Pubblicazioni - Maloberti Dott. Alessandro

• Relationships between diuretic-related hyperuricemia and cardiovascular events: data from the URic acid Right for heArt Health study.
  J Hypertens

  2021 Feb;39(2):333-340. doi: 10.1097/HJH.0000000000002600.
  
  Maloberti Alessandro, Bombelli Michele, Facchetti Rita, Barbagallo Carlo Maria, Bernardino Bruno, Rosei Enrico Agabiti, Casiglia Edoardo, Cicero Arrigo Francesco Giuseppe, Cirillo Massimo, Cirillo Pietro, Desideri Giovambattista, D'elia Lanfranco, Dell'Oro Raffaella, Ferri Claudio, Galletti Ferruccio, Giannattasio Cristina, Loreto Gesualdo, Iaccarino Guido, Lippa Luciano, Mallamaci Francesca, Masi Stefano, Mazza Alberto, Muiesan Maria Lorenza, Nazzaro Pietro, Parati Gianfranco, Palatini Paolo, Pauletto Paolo, Pontremoli Roberto, Quarti-Trevano Fosca, Rattazzi Marcello, Rivasi Giulia, Salvetti Massimo, Tikhonoff Valerie, Tocci Giuliano, Ungar Andrea, Verdecchia Paolo, Viazzi Francesca, Volpe Massimo, Virdis Agostino, Grassi Guido, Borghi Claudio,
  
  Abstract
  
  OBJECTIVE:
  Although the relationship between hyperuricemia and cardiovascular events has been extensively examined, data on the role of diuretic-related hyperuricemia are still scanty. The present study was designed to collect information on the relationship between diuretic-related hyperuricemia and cardiovascular events.
  
  METHODS:
  The URic acid Right for heArt Health (URRAH) study is a nationwide, multicentre, observational cohort study involving data on individuals recruited from all the Italy territory under the patronage of the Italian Society of Hypertension with an average follow-up period of 122.3?±?66.9 months. Patients were classified into four groups according to the diuretic use (yes vs. no) and serum uric acid (SUA) levels (higher vs. lower than the median value of 4.8?mg/dl). All-cause death, cardiovascular deaths and first cardiovascular event were considered as outcomes.
  
  RESULTS:
  Seventeen thousand, seven hundred and forty-seven individuals were included in the analysis. Mean age was 57.1?±?15.2 years, men were 45.3% and SBP and DBP amounted to 144.1?±?24.6 and 85.2?±?13.2?mmHg. 17.2% of individuals take diuretics of whom 58% had SUA higher than median value. Patients with hyperuricemia without diuretic use served as reference group. In multivariate adjusted analysis (sex, age, SBP, BMI, glucose, total cholesterol, and glomerular filtration rate) individuals with hyperuricemia and diuretic use exhibit a similar risk for the three outcomes as compared with the reference group.
  
  CONCLUSION:
  Our study showed that diuretic-related hyperuricemia carry a similar risk of cardiovascular events and all-cause mortality when compared with individuals that present hyperuricemia in absence of diuretic therapy.
  
  Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
  
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• Costs and effects of cardiovascular risk reclassification using the ankle-brachial index (ABI) in addition to the Framingham risk scoring in women.
  Atherosclerosis

  2021 Jan;317():59-66. doi: S0021-9150(20)31498-2.
  
  Cortesi Paolo Angelo, Maloberti Alessandro, Micale Mariangela, Pagliarin Federica, Antonazzo Ippazio Cosimo, Mazzaglia Giampiero, Giannattasio Cristina, Mantovani Lorenzo Giovanni
  
  Abstract
  
  BACKGROUND AND AIMS:
  Ankle brachial index (ABI) is a simple and cheap parameter to assess the presence of atherosclerosis. It could also help correctly reclassify the cardiovascular risk when added to the Framingham risk score (FRS). Recent evidence has demonstrated improvement in prediction performance of ABI when added to FRS, particularly in women. However, no studies have been published yet evaluating the cost-effectiveness of this approach. This study attempts to fill in this gap by assessing the cost-effectiveness of ABI measurements in primary prevention in women.
  
  METHODS:
  We developed a Markov model to compare two different strategies for assessing the cardiovascular risk (low, intermediate and high) among women in the general population: 1) FRS strategy, and 2) FRS + ABI strategy; and the relative impact associated with interventions for preventing CV events in intermediate and high-risk categories.
  
  RESULTS:
  In the base-case analysis, FRS + ABI reported an additional cost of ? 110 and a gain of 0.0039 QALYs per patient, resulting in an ICER of ? 27.986/QALY, when compared to FRS alone. The ICER improved to ?1.641/QALY when using a lifetime horizon. The effectiveness of preventive CV disease interventions reported also a significant impact. A 32% reduction of CV events was the minimum value estimated to maintain FRS + ABI as a cost-effective strategy.
  
  CONCLUSIONS:
  The addition of ABI to FRS is a cost-effective approach in women classified at low and intermediate risk with FRS only. This new approach gives the possibility to reclassify and allocate them into the appropriate risk group and treatment.
  
  Copyright © 2020 Elsevier B.V. All rights reserved.
  
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• Hyperuricemia prevalence in healthy subjects and its relationship with cardiovascular target organ damage.
  Nutr Metab Cardiovasc Dis

  2020 Aug;():. doi: S0939-4753(20)30353-7.
  
  Maloberti Alessandro, Qualliu Esmerilda, Occhi Lucia, Sun Jinwei, Grasso Enzo, Tognola Chiara, Tavecchia Giovanni, Cartella Iside, Milani Martina, Vallerio Paola, Signorini Stefano, Brambilla Paolo, Casati Marco, Bombelli Michele, Grassi Guido, Giannattasio Cristina
  
  Abstract
  
  BACKGROUND AND AIM:
  Heterogeneous results have been obtained in the relationship between Uric Acid (UA) and Target Organ Damage (TOD). In the present study we sought to assess the prevalence of hyperuricemia in healthy subjects as well as the role of UA in determining TOD. We evaluated vascular, cardiac and renal TODs in the whole population as well as sub-grouped by gender.
  
  METHODS AND RESULTS:
  As many as 379 blood donors participated at the present analysis. TOD was evaluated as Pulse Wave Velocity (PWV), Left Ventricular Mass Index (LVMI) and carotid Intima-Media Thickness (IMT). Hyperuricemia was defined with the classic cut-off (>7.0 in men and >6.0 mg/dL in women) but also with a most recently defined one (5.6 mg/dL for both sex). Hyperuricemia was present in 6.3% of the whole population (7.3% males, 2.8% females) considering the classic cut-off, while, with the recently identified one, it was present in 28.2% of the whole population (37.3% males, 4.7% females). Despite all the evaluated TODs significantly correlated with UA, linear multivariate regression analysis showed that none of them, except for GFR, displayed UA as a significant covariate. Similar figures were found also when both correlation and linear regression analyses were repeated in the two genders separately.
  
  CONCLUSIONS:
  Hyperuricemia is an important problem also in healthy subjects and its prevalence could further increase if lower cut-off will be used. In this specific population UA is significantly associated with renal impairment while this was not the case for cardiac and vascular damage.
  
  Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
  
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• Impact of admission serum acid uric levels on in-hospital outcomes in patients with acute coronary syndrome.
  Eur J Intern Med

  2020 Dec;82():62-67. doi: S0953-6205(20)30296-X.
  
  Centola Marco, Maloberti Alessandro, Castini Diego, Persampieri Simone, Sabatelli Ludovico, Ferrante Giulia, Lucreziotti Stefano, Morici Nuccia, Sacco Alice, Oliva Fabrizio, Rebora Paola, Giannattasio Cristina, Mafrici Antonio, Carugo Stefano
  
  Abstract
  
  BACKGROUND:
  To assess the association between admission serum uric acid (SUA) levels and in-hospital outcomes in a real-world patients population with acute coronary syndrome (ACS) and to investigate the potential incremental prognostic value of SUA added to GRACE score (GRACE-SUA score).
  
  METHODS:
  The data of consecutive ACS patients admitted to Coronary Care Unit of San Paolo and Niguarda hospitals in Milan (Italy) were retrospectively analyzed.
  
  RESULTS:
  1088 patients (24% female) were enrolled. Mean age was 68 years (IQR 60-78). STEMI and NSTE-ACS patients were 504 (46%) and 584 (54%) respectively. SUA (OR 1.72 95%CI 1.33-2.22, p < 0.0001) and GRACE score (OR 1.04 95%CI 1.02-1.06, p < 0.0001) were significantly associated with an increased risk of in-hospital death at the multivariate analysis. Admission values of SUA were stratified in four quartiles. Rates of acute kidney injury, implantation of intra-aortic balloon pump and non-invasive ventilation use were significantly higher in the last quartile compared to Q1, Q2 and Q3 (p < 0.01). The areas under the ROC curve (AUC) for GRACE score and for SUA were 0.91 (95% CI 0.89-0.93, p < 0.0001) and 0.79 (95% CI 0.76-0.81, p < 0.0001) respectively. The AUC was larger for predicting in-hospital mortality with the GRACE-SUA score (0.94; 95% CI 0.93-0.95).
  
  CONCLUSIONS:
  High admission levels of SUA are independently associated with in-hospital adverse outcomes and mortality in a contemporary population of ACS patients. The inclusion of SUA to GRACE risk score seems to lead to a more accurate prediction of in-hospital mortality in this study population.
  
  Copyright © 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
  
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• Serum uric acid, predicts heart failure in a large Italian cohort: search for a cut-off value the URic acid Right for heArt Health study.
  J Hypertens

  2021 Jan;39(1):62-69. doi: 10.1097/HJH.0000000000002589.
  
  Muiesan Maria L, Salvetti Massimo, Virdis Agostino, Masi Stefano, Casiglia Edoardo, Tikhonoff Valérie, Barbagallo Carlo M, Bombelli Michele, Cicero Arrigo F G, Cirillo Massimo, Cirillo Pietro, Desideri Giovambattista, D'Eliak Lanfranco, Ferri Claudio, Galletti Ferruccio, Gesualdo Loreto, Giannattasio Cristina, Iaccarino Guido, Mallamaci Francesca, Maloberti Alessandro, Mazza Alberto, Nazzaro Pietro, Palatini Paolo, Parati Gianfranco, Pontremoli Roberto, Rattazzi Marcello, Rivasi Giulia, Tocci Giuliano, Ungar Andrea, Verdecchia Paolo, Viazzi Francesca, Volpe Massimo, Grassi Guido, Borghi Claudio,
  
  Abstract
  
  OBJECTIVE:
  To assess the prognostic cut-off values of serum uric acid (SUA) in predicting fatal and morbid heart failure in a large Italian cohort in the frame of the Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension.
  
  METHODS:
  The URic acid Right for heArt Health (URRAH) study is a nationwide, multicentre, cohort study involving data on individuals aged 18-95 years, recruited on a community basis from all regions of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 128?±?65 months. Incident heart failure was defined on the basis of International Classification of Diseases Tenth Revision codes and double-checked with general practitioners and hospital files. Multivariate Cox regression models having fatal and morbid heart failure as dependent variables, adjusted for sex, age, SBP, diabetes, estimated glomerular filtration rate, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol, previous diagnosis of heart failure and use of diuretics as possible confounders, were used to search for an association between SUA as a continuous variable and heart failure. By means of receiver operating characteristic curves, two prognostic cut-off values (one for all heart failure and one for fatal heart failure) were identified as able to discriminate between individuals doomed to develop the event. These cut-off values were used as independent predictors to divide individuals according to prognostic cut-off values in a multivariate Cox models, adjusted for confounders.
  
