Pubblicazioni - Prof.ssa Giannattasio Cristina

• Effects of intensive urate lowering therapy with febuxostat in comparison with allopurinol on pulse wave velocity in patients with gout and increased cardiovascular risk: the FORWARD study.
  Eur Heart J Cardiovasc Pharmacother

  2021 Jan;():. doi: pvaa144.
  
  Desideri Giovambattista, Rajzer Marek, Gerritsen Martijn, Nurmohamed Michael T, Giannattasio Cristina, Tausche Anne-Kathrin, Borghi Claudio
  
  Abstract
  
  AIMS:
  Hyperuricaemia and gout are strongly related with traditional cardiovascular risk factors and vascular damage. This study aimed to assess whether febuxostat and allopurinol could differently influence carotid-femoral pulse wave velocity (cfPWV) in patients with gout and elevated serum uric acid (SUA) levels.
  
  METHODS AND RESULTS:
  A multi-centre, multinational, phase IV, randomized, parallel-group, active-controlled, open label trial with blind end-points evaluation. One hundred and ninetyseven adults with gout and SUA levels ?8?mg/dL were randomised to febuxostat or allopurinol in a 1:1 ratio for 36?weeks. The primary outcome was the comparison of the effects of febuxostat and allopurinol on changes in cfPWV. The mean cfPWV values at randomisation and week 36 were respectively 8.69?m/s and 9.00?m/s for subjects randomised to febuxostat and 9.02?m/s and 9.05?m/s for subjects randomised to allopurinol. No statistically significant changes in cfPWV by treatment assignment were observed at any time point for any of the assessed parameters. More subjects who received febuxostat had serum urate concentrations ?6?mg/dL following treatment (78.3% vs 61.1% at week 36, p?=?0.0137). Treatment-emergent adverse events were reported by 51 (52.0%) patients randomised to febuxostat and 63 (62.5%) patients randomised to allopurinol. The majority of events were mild in both treatment groups and included gout flares and arthralgia.
  
  CONCLUSIONS:
  In patients with gout and elevated SUA levels the arterial stiffness remained stable both with febuxostat and allopurinol. Febuxostat was more effective and faster than allopurinol in achieving the SUA target. Both treatments were safe and well tolerated.
  
  © Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2021. For permissions, please email: journals.permissions@oup.com.
  
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• 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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• Determinants of healing among patients with coronavirus disease 2019: the results of the SARS-RAS study of the Italian Society of Hypertension.
  J Hypertens

  2021 02;39(2):376-380. doi: 10.1097/HJH.0000000000002666.
  
  Mancusi Costantino, Grassi Guido, Borghi Claudio, Carugo Stefano, Fallo Francesco, Ferri Claudio, Giannattasio Cristina, Grassi Davide, Letizia Claudio, Minuz Pietro, Muiesan Maria Lorenza, Perlini Stefano, Pucci Giacomo, Rizzoni Damiano, Salvetti Massimo, Sarzani Riccardo, Sechi Leonardo, Veglio Franco, Volpe Massimo, Iaccarino Guido,
  
  Abstract
  
  OBJECTIVE:
  The burst of COVID-19 epidemics in Italy prompted the Italian Society of Hypertension to start an observational study to explore the characteristics of the hospitalized victims of the disease. The current analysis aimed to investigate the predictors of healing among Italian COVID-19 patients. We also assessed the effect of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers on the outcome.
  
  METHODS:
  We designed a cross-sectional, observational, multicenter, nationwide survey in Italy to explore the demographic and clinical characteristics of patients with confirmed COVID-19 infection. We analyzed information from 2446 charts of Italian patients admitted for certified COVID-19 in 27 hospitals. Healing from COVID-19 infection, defined as two consecutive negative swabs, was reported in 544 patients (22.2%), 95% of them were hospitalized.
  
  RESULTS:
  Age and Charlson Comorbidity Index were significantly lower in healing compared with nonhealing patients (63?±?15 vs. 69?±?15 and 2?±?2 vs. 3?±?2, both P?
  CONCLUSION:
  Our study demonstrated that younger age and absence of comorbidities play a major role in determining healing in patients with COVID-19. No effects of ACE inhibitors and angiotensin receptor blockers on the outcome was reported.
  
  Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
  
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• Nutraceuticals in Chronic Coronary Syndromes: Preclinical Data and Translational Experiences.
  High Blood Press Cardiovasc Prev

  2020 Oct;():. doi: 10.1007/s40292-020-00416-8.
  
  Tognola Chiara, Alessandro Maloberti, Milani Martina, Cartella Iside, Tavecchia Giovanni, Grasso Enzo, Sun Jinwey, Giannattasio Cristina
  
  Abstract
  
  Non-pharmacological treatments have always been considered important in the management of Chronic Coronary Syndromes. Nutraceuticals ("Nutrition" + "Pharmaceutical") could fall both under the definition of non-pharmacological treatment and pharmacological one or, probably more correctly, in the middle of these two kinds of therapies. However, the word "nutraceuticals" never appears in the latest guidelines on this issue. This is probably determined by the fact that evidences on this topic are scarce and most of the published articles are based on preclinical data while translational experiences are available only for some molecules. In this review we will focus on nutraceutical strategies that act on the ischemic myocardium itself and not only on the cardiovascular risk factors. As demonstrated by the important number of papers published in recent years, this is an evolving topic and evaluated substances principally act on two mechanisms (cardiac energetics and ischemia-reperfusion damage) that will be also reviewed.
  
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• Gender differences in predictors of intensive care units admission among COVID-19 patients: The results of the SARS-RAS study of the Italian Society of Hypertension.
  PLoS One

  2020 ;15(10):e0237297. doi: 10.1371/journal.pone.0237297.
  
  Iaccarino Guido, Grassi Guido, Borghi Claudio, Carugo Stefano, Fallo Francesco, Ferri Claudio, Giannattasio Cristina, Grassi Davide, Letizia Claudio, Mancusi Costantino, Minuz Pietro, Perlini Stefano, Pucci Giacomo, Rizzoni Damiano, Salvetti Massimo, Sarzani Riccardo, Sechi Leonardo, Veglio Franco, Volpe Massimo, Muiesan Maria Lorenza,
  
  Abstract
  
  BACKGROUND:
  The global rate of intensive care unit (ICU) admission during the COVID-19 pandemic varies within countries and is among the main challenges for health care systems worldwide. Conflicting results have been reported about the response to coronavirus infection and COVID-19 outcomes in men and women. Understanding predictors of intensive care unit admission might be of help for future planning and management of the disease.
  
  METHODS AND FINDINGS:
  We designed a cross-sectional observational multicenter nationwide survey in Italy to understand gender-related clinical predictors of ICU admission in patients with COVID-19. We analyzed information from 2378 charts of Italian patients certified for COVID-19 admitted in 26 hospitals. Three hundred ninety-five patients (16.6%) required ICU admission due to COVID19 infection, more frequently men (74%), with a higher prevalence of comorbidities (1,78±0,06 vs 1,54±0,03 p<0.05). In multivariable regression model main predictors of admission to ICU are male gender (OR 1,74 95% CI 1,36-2,22 p<0.0001) and presence of obesity (OR 2,88 95% CI 2,03-4,07 p<0.0001), chronic kidney disease (OR: 1,588; 95%, 1,036-2,434 p<0,05) and hypertension (OR: 1,314; 95% 1,039-1,662; p<0,05). In gender specific analysis, obesity, chronic kidney disease and hypertension are associated with higher rate of admission to ICU among men, whereas in women, obesity (OR: 2,564; 95% CI 1,336-4.920 p<0.0001) and heart failure (OR: 1,775 95% CI: 1,030-3,057) are associated with higher rate of ICU admission.
  
