clinical, biochemical, treatment and outcome data were extracted from the in-hospital medical records. The primary endpoint was incidence of in-hospital COVID-19 associated death. RESULTS: hsTnT was significantly associated with the risk of mortality, even after adjustment for age, creatinine, sex and history of cardiovascular disease. D-dimer and CRP presented stronger associations with hsTnT than PaO 2 . Changes of hsTnT were associated with changes in the D-dimer and CRP concentrations. Only D-dimer, however, was associated with increased risk of mortality, while CRP was a strong predictor of respiratory complications. Among treatments, only low molecular weight heparin showed convincing evidence for attenuation of the mortality risk in the whole population. This benefit was higher in subjects with higher levels of hsTnT. CONCLUSIONS: The strong relationship of D-dimer with both hsTnT and mortality, as well as the greater mortality benefits obtained with anticoagulant treatment in people with higher hsTnT suggest that the SARS-CoV-2 coagulopathy might represents an important determinant of the hsTnT elevation and of its relationship with mortality in COVID-19.

INTRODUCTION: The prevalence of kidney involvement during SARS-CoV-2 infection has been reported to be high in several clinical records around the world. Nevertheless, depending by study population, definitions of kidney involvement and length of observation, the pictures described are inconsistent.

We collected data on patient demographics, baseline history of comorbid conditions, home medications, details about triage vitals, baseline laboratory test results and in-hospital treatment in the first 854 patients who received a diagnosis of COVID-19 consecutively admitted to our Institution in Genoa-north of Italy. The diagnosis of chronic kidney disease (CKD) was based on the median serum creatinine and on the presence of proteinuria at urinalysis when available within 180 days prior to hospital admission. Acute kidney injury (AKI) was defined according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The primary and secondary outcome were the development of AKI and death. RESULTS: Of 777 patients admitted with Covid-19 and with available kidney data within 6 months before, AKI developed in 176 patients (22.6%). Of these, 79 (45%) showed an acute worsening of a pre-existing CKD, and 12.6% required kidney replacement therapy. Independent associates of AKI were CKD, PCR, the need for ventilation. Among patients with AKI, 111 died (63%) and its occurrence increased by 60% the risk for death (HR 1.60 [95% IC 1.21-2.49] p = 0.002) independently by potential confounding factors including hypertension, pre-existing kidney damage, and comorbidity index. Treatment with HCQ was associated with a decreased risk of AKI and death (by 60 and 50%, respectively). Patients with kidney damage showed a similar distribution of the causes of death as compared to the whole population except for bleeding who was significantly more frequent in AKI as compared to CKD and the whole population (7.5 vs 1.5 vs 3.5%, respectively We performed a study on ED to check patients in three non-COVID ED compared to COVID ED. Together these hospitals take care of more than 1,000,000 residents. We compared discharges between March 11th and April 10th, 2020 to the same interval in 2019 and 2018. METHODS: Using ICD9 discharge diagnosis code, we focused our preliminary analysis on cardiovascular diseases: ischemic cardiac pain, both as myocardial infarction and ischemic angina, Stroke, Heart failure, Cardiac Arrest, Hypertension, and Cardiac Arrhythmias. We also analyzed data on non-cardiac chest pain and Anxiety. All patients were SARS-CoV-2 negative at reverse transcriptionpolymerase chain reaction analysis on the swab sample. All listed diagnosis were related to the population cared.Variables are compared using Pearson's Chi square test. A p value \ 0.05 was considered statistically significant. RESULTS: We found out that during 2020 lockdown the global number of patients admitted to ED significantly decreased compared to the same period of two previous years. Discharges in 2020 were significantly reduced for ischemic disease, stroke, hypertension and cardiac arrhythmias. In addition, non-cardiac chest pain and anxiety were significantly reduced in 2020. On the contrary, heart failure was stable during years since no significant difference in 2020 compared to 2019 and 2018 were seen. We also found a significant increase in cardiac arrests in 2020 compared to 2018 and 2019. These results are the same also splitting COVID and non-COVID EDs data. CONCLUSIONS: The difference in the 2020 diagnoses may also imply a consequence for the future. Differently to past successes, after COVID-19 a possible increase in chronic consequence like heart failure or stroke sequelae INTRODUCTION: Different studies highlighted the association between home blood pressure (HBP), compliance to the treatment and hypertensive state but in very few the individual wellbeing could be detected during social stress conditions. AIM: to verify these associations with the vascular damage markers previously found 10-14 months before the Covid 19 pandemic phase 1. HBP> 8±16/1±13*** 36±73*** 121±14*** 10.5±2.6*** 17.2±2.9*** 9.4±1.8*** COGtot (24.8±7.8 vs 29.3±8.4***), HTNqol (4.5±0.9 vs 3.9±0.9***) e TREATqol (4.6±0.8 vs 4.1±0.9***) were impaired in HBP >paƟents. The Pearson test showed the significant associaƟon between SBPdom-off and SBPcar (0.513***) and PWVcf (0.272**).

The findings demonstrate that the wellbeing in hypertensives is associated to compliance, preserved vascular function and cognitive capabilities also during social stress. These variables should be considered along the follow-up of hypertensives to enhance the efficacy of treatment since early phases of the disease. INTRODUCTION: Hypertension (HT) is a major risk factor of mortality and its impact in patients affected by SARS-COV-2 is further emphasized worldwide. RAAS imbalance hypothesis has been involved in the explanation of the mortality rates of compromised patients. Nevertheless, a better understanding of the relationship between blood pressure (BP) behaviour, RAAS-inhibition (RAAS-I) and death in patients affected by COVID-19 is needed.

We collected data on patient demographics, baseline history of comorbid conditions, home medications, details about triage vitals, baseline laboratory test results and in-hospital treatment in the first 854 patients consecutively admitted to our Institution in Genoa-Northern Italy who received a diagnosis of COVID-19. Systolic blood pressure (SBP) tertiles were defined as \ 120, 120-139 and C 140 mmHg. The primary endpoint was allcause mortality. RESULTS: Among 750 patients with all information available, 371 patients (49%) had a history of hypertension and 266 (35%) died during a 36 ± 22 days of follow-up. The presence of HT increased by 40% the risk for death ] p \ 0.0001) independently by potential confounding factors including age, gender, diabetes, pre-existing kidney damage, the need for invasive ventilation and treatment with ACE-Inhibitors or Angiotensin receptor blockers. When we analysed the whole study population on the basis of BP tertiles we found a j-shaped relationship between BP values and the occurrence of acute kidney injury and of all cause death. Patients with BP values between 120 and 140 mmHg showed a significantly lower risk for death as compared to those with BP values above 140 or below 120 mmHg. This finding is shown as Kaplan-Maier plot (Log rank test p \ 0.0001). CONCLUSIONS: HT entails a worse prognosis in COVID-19. RAAS-I is not associated with a different severity in outcome. The relationship between BP values, renal function and death seems to be J-shaped, with optimal SBP values between 120 and 140 mmHg.