  RESULTS:
  A total of 21?386 individuals were included in the analysis. In Cox analyses, SUA as a continuous variable was a significant predictor of all [hazard ratio 1.29 (1.23-1.359), P?
  CONCLUSION:
  The results of the current study confirm that SUA is an independent risk factor for all heart failure and fatal heart failure, after adjusting for potential confounding variables and demonstrate that a prognostic cut-off value can be identified for all heart failure (>5.34?mg/dl) and for fatal heart failure (>4.89?mg/dl).
  
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• Thoracic radiotherapy as a risk factor for heart ischemia in subjects treated with chest irradiation and chemotherapy and without classic cardiovascular RISK factors.
  Radiother Oncol

  2020 Nov;152():146-150. doi: S0167-8140(20)30397-2.
  
  Vallerio Paola, Maloberti Alessandro, Palazzini Matteo, Occhi Lucia, Peretti Alessio, Nava Stefano, Soriano Francesco, Musca Francesco, De Chiara Benedetta, Belli Oriana, Moreo Antonella, Bisceglia Irma, Lestuzzi Chiara, Giannattasio Cristina
  
  Abstract
  
  BACKGROUND AND PURPOSE:
  Radiation Induced Heart Disease (RIHD) represents a late effect of chest irradiation, contributing in increasing mortality rate in oncological patients by affecting pericardium, myocardium, valvs and coronaries. Currently, regarding the risk of Coronary Artery Disease (CAD), a cardiological screening involving exercise stress electrocardiography after 5-10 years from radiotherapy is advised. We sought to determine the rate of ischemia at exercise stress electrocardiography in a population of patients without cardiovascular risk factors who sustained radiotherapy, using a cohort of patients presenting with at least one cardiovascular risk factor as control group.
  
  DESIGN AND METHODS:
  A population of 115 patients who sustained chest irradiation (and associated chemotherapy), presenting without classic cardiovascular risk factors or typical symptoms suggesting CAD, was evaluated with exercise stress electrocardiography. 135 patients with at least one risk factor for cardiovascular disease candidate to stress testing for primary prevention or for atypical symptoms served as control group.
  
  RESULTS:
  The cohort of irradiated patients without classical cardiovascular risk factors is younger (48.7 ± 10.1 vs 60.5 ± 10.8 years, p < 0.001) and presents a lower percentage of males when compared with the control group. In this latter group 25.9% of subjects has diabetes, 62.9% dyslipidaemia, 67.4% hypertension and 19.2% actively smoke. Despite this important differences regarding classic cardiovascular risk factors, no significant differences were found in the number of positive exercise stress electrocardiography (10.4 vs 5.9%, p = ns).
  
  CONCLUSIONS:
  Chest irradiation represents a strong cardiovascular risk factor. In fact, prevalence of positive ECG-stress test is not different (nor higher and nor lower) in irradiated subjects without cardiovascular risk and not irradiated patients with classic cardiovascular risk.
  
  Copyright © 2020 Elsevier B.V. All rights reserved.
  
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• Functional Improvement After Outpatient Cardiac Rehabilitation in Acute Coronary Syndrome Patients is Not Related to Improvement in Left Ventricular Ejection Fraction.
  High Blood Press Cardiovasc Prev

  2020 Jun;27(3):225-230. doi: 10.1007/s40292-020-00374-1.
  
  Peretti A, Maloberti Alessandro, Garatti L, Palazzini M, Triglione N, Occhi L, Sioli S, Sun J W, Moreo A, Beretta G, Giannattasio C, Riccobono S
  
  Abstract
  
  INTRODUCTION:
  Cardiac rehabilitation (CR) improves the functional capacity and the prognosis of patients with coronary artery disease.
  
  AIM:
  Our study was aimed at assessing the relationship between functional improvement (evaluated with 6-min Walk Test-6MWT) and the improvement in left ventricular ejection fraction (LVEF) after CR.
  
  METHODS:
  We collected data from 249 patients (age 66.79?±?11.06 years; males 81.52%) with a recent history of Acute Coronary Syndrome that performed CR. The functional improvement after CR was expressed as the ? between distance covered at the final versus the initial 6-min Walking Test (6-MWT), while LVEF was calculated with transthoracic echocardiogram at the beginning and at the end of the CR.
  
  RESULTS:
  Patients were divided accordingly to their pre-rehab LVEF (??55% vs?
  CONCLUSION:
  Although it could be expected that an increase in LVEF is related to the functional improvement after CR, no significant correlation was found in our population.
  
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• What hypertensive patients want to know [and from whom] about their disease: a two-year longitudinal study.
  BMC Public Health

  2020 Mar;20(1):308. doi: 10.1186/s12889-020-8421-6.
  
  Cappelletti Erika R, Greco Andrea, Maloberti Alessandro, Giannattasio Cristina, Steca Patrizia, D'Addario Marco
  
  Abstract
  
  BACKGROUND:
  This study explored both the evolution of the information needs and the perceived relevance of different health information sources in patients with essential hypertension. It also investigated the relationships between information needs and the perceived relevance of information sources with socio-demographic and clinical variables.
  
  METHODS:
  Two hundred and two patients with essential arterial hypertension were enrolled in the study and evaluated at baseline and during three follow-ups at 6, 12 and 24?months after baseline. Patients had a mean age of 54.3?years [range 21-78; SD?=?10.4], and 43% were women. Repeated measures ANOVA, Bonferroni post hoc tests, and Cochran's Q Test were performed to test differences in variables of interest over time.
  
  RESULTS:
  It was observed a significant reduction in all the domains of information needs related to disease management except for pharmacological treatment and risks and complications. At baseline, patients reported receiving health information primarily from specialists, general practitioners, relatives, and television, but the use of these sources decreased over time, even if the decrease was significant only for relatives. Multiple patterns of relationships were found between information needs and the perceived relevance of sources of information and socio-demographics and clinical variables, both at baseline and over time.
  
  CONCLUSIONS:
  The findings showed a general decrease in both the desire for information and the perceived relevance of different information sources. Hypertensive patients appeared to show little interest in health communication topics as their disease progressed. Understanding patients' information needs and the perceived relevance of different information sources is the first step in implementing tailored communication strategies that can promote patients' self-management skills and optimal clinical outcomes.
  
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• Hyperuricemia and Risk of Cardiovascular Outcomes: The Experience of the URRAH (Uric Acid Right for Heart Health) Project.
  High Blood Press Cardiovasc Prev

  2020 Apr;27(2):121-128. doi: 10.1007/s40292-020-00368-z.
  
  Maloberti Alessandro, Giannattasio C, Bombelli M, Desideri G, Cicero A F G, Muiesan M L, Rosei E A, Salvetti M, Ungar A, Rivasi G, Pontremoli R, Viazzi F, Facchetti R, Ferri C, Bernardino B, Galletti F, D'Elia L, Palatini P, Casiglia E, Tikhonoff V, Barbagallo C M, Verdecchia P, Masi S, Mallamaci F, Cirillo M, Rattazzi M, Pauletto P, Cirillo P, Gesualdo L, Mazza A, Volpe M, Tocci G, Iaccarino G, Nazzaro P, Lippa L, Parati G, Dell'Oro R, Quarti-Trevano F, Grassi G, Virdis A, Borghi C,
  
  Abstract
  
  The latest European Guidelines of Arterial Hypertension have officially introduced uric acid evaluation among the cardiovascular risk factors that should be evaluated in order to stratify patient's risk. In fact, it has been extensively evaluated and demonstrated to be an independent predictor not only of all-cause and cardiovascular mortality, but also of myocardial infraction, stroke and heart failure. Despite the large number of studies on this topic, an important open question that still need to be answered is the identification of a cardiovascular uric acid cut-off value. The actual hyperuricemia cut-off (>?6 mg/dL in women and 7 mg/dL in men) is principally based on the saturation point of uric acid but previous evidence suggests that the negative impact of cardiovascular system could occur also at lower levels. In this context, the Working Group on uric acid and CV risk of the Italian Society of Hypertension has designed the Uric acid Right for heArt Health project. The primary objective of this project is to define the level of uricemia above which the independent risk of CV disease may increase in a significantly manner. In this review we will summarize the first results obtained and describe the further planned analysis.
  
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• Association between uric acid and pulse wave velocity in hypertensive patients and in the general population: a systematic review and meta-analysis.
  Blood Press

  2020 08;29(4):220-231. doi: 10.1080/08037051.2020.1735929.
  
  Rebora Paola, Andreano Anita, Triglione Nicola, Piccinelli Enrico, Palazzini Matteo, Occhi Lucia, Grassi Guido, Valsecchi Maria Grazia, Giannattasio Cristina, Maloberti Alessandro
  
  Abstract
  
  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. The purpose of this study was 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. Carotid-femoral and brachial-ankle PWV (cf- and ba-PWV) have been analyzed separately and subgroup analyses by gender are reported. Among 692 potentially relevant works, 24 articles were analyzed. Seven studies referred to cf-PWV in the general population with an overall positive association at adjusted analysis for both males and females (beta regression coefficient (ß): 0.07; 95%CI: 0.03; 0.11 and ß: 0.06; 95%CI: 0.03; 0.09, respectively). Twelve studies referred to ba-PWV in the general population with the finding of a positive association at adjusted analysis for females (ß: 0.04; 95% confidence interval (CI): 0.01;0.07), but not for males (ß: 0.13; 95%CI: -0.09; 0.34). In hypertensive patients only four studies evaluated cf-PWV and one ba-PWV with only one study (with cf-PWV) finding positive association. 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 cf- and ba-PWV in hypertensive subjects.
  
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• Identification of the Uric Acid Thresholds Predicting an Increased Total and Cardiovascular Mortality Over 20 Years.
  Hypertension

  2020 02;75(2):302-308. doi: 10.1161/HYPERTENSIONAHA.119.13643.
  
  Virdis Agostino, Masi Stefano, Casiglia Edoardo, Tikhonoff Valerie, Cicero Arrigo F G, Ungar Andrea, Rivasi Giulia, Salvetti Massimo, Barbagallo Carlo M, Bombelli Michele, Dell'Oro Raffaella, Bruno Berardino, Lippa Luciano, D'Elia Lanfranco, Verdecchia Paolo, Mallamaci Francesca, Cirillo Massimo, Rattazzi Marcello, Cirillo Pietro, Gesualdo Loreto, Mazza Alberto, Giannattasio Cristina, Maloberti Alessandro, Volpe Massimo, Tocci Giuliano, Georgiopoulos Georgios, Iaccarino Guido, Nazzaro Pietro, Parati Gianfranco, Palatini Paolo, Galletti Ferruccio, Ferri Claudio, Desideri Giovambattista, Viazzi Francesca, Pontremoli Roberto, Muiesan Maria Lorenza, Grassi Guido, Borghi Claudio,
  
  Abstract
  
  Serum uric acid (SUA) levels discriminating across the different strata of cardiovascular risk is still unknown. By utilizing a large population-based database, we assessed the threshold of SUA that increases the risk of total mortality and cardiovascular mortality (CVM). The URRAH study (Uric Acid Right for Heart Health) is a multicentre retrospective, observational study, which collected data from several large population-based longitudinal studies in Italy and subjects recruited in the hypertension clinics of the Italian Society of Hypertension. Total mortality was defined as mortality for any cause, CVM as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure. A total of 22 714 subjects were included in the analysis. Multivariate Cox regression analyses identified an independent association between SUA and total mortality (hazard ratio, 1.53 [95% CI, 1.21-1.93]) or CVM (hazard ratio, 2.08 [95% CI, 1.146-2.97]; <0.001). Cutoff values of SUA able to discriminate total mortality (4.7 mg/dL [95% CI, 4.3-5.1 mg/dL]) and CVM status (5.6 mg/dL [95% CI, 4.99-6.21 mg/dL]) were identified. The information on SUA levels provided a significant net reclassification improvement of 0.26 and of 0.27 over the Heart Score risk chart for total mortality and CVM, respectively (<0.001). Sex-specific cutoff values for total mortality and CVM were also identified and validated. In conclusion, SUA levels increasing the risk of total mortality and CVM are significantly lower than those used for the definition of hyperuricemia in clinical practice. Our data provide evidence of a cardiovascular SUA threshold that might contribute in clinical practice to improve identification of patients at higher risk of CVM.
  