  CONCLUSIONS:
  Our study demonstrates that gender is the primary determinant of the disease's severity among COVID-19. Obesity is the condition more often observed among those admitted to ICU within both genders.
  
  TRIAL REGISTRATION:
  Clinicaltrials.gov: NCT04331574.
  
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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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• Predictors of medium- and long-term mortality in elderly patients with acute pulmonary embolism.
  Heliyon

  2020 Sep;6(9):e04857. doi: 10.1016/j.heliyon.2020.e04857.
  
  Polo Friz Hernan, Orenti Annalisa, Gelfi Elia, Motto Elena, Primitz Laura, Cavalieri d'Oro Luca, Giannattasio Cristina, Vighi Giuseppe, Cimminiello Claudio, Boracchi Patrizia
  
  Abstract
  
  Introduction:
  Data on medium- and long-term prognostic factors for death in elderly patients with acute Pulmonary Embolism (APE) are lacking. The present study aimed to assess sPESI score and the Charlson Comorbidity Index (CCI) as medium- and long-term predictors of mortality in elderly patients with haemodinamically stable APE.
  
  Methods:
  All consecutive patients aged?65 years old, evaluated at the emergency department (ED) of our hospital from 2010 through 2014, with a final diagnosis of APE, were included in this retrospective cohort study.
  
  Results:
  Study population:162 patients, female:36.5%, median age:79 years old, 74% presented a sPESI score>0, and 61% a CCI? 1. All causes mortality: 19.8%, 23.5%, 26.5%, 32.1% and 48.2% at 3, 6 months, 1, 2 and 5 years after APE. Univariate regression analysis: CCI?1 was associated with a higher mortality at 3, 6 months, 1, 2 and 5 years. Multivariate Cox analysis: CCI?1 associated with increased mortality at 3 months (HR:4.29; IC95%:1.46-12.59), 6 months (HR:5.33; IC95%:1.84-15.44), 1 year (HR:4.87; IC95%:1.87-12.70), 2 years (HR:3.78; IC95%:1.74-8.25), and 5 years (HR:2.30; IC95%:1.33-3.99). sPESI score?1 was not found to be related to an increased medium-or long-term mortality. Negative predictive values (IC95%) of CCI?1 were 93.65% (87.61-99.69), 93.65% (87.61-99.69), 92.06% (85.37-98.76), 87.3% (79.05-95.55) and 71.61% (60.13-83.1) for mortality at 3, 6 months, 1, 2 and 5 years.
  
  Conclusion:
  In elderly patients with a confirmed normotensive APE, unlike sPESI score, CCI showed to be an independent prognostic factor for medium- and long-term mortality. In these patients, after the acute phase following a PE event, the assessment of the comorbidities burden represents the most appropriate approach for predicting medium- and long-term mortality.
  
  © 2020 The Author(s).
  
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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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• Long-Term Risk of Major Adverse Cardiovascular Events in Patients With Acute Coronary Syndrome: Prognostic Role of Complete Blood Cell Count.
  Angiology

  2020 10;71(9):831-839. doi: 10.1177/0003319720938619.
  
  Morici Nuccia, Molinari Valentina, Cantoni Silvia, Rubboli Andrea, Antolini Laura, Sacco Alice, Cattaneo Marco, Alicandro Gianfranco, Oreglia Jacopo A, Oliva Fabrizio, Giannattasio Cristina, Brunelli Dario, La Vecchia Carlo, Valgimigli Marco, Savonitto Stefano
  
  Abstract
  
  Individual parameters of complete blood count (CBC) have been associated with worse outcome in patients with acute coronary syndrome (ACS). However, the prognostic role of CBC taken as a whole has never been evaluated for long-term incidence of major adverse cardiovascular events (MACEs). Patients were grouped according to their hematopoietic cells' inflammatory response at different time points during hospital stay. Patients with admission white blood cell count >10 × 10/L, discharge hemoglobin <120 g/L, and discharge platelet count >250 × 10/L were defined as "high-risk CBC." Among 1076 patients with ACS discharged alive, 129 (12%) had a "high-risk CBC" and 947 (88%) had a "low-risk CBC." Patients with "high-risk CBC" were older and had more comorbidities. Over a median follow-up of 665 days, they experienced a higher incidence of MACE compared to "low-risk CBC" patients (18.6% vs 8.1%). After adjustment for age, age-adjusted Charlson comorbidity index, female sex, cardiac arrest, suboptimal discharge therapy, coronary artery bypass, and ejection fraction, a high-risk CBC was significantly associated with increased MACE occurrence (adjusted hazard ratio 1.80; 95% CI: 1.09-3.00). The CBC was a prognostic marker in patients with ACS, and its evaluation at admission and discharge could better classify patient's risk and improve therapeutic management.
  
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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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• 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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• Usefulness of Cardiac Magnetic Resonance for Recurrent Pericarditis.
  Am J Cardiol

  2020 01;125(1):146-151. doi: S0002-9149(19)31094-X.
  
  Imazio Massimo, Pivetta Emanuele, Palacio Restrepo Sara, Sormani Paola, Pedrotti Patrizia, Quarta Giovanni, Brucato Antonio, Bubbico Elisa, Dal Corso Maria, Milazzo Angela, Quattrocchi Giuseppina, Andriani Monica, Lobetti Bodoni Luisa, Davini Ottavio, Sironi Sandro, Giannattasio Cristina, Giustetto Carla, Bogaert Jan, Adler Yehuda, Bucciarelli Ducci Chiara, De Ferrari Gaetano Maria
  
  Abstract
  
  Cardiac magnetic resonance (CMR) offers the capability to objectively detect pericarditis by identifying pericardial thickening, edema/inflammation by Short-TI Inversion Recovery-T2 weighted (STIR-T2w) imaging, edema/inflammation or fibrosis by late gadolinium enhancement (LGE), and presence of pericardial effusion. This is especially helpful for the diagnosis of recurrent pericarditis. Aim of the present paper is to assess the diagnostic accuracy of CMR findings as well as their potential prognostic value for the diagnosis of recurrent pericarditis. Multicenter cohort study of consecutive patients with recurrent pericarditis evaluated by CMR. We included 128 consecutive cases (60 males, 47%; mean age 48 ± 14 years). CMR was performed at a mean time of 12 days (95% confidence interval 15 to 21) after the clinical diagnosis. We evaluated the diagnostic accuracy and areas under the receiver operating characteristic (ROC) curve for CMR diagnostic criteria and complications (additional recurrences, cardiac tamponade, and constrictive pericarditis). Areas under the ROC curve were respectively 64% for pericardial thickening, 84% for pericardial edema, 82% for pericardial LGE, and 71% for pericardial effusion. After a mean follow-up of 34 months, recurrences occurred in 52% of patients, tamponade in 6%, and constrictive pericarditis in 11%. Using a multivariable Cox model, elevation of CRP and presence of CMR pericardial thickening were predictors of adverse events, whereas the presence of CMR LGE was associated with a lower risk. The prognostic model for adverse events using gender, age, CRP level, and all CMR variables showed a C-index of 0.84. In conclusion, CMR findings show high diagnostic accuracy and may help identifying patients at higher risk of complications.
  
  Copyright © 2019 Elsevier Inc. All rights reserved.
  
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• Short and long-term mortality in elderly patients with suspected not confirmed pulmonary embolism.
  Eur J Intern Med

  2020 03;73():36-42. doi: S0953-6205(19)30376-0.
  
  Polo Friz Hernan, Orenti Annalisa, Brambilla Mattia, Caleffi Alessandro, Pezzetti Valentina, Cavalieri d'Oro Luca, Giannattasio Cristina, Vighi Giuseppe, Cimminiello Claudio, Boracchi Patrizia
  
  Abstract
  
  INTRODUCTION:
  Most patients evaluated for suspected pulmonary embolism(PE) conclude the Emergency Department(ED) work-up with a diagnosis of PE not confirmed(PE excluded;PE-E). We aimed to investigate the clinical features, short and long-term mortality, and prognostic factors for death in elderly with PE-E, and to compare these figures with those of patients with PE confirmed(PE-C).
  
  METHODS:
  Consecutive patients ?65 years old evaluated in the ED for clinically suspected hemodynamically stable acute PE were included in this retrospective cohort study.
  
  RESULTS:
  Study population: 657 patients with suspected PE, PE-C:162(24.65%). When compared with PE-C, patients with PE-E presented a higher prevalence of chronic cardiopulmonary disease (17.37% vs 8.02%, p?=?0.003), a lower prevalence of pulse rate >110 (13.13% vs 25.93%; p<0.001), of arterial oxygen saturation <90% (16.16% vs. 25.93%; p?=?0.007) and of hospitalized patients (52.93% vs 98.15%; p < 0.001). Thirty-day, 90-day, 1-year, 2-year and 5-year overall mortality was 8.83%, 15.98%, 23.59%, 29.68%, and 51.09%, respectively, differences between PE-E and PE-C non statistically significant. Among patients with PE-E, multivariate analysis showed that simplified Pulmonary Embolism Severity Index score>0 was associated with higher short and long-term mortality (30-day:HR:5.31,p?=?0.029; 5 year:HR:2.18, p < 0.001), meanwhile comorbidity (Charlson Comorbidity Index>0) only with higher long-term mortality (30-day: HR:1.60, p?=?0.342; 5 year: HR:1.41, p?=?0.038).
  
  CONCLUSION:
  In real world haemodinamically stable elderly patients evaluated in the ED for suspected PE, short and long-term mortality was markedly high regardless whether PE was confirmed or excluded. At the time to set management and follow up strategies, elderly patients with PE excluded should not be considered a low-risk population.
  
  Copyright © 2019 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
  
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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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• Getting to the heart of the matter in a multisystem disorder: Erdheim-Chester disease.
  Lancet

  2019 Aug;394(10198):e19. doi: S0140-6736(19)31787-8.
  
  Buono Andrea, Bassi Ilaria, Santolamazza Caterina, Moreo Antonella, Pedrotti Patrizia, Sacco Alice, Morici Nuccia, Giannattasio Cristina, Oliva Fabrizio, Ammirati Enrico
  
  
  
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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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• Unusual presence of 'ghosts' following lead extraction for recurrent reactive pericarditis: a case report.
  Eur Heart J Case Rep

  2018 Dec;2(4):yty127. doi: 10.1093/ehjcr/yty127.
  
  Bentivegna Riccardo, Cattafi Giuseppe, Giannattasio Cristina, Moreo Antonella
  
  Abstract
  
  Background:
  The presence of a persistent fibrous sheath in right-sided heart chambers after transvenous lead extraction has already been described in some studies as echocardiographic tubular mobile masses called 'ghosts'. Their presence has been associated with cardiac device-related infective endocarditis or local device infection, but to the best of our knowledge, this is the first case where 'ghosts' have been reported among non-infected patients.
  
  Case summary:
  We present a case of a 73-year-old woman hospitalized due to worsening dyspnoea and a significant pericardial effusion, relapsed after pericardiocentesis with removal of about 1500?mL of non-haemorrhagic fluid. The patient's history revealed a previous dual-chamber pacemaker implantation due to symptomatic sick sinus syndrome. Transoesophageal echocardiography (TOE), essential to exclude endocarditis vegetations suggested an etiopathogenesis of mechanical irritation caused by the distal end of the passive fixation atrial lead on the right atrial appendage wall. Considering the echocardiographic report and the condition of reactive pericarditis with the early relapse of the significant pericardial effusion after pericardiocentesis, we opted for a lead removal procedure to eliminate the stimulus causing the irritation, with transoesophageal echocardiographic monitoring, thus the early detection of a 'ghost' was possible.
  
  Discussion:
  This is the first clinical case describing the presence of fibrin 'ghosts' sometime after the implantation of a pacemaker, highlighting a non-exclusively infectious genesis, and emphasizing the importance of TOE for the early detection of this post-extraction complication and its monitoring.
  
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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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• A longitudinal inquiry into directionality of effects between coping and information needs in hypertensive patients.
  Psychol Res Behav Manag

  2018 ;11():567-580. doi: 10.2147/PRBM.S168912.
  
  Greco Andrea, Cappelletti Erika Rosa, Luyckx Koen, D'Addario Marco, Giannattasio Cristina, Steca Patrizia
  
  Abstract
  
  Purpose:
  It is well recognized that effective health communication is associated with better adherence to medical prescriptions, behavioral changes, and enhanced perception of control over the disease. However, there is limited knowledge about the variables on which to tailor health messages. This study examined whether coping strategies were related to information needs over time in a sample of patients with hypertension.
  
  Patients and methods:
  A three-wave longitudinal design was used to examine the potential reciprocal relationships among variables. The sample included 271 patients (43.5% women) affected by essential arterial hypertension with a mean age of 54.66 years (SD =10.74 years; range 30-78 years). Data on patients' demographic characteristics, coping strategies, and information needs were collected three times over 12 months. To test the directionality of the relationships linking coping to information needs, cross-lagged path analyses were applied in a structural equation modeling approach.
  
  Results:
  Active coping was related to a greater need for information regarding behavioral habits; avoidance coping was negatively associated with the need for information regarding daily life activities, while passive coping showed a positive relationship with this need. Moreover, results sustained the hypothesis that the relationship between coping and information needs was bi-directional. In fact, greater need for information about the disease and its pharmacological treatment was related to greater adoption of active coping strategies. The need for information about risk and complications was associated with the coping strategy related to alcohol use.
  
  Conclusion:
  These results provide important suggestions for implementing more effective intervention programs aimed at fostering patients' self-care abilities. As it was possible to modify coping strategies, health care providers may consider measuring patients' strategies before the medical examination so they have time to refine the information they give to patients.
  
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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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• Clustering of Lifestyle Risk Factors in Acute Coronary Syndrome: Prevalence and Change after the First Event.
  Appl Psychol Health Well Being

  2018 11;10(3):434-456. doi: 10.1111/aphw.12141.
  
  Monzani Dario, D'Addario Marco, Fattirolli Francesco, Giannattasio Cristina, Greco Andrea, Quarenghi Francesco, Steca Patrizia
  
  Abstract
  
  BACKGROUND:
  Healthy lifestyles are modifiable risk factors for acute coronary syndrome (ACS) onset and recurrence. While unhealthy lifestyles tend to cluster together within the general healthy population, little is known about the prevalence and clustering of these behaviours in people with ACS before and after the first acute event. The aim of this study was to identify lifestyle profiles of patients with ACS and to explore their change after their first coronary event.
  
  METHODS:
  Three hundred and fifty-six patients completed self-report measures of healthy habits at the beginning of cardiac rehabilitation and 6 months later. By adopting a person-oriented approach, we analysed lifestyle clustering and its change over time. Differences in depression, anxiety, and negative illness perception among lifestyle profiles were assessed.
  
  RESULTS:
  We identified seven profiles, ranging from more maladaptive to healthier clusters. Findings showed a strong interrelation among unhealthy habits in patients. We highlighted a moderate individual and group stability of cluster membership over time. Moreover, unhealthier lifestyle profiles were associated with higher levels of depression, anxiety, and negative illness perception.
  
  CONCLUSION:
  These results may have implications for the development and implementation of multimodal interventions addressing wider-ranging improvement in lifestyles by targeting multiple unhealthy behaviours in patients with ACS.
  
  © 2018 The International Association of Applied Psychology.
  