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• Serum uric acid and fatal myocardial infarction: detection of prognostic cut-off values: The URRAH (Uric Acid Right for Heart Health) study.
  J Hypertens

  2020 03;38(3):412-419. doi: 10.1097/HJH.0000000000002287.
  
  Casiglia Edoardo, Tikhonoff Valérie, Virdis Agostino, Masi Stefano, Barbagallo Carlo M, Bombelli Michele, Bruno Bernardino, Cicero Arrigo F G, Cirillo Massimo, Cirillo Pietro, Desideri Giovambattista, D'Elia Lanfranco, Ferri Claudio, Galletti Ferruccio, Gesualdo Loreto, Giannattasio Cristina, Iaccarino Guido, Lippa Luciano, Mallamaci Francesca, Maloberti Alessandro, Mazza Alberto, Muiesan Maria Lorenza, Nazzaro Pietro, Palatini Paolo, Parati Gianfranco, Pontremoli Roberto, Quarti-Trevano Fosca, Rattazzi Marcello, Rivasi Giulia, Salvetti Massimo, Tocci Giuliano, Ungar Andrea, Verdecchia Paolo, Viazzi Francesca, Volpe Massimo, Grassi Guido, Borghi Claudio,
  
  Abstract
  
  OBJECTIVE:
  The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad-hoc study aimed at searching for prognostic cut-off values of serum uric acid (SUA) in predicting fatal myocardial infaction (MI) in women and men.
  
  METHODS:
  The URic acid Right for heArt Health study is a nationwide, multicentre, observational cohort study involving data on individuals aged 18-95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 122.3?±?66.9 months.
  
  RESULTS:
  A total of 23?467 individuals were included in the analysis. Cut-off values of SUA able to discriminate MI status were identified by mean of receiver operating characteristic curves in the whole database (>5.70?mg/dl), in women (>5.26?mg/dl) and in men (>5.49?mg/dl). Multivariate Cox regression analyses adjusted for confounders (age, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol and use of diuretics) identified an independent association between SUA and fatal MI in the whole database (hazard ratio 1.381, 95% confidence intervals, 1.096-1.758, P?=?0.006) and in women (hazard ratio 1.514, confidence intervals 1.105-2.075, P?
  CONCLUSION:
  The results of the current study confirm that SUA is an independent risk factor for fatal MI after adjusting for potential confounding variables, and demonstrate that a prognostic cut-off value associated to fatal MI can be identified at least in women.
  
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• Evaluation of Unattended Automated Office, Conventional Office and Ambulatory Blood Pressure Measurements and Their Correlation with Target Organ Damage in an Outpatient Population of Hypertensives: Study Design and Methodological Aspects.
  High Blood Press Cardiovasc Prev

  2019 Dec;26(6):493-499. doi: 10.1007/s40292-019-00344-2.
  
  Mancusi Costantino, Saladini Francesca, Pucci Giacomo, Bertacchini Fabio, Bisogni Valeria, Bruno Rosa Maria, Rivasi Giulia, Maloberti Alessandro, Manzi Maria Virginia, Rosticci Martina, Monticone Silvia, de Feo Martina, Del Pinto Rita, Geraci Giulio, Canciello Grazia, Pengo Martino, Parati Gianfranco,
  
  Abstract
  
  Accurate measurement of blood pressure (BP) has a pivotal role in the management of patients with arterial hypertension. Recently, introduction of unattended office BP measurement has been proposed as a method allowing more accurate management of hypertensive patients and prediction of hypertension-mediated target organ damage (HMOD). This approach to BP measurement has been in particular proposed to avoid the white coat effect (WCE), which can be easily assessed once both attended and unattended BP measurements are obtained. In spite of its interest, the role of WCE in predicting HMOD remains largely unexplored. To fill this gap the Young Investigator Group of the Italian Hypertension Society (SIIA) conceived the study "Evaluation of unattended automated office, conventional office and ambulatory blood pressure measurements and their correlation with target organ damage in an outpatient population of hypertensives". This is a no-profit multicenter observational study aiming to correlate attended and unattended BP measurements for quantification of WCE and to correlate WCE with markers of HMOD, such us left ventricular hypertrophy, left atrial dilatation, and peripheral atherosclerosis. The Ethical committee of the Federico II University hospital has approved the study.
  
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• Cardiovascular Remodeling after Endovascular Treatment for Thoracic Aortic Injury.
  Ann Vasc Surg

  2019 Nov;61():134-141. doi: S0890-5096(19)30468-6.
  
  Vallerio Paola, Maloberti Alessandro, D'Alessio Ilenia, Lista Alfredo, Varrenti Marisa, Castelnuovo Samuela, Marone Matteo, Piccinelli Enrico, Grassi Guido, Palmieri Bruno, Giannattasio Cristina
  
  Abstract
  
  BACKGROUND:
  Thoracic endovascular aortic repair (TEVAR) currently represents the gold standard of treatment for thoracic aortic injury (TAI). Nevertheless, there is an ongoing debate surrounding its safety and subsequent cardiovascular effects. Our aim is to assess heart and vascular structure and function remodeling after TEVAR in TAI young patients.
  
  METHODS:
  We evaluated 20 patients (18 men, age 41 ± 14 years, 11 treated with Gore CTAG, 9 with Medtronic Valiant) with office and 24-hr blood pressure (BP) with specific vascular stiffness analysis (Mobil-O-Graph), aortic diameters (computed tomography scan) and left ventricular mass index (LVMI echocardiogram). Evaluation was done after a median time of 5.0 ± 3.5 years from the trauma.
  
  RESULTS:
  After TAI 12 patients (55%) developed hypertension. When patients were divided according to treating time, those treated for more than 3 years show higher LVMI, PWV, and ascending aorta dilatation.
  
  CONCLUSIONS:
  Our study shows that TEVAR for TAI is associated with heart and vascular remodeling. The presence of TEVAR modifies aortic functional properties and could induce an increase in BP that can promote aortic and cardiac damage, even in young patients.
  
  Copyright © 2019 Elsevier Inc. All rights reserved.
  
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• Could two-dimensional radial strain be considered as a novel tool to identify pre-clinical hypertrophic cardiomyopathy mutation carriers?
  Int J Cardiovasc Imaging

  2019 Dec;35(12):2167-2175. doi: 10.1007/s10554-019-01668-9.
  
  Santambrogio Gloria Maria, Maloberti Alessandro, Vallerio Paola, Peritore Angelica, Spanò Francesca, Occhi Lucia, Musca Francesco, Belli Oriana, De Chiara Benedetta, Casadei Francesca, Facchetti Rita, Turazza Fabio, Manfredini Emanuela, Giannattasio Cristina, Moreo Antonella
  
  Abstract
  
  Treatment of overt form of hypertrophic cardiomyopathy (HCM) is often unsuccessful. Efforts are focused on a possible early identification in order to prevent or delaying the development of hypertrophy. Our aim was to find an echocardiographic marker able to distinguish mutation carriers without left ventricular hypertrophy (LVH) from healthy subjects. We evaluated 28 patients, members of eight families. Three types of mutation were recognized: MYBPC3 (five families), MYH7 (two families) and TNNT2 (one family). According to genetic (G) and phenotypic (Ph) features, patients were divided in three groups: Group A (10 patients), mutation carriers with LVH (G+/Ph+); Group B (9 patients), mutation carriers without LVH (G+/Ph-); Group C (9 patients), healthy subjects (G-/Ph-). Echocardiography examination was performed acquiring standard 2D, DTI and 2D-strain imaging. Global longitudinal strain (GLS) and global radial strain (GRS) at basal and mid-level were measured. GRS was significantly different between group B and C at basal level (32.18%?±?9.6 vs. 44.59%?±?12.67 respectively; p-value?
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• Pulse wave velocity progression over a medium-term follow-up in hypertensives: Focus on uric acid.
  J Clin Hypertens (Greenwich)

  2019 07;21(7):975-983. doi: 10.1111/jch.13603.
  
  Maloberti Alessandro, Rebora Paola, Andreano Anita, Vallerio Paola, De Chiara Benedetta, Signorini Stefano, Casati Marco, Besana Silvia, Bombelli Michele, Grassi Guido, Valsecchi Maria Grazia, Giannattasio Cristina
  
  Abstract
  
  The role of uric acid (UA) on the arterial stiffness progression has been evaluated only in three studies. Our aim was to evaluate its role as a possible determinant of the pulse wave velocity (PWV) progression over a 3.7 ± 0.5 years follow-up period in hypertensive patients. Specific sex analysis was done due to the well-known sex interaction with UA levels. We enrolled 422 consecutive hypertensive outpatients. At baseline anamnestic, blood pressure (BP) and laboratory data as well as PWV were assessed. PWV was performed again at follow-up examination. Hyperuricemia was defined as a UA > 6 mg/dL for women and > 7 mg/dL for men. Baseline age was 53.2 ± 13 years, 58% were males, systolic and diastolic BP (SBP/DBP) 141.7 ± 17.7/86.8 ± 10.8 mm Hg, UA 5.2 ± 1.4 mg/dL, and PWV 8.5 ± 1.9 m/s. At follow-up, despite better BP values (-8.5 ± 24.6 for SBP and -7.5 ± 15.4 for DBP), PWV increases to 9.1 ± 2.3 m/s (P < 0.001) with mean ?PWV of+ 0.5 ± 2.2 m/s. A total of 61 patients were hyperuricemic (14.4%), and they present higher PWV baseline (9.0 ± 2.5 vs 8.5 ± 1.8 m/s, P = 0.03) without significant differences in ?PWV. Hyperuricemic female (6.2%, 11 patients) presents higher baseline PWV without significant differences in ?PWV. No differences were found in arterial stiffness in hyperuricemic males (20.4%, 50 patients). UA showed association with baseline and ?PWV in the whole population but it loses statistical significance at the linear regression model. Same figures were also for sex analysis. Our findings provide evidence that baseline UA levels are not determinants of PWV progression over a median follow-up of 3.8 years' in hypertensive patients.
  
  ©2019 Wiley Periodicals, Inc.
  
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• Vascular Aging and Disease of the Large Vessels: Role of Inflammation.
  High Blood Press Cardiovasc Prev

  2019 Jun;26(3):175-182. doi: 10.1007/s40292-019-00318-4.
  
  Maloberti Alessandro, Vallerio Paola, Triglione Nicola, Occhi Lucia, Panzeri Francesco, Bassi Ilaria, Pansera Francesco, Piccinelli Enrico, Peretti Alessio, Garatti Laura, Palazzini Matteo, Sun Jinwei, Grasso Enzo, Giannattasio Cristina
  
  Abstract
  
  Structural and functional arterial properties commonly impair with aging process. These effects on vasculature could act at many levels from microcirculation to large vessels. Above normal aging process classic cardio-vascular risk factors (hypertension, diabetes mellitus, dyslipidemia, etc.) accelerate the physiological process leading to premature structural and functional alterations that has also been termed early vascular aging. Target organ damage evaluation could be clinically important since these alterations precede by many years' cardiovascular events and so their assessment can predict the onset of more serious and costly events giving the opportunity to prevent CV events by earlier therapeutic intervention. This review will focus on large artery functional properties and particularly on the role of inflammation on the aortic stiffening process.
  