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• Comorbidity burden conditions the prognostic performance of D-dimer in elderly patients with acute pulmonary embolism.
  Am J Emerg Med

  2019 05;37(5):799-804. doi: S0735-6757(18)30593-X.
  
  Polo Friz Hernan, Pezzetti Valentina, Orenti Annalisa, Caleffi Alessandro, Corno Valeria, Crivellari Chiara, Petri Francesco, Polo Friz Melisa, Punzi Veronica, Teruzzi Daniela, d'Oro Luca Cavalieri, Giannattasio Cristina, Vighi Giuseppe, Cimminiello Claudio, Boracchi Patrizia
  
  Abstract
  
  INTRODUCTION:
  The prognostic accuracy of D-dimer for risk assessment in acute Pulmonary Embolism (APE) patients may be hampered by comorbidities. We investigated the impact of comorbidity burden (CB) by using the Charlson Comorbidity Index (CCI), on the prognostic ability of D-dimer to predict 30 and 90-day mortality in hemodynamically stable elderly patients with APE.
  
  METHODS:
  All patients aged >65?years with normotensive APE, consecutively evaluated in the Emergency Department since 2010 through 2014 were included in this retrospective cohort study. Area under the curve (AUC) and ½ Net Reclassification Improvement (NRI) were calculated.
  
  RESULTS:
  Study population: 162 patients, median age: 79.2?years. The optimal cut-off value of CCI score for predicting mortality was ?1 (Low CB) and >1 (High CB), AUC?=?0.786. Higher levels of D-dimer were associated with an increased risk death at 30 (HR?=?1.039, 95%CI:1.000-1.080, p?=?0.049) and 90?days (HR?=?1.039, 95%CI:1.009-1.070, p?=?0.012). When added to simplified Pulmonary Embolism Severity Index (sPESI) score, D-dimer increased significantly the AUC for predicting 30-day mortality in Low CB (AUC?=?0.778, 95%CI:0.620-0.937, ½NRI?=?0.535, p?=?0.015), but not in High CB patients (AUC?=?0.634, 95%CI:0.460-0.807, ½ NRI?=?0.248, p?=?0.294). Similarly, for 90-day mortality D-dimer increased significantly the AUC in Low CB (AUC?=?0.786, 95%CI:0.643-0.929, ½NRI?=?0.424, p-value?=?0.025), but not in High CB patients (AUC?=?0.659, 95%CI:0.541-0.778, ½NRI?=?0.354, p-value?=?0.165).
  
  CONCLUSION:
  In elderly patients with normotensive APE, comorbidities condition the prognostic performance of D-dimer, which was found to be a better predictor of death in subjects with low CB. These results support multimarker strategies for risk assessment in this population.
  
  Copyright © 2018 Elsevier Inc. All rights reserved.
  
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• Impact of serial echocardiography in the management of primary cardiac lymphoma.
  J Saudi Heart Assoc

  2018 Apr;30(2):160-163. doi: 10.1016/j.jsha.2017.08.001.
  
  Cereda Alberto Francesco, Moreo Antonella Maurizia, Sormani Paola, De Chiara Benedetta, Casadei Francesca, Zancanella Michelle, Rusconi Chiara, Cairoli Roberto, Giannattasio Cristina
  
  
  
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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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• Not every fulminant lymphocytic myocarditis fully recovers.
  J Cardiovasc Med (Hagerstown)

  2018 Aug;19(8):453-454. doi: 10.2459/JCM.0000000000000664.
  
  Veronese Giacomo, Cipriani Manlio, Petrella Duccio, Pedrotti Patrizia, Giannattasio Cristina, Garascia Andrea, Oliva Fabrizio, Klingel Karin, Frigerio Maria, Ammirati Enrico
  
  
  
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• In Memoriam: Alberto Zanchetti (Parma July 27, 1926 - Milan March 24, 2018).
  J Clin Hypertens (Greenwich)

  2018 05;20(5):826-828. doi: 10.1111/jch.13315.
  
  Mancia Giuseppe, Magrini Fabio, Morganti Alberto, Stella Andrea, Schwartz Peter J, Cuspidi Cesare, Giannattasio Cristina, Grassi Guido, Parati Gianfranco, , Weber Michael A, Lackland Daniel
  
  
  
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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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• Clinical Presentation and Outcome in a Contemporary Cohort of Patients With Acute Myocarditis: Multicenter Lombardy Registry.
  Circulation

  2018 09;138(11):1088-1099. doi: 10.1161/CIRCULATIONAHA.118.035319.
  
  Ammirati Enrico, Cipriani Manlio, Moro Claudio, Raineri Claudia, Pini Daniela, Sormani Paola, Mantovani Riccardo, Varrenti Marisa, Pedrotti Patrizia, Conca Cristina, Mafrici Antonio, Grosu Aurelia, Briguglia Daniele, Guglielmetto Silvia, Perego Giovanni B, Colombo Stefania, Caico Salvatore I, Giannattasio Cristina, Maestroni Alberto, Carubelli Valentina, Metra Marco, Lombardi Carlo, Campodonico Jeness, Agostoni Piergiuseppe, Peretto Giovanni, Scelsi Laura, Turco Annalisa, Di Tano Giuseppe, Campana Carlo, Belloni Armando, Morandi Fabrizio, Mortara Andrea, Cirò Antonio, Senni Michele, Gavazzi Antonello, Frigerio Maria, Oliva Fabrizio, Camici Paolo G,
  
  Abstract
  
  BACKGROUND:
  There is controversy about the outcome of patients with acute myocarditis (AM), and data are lacking on how patients admitted with suspected AM are managed. We report characteristics, in-hospital management, and long-term outcome of patients with AM based on a retrospective multicenter registry from 19 Italian hospitals.
  
  METHODS:
  A total of 684 patients with suspected AM and recent onset of symptoms (<30 days) were screened between May 2001 and February 2017. Patients >70 years of age and those >50 years of age without coronary angiography were excluded. The final study population comprised 443 patients (median age, 34 years; 19.4% female) with AM diagnosed by either endomyocardial biopsy or increased troponin plus edema and late gadolinium enhancement at cardiac magnetic resonance.
  
  RESULTS:
  At presentation, 118 patients (26.6%) had left ventricular ejection fraction <50%, sustained ventricular arrhythmias, or a low cardiac output syndrome, whereas 325 (73.4%) had no such complications. Endomyocardial biopsy was performed in 56 of 443 (12.6%), and a baseline cardiac magnetic resonance was performed in 415 of 443 (93.7%). Cardiac mortality plus heart transplantation rates at 1 and 5 years were 3.0% and 4.1%. Cardiac mortality plus heart transplantation rates were 11.3% and 14.7% in patients with complicated presentation and 0% in uncomplicated cases (log-rank P<0.0001). Major AM-related cardiac events after the acute phase (postdischarge death and heart transplantation, sustained ventricular arrhythmias treated with electric shock or ablation, symptomatic heart failure needing device implantation) occurred in 2.8% at the 5-year follow-up, with a higher incidence in patients with complicated forms (10.8% versus 0% in uncomplicated AM; log-rank P<0.0001). ?-Adrenoceptor blockers were the most frequently used medications both in complicated (61.9%) and in uncomplicated forms (53.8%; P=0.18). After a median time of 196 days, 200 patients had follow-up cardiac magnetic resonance, and 8 of 55 (14.5%) with complications at presentation had left ventricular ejection fraction <50% compared with 1 of 145 (0.7%) of those with uncomplicated presentation.
  
  CONCLUSIONS:
  In this contemporary study, overall serious adverse events after AM were lower than previously reported. However, patients with left ventricular ejection fraction <50%, ventricular arrhythmias, or low cardiac output syndrome at presentation were at higher risk compared with uncomplicated cases that had a benign prognosis and low risk of subsequent left ventricular systolic dysfunction.
  