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• Kounis Syndrome: Report of Two Cases with Peculiar Presentation and Diagnostic Issues.
  High Blood Press Cardiovasc Prev

  2019 Apr;26(2):145-149. doi: 10.1007/s40292-019-00312-w.
  
  Maloberti Alessandro, Pansera Francesco, Sala Oscar, Fusco Rossana, Pierri Alessandra, Bossi Irene, Giannattasio Cristina
  
  
  
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• Relationship between vascular damage and left ventricular concentric geometry in patients undergoing coronary angiography: a multicenter prospective study.
  J Hypertens

  2019 06;37(6):1183-1190. doi: 10.1097/HJH.0000000000002052.
  
  Salvetti Massimo, Paini Anna, Facchetti Rita, Moreo Antonella, Carerj Scipione, Maloberti Alessandro, Gaibazzi Nicola, Faggiano Pompilio, Mureddu Gianfranco, Rigo Fausto, Giannattasio Cristina, Muiesan Maria Lorenza,
  
  Abstract
  
  BACKGROUND:
  Vascular structural (intima-media thickness) and functional (carotid pulse wave velocity, cPWV) alterations are related to different patterns of left ventricular (LV) geometry in general population samples and in hypertensive patients. The relationship between vascular damage, evaluated by both echotracking ultrasound and coronary angiography, and LV geometry has not been prospectively analyzed.
  
  METHODS:
  In eight Italian centers, 399 consecutive patients, without history of prior coronary artery disease and with clinical indication to coronary angiography, prospectively underwent cardiac standard ultrasound examination for the evaluation of LV mass, indexed by height to 2.7 power (LVMi?g/m) and relative wall thickness (RWT), the measurement of Doppler flow in the left anterior descending artery (LAD) and the echocardiographic calcium score (eCS). In all patients measurement of common carotid intima-media thickness (cIMT) and cPWV by carotid ultrasound, with the realtime echotracking system was performed. The noninvasive evaluations were performed blindly to clinical information, before coronary angiography.
  
  RESULTS:
  cIMT and cPWV were higher in patients with concentric LV hypertrophy (LVH) (LVMi???49?g/m in men and ?47?g/m in women and RWT???0.42) as compared with those with normal LVMi and geometry (N: LVMi?50%) was greater in patients with concentric LVH and concentric remodeling, as compared with N. Patients with both concentric LVH and concentric remodeling showed higher values of cIMT and cPWV and distal LAD velocity and a greater prevalence of coronary stenosis (>50%) than patients with RWT less than 0.42.
  
  CONCLUSION:
  Our results further reinforced the observation that in patients undergoing elective coronary angiography, concentric geometry is associated with structural and functional carotid alterations, with higher distal LAD flow velocity and eCS. In this large group of patients, concentric geometry is associated with a greater prevalence of coronary stenosis, as assessed by coronary angiography. These results might contribute to explain the greater cardiovascular risk associated with concentric remodeling and LVH.
  
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• Mycotic coronary aneurysms.
  J Cardiovasc Med (Hagerstown)

  2019 Jan;20(1):10-15. doi: 10.2459/JCM.0000000000000734.
  
  Buono Andrea, Maloberti Alessandro, Bossi Irene M, Piccaluga Emanuela, Piccalò Giacomo, Oreglia Jacopo A, Moreo Antonella, Russo Claudio F, Oliva Fabrizio, Giannattasio Cristina
  
  Abstract
  
  : Mycotic coronary aneurysm is a rare infective disease of arterial vessel walls. Their development could be linked to the presence of an infective endocarditis or could represent a primary infection at the site of an implanted intracoronary stent. Bacterial agents, particularly Staphylococcus aureus, are the most common etiological agents. Due to an aspecific clinical presentation and examination, diagnosis could be challenging. Multiple imaging techniques (both invasive and noninvasive) are often required to reach the final diagnosis. Prognosis is characterized by high morbidity and mortality rates and, in fact, a tempestive treatment is required, although, to date, scanty data concerning the optimal treatment choice are present in literature.
  
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• Gender-related differences in serum uric acid in treated hypertensive patients from central and east European countries: findings from the Blood Pressure control rate and CArdiovascular Risk profilE study.
  J Hypertens

  2019 02;37(2):380-388. doi: 10.1097/HJH.0000000000001908.
  
  Redon Pau, Maloberti Alessandro, Facchetti Rita, Redon Josep, Lurbe Empar, Bombelli Michele, Mancia Giuseppe, Grassi Guido
  
  Abstract
  
  OBJECTIVE:
  Hyperuricemia has been associated with high blood pressure (BP) values, diabetes mellitus, metabolic syndrome and chronic kidney disease (CKD). In the present study, we assessed the gender-related relationships between serum uric acid (SUA) and cardionephrometabolic variables in central and east European hypertensive patients.
  
  METHODS:
  A total of 3206 treated hypertensive patients with available SUA levels from the BP-CARE study was analyzed. Correlations among SUA, BP values, BP control, diabetes mellitus, metabolic syndrome and CKD were performed according to gender.
  
  RESULTS:
  Twenty-five percent of the whole population showed hyperuricemia (28% in women and 23% in men). These patients were older and showed a greater burden of cardiovascular risk factors (high BP, BMI, glucose, total cholesterol and triglyceridemia). They also showed a greater prevalence of metabolic syndrome, diabetes mellitus, rate of uncontrolled BP, more than high cardiovascular risk and CKD. Prevalence of metabolic syndrome and uncontrolled BP was similar in normouricemic and hyperuricemic women, the latter displaying a higher prevalence of diabetes mellitus, high cardiovascular risk and CKD. Hyperuricemic men were characterized by a greater prevalence of metabolic syndrome, diabetes mellitus, high cardiovascular risk, rate of uncontrolled BP and CKD but not polytherapy. Logistic regression analysis showed that none of the evaluated variables, except CKD, displayed SUA as significant covariate.
  
  CONCLUSION:
  Our findings provide evidence that a high prevalence of hyperuricemia occurs in hypertensive patients from central and east Europe. The data also show that gender-related differences in the association between SUA and cardionephrometabolic variables exist. This is also the case for the relationships between SUA and CKD.
  
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• Evaluation of adhesion molecules and immune parameters in HIV-infected patients treated with an atazanavir/ritonavir- compared with a lopinavir/ritonavir-based regimen.
  J Antimicrob Chemother

  2018 08;73(8):2162-2170. doi: 10.1093/jac/dky178.
  
  Squillace Nicola, Trabattoni Daria, Muscatello Antonio, Sabbatini Francesca, Maloberti Alessandro, Giannattasio Cristina, Masetti Michela, Fenizia Claudio, Soria Alessandro, Clerici Mario, Gori Andrea, Bandera Alessandra
  
  Abstract
  
  Objectives:
  To evaluate changes in pro-atherosclerotic biomarkers and endothelial function in patients initiating two different PI-based regimens as part of ART.
  
  Design:
  Prospective randomized 24?week study. Treatment-naive HIV-infected patients with CD4+ T cell count >250?cells/mm3 started PI-based regimens including atazanavir/ritonavir (Group A) or lopinavir/ritonavir (Group B) and were followed up in an observational follow-up study until week 96.
  
  Methods:
  The expression of immune activation and adhesion molecules on CD4+ and CD8+ cells and plasma cytokine levels were assessed at weeks 0, 4, 12, 24, 48, 72 and 96. Flow-mediated dilation (FMD), pulse-wave velocity (PWV) and intima-media thickness (IMT) were measured at weeks 0 and 24. Median changes within (signed rank test) and between (Wilcoxon test) arms were calculated.
  
  Results:
  Twenty-seven patients were enrolled, of whom 15 were treated with atazanavir/ritonavir and 12 with lopinavir/ritonavir. After 96?weeks of ART, CD25+/CD8+ T cells and plasma concentration of MCP-1/CCL-2 rose whereas CD44+/CD8+ T cells decreased significantly in both groups. Differences between treatments were noted for HLA-DRII+/CD8+, CD44+/CD4+ and CD11a+/CD4+, with significant increases in Group B versus Group A. No differences between groups regarding IMT, PWV and FMD were found at baseline and week 24.
  
  Conclusions:
  ART initiation with PI-based regimens led to a decrease in pro-atherosclerotic biomarkers at week 24, which then rebounded at week 96. Lopinavir/ritonavir treatment resulted in an unfavourable modulation of such markers compared with atazanavir/ritonavir treatment.
  
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• Therapeutic Approach to Hypertension Urgencies and Emergencies in the Emergency Room.
  High Blood Press Cardiovasc Prev

  2018 Jun;25(2):177-189. doi: 10.1007/s40292-018-0261-4.
  
  Maloberti Alessandro, Cassano Giulio, Capsoni Nicolò, Gheda Silvia, Magni Gloria, Azin Giulia Maria, Zacchino Massimo, Rossi Adriano, Campanella Carlo, Beretta Andrea Luigi Roberto, Bellone Andrea, Giannattasio Cristina
  
  Abstract
  
  Hypertensive urgencies-emergencies are important and common events. They are defined as a severe elevation in BP, higher than 180/120 mmHg, associated or not with the evidence of new or worsening organ damage for emergencies and urgencies respectively. Anamnestic information, physical examination and instrumental evaluation determine the following management that could need oral (for urgencies) or intravenous (for emergencies) anti-hypertensives drugs. The choice of the specific drugs depend on the underlying causes of the crisis, patient's demographics, cardiovascular risk and comorbidities. For emergencies a maximum BP reduction of 20-25% within the first hour and then to 160/110-100 over next 2-6 h, is considered appropriate with a further gradual decrease over the next 24-48 h to reach normal BP levels. In the case of hypertensive urgencies, a gradual lowering of BP over 24-48 h with an oral medication is the best approach and an aggressive BP lowering should be avoided. Subsequent management with particular attention on chronic BP values control is important as the right treatment of the acute phase.
  
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• In healthy normotensive subjects age and blood pressure better predict subclinical vascular and cardiac organ damage than atherosclerosis biomarkers.
  Blood Press

  2018 10;27(5):262-270. doi: 10.1080/08037051.2018.1461010.
  
  Maloberti Alessandro, Farina Francesca, Carbonaro Marco, Piccinelli Enrico, Bassi Ilaria, Pansera Francesco, Grassi Guido, Mancia Giuseppe, Palestini Paola, Giannattasio Cristina
  
  Abstract
  
  PURPOSE:
  Only few studies evaluated biomarkers useful for defining the cardiovascular risk of a subject in a pre-clinical condition (i.e. healthy subjects). In this context we sought to determine the relationships of Plasminogen activator inhibitor type 1 (PAI-1), P-Selectin, Tissue Inhibitors Metalloproteinases type 1 (TIMP-1) and Cystatin-C with subclinical Target Organ Damage (TOD) in normotensive and normoglycemic subjects without known cardiovascular and kidney diseases.
  
  MATERIALS AND METHODS:
  480 blood donors participated at the present analysis. TOD was evaluated as Pulse Wave Velocity (PWV), Left Ventricular Hypertrophy (LVH) and Intima Media Thickness (IMT) and carotid plaque presence) grouped together under carotid TOD.
  
  RESULTS:
  3.1% of the subjects showed a PWV higher than 10?m/sec with those subjects exerting significantly lower values of P-Selectine (0.068?±?0.015 vs 0.08?±?0.036?mg/L, p?=?.014). 8.8% of the subjects showed carotid TOD that was associated with higher Cystatin-C values (0.67?±?0.17 vs 0.63?±?0.14?mg/L, p?=?.045). Finally 23.8% of the subjects showed LVH with no significant differences regarding biomarkers. Despite some significant correlations between biomarkers and TOD, at the multivariate analysis none came out to be as significant predictor of the assessed TOD.
  