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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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• Isolated systolic hypertension in the young: a position paper endorsed by the European Society of Hypertension.
  J Hypertens

  2018 06;36(6):1222-1236. doi: 10.1097/HJH.0000000000001726.
  
  Palatini Paolo, Rosei Enrico Agabiti, Avolio Alberto, Bilo Gregorz, Casiglia Edoardo, Ghiadoni Lorenzo, Giannattasio Cristina, Grassi Guido, Jelakovich Bojan, Julius Stevo, Mancia Giuseppe, McEniery Carmel M, O'Rourke Michael F, Parati Gianfranco, Pauletto Paolo, Pucci Giacomo, Saladini Francesca, Strazzullo Pasquale, Tsioufis Konstantinos, Wilkinson Ian B, Zanchetti Alberto
  
  Abstract
  
  : Whether isolated systolic hypertension in the young (ISHY) implies a worse outcome and needs antihypertensive treatment is still a matter for dispute. ISHY is thought to have different mechanisms than systolic hypertension in the elderly. However, findings from previous studies have provided inconsistent results. From the analysis of the literature, two main lines of research and conceptualization have emerged. Simultaneous assessment of peripheral and central blood pressure led to the identification of a condition called pseudo or spurious hypertension, which was considered an innocent condition. However, an increase in pulse wave velocity has been found by some authors in about 20% of the individuals with ISHY. In addition, obesity and metabolic disturbances have often been documented to be associated with ISHY both in children and young adults. The first aspect to consider whenever evaluating a person with ISHY is the possible presence of white-coat hypertension, which has been frequently found in this condition. In addition, assessment of central blood pressure is useful for identifying ISHY patients whose central blood pressure is normal. ISHY is infrequently mentioned in the guidelines on diagnosis and treatment of hypertension. According to the 2013 European Guidelines on the management of hypertension, people with ISHY should be followed carefully, modifying risk factors by lifestyle changes and avoiding antihypertensive drugs. Only future clinical trials will elucidate if a benefit can be achieved with pharmacological treatment in some subgroups of ISHY patients with associated risk factors and/or high central blood pressure.
  
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• High sodium intake and arterial stiffness.
  J Hypertens

  2018 04;36(4):754-758. doi: 10.1097/HJH.0000000000001658.
  
  Salvi Paolo, Giannattasio Cristina, Parati Gianfranco
  
  
  
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• Role of T1 mapping as a complementary tool to T2* for non-invasive cardiac iron overload assessment.
  PLoS One

  2018 ;13(2):e0192890. doi: 10.1371/journal.pone.0192890.
  
  Torlasco Camilla, Cassinerio Elena, Roghi Alberto, Faini Andrea, Capecchi Marco, Abdel-Gadir Amna, Giannattasio Cristina, Parati Gianfranco, Moon James C, Cappellini Maria D, Pedrotti Patrizia
  
  Abstract
  
  BACKGROUND:
  Iron overload-related heart failure is the principal cause of death in transfusion dependent patients, including those with Thalassemia Major. Linking cardiac siderosis measured by T2* to therapy improves outcomes. T1 mapping can also measure iron; preliminary data suggests it may have higher sensitivity for iron, particularly for early overload (the conventional cut-point for no iron by T2* is 20ms, but this is believed insensitive). We compared T1 mapping to T2* in cardiac iron overload.
  
  METHODS:
  In a prospectively large single centre study of 138 Thalassemia Major patients and 32 healthy controls, we compared T1 mapping to dark blood and bright blood T2* acquired at 1.5T. Linear regression analysis was used to assess the association of T2* and T1. A "moving window" approach was taken to understand the strength of the association at different levels of iron overload.
  
  RESULTS:
  The relationship between T2* (here dark blood) and T1 is described by a log-log linear regression, which can be split in three different slopes: 1) T2* low, <20ms, r2 = 0.92; 2) T2* = 20-30ms, r2 = 0.48; 3) T2*>30ms, weak relationship. All subjects with T2*<20ms had low T1; among those with T2*>20ms, 38% had low T1 with most of the subjects in the T2* range 20-30ms having a low T1.
  
  CONCLUSIONS:
  In established cardiac iron overload, T1 and T2* are concordant. However, in the 20-30ms T2* range, T1 mapping appears to detect iron. These data support previous suggestions that T1 detects missed iron in 1 out of 3 subjects with normal T2*, and that T1 mapping is complementary to T2*. The clinical significance of a low T1 with normal T2* should be further investigated.
  
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• Cardiac Biomarkers Release in Preadolescent Athletes After an High Intensity Exercise.
  High Blood Press Cardiovasc Prev

  2018 Mar;25(1):89-96. doi: 10.1007/s40292-017-0243-y.
  
  Peretti A, Mauri L, Masarin A, Annoni G, Corato A, Maloberti A, Giannattasio Cristina, Vignati G
  
  Abstract
  
  INTRODUCTION:
  An elevation of cardiac troponins has been described in healthy athletes after endurance exercises. The clinical significance of this increase is unclear and the lack of awareness of this phenomenon may lead to inappropriate management of these subjects.
  
  AIM:
  We sought to determine wether an intensive cycling training could determine a biomarkers elevation.
  
  METHODS:
  We evaluated serum high sensitivity cardiac troponin T, NH(2)-terminal pro-brain natriuretic peptide, CK-MB and CK in 21 healthy male preadolescent athletes (age 9.2 ± 1.7 years) after an intensive cycling training prolonged until muscular exhaustion (mean duration 16'41?). During exercise heart rhythm and rate were monitored with Holter.
  
  RESULTS:
  62% of the group had an elevation of cardiac biomarkers: specifically, 6 children had an increase in troponin levels; 3 of them had an elevation of pro-brain natriuretic peptides as well. Pro-brain natriuretic peptides resulted increased in 9 subjects. There was no relation between troponin elevation and heart rate, age or exercise duration; subjects with increased pro-brain natriuretic peptides had mean and maximal heart rates lower than children with normal natriuretic peptides levels. Other sports were performed in 50% of subjects with normal troponins and only in 17% of those with increased values.
  
  CONCLUSIONS:
  A short, high-intensity exercise caused an elevation of cardiac biomarkers in 62% of our subjects. The grade of training may influence the release of troponin and this increase is probably related to a temporary discrepancy between O2 delivery and consumption. Increases in natriuretic peptides levels are possibly expression of different adaptations to exercise.
  
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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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• Comorbidity assessment as predictor of short and long-term mortality in elderly patients with hemodynamically stable acute pulmonary embolism.
  J Thromb Thrombolysis

  2017 Oct;44(3):316-323. doi: 10.1007/s11239-017-1540-y.
  
  Polo Friz Hernan, Corno Valeria, Orenti Annalisa, Buzzini Chiara, Crivellari Chiara, Petri Francesco, Polo Friz Melisa, Punzi Veronica, Teruzzi Daniela, Cavalieri d'Oro Luca, Giannattasio Cristina, Vighi Giuseppe, Cimminiello Claudio, Boracchi Patrizia
  
  Abstract
  
  Elderly patients presenting with acute pulmonary embolism (PE) frequently have significant underlying comorbidities which may condition the prognosis. The current study aimed to determine the ability of Charlson comorbidity index (CCI) score to predict short and long-term mortality in elderly patients with hemodynamically stable acute PE. All hemodynamically stable patients aged >65 years with acute PE, evaluated in the Emergency Department since 2010 through 2014, were included in this retrospective cohort study. CCI, simplified pulmonary embolism severity index (sPESI) scores and vital status were recorded. Were included 162 patients with confirmed PE, out of 657 suspected cases (24.7%). Median age: 79.2 years, 74.1% presented an sPESI?>?1 and 61.1% a CCI?>?1. The overall 30, 90-day and 2-year mortality was 11.7% (95%CI 6.6-16.6), 19.8% (95%CI 13.4-25.7) and 31.8% (95%CI 24.1-38.8). For 30-day mortality sPESI showed an AUC 0.642 (95%CI 0.511-0.772) and adding CCI as covariate did not increase its prognostic performance. For 90-day mortality, in an adjusted model including sPESI and CCI, CCI showed a HR 1.282 (95%CI 1.151-1.429, p-value?
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• Medium-term effect of sublingual l-glutathione supplementation on flow-mediated dilation in subjects with cardiovascular risk factors.
  Nutrition