  CONCLUSIONS:
  in normotensive and normoglycemic healthy subjects, the evaluated biomarkers of atherosclerotic process didn't show any significant association with cardiac, carotid and vascular TOD while age and BP are its principal predictors.
  
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• Association Between Atrial, Ventricular and Vascular Morphofunctional Alterations in Rheumatoid Arthritis.
  High Blood Press Cardiovasc Prev

  2018 Mar;25(1):97-104. doi: 10.1007/s40292-017-0246-8.
  
  Maloberti Alessandro, Riva Marta, Tadic Marijana, Valena Carlo, Villa Paolo, Boggioni Ilenia, Pozzi Maria Rosa, Grassi Guido
  
  Abstract
  
  INTRODUCTION:
  Rheumatoid arthritis (RA) represents a risk of non-fatal and cardiovascular events. The aim of the present study was to evaluate simultaneously left and right atrial and ventricular function, as well as arterial stiffness, in RA patients.
  
  METHODS:
  This cross-sectional study included 55 consecutive RA patients and 55 healthy age and gender-matched controls. Blood pressure and arterial stiffness were assessed in all participants, who also underwent a complete echocardiographic examination.
  
  RESULTS:
  RA patients were treated with steroid therapy (52.7%), methotrexate (66.6%) and biological therapy (54.5%). Disease activity score revealed low average RA activity. Augmentation index was significantly higher in RA patients (32.2 ± 8.6 vs. 28.4 ± 8.9%, P = 0.02). Left atrial volume was also higher among RA patients (23.1 ± 8.2 vs. 20.1 ± 7.1 ml/m, P = 0.04), whereas mitral and tricuspid E/A ratios were significantly lower in RA individuals (0.90 ± 0.24 vs. 1.03 ± 0.35, P = 0.02; 1.07 ± 0.31 vs. 1.27 ± 0.35, P = 0.003, respectively). Tissue Doppler systolic and diastolic velocities were similar between the observed groups. Arterial stiffness index showed significant correlation with disease duration (r = 0.29; P = 0.03). Tissue Doppler-derived transmitral late diastolic velocity (A') showed significant correlation with index of disease activity in the RA patients.
  
  CONCLUSIONS:
  Our results showed that left and right ventricular diastolic function and arterial stiffness were significantly deteriorated in the RA patients comparing with controls. The assessment of left and right ventricular diastolic function, as well as vascular function, should be an essential part of clinical evaluation in the RA patients.
  
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• Sex-related relationships between uric acid and target organ damage in hypertension.
  J Clin Hypertens (Greenwich)

  2018 01;20(1):193-200. doi: 10.1111/jch.13136.
  
  Maloberti Alessandro, Maggioni Simone, Occhi Lucia, Triglione Nicola, Panzeri Francesco, Nava Stefano, Signorini Stefano, Falbo Rosanna, Casati Marco, Grassi Guido, Giannattasio Cristina
  
  Abstract
  
  Heterogeneous results have been obtained in the relationship between serum uric acid (SUA) and target organ damage (TOD) in patients with hypertension. Clinic blood pressure, SUA, and cardiac, arterial (carotid and aortic), and renal TOD were assessed in 762 consecutive patients with hypertension. Hyperuricemia was defined as an SUA >7.0 in men and >6.0 mg/dL in women. Men with hyperuricemia compared with those with normal SUA showed lower estimated glomerular filtration rates and E/A ratios and a higher prevalence of carotid plaques. Women with hyperuricemia showed lower estimated glomerular filtration rates and E/A ratios and a higher intima-media thickness. Except for pulse wave velocity, all TODs significantly correlated with SUA. However, at multivariate analysis, only estimated glomerular filtration rate was significantly determined by SUA. Our data provide evidence on the role of SUA in the development of TOD only in the case of renal alteration. It is likely that SUA may indirectly act on the other TODs through the increase in blood pressure and the decrease in glomerular filtration rate.
  
  ©2017 Wiley Periodicals, Inc.
  
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• Relationship Between 24-Hour Ambulatory Central Systolic Blood Pressure and Left Ventricular Mass: A Prospective Multicenter Study.
  Hypertension

  2017 12;70(6):1157-1164. doi: 10.1161/HYPERTENSIONAHA.117.09917.
  
  Weber Thomas, Wassertheurer Siegfried, Schmidt-Trucksäss Arno, Rodilla Enrique, Ablasser Cornelia, Jankowski Piotr, Lorenza Muiesan Maria, Giannattasio Cristina, Mang Claudia, Wilkinson Ian, Kellermair Jörg, Hametner Bernhard, Pascual Jose Maria, Zweiker Robert, Czarnecka Danuta, Paini Anna, Salvetti Massimo, Maloberti Alessandro, McEniery Carmel
  
  Abstract
  
  We investigated the relationship between left ventricular mass and brachial office as well as brachial and central ambulatory systolic blood pressure in 7 European centers. Central systolic pressure was measured with a validated oscillometric device, using a transfer function, and mean/diastolic pressure calibration. M-mode images were obtained by echocardiography, and left ventricular mass was determined by one single reader blinded to blood pressure. We studied 289 participants (137 women) free from antihypertensive drugs (mean age: 50.8 years). Mean office blood pressure was 145/88 mm?Hg and mean brachial and central ambulatory systolic pressures were 127 and 128 mm?Hg, respectively. Mean left ventricular mass was 93.3 kg/m, and 25.6% had left ventricular hypertrophy. The correlation coefficient between left ventricular mass and brachial office, brachial ambulatory, and central ambulatory systolic pressure was 0.29, 0.41, and 0.47, respectively (=0.003 for comparison between brachial office and central ambulatory systolic pressure and 0.32 for comparison between brachial and central ambulatory systolic pressure). The results were consistent for men and women, and young and old participants. The areas under the curve for prediction of left ventricular hypertrophy were 0.618, 0.635, and 0.666 for brachial office, brachial, and central ambulatory systolic pressure, respectively (=0.03 for comparison between brachial and central ambulatory systolic pressure). In younger participants, central ambulatory systolic pressure was superior to both other measurements. Central ambulatory systolic pressure, measured with an oscillometric cuff, shows a strong trend toward a closer association with left ventricular mass and hypertrophy than brachial office/ambulatory systolic pressure.
  
  CLINICAL TRIAL REGISTRATION:
  URL: https://www.clinicaltrials.gov. Unique identifier: NCT01278732.
  
  © 2017 American Heart Association, Inc.
  
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• Determinants of carotid-femoral pulse wave velocity progression in hypertensive patients over a 3.7 years follow-up.
  Blood Press

  2018 02;27(1):32-40. doi: 10.1080/08037051.2017.1378069.
  
  Meani Paolo, Maloberti Alessandro, Sormani Paola, Colombo Giulia, Giupponi Luca, Stucchi Miriam, Varrenti Marisa, Vallerio Paola, Facchetti Rita, Grassi Guido, Mancia Giuseppe, Giannattasio Cristina
  
  Abstract
  
  OBJECTIVE:
  The role of risk factors on the progression of arterial stiffness has not yet been extensively evaluated. The aim of the current longitudinal study was to evaluate the determinants of the PWV progression over a 4 years follow-up period in hypertensive subjects.
  
  MATERIALS AND METHODS:
  We enrolled 333 consecutive hypertensive outpatients 18-80 aged, followed by the Hypertension Unit of St. Gerardo Hospital (Monza, Italy). At baseline anamnestic, clinical, BP, laboratory data and cfPWV were assessed. We performed a PWV follow-up examination with a median time amounting to 3.75?±?0.53 years.
  
  RESULTS:
  At baseline the mean age was 54.5?±?12.6 years, SBP and DBP were 141.3?±?18.6 and 86.4?±?10.4?mmHg and PWV was 8.56?±?1.92 m/s. Despite an improvement in BP control (from 37 to 60%), at follow-up the population showed a PWV increase (?PWV 0.87?±?3.05 m/s). PWV and ?PWV gradually increased in age decades. In patients with uncontrolled BP values at follow-up ?PWV showed a greater increase as compared to patients with controlled BP (1.46?±?3.67 vs 0.62?±?2.61 m/s, p?
  CONCLUSIONS:
  the accelerated arterial aging in treated hypertensive subjects is in large measure explained by age and BP values. PWV changes over time would probably give important information that need further future research studies.
  
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• Long-term Saxagliptin Treatment Improves Endothelial Function but not Pulse Wave Velocity and Intima-Media Thickness in Type 2 Diabetic Patients.
  High Blood Press Cardiovasc Prev

  2017 Dec;24(4):393-400. doi: 10.1007/s40292-017-0215-2.
  
  Dell'Oro Raffaella, Maloberti Alessandro, Nicoli Francesco, Villa Paolo, Gamba Pierluigi, Bombelli Michele, Mancia Giuseppe, Grassi Guido
  
  Abstract
  
  INTRODUCTION:
  Pharmacological inhibition of dipeptidyl-peptidase-4 may represent a promising therapeutic approach for glucose control and vascular protection. No information is available on the effects of saxagliptin (S) on aortic pulse wave velocity, carotid intima-media thickness and flow-mediated dilation (FMD, brachial artery) in diabetes.
  
  AIM:
  We investigated the long-term effects of S, as add-on therapy to metformin, on the above mentioned variables.
  
  METHODS:
  In 16 patients with decompensated diabetes aortic pulse wave velocity, carotid intima-media thickness and FMD, office and 24-h ambulatory blood pressure, anthropometric, biochemical and metabolic parameters were measured at baseline and after 6 and 12 months of treatment. A group of 16 compensated diabetics served as controls.
  
  RESULTS:
  The two groups showed superimposable values of the different parameters, with the exception of glycated hemoglobin, blood glucose significantly (P < 0.05) greater in the S-treated patients. In the S-group glucose metabolism and FMD significantly improved during the follow-up (from 169.3 ± 8 to 157.1 ± 9 mg/dl, P < 0.05, from 7.9 ± 0.1 to 6.9 ± 0.2%, P < 0.001 and from 3.6 ± 0.3 to 7.4 ± 0.8%, respectively P < 0.05). No significant difference was detected in the other parameters, including blood pressure.
  
  CONCLUSIONS:
  Thus treatment with S added-on to metformin results in beneficial effects on endothelial function, related at least in part to the concomitant improvement in glucose metabolism. This may represent a first step in the chain of events leading to a reduction in the progression of the vascular atherogenic process.
  
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• Arterial Stiffness in Aortic Stenosis: Relationship with Severity and Echocardiographic Procedures Response.
  High Blood Press Cardiovasc Prev

  2017 Mar;24(1):19-27. doi: 10.1007/s40292-016-0176-x.
  
  Bruschi Giuseppe, Maloberti Alessandro, Sormani Paola, Colombo Giulia, Nava Stefano, Vallerio Paola, Casadei Francesca, Bruno Jolie, Moreo Antonella, Merlanti Bruno, Russo Claudio, Oliva Fabrizio, Klugmann Silvio, Giannattasio Cristina
  
  Abstract
  
  INTRODUCTION:
  Aortic stenosis (AS) is more than only a degenerative disease, it could be also an atherosclerotic-like process involving the valve instead of the vessels. Little is known about the relation of arterial stiffness and AS.
  
  AIM:
  We sought to determine wether pulse wave velocity (PWV), is related to AS severity and to the procedures response, both as surgical aortic-valve-replacement (AVR) and trascatheter-aortic-valve-implantation (TAVI).
  
  METHODS:
  30 patients with severe AS were treated (15 AVR, 15 TAVI). Before the procedures (t0) and after 1 week (t1) echocardiography and PWV were evaluated.
  
  RESULTS:
  On the whole population, subjects with higher PWV showed higher transvalvular pressure gradient at baseline (mean: 56.5 ± 15.1 vs 45.4 ± 9.5; peak: 93.3 ± 26.4 vs 73.3 ± 14.9, p = 0.02) and, a significantly greater response to the procedures (mean: -42.9 ± 17.2 vs -27.9 ± 10.1, peak: -68.7 ± 29.2 vs -42.8 ± 16.4, p = 0.02). When the two different procedures groups were separated, data were confirmed only in the TAVI subgroup.
  
  CONCLUSIONS:
  In patients undergoing procedures for AS, PWV is correlated with transvalvular gradient and, in TAVI subjects, is able to predict the echocardiographic response. Baseline evaluation of PWV in patients candidates to TAVI can help the selection of subjects, even if larger and longer studies are needed before definitive conclusion can be drawn.
  
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• Annexin A5 in treated hypertensive patients and its association with target organ damage.
  J Hypertens

  2017 01;35(1):154-161.
  
  Maloberti Alessandro, Meani Paolo, Vallerio Paola, Varrenti Marisa, Casadei Francesca, Musca Francesco, Facchetti Rita, Di Blasio Anna M, Ravassa Susanna, Mancia Giuseppe, Giannattasio Cristina
  
  Abstract
  
  OBJECTIVE:
  Annexin A5 (AnxA5) has been previously linked to the presence of carotid and cardiac target organ damage (TOD) in the context of heart failure and rheumatologic patients. However, information is scant in the context of hypertension. Aim of our study was to evaluate AnxA5 in treated hypertension patients compared with normotensive controls and to determine whether it is associated with vascular and heart TOD evaluated as arterial stiffness, carotid plaque and left ventricular hypertrophy.
  
  METHODS:
  We enrolled 123 consecutive treated hypertension and 124 normotensive controls. TOD was evaluated as pulse wave velocity (PWV, complior), left ventricular hypertrophy (echocardiography) and intima-media thickness and carotid plaque presence (ecographic methods). AnxA5 levels was dosed and compared in patients with and without hypertension and with and without TOD.
  
  RESULTS:
  With similar age hypertension patients showed higher SBP, DBP and AnxA5 levels (13.9?±?11.1 vs 10.1?±?8.4?ng/ml, P?
  CONCLUSION:
  Our data have shown that AnxA5 levels are increased in treated hypertension patients. In this condition, it is probably released in the plasma as a defensive mechanism through its anti-inflammatory and anticoagulants effects. We found a significant association with arterial stiffness, but AnxA5 was not found to be a significant predictor of TOD.
  
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• Long-Term Effects of Radiotherapy on Arterial Stiffness in Breast Cancer Women.
  Am J Cardiol

  2016 09;118(5):771-6. doi: 10.1016/j.amjcard.2016.06.001.
  
  Vallerio Paola, Sarno Laura, Stucchi Miriam, Musca Francesco, Casadei Francesca, Maloberti Alessandro, Lestuzzi Chiara, Mancia Giuseppe, Moreo Antonella, Palazzi Mauro, Giannattasio Cristina
  
  Abstract
  
  Radiotherapy for breast cancer may expose heart and vessels to late radiation-induced complications. Although recent technical progress in radiation therapy (RT) has been associated with drastic reduction in cardiovascular (CV) mortality, the prolonged life expectancy of patients with cancer requires CV evaluation for many years. The aim of our study was to evaluate local changes in vascular and cardiac function because of previous breast RT. We enrolled 43 patients treated with RT 15 years ago for breast cancer. CV risk factors and atherosclerotic carotid damage were investigated in all women. We divided patients into 2 groups: R (n = 25) treated to right breast and L (n = 18) to left breast. All subjects were submitted to standard echocardiography and functional arteries evaluation by carotid-radial pulse-wave velocity (crPWV; Complior) and AIx (Sphygmocor; Atcor Medical). Global mean age was 69.5 ± 8 years old. CV risk factors were equally allocated in 2 groups. No patients had history of cardiac or artery disease. R had a significantly increased crPWV (9.9 ± 1.4 vs 8.9 ± 1.1, p = 0.001) on right arm compared with left arm, and in L group, crPWV was similarly higher on the left arm than on right arm (9.6 ± 1.5 vs 8.9 ± 1.4, p = 0.011). AIx was significantly increased in the ipsilateral arm only in L (32.1 ± 7.6 vs 28.3 ± 6.8, p = 0.05). Central blood pressure estimation was not different in the right and left arms. No correlations were found with hormone therapy or chemotherapy. Our data show a local arterial stiffening because of radiation that can be involved in increased CV risk in breast cancer-treated patients.
  
  Copyright © 2016 Elsevier Inc. All rights reserved.
  
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• Prognostic relevance of electrocardiographic Tpeak-Tend interval in the general and in the hypertensive population: data from the Pressioni Arteriose Monitorate E Loro Associazioni study.
  J Hypertens

  2016 09;34(9):1823-30. doi: 10.1097/HJH.0000000000001005.
  
  Bombelli Michele, Maloberti Alessandro, Raina Lara, Facchetti Rita, Boggioni Ilenia, Pizzala Daniela Prata, Cuspidi Cesare, Mancia Giuseppe, Grassi Guido
  
  Abstract
  
  BACKGROUND:
  EKG Tpeak-Tend (Tp-Te) interval, an index of transmural dispersion of myocardial repolarization, is gaining interest as possible cardiovascular prognostic variable. Evidence that this is the case in the general population is scanty, however. This was tested in the Pressioni Arteriose Monitorate E Loro Associazioni population.
  
  METHODS AND RESULTS:
  EKG, echocardiographic, office, home and ambulatory (24-h) blood pressure (BP), metabolic and laboratory data were assessed. Cardiovascular and all-cause mortality were evaluated over a mean follow-up of 16 years. Repetition of all measurements after 10 years allowed to evaluate also the risk of developing office and out-of-office hypertension and echocardiographic left ventricular hypertrophy. At baseline, Tp-Te adjusted for confounders (c) showed a significant correlation with office, home and 24-h blood pressure but not with left ventricular mass. The cTp-Te value predicted the risk of cardiovascular and all-cause mortality before and after adjustment for demographic and clinical variables, the increase being 31 and 13% for 1-SD cTp-Te increase, respectively (P?
  CONCLUSION:
  Tp-Te interval retains an independent prognostic value both in the general population and in its hypertensive fraction. This easily and cheaply obtainable variable may be employed for improving cardiovascular-risk stratification, representing a useful measure to add to the recommended screening in hypertension.
  
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• Effects of chronic carotid baroreceptor activation on arterial stiffness in severe heart failure.
  Clin Res Cardiol

  2016 Oct;105(10):838-46. doi: 10.1007/s00392-016-0992-y.
  
  Gronda Edoardo, Brambilla GianMaria, Seravalle Gino, Maloberti Alessandro, Cairo Matteo, Costantino Giuseppe, Lovett Eric, Vanoli Emilio, Mancia Giuseppe, Grassi Guido
  
  Abstract
  
  BACKGROUND:
  Heart failure with reduced ejection fraction (HFrEF) is characterized by activation of the sympathetic nervous system and increased arterial stiffness, leading to an impaired ventricular-vascular coupling. Baroreflex activation therapy (BAT) has been shown to reduce muscle sympathetic nerve activity (MSNA) and improve clinical status of patients with HFrEF. The purpose of this investigation was to determine the effects of BAT on arterial stiffness in HFrEF.
  
  METHODS AND RESULTS:
  MSNA, clinical variables, and parameters of central blood pressure (BP) and arterial stiffness were collected in 18 NYHA Class III HFrEF patients, nine receiving BAT and nine continuing with optimal medical management alone. Patients were followed for 3 months, with measurements at that time compared to baseline evaluation. Baseline characteristics of the groups were well matched. At 3 months, BAT did not improve central BP and arterial stiffness despite a significant amelioration of MSNA, NYHA class, Minnesota living with heart failure questionnaire score, number of heart failure medications and six-minute walking distance. The control group exhibited no significant changes in all the measured variables.
  
  CONCLUSIONS:
  Despite significant reductions in MSNA and clinical improvement, BAT does not appear to chronically modify arterial stiffness within this HFrEF cohort. Additional study is required to determine if this result applies to the HFrEF population as a whole.
  
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• Asymptomatic aortic mural thrombus in a minimally atherosclerotic vessel.
  Interact Cardiovasc Thorac Surg

  2016 Mar;22(3):371-3. doi: 10.1093/icvts/ivv349.
  
  Maloberti Alessandro, Oliva Fabrizio, De Chiara Benedetta, Giannattasio Cristina
  
  Abstract
  
  Aortic mural thrombi in a normal (non-aneurysmal or minimally atherosclerotic) vessel are an uncommon condition. They are usually located in the descending aorta and, less frequently, in the aortic arch or in the abdominal aorta. The typical clinical presentation is the appearance of symptoms/signs of peripheral arterial embolization, such as lower limb or visceral ischaemia, but these can also be accidentally found in asymptomatic patients. We report the case of a 40-year old man with untreated hypertension and dyslipidaemia admitted to hospital for atypical chest pain associated with an elevation in high-sensitivity troponin T with normal creatine kinase isoenzime MB creatine kinase isoenzyme. Elektrocardiogram (EKG) and transthoracic echocardiography were non-diagnostic; in order to exclude an aortic dissection, a gated chest computed tomography was performed and showed an aortic thrombus on a minimally atherosclerotic wall. Then, a transoesophageal echocardiography confirmed an aortic floating thrombus (7 × 4 mm). Cardiac surgeons advised against surgery and therapy with antiplatelet, low molecular weight heparin, ?-blocker, antihypertensive and lipid-lowering drugs was initiated. A complete resolution of the thrombus was observed at the 12-day tomographic control.
  
  © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
  
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• Erratum to: Effects of Renal Sympathetic Denervation on Arterial Stiffness and Blood Pressure Control in Resistant Hypertensive Patients: A Single Centre Prospective Study.
  High Blood Press Cardiovasc Prev

  2015 Dec;22(4):451. doi: 10.1007/s40292-015-0124-1.
  
  Baroni Matteo, Nava Stefano, Giupponi Luca, Meani Paolo, Panzeri Francesco, Varrenti Marisa, Maloberti Alessandro, Soriano Francesco, Agrati Antonio Maria, Ferraro Giovanni, Colombo Fabrizio, Rampoldi Antonio, Mancia Giuseppe, Colombo Paola, Klugmann Silvio, Giannattasio Cristina
  
  
  
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• A case of Pseudomonas Aeruginosa commercial tattoo infection.
  G Ital Dermatol Venereol

  2018 Apr;153(2):301-302. doi: 10.23736/S0392-0488.17.04937-9.
  
  Maloberti Alessandro, Betelli Mauro, Perego Maria R, Foresti Sergio, Scarabelli Gabriele, Grassi Guido
  
  
  
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• Effects of Renal Sympathetic Denervation on Arterial Stiffness and Blood Pressure Control in Resistant Hypertensive Patients: A Single Centre Prospective Study.
  High Blood Press Cardiovasc Prev

  2015 Dec;22(4):411-6. doi: 10.1007/s40292-015-0121-4.
  
  Baroni Matteo, Nava Stefano, Giupponi Luca, Meani Paolo, Panzeri Francesco, Varrenti Marisa, Maloberti Alessandro, Soriano Francesco, Agrati Antonio Maria, Ferraro Giovanni, Colombo Fabrizio, Rampoldi Antonio, Mancia Giuseppe, Colombo Paola, Klugmann Silvio, Giannattasio Cristina
  
  Abstract
  
  Renal denervation (RD) is an intriguing treatment strategy for resistant hypertension. However, limited data are available about its long time efficacy as well as its effects on intermediate phenotypes like arterial stiffness and carotid IMT. 12 patients (9 males, mean 69 years) with resistant hypertension underwent bilateral RDN (Medtronic System) since April 2012 in Niguarda Ca' Granda Hospital (Milan). Patients were studied before intervention, and at 1, 3, 6 and 12 months after RD. Carotid intima media thickness (Esaote Mylab) and carotid-femoral pulse wave velocity (Complior, Alam medical) were assessed at each step. Compared to baseline, patients showed a marked reduction of office systolic blood pressure at each follow-up step (p < 0.05 versus baseline for all steps) as well as pulse wave velocity (p < 0.01 at 1 year versus baseline). Moreover, reduction in pulse wave velocity was higher than the expected value obtained only considering blood pressure drop. Conversely, no significant effect was observed on diastolic blood pressure as well as carotid intima-media thickness. In our study, renal denervation was a safe and effective procedure. The BP lowering effect was maintained during follow-up and a beneficial effect on arterial stiffness was observed, which implies that this effect can't passively originate from the BP fall but rather from an improvement of arterial mechanical properties, possibly related to a reduced sympathetic arterial drive.
  