  2017 Jun;38():41-47. doi: S0899-9007(17)30001-1.
  
  Campolo Jonica, Bernardi Stefano, Cozzi Lorena, Rocchiccioli Silvia, Dellanoce Cinzia, Cecchettini Antonella, Tonini Annamaria, Parolini Marina, De Chiara Benedetta, Micheloni Gianpaolo, Pelosi Gualtiero, Passino Claudio, Giannattasio Cristina, Parodi Oberdan
  
  Abstract
  
  OBJECTIVE:
  Supplementation of glutathione (GSH) may be a positive strategy to improve the endogenous antioxidant defense required to counteract many acute and chronic diseases. However, the efficacy of GSH treatment seems to be closely related to type of administration, degree of absorption, and increase of its concentrations. The aim of this study was to test a new sublingual formulation of L-GSH, which enters directly the systemic circulation, to assess its efficacy on circulating biochemical markers of hepatic metabolism, lipid profile, and oxidative stress and on peripheral vascular function compared with placebo in patients with cardiovascular risk factors (CVRF).
  
  METHODS:
  We enrolled 16 healthy men with CVRF in a double-blinded, randomized placebo-controlled crossover study. At each visit, blood samples were collected for biochemistry analyses and peripheral endothelial function (reactive hyperemia index [RHI]) and stiffness were measured by Endo-PAT2000.
  
  RESULTS:
  In the overall population, a decrease in total and low-density lipoprotein cholesterol was highlighted after L-GSH supplementation compared with placebo (P = 0.023 and P = 0.04, respectively). On the contrary, no difference was observed in RHI and oxidative stress markers between L-GSH and placebo in the study population. However, seven participants with baseline abnormal RHI (?1.67) compared with those with normal RHI showed a significant reduction of arterial stiffness after L-GSH administration, (P = 0.007 and P = 0.037, respectively).
  
  CONCLUSIONS:
  Supplementation of L-GSH compared with placebo influences the lipid profile of patients with CVRF. Sublingual L-GSH may represent a valid prevention of vascular damage in patients with CVRF and endothelial dysfunction.
  
  Copyright © 2017 Elsevier Inc. All rights reserved.
  
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• Late Echocardiographic Study of Aortic Valve and Aortic Root after Surgery for Type A Acute Aortic Dissection.
  J Cardiovasc Echogr

  ;26(3):78-82. doi: 10.4103/2211-4122.187948.
  
  Molteni Martina, De Chiara Benedetta, Casadei Francesca, Botta Luca, Merlanti Bruno, Russo Claudio Francesco, Giannattasio Cristina, Moreo Antonella
  
  Abstract
  
  OBJECTIVE:
  In case of concomitant aortic regurgitation (AR) valve, sparing operation is considered the first choice in selected patients. The aim of this retrospective clinical and echocardiographic study was to evaluate the long-term survival results of conservative approach and the determinants of recurrent AR.
  
  METHODS:
  From 2000 to 2011, fifty patients (median: 63 years and interquartile range: 53-72) underwent an aortic valve-sparing procedure for acute aortic dissection, and discharged alive. The long-term clinical and echocardiographic outcome was analyzed.
  
  RESULTS:
  Late all-causes mortality was 18% (nine patients) at a median follow-up of 55.8 months. Ten patients (20%) underwent re-operations, five of them for aortic valve/root recurrent disease; freedom from proximal re-operation was 90%. Two-third of the patients had a preoperative AR grade <3; a non-negligible number of patients with acute significant AR (23% with grade ?3) at the time of surgery underwent conservative aortic valve surgery. At a median echocardiographic follow-up of 50.5 months, we found no significant correlation between late recurrent AR and AR grade at the time of surgery and the aortic root diameter. Late recurrent AR grade was significantly higher in patients who underwent aortic commissures and cusps resuspension than those who underwent lone ascending aorta replacement (2.29 ± 1.05 vs. 1.58 ± 1.03, = 0.028).
  
  CONCLUSIONS:
  Preoperative AR and late aortic root diameter were not the predictors of late AR. Late AR is higher in patients who underwent aortic commissures and cusps resuspension compared to the only replacement of the ascending aorta.
  
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• Mitral periprosthetic leakage: contemporary results of surgical correction at a single centre.
  Interact Cardiovasc Thorac Surg

  2017 08;25(2):185-190. doi: 10.1093/icvts/ivx101.
  
  Botta Luca, De Chiara Benedetta, Quattrocchi Salvina, Casadei Francesca, Borgia Francesco, Giannattasio Cristina, Moreo Antonella, Russo Claudio Francesco
  
  Abstract
  
  OBJECTIVES:
  Mitral periprosthetic leakage (PPL) is a serious complication following valve replacement. Conflicting outcomes of surgical treatment have been reported in the presence of multiple previous cardiac operations and associated co-pathological conditions.
  
  METHODS:
  Sixty-five symptomatic patients (37 women, mean age 64.8 years) underwent conventional operations at our hospital from 2006 to 2015. Mitral PPL was the leading surgical indication, although associated procedures were included. Previous transcatheter procedures and leaks involving multiple prostheses were excluded. The median number of past mitral operations was 2 (range 1-5). PPL recurrence was observed in 29% of cases. A previous operation on the aortic or tricuspid valve was performed in 31 patients.
  
  RESULTS:
  Mitral PPL involved one-, two- or three-quarters of the mitral perimeter in 46, 43 and 11% of cases. Prosthetic refixation or replacement was performed in 24 and 41 patients, respectively. Annular reconstruction was necessary in 17% of prosthetic replacements. Associated procedures were performed in 19 patients. The operation was executed through a right minithoracotomy (unclamped aorta) in 20% of patients. In-hospital deaths occurred in 3.1%. After a median follow-up of 60 months, freedom from all-cause mortality was 96.8, 91.5 and 88.8% at 1, 3 and 5 years. Lateral leaks [P?=?0.03; hazard ratio (HR)?=?4.57, 95% confidence interval (CI): 1.13-18.3] and PPL relapse (P?=?0.03; HR?=?4.33, 95% CI: 1.12-16.7) were independently associated with death. At follow-up, 4 patients had a?>2+ recurrent leak and 2 were reoperated.
  
  CONCLUSIONS:
  A customized conventional mitral reoperation still represents a satisfactory and effective treatment option for PPL and should be considered even in patients with very complex issues.
  
  © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
  
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• [Catecholamine-induced myocarditis in pheochromocytoma].
  G Ital Cardiol (Rome)

  2017 Feb;18(2):164-168. doi: 10.1714/2663.27302.
  
  Muratori Davide, Pedrotti Patrizia, Baroni Matteo, Belloni Armando, Quattrocchi Giuseppina, Milazzo Angela, Giannattasio Cristina, Roghi Alberto
  
  Abstract
  
  Pheochromocytoma is a rare tumor, usually benign, potentially lethal in case of crisis with acute release of catecholamines. The heart is a target and the clinical presentation can mimic various cardiac conditions, thus rendering diagnosis elusive. Cardiac magnetic resonance is a valuable non-invasive diagnostic tool for the evaluation of cardiomyopathies; it allows the identification of catecholamine-induced myocarditis pattern and, in some cases, it can detect the primary tumor. The definitive treatment of pheochromocytoma is surgical, while the acute crisis may require mechanical support to circulation. We here report a case of pheochromocytoma in a 25-year-old man complicated by catecholamine-induced myocarditis and heart failure.
  