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• Within-visit BP variability, cardiovascular risk factors, and BP control in central and eastern Europe: findings from the BP-CARE study.
  J Hypertens

  2015 Nov;33(11):2250-6. doi: 10.1097/HJH.0000000000000700.
  
  Grassi Guido, Seravalle Gino, Maloberti Alessandro, Facchetti Rita, Cuspidi Cesare, Bombelli Michele, Laurent Stephane, Redon Josep, Mancia Giuseppe
  
  Abstract
  
  INTRODUCTION AND OBJECTIVE:
  Blood pressure variability (BPV) within 24?h or between visits has been found to represent an independent risk factor for cardiovascular disease. The present study was aimed at determining whether a clinical significance can be given also to the BP variations occurring within a single clinical visit.
  
  METHODS:
  BPV was quantified as coefficient of variation and as standard deviation (SD) of the mean of three systolic SBP values within a visit in the context of a large-cross subclinical survey (BP-CARE) of treated hypertensive patients living in Eastern European countries. The study population was divided into coefficient of variation and SD quartiles and for each quartile a relationship was sought with a large number of cardiovascular risk factors based on patients' history, physical and laboratory examinations.
  
  RESULTS:
  The 6425 hypertensive patients had an age of 59.2?±?11 years (mean?±?SD); they were equally distributed by sex and displayed an average SD and coefficient of variation amounting to 5.1?±?6.2?mmHg and 3.5?±?4.0%, respectively. Compared with the lowest coefficient of variation quartile (Q1), patients in the highest quartile (Q4) showed a significantly greater prevalence of several cardiovascular risk factors, such as age (Q1: 58.5?±?11 vs. Q4: 60.3?±?11 years, P?
  CONCLUSION:
  Our study provides evidence that greater within-visit BP variabilities are associated with a worse cardiovascular risk profile. This suggests that even this type of BPV may have clinical significance.
  
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• Iron Stores, Hepcidin, and Aortic Stiffness in Individuals with Hypertension.
  PLoS One

  2015 ;10(8):e0134635. doi: 10.1371/journal.pone.0134635.
  
  Valenti Luca, Maloberti Alessandro, Signorini Stefano, Milano Marta, Cesana Francesca, Cappellini Fabrizio, Dongiovanni Paola, Porzio Marianna, Soriano Francesco, Brambilla Maura, Cesana Giancarlo, Brambilla Paolo, Giannattasio Cristina, Fargion Silvia
  
  Abstract
  
  BACKGROUND & AIMS:
  Iron accumulation within the arterial wall has been hypothesized to promote atherosclerosis progression. Aim of this study was to evaluate whether the hormone hepcidin and iron stores are associated with arterial stiffness in subjects with essential hypertension.
  
  METHODS:
  Circulating hepcidin, ferritin, and mutations in the hemochromatosis gene were compared between subjects included in the first vs. third tertile (n=284 each) of carotid-femoral pulse wave velocity (PWV) in an unselected cohort of patients with arterial hypertension.
  
  RESULTS:
  At univariate logistic regression analysis, high PWV was associated with higher ferritin levels (p=0.010), but lower hepcidin (p=0.045), and hepcidin ferritin/ratio (p<0.001). Hemochromatosis mutations predisposing to iron overload were associated with high PWV (p=0.025). At multivariate logistic regression analysis, high aortic stiffness was associated with older age, male sex, lower BMI, higher systolic blood pressure and heart rate, hyperferritinemia (OR 2.05, 95% c.i. 1.11-3.17 per log ng/ml; p=0.022), and lower circulating hepcidin concentration (OR 0.29, 95% c.i. 0.16-0.51 per log ng/ml; p<0.001). In subgroup analyses, high PWV was associated with indices of target organ damage, including micro-albuminuria (n=125, p=0.038), lower ejection fraction (n=175, p=0.031), cardiac diastolic dysfunction (p=0.004), and lower S wave peak systolic velocity (p<0.001). Ferritin was associated with cardiac diastolic dysfunction, independently of confounders (p=0.006).
  
  CONCLUSIONS:
  In conclusion, hyperferritinemia is associated with high aortic stiffness and cardiac diastolic dysfunction, while low circulating hepcidin with high aortic stiffness.
  
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• Effects of Cancer Therapy Targeting Vascular Endothelial Growth Factor Receptor on Central Blood Pressure and Cardiovascular System.
  Am J Hypertens

  2016 Feb;29(2):158-62. doi: 10.1093/ajh/hpv077.
  
  Moreo Antonella, Vallerio Paola, Ricotta Riccardo, Stucchi Miriam, Pozzi Mattia, Musca Francesco, Meani Paolo, Maloberti Alessandro, Facchetti Rita, Di Bella Sara, Giganti Maria Olga, Sartore-Bianchi Andrea, Siena Salvatore, Mancia Giuseppe, Giannattasio Cristina
  
  Abstract
  
  BACKGROUND:
  In the last 2 decades, new drugs that oppose the effects of vascular endothelial growth factor receptor (VEGFR), and thus angiogenesis, have considerably improved treatment of solid tumors. These anti-VEGFR drugs, however, are burdened by several side effects, particularly relevant on heart and vessels. The aim of this study was to analyze the changes in cardiovascular structure and function associated with use of anti-VEGFR drugs.
  
  METHODS:
  Twenty-nine patients (27 affected by renal and 2 by thyroid cancer), received treatment with anti-VEGFR drugs. Brachial blood pressure (BP), central BP, carotid-femoral pulse wave velocity (cfPWV), augmentation index (Aix), and several echocardiographic markers of systolic and diastolic left ventricular functions including global longitudinal strain were measured before starting treatment (T0), after 2 (T1), and 6 weeks (T2) of treatment.
  
  RESULTS:
  Anti-VEGFR treatment was accompanied by a significant increase of both peripheral (systolic BP +13±15.5mm Hg, diastolic BP +7.1±9.3mm Hg, P < 0.001) and central BP (systolic BP +14±14.2mm Hg, diastolic BP +7.3±10.4mm Hg, P < 0.001) and a significant raise of cfPWV (+1.3±1.8 m/sec, P = 0.003). There was also a significant alteration of markers of diastolic and subclinical left ventricular systolic function, including global longitudinal strain (-19.9±3.8% at T0, -17.8±2.6% at T2, P < 0.05). All the changes were already evident at T1, worsened at T2 in patients who maintained oncological treatment, but disappeared at T2 in patients in whom treatment was stopped.
  
  CONCLUSIONS:
  All the changes regarding BP and cfPWV appear early after treatment initiation and seem to be reversible if treatment is stopped, instead diastolic and systolic left ventricular function are persistently altered by anti-VEGFR drugs.
  
  © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
  
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• Clinical value of NT-proBNP assay in the emergency department for the diagnosis of heart failure (HF) in very elderly people.
  Arch Gerontol Geriatr

  ;61(2):296-300. doi: 10.1016/j.archger.2015.05.001.
  
  Bombelli Michele, Maloberti Alessandro, Rossi Stefano, Rea Federico, Corrao Giovanni, Bonicelli Della Vite Carlo, Mancia Giuseppe, Grassi Guido
  
  Abstract
  
  OBJECTIVE:
  Scanty data are available on the accuracy of NT-proBNP in the diagnosis of HF and effects of comorbidities in very elderly patients.
  
  METHODS:
  Symptoms, signs, NT-proBNP, eGFR, Ht, CRP and the presence of cardiomegaly and pleuric effusion were assessed in 895 consecutive patients aged 86±4.3 years admitted to Emergency Department and used to define the diagnosis of HF according to Framingham criteria. Receiver operating characteristic curves (ROC) were used to calculate diagnostic performance and cutoff of NT-proBNP. Sensitivity (Sn), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) were computed for all NT-proBNP cutoffs.
  
  RESULTS:
  Satisfactory diagnostic performance was obtained with a lower threshold of 980pg/mL (Sn 0.95; NPV 0.90) and a higher threshold of 5340 (Sp 0.85; PPV 0.76) but with 42.4% of patients in the uncertainty area. We determined a second couple of cutoffs (1470-4200) that reduced the gray-area to 27.4%, maintaining an acceptable diagnostic performance compared to commonly used cutoffs (300-1800). Ht, CRP and eGFR all correlated with NT-proBNP in groups with and without HF but none affected diagnostic performance.
  
  CONCLUSION:
  NT-proBNP performs satisfactorily for the diagnosis of HF in very elderly patients. Proposed threshold couple, compared with the most used cutoffs, showed a gain in Sp and PPV with a slightly lower performance in Sn and NPV and with a decrease in the gray-area with the second one. Our data do not support the use of different NT-proBNP cutoffs depending on eGFR, Ht and CRP.
  
  Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
  
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• Structural and Functional Abnormalities of Carotid Artery and Their Relation with EVA Phenomenon.
  High Blood Press Cardiovasc Prev

  2015 Dec;22(4):373-9. doi: 10.1007/s40292-015-0100-9.
  
  Maloberti Alessandro, Meani Paolo, Varrenti Marisa, Giupponi Luca, Stucchi Miriam, Vallerio Paola, Giannattasio Cristina
  
  Abstract
  
  Early vascular aging is a process characterized by a reduction in arterial elastin with an increase in collagen that has been related to cardiovascular risk factor and can determine an increased arterial stiffness and central blood pressure. It can be measured by several non invasive methods and in different arterial segment. The present paper will focus on functional (local stiffness parameter) and structural (intima media thickness) carotid arteries alterations typically evaluated by ultrasound methods. Methodological, research and clinical issue has been reviewed.
  
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• Increased nocturnal heart rate and wave reflection are early markers of cardiovascular disease in Williams-Beuren syndrome children.
  J Hypertens

  2015 Apr;33(4):804-9; discussion 809. doi: 10.1097/HJH.0000000000000454.
  
  Maloberti Alessandro, Cesana Francesca, Hametner Bernhard, Dozio Dario, Villa Paolo, Hulpke-Wette Martin, Schwarz Achim, Selicorni Angelo, Wassertheurer Siegfried, Mancia Giuseppe, Giannattasio Cristina
  
  Abstract
  
  OBJECTIVE:
  Williams-Beuren syndrome (WBS) is a genetic disorder that involves elastin gene causing cardiovascular abnormalities and increased risk. However, data on arterial function in these patients are only few and conflicting. Aim of this study was to evaluate dynamic behaviour of central and peripheral blood pressure (BP) and arterial stiffness parameters early in the course of WBS.
  
  METHODS:
  We enrolled 19 WBS paediatric patients (age 13?±?4 years) and 23 age, height and BP-matched controls (10?±?4 years). We evaluated 24-h ambulatory BP values via an ambulatory blood pressure monitoring (ABPM) system (Mobil-O-Graph) also capable to calculate 24-h central BP and 24-h arterial stiffness parameters. Carotid-femoral PWV (cf-PWV) was assessed in all WBS individuals (Complior).
  
  RESULTS:
  BP values were similar in WBS and control, during the daytime and the night-time. The same behaviour applies to 24-h central BP. However, during the night, WBS showed heart rate values (HR; 78?±?10 vs. 71?±?9?bpm; P?
  CONCLUSION:
  In WBS children, the higher night-time HR, Aix and reflection magnitude and their impaired physiological reduction in the day-night shift suggests an abnormal sympathetic cardiovascular control, an augmented wave reflection and an increase in small arteries resistance. These alterations possibly due to a sympathetic overactivity can be regarded as earlier hallmarks of cardiovascular dysfunction in these patients.
  
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• Brachial and central blood pressure in HIV-infected subjects.
  Hypertens Res

  2015 Jun;38(6):405-12. doi: 10.1038/hr.2015.25.
  
  Maloberti Alessandro, Dozio Dario, Betelli Mauro, Bandera Alessandra, Squillace Nicola, Gori Andrea, Castoldi Giovanna, Stella Andrea, Mancia Giuseppe, Giannattasio Cristina
  
  Abstract
  
  HIV infected subjects present an unfavorable cardiovascular (CV) risk profile that is determined by the infection itself, highly active anti-retroviral therapy (HAART) and other factors, such as chronic kidney disease (CKD). Information is scant and contradictory on whether these factors are associated with arterial stiffness and blood pressure (BP) alteration. Our study aimed to evaluate those parameters in HIV-positive subjects both with and without HAART and with and without CKD, which was defined as the presence of microalbuminuria with a normal glomerular filtration rate. We enrolled 94 HIV-infected subjects without known CV risk factors and compared them with 37 control subjects. We recorded brachial and central BP (pulse wave analysis) and pulse wave velocity ( SphygmoCor). HIV-positive subjects of similar ages and with similar BP values showed central pulse pressure values that were significantly greater than those of controls; this was also the case for the Aix value. Central systolic and pulse pressure values and Aix were significantly greater in HIV-positive subjects with HAART and CKD than in the other HIV-positive subgroups and control subjects. PWV was also superimposable between groups when the data were analyzed relative to the presence of HAART and CKD. Our study shows that the unfavorable CV risk profile associated with HIV infection includes an increase in both central BP and Aix. The central BP increase seems to be favored by renal damage, which apparently has a role in the early stages of the disease.
  
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• Metabolic syndrome in human immunodeficiency virus-positive subjects: prevalence, phenotype, and related alterations in arterial structure and function.
  Metab Syndr Relat Disord

  2013 Dec;11(6):403-11. doi: 10.1089/met.2013.0008.
  
  Maloberti Alessandro, Giannattasio Christina, Dozio Dario, Betelli Mauro, Villa Paulo, Nava Stefano, Cesana Francesca, Facchetti Rita, Giupponi Luca, Castagna Francesco, Sabbatini Francesca, Bandera Alessandra, Gori Andre, Grassi Guido, Mancia Giuseppe
  
  Abstract
  
  BACKGROUND:
  Human immunodeficiency virus (HIV) infection itself and highly active antiretroviral treatment (HAART) have been proposed to be associated with a higher prevalence of metabolic syndrome, but, to date, prevalence and phenotype of metabolic syndrome among HIV subjects and the related structural and functional vascular alterations are not conclusively defined.
  
  METHODS:
  We analyzed the data of 108 HIV-infected subjects without known cardiovascular risk factors: 72 were on HAART (group A, age 46.5±7.5 years, clinical blood pressure 125.7/74.9±11.6/7.8?mmHg) and there 36 in a naïve group (group B, age 40.7±7.9 years, blood pressure 126/75.8±9.8/7.7?mmHg). A total of 224 healthy subjects served as controls (group C, age 44.9±6.9 years, blood pressure 123.7/75.7±9.8/7.1?mmHg). Arterial stiffness was measured by aorto-femoral pulse wave velocity (PWV, sfigmocor), and carotid intima media thickness (IMT) was measured by a semiautomatic echotracking system (Esaote-WTS).
  
  RESULTS:
  Metabolic syndrome was more frequent in HIV-positive subjects than in controls (19.4%, 13.8%, 4.5% for groups A, B, and C; P<0.001), with no significant difference between HAART and naïve. In metabolic syndrome subjects, group A displayed lipid profile alterations more frequently (91%, 50%, 57% for groups A, B, and C; P<0.05), whereas others metabolic syndrome components were equally represented in the three groups. In metabolic syndrome subjects, IMT was similar [556±108, 542±164, and 564±110.4 ?m for groups A, B, and C; P=not significant (NS)], whereas PWV was significantly greater in HAART subjects when compared with controls (10.8±1.8, 9.±1.1, 9.3±1?cm/sec for groups A, B, and C; P=0.02 for A vs. C). Moreover, in this group (metabolic syndrome+HAART), PWV was higher than in subjects on HAART but without metabolic syndrome.
  
  CONCLUSIONS:
  HIV subjects showed a higher prevalence and a different pattern of metabolic syndrome components. HAART, more than HIV infection per se, appeared to be responsible for the increased prevalence of metabolic syndrome and arterial function derangement.
  
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• Does the 9p region affect arterial stiffness? Results from a cohort of hypertensive individuals.
  Blood Press

  2013 Oct;22(5):302-6. doi: 10.3109/08037051.2013.765627.
  
  Cesana Francesca, Nava Stefano, Menni Cristina, Boffi Lucia, Varrenti Marisa, Meani Paolo, Maloberti Alessandro, Grassi Guido, Giannattasio Cristina, Mancia Giuseppe
  
  Abstract
  
  OBJECTIVE:
  Evidence exists that arterial stiffness, i.e. an independent predictor of cardiovascular and all-causes mortality, has a genetic component. The 9p21 region is associated with a greater susceptibility to coronary disease. Whether this can be ascribed to the fact that genes located on chromosome 9p may also regulate arterial stiffness is largely unknown, however. We evaluate the influence of single nucleotide polymorphisms (SNPs) from 9p on carotid-femoral pulse wave velocity (C-F PWV), measured via the Complior method, in a cohort of 821 hypertensive subjects.
  
  DESIGN:
  The selected tagSNPs were screened with a custom-designed 384-plex VeraCode GoldenGate Genotyping assay on Illumina BeadXpress Reader platform. Association analysis was done using PLINK considering C-F PWV as a quantitative trait (linear regression assuming an additive model) adjusting for sex, age, systolic blood pressure and body mass index (BMI). We used false discovery rate (FDR) to account for multiple testing.
  
  RESULTS:
  Although none of the 384 SNPs was significant after adjusting for multiple testing, probably due to the small sample size of the study population, a trend of association with C-F PWV was observed for rs300622 and rs2381640.
  
  CONCLUSIONS:
  These data suggest that SNPs located on chromosome 9p may affect arterial stiffness. Further studies are needed to confirm our finding on a larger sample and define the physiopathological link of the present results.
  
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• Comparison of echotracking and magnetic resonance assessment of abdominal aorta distensibility and relationships with pulse wave velocity.
  Ultrasound Med Biol

  2011 Dec;37(12):1970-6. doi: 10.1016/j.ultrasmedbio.2011.09.009.
  
  Giannattasio Cristina, Cesana Francesca, Maestroni Silvia, Salvioni Alessandra, Maloberti Alessandro, Nava Stefano, Cairo Matteo, Madotto Fabiana, Zerboni Filippo, Sironi Sandro, Grassi Guido, Mancia Giuseppe
  
  Abstract
  
  Arterial distensibility can be measured either by echotracking or by nuclear magnetic resonance (MRI). Little information, however, is available on the comparison between the two methods and on the relationships between the results obtained with the two approaches and the arterial stiffness gold standard measurement, i.e., pulse wave velocity (PWV). In 28 normotensive subjects (age 33.0 ± 10.4 years, mean ± SD) we measured aortic diameter 1 cm above iliac bifurcation, aortic pulse pressure by tonometry and calculated arterial distensibility via the Reneman formulae for both methods. Aortic diameter and aortic distensibility were not superimposable and higher values were systematically detected with the MRI approach than with the ultrasound one. However, PWV showed a significant correlation with aortic distensibility values obtained by both methods (r = 0.50 and r = 0.49, p < 0.05). These data provide evidence that MRI-measured distensibility value is higher than that obtained via echotracking. The significant correlation with PWV, however, suggests that both methods can be regarded as valuable approaches. Considering the greater economic cost and the lower availability in daily clinical and research practice of MRI, echotracking ultrasonography can be regarded as a reliable and feasible method to assess aortic distensibility.
  
  Copyright © 2011. Published by Elsevier Inc.
  
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• Persistence of arterial functional abnormalities after successful coronary revascularization.
  J Hypertens

  2011 Jul;29(7):1374-9. doi: 10.1097/HJH.0b013e328347a0e3.
  
  Giannattasio Cristina, Capra Anna C M, Calchera Ivan, Colombo Virgilio, Cesana Francesca, Nava Stefano, Maloberti Alessandro, Alloni Marta, Facchetti Rita, Trocino Giuseppe, Grassi Guido, Paolini Giovanni, Mancia Giuseppe
  
  Abstract
  
  BACKGROUND:
  In patients with myocardial ischemia and coronary atherosclerosis, arterial stiffness and endothelial function are impaired. Whether these alterations can be favorably affected by successful coronary revascularization is debated.
  
  METHODS:
  We studied 39 hospitalized patients 59.3 ± 3.2 years old (mean ± SEM). In 21 patients with angiographic evidence of significant coronary artery stenosis, revascularization procedures were performed (stenting n = 11 and bypass surgery n = 10). The remaining patients had no significant stenosis and thus served as controls. Prerevascularization measurements included carotido-femoral pulse wave velocity (PWV), radial artery flow-mediated vasodilatation and a complete echocardiographic examination. The same measurements were performed 6 months later. Pharmacological treatment consisted of different cardiovascular drugs and remained substantially unchanged over the 6-month follow-up period.
  
  RESULTS:
  With the exception of an increased left ventricular mass index (LVMI; 130 ± 5.3 versus 105.8 ± 7.2 g/m(2), P < 0.05) and a lower Em/Am (0.6 ± 0.01 and 0.8 ± 0.01 respectively, P < 0.05) observed in patients with coronary stenosis, all other hemodynamic, cardiac and vascular variables were similar in the two groups. Following the 6-month follow-up period, all variables remained substantially unchanged, with the exception, in revascularized patients, of a significant reduction in LVMI (-12%, P < 0.05) and an improvement in Tissue Doppler Imaging-measured diastolic function (Em/Am + 30%, P < 0.05). This was not associated, however, with any significant change in PWV and in flow-mediated vasodilatation.
  
  CONCLUSION:
  Cardiac revascularization has no effect on arterial function, assessed either as arterial stiffness or as flow-mediated vasodilatation. On the contrary, the improvement in coronary blood flow triggers local cardiac changes, namely, a reduction in LVMI and an improvement in diastolic function.
  
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