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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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• Quantitative changes in late gadolinium enhancement at cardiac magnetic resonance in the early phase of acute myocarditis.
  Int J Cardiol

  2017 Mar;231():216-221. doi: S0167-5273(16)32250-1.
  
  Ammirati Enrico, Moroni Francesco, Sormani Paola, Peritore Angelica, Milazzo Angela, Quattrocchi Giuseppina, Cipriani Manlio, Oliva Fabrizio, Giannattasio Cristina, Frigerio Maria, Roghi Alberto, Camici Paolo G, Pedrotti Patrizia
  
  Abstract
  
  BACKGROUND:
  The presence of late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR) has diagnostic and prognostic value in patients with acute myocarditis (AM). Aim of our study was to quantify the changes in LGE extension (LGE%) early after AM and evaluate its relations with biventricular function and morphology.
  
  METHODS:
  We investigated 76 consecutive patients with AM (acute onset of chest pain/heart failure/ventricular arrhythmias not explained by other causes, and raised troponin) that met CMR criteria based on myocardial oedema at T2-weighted images and LGE on post-contrast images at median time of 6days from onset of symptoms. We quantified LGE% at baseline and after 148days in 49 patients.
  
  RESULTS:
  Median left ventricular (LV)-ejection fraction (EF) was 64% (interquartile range [Q1-Q3]: 56-67%), and LGE% 9.4% (Q1-Q3: 7.5-13.2%). LGE% was correlated with LV end-systolic volume index (LV-ESVi; r=+0.34; p=0.003). LGE% was inversely correlated with LV-EF (r=-0.31; p=0.009) and time to CMR scan (r=-0.25; p=0.028). In the 49 patients with a second CMR scan, despite no significant variations in LV-EF, a significant decrease of LGE% was observed (p<0.0001) with a relative reduction of 42% compared with baseline. Patients showing increased LV-ESVi at follow up had a lower decrease of LGE% (p=0.038).
  
  CONCLUSIONS:
  In the acute phase of AM the LGE extension is a dynamic process that reflects impairment of LV function and is time dependent. LGE% appears one of the CMR parameters with the largest relative variations in the first months after AM.
  
  Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
  
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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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• Evolut R Implantation to Treat Severe Pure Aortic Regurgitation in a Patient With Mitral Bioprosthesis.
  Ann Thorac Surg

  2016 Dec;102(6):e521-e524. doi: S0003-4975(16)30549-5.
  
  Bruschi Giuseppe, Colombo Paola, Nava Stefano, Musca Francesco, Merlanti Bruno, Belli Oriana, Soriano Francesco, Botta Luca, De Caria Danile, Giannattasio Cristina, Russo Claudio F
  
  Abstract
  
  Transcatheter aortic valves have been designed to treat high-risk surgical candidates affected by severe aortic stenosis, but little is known about the use of transcatheter valves in patients with severe pure aortic regurgitation. We describe the implantation of Medtronic CoreValve Evolut R (Medtronic, Minneapolis, MN) to treat an 82-year-old patient affected by severe pure aortic regurgitation who underwent prior mitral valve replacement with a biological valve protruding into the left ventricular outflow tract.
  
  Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
  
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• Mast cells and acute coronary syndromes: relationship between serum tryptase, clinical outcome and severity of coronary artery disease.
  Open Heart

  ;3(2):e000472.
  
  Morici Nuccia, Farioli Laura, Losappio Laura Michelina, Colombo Giulia, Nichelatti Michele, Preziosi Donatella, Micarelli Gianluigi, Oliva Fabrizio, Giannattasio Cristina, Klugmann Silvio, Pastorello Elide Anna
  
  Abstract
  
  OBJECTIVE:
  To assess the relationship between serum tryptase and the occurrence of major cardiovascular and cerebrovascular events (MACCE) at 2-year follow-up in patients admitted with acute coronary syndrome (ACS). To compare serum tryptase to other validated prognostic markers (maximum high-sensitivity troponin (hs-Tn), C reactive protein (CRP) levels at admission, Synergy between percutaneous coronary intervention with Taxus and Cardiac Surgery (SYNTAX) score).
  
  METHODS:
  We measured serum tryptase at admission in 140 consecutive patients with ACS and in 50 healthy controls. The patients' follow-up was maintained for 2?years after discharge. The predictive accuracy of serum tryptase for 2-year MACCE was assessed and compared with hs-Tn, CRP and SYNTAX score.
  
  RESULTS:
  Serum tryptase levels at admission were significantly higher in patients with ACS compared with the control group (p=0.0351). 2 years after discharge, 28/140 patients (20%) experienced MACCE. Serum tryptase levels, maximum hs-Tn measurements and SYNTAX score were higher in patients who experienced MACCE compared with those without (p<0.0001). Conversely, we found no significant association between MACCE and CRP. The predictive accuracy of serum tryptase for MACCE was set at the cut-off point of 6.7?ng/mL (sensitivity 46%, specificity 84%).
  
  CONCLUSIONS:
  In patients with ACS, serum tryptase measured during index admission is significantly correlated to the development of MACCE up to 2?years, demonstrating a possible long-term prognostic role of this biomarker.
  
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• Comprehensive evaluation of cardiac involvement in eosinophilic granulomatosis with polyangiitis (EGPA) with cardiac magnetic resonance.
  Eur J Intern Med

  2017 Apr;39():51-56. doi: S0953-6205(16)30315-6.
  
  Cereda Alberto Francesco, Pedrotti Patrizia, De Capitani Lucio, Giannattasio Cristina, Roghi Alberto
  
  Abstract
  
  BACKGROUND:
  Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic necrotizing vasculitis characterized by hypereosinophilia. EGPA typically develops in three clinical phases, beginning with asthma, followed by tissue eosinophilia and finally systemic vasculitis. Cardiac involvement is the most important predictor of mortality; it occurs in approximately 15-60% of EGPA patients, a significant proportion of whom are asymptomatic and have normal electrocardiogram (ECG) and echocardiogram. Early detection and management of cardiac disease could positevely affect prognosis. Cardiovascular magnetic resonance (CMR) has emerged as the gold standard cardiac imaging technique in the evaluation of cardiomyopathies, due to its ability to reliably assess anatomy, function, and tissue characterization.
  
  AIM:
  Purpose of this study was to assess the role of CMR in detecting cardiac disease in patients with EGPA in clinical remission.
  
  METHODS:
  A dedicated CMR protocol including functional analysis, and pre and post-contrast tissue characterization was performed in 11 patients with EGPA and the results were compared with 11 healthy subjects.
  
  RESULTS:
  EGPA patients had lower left ventricular ejection fraction compared to controls (56±19 vs 68.7±5.2, p value 0.02). Late gadolinium enhancement (LGE), representing replacement fibrosis, was positive in 9/11 (82%) patients, mainly with a non-ischemic pattern. In 3/11 (27%) patients a left ventricular thrombus was detected; in 3/11 (27%) patients myocardial edema was detected. CMR parameters of interstitial fibrosis were significantly more elevated in EGPA patients compared to controls.
  
  CONCLUSIONS:
  Patients with EGPA in clinical remission showed a high cardiovascular burden as demonstrated by lower EF, signs of active inflammation, presence of interstitial and replacement fibrosis and intraventricular thrombosis. Further studies on wider populations are warranted to better understand how these findings could impact on prognosis and eventually guide therapy.
  
  Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
  
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• Prognostic impact of late gadolinium enhancement in the risk stratification of heart transplant patients.
  Eur Heart J Cardiovasc Imaging

  2017 Feb;18(2):130-137. doi: 10.1093/ehjci/jew186.
  
  Pedrotti Patrizia, Vittori Claudia, Facchetti Rita, Pedretti Stefano, Dellegrottaglie Santo, Milazzo Angela, Frigerio Maria, Cipriani Manlio, Giannattasio Cristina, Roghi Alberto, Rimoldi Ornella
  
  Abstract
  
  AIMS:
  The aim of the present study was to assess the association of the presence and amount of late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR) with cardiovascular adverse events in patients with orthotopic heart transplantation (HTx).
  
  METHODS AND RESULTS:
  We enrolled 48 patients (mean age, 54.7 ± 14.6 years; 37 men) at various stages after HTx. All patients underwent standard CMR at 1.5 T, to characterize both cardiac anatomy and LGE. Late gadolinium enhancement was detected in 26 patients (54%). All-cause and cardiovascular mortalities, and a composite of major adverse cardiovascular events (MACE) recurrence were evaluated during the follow-up period for a median of 5.16 years. Ten patients (21%) died and 26 (54%) were readmitted because of MACE. Multivariate Cox analysis identified as independent predictors of MACE a diagnosis of cardiac allograft vasculopathy (CAV) (HR 3.63; 1.5-8.7 95% CI; P = 0.0039), left ventricular end systolic volume index (HR 1.04; 95% CI 1.01-1.079; P = 0.008), LGE mass (HR 1.04; 1.01-1.06 95% CI; P = 0.0007), LGE % of left ventricular mass (HR 1.083; 1.03-1.13 95% CI; P = 0.0002). Independent predictors of all-cause death were CAV (HR 6.33; 95% CI 1.33-30.03; P = 0.0201), LGE mass (HR 1.04; 1.01-1.07 95% CI; P = 0.005), LGE % of left ventricular mass (HR 1.075; 1.02-1.13 95% CI; P = 0.007). Patients with CAV had a risk of MACE by 5 years of 67% (95% CI 0.309-0.851%); the addition of 7.9 LGE % to the risk model increased the predicted risk to 88% (95% CI 0.572-0.967%).
  
  CONCLUSIONS:
  The current study demonstrated that the presence of CAV and the total amount of LGE have a significant independent association with MACE and mortality in HTx patients.
  
  Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.
  
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• A Type A and Type D Combined Personality Typology in Essential Hypertension and Acute Coronary Syndrome Patients: Associations with Demographic, Psychological, Clinical, and Lifestyle Indicators.
  PLoS One

  2016 ;11(9):e0161840. doi: 10.1371/journal.pone.0161840.
  
  Steca Patrizia, D'Addario Marco, Magrin Maria Elena, Miglioretti Massimo, Monzani Dario, Pancani Luca, Sarini Marcello, Scrignaro Marta, Vecchio Luca, Fattirolli Francesco, Giannattasio Cristina, Cesana Francesca, Riccobono Salvatore Pio, Greco Andrea
  
  Abstract
  
  Many studies have focused on Type A and Type D personality types in the context of cardiovascular diseases (CVDs), but nothing is known about how these personality types combine to create new profiles. The present study aimed to develop a typology of Type A and Type D personality in two groups of patients affected by and at risk for coronary disease. The study involved 711 patients: 51.6% with acute coronary syndrome, 48.4% with essential hypertension (mean age = 56.4 years; SD = 9.7 years; 70.7% men). Cluster analysis was applied. External variables, such as socio-demographic, psychological, lifestyle, and clinical parameters, were assessed. Six groups, each with its own unique combined personality profile scores, were identified: Type D, Type A-Negatively Affected, Not Type A-Negatively Affected, Socially Inhibited-Positively Affected, Not Socially Inhibited, and Not Type A-Not Type D. The Type A-Negatively Affected cluster and, to a lesser extent, the Type D cluster, displayed the worst profile: namely higher total cardiovascular risk index, physical inactivity, higher anxiety and depression, and lower self-esteem, optimism, and health status. Identifying combined personality profiles is important in clinical research and practice in cardiovascular diseases. Practical implications are discussed.
  
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• Total pericardial agenesis mimicking arrhythmogenic right ventricular dysplasia.
  J Cardiovasc Med (Hagerstown)

  2016 Dec;17 Suppl 2():e216-e217. doi: 10.2459/JCM.0000000000000425.
  
  Pedrotti Patrizia, Peritore Angelica, Cereda Alberto, Giannattasio Cristina, Imazio Massimo
  
  Abstract
  
  : We report the incidental finding of pericardial agenesis in a patient with electrocardiographic and echocardiographic abnormalities mimicking arrhythmogenic right ventricular dysplasia. The anatomic findings were clearly depicted by cardiac magnetic resonance. The patient was asymptomatic and the clinical relevance of this finding would be raised in case a possible differential diagnosis of right heart overload should be necessary. Diagnosis may be easily suspected from the ECG and echocardiography; MRI will provide definite diagnosis.
  
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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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• Infective endocarditis of an aortic intimal flap due to Streptococcus agalactiae in a patient with Sjögren's syndrome: an unusual clinical case report.
  Echocardiography

  2016 Sep;33(9):1434-5. doi: 10.1111/echo.13274.
  
  De Chiara Benedetta, Peritore Angelica, Sara Roberto, Giannattasio Cristina, Moreo Antonella
  
  
  
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• Partial Anomalous Pulmonary Venous Return as Rare Cause of Right Ventricular Dilation: A Retrospective Analysis.
  Congenit Heart Dis

  2016 Jul;11(4):365-8. doi: 10.1111/chd.12382.
  
  Sormani Paola, Roghi Alberto, Cereda Alberto, Peritore Angelica, Milazzo Angela, Quattrocchi Giuseppina, Giannattasio Cristina, Pedrotti Patrizia
  
  Abstract
  
  INTRODUCTION:
  Partial anomalous pulmonary venous return (PAPVR) is an uncommon cause of right ventricular dilation. It may be difficult to identify and often remains undiagnosed.
  
  METHODS:
  We reviewed the database of the Cardiac Magnetic Resonance (CMR) Laboratory of Niguarda Hospital, in order to identify the cases of PAPVR between 2008 and 2014.
  
  RESULTS:
  On a total number of 7832 CMR scans, we identified 24 patients with PAPVR (14 male, age 41?±?18 y) corresponding to 0.31% of the total population. Only 30% of patients had been referred for known or suspected PAPVR, 33% of patients had been referred for suspected right ventricular arrhythmogenic dysplasia and 37% had been referred for other cardiac disease. PAPVR involved mainly the right pulmonary veins (18 patients, 75%) and in 62% of our cases was associated with an atrial septal defect. Eight patients underwent corrective surgery in our institution, which confirmed and successfully repaired the anomalies.
  
  CONCLUSIONS:
  PAPVR is a rare congenital cardiac pathology which should be suspected in case of unexplained right chambers enlargement. CMR imaging allows an accurate anatomic and functional definition of this pathology and associated abnormalities. Early correction has an excellent prognosis and prevents long term complications like pulmonary hypertension, right ventricular failure and atrial fibrillation.
  
  © 2016 Wiley Periodicals, Inc.
  
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• Giant apparently not dissecting aneurysm and severe aortic valve insufficiency in an elite athlete.
  Eur Heart J

  2016 08;37(32):2527. doi: 10.1093/eurheartj/ehv683.
  
  Cereda Alberto, Sormani Paola, Russo Claudio F, Moreo Antonella, Giannattasio Cristina
  
  
  
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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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• Acute coronary syndrome: a rare case of multiple endocrine neoplasia syndromes with pheochromocytoma and medullary thyroid carcinoma.
  Cancer Biol Med

  2015 Sep;12(3):255-8. doi: 10.7497/j.issn.2095-3941.2015.0016.
  
  Maloberti Alessadro, Meani Paolo, Pirola Roberto, Varrenti Marisa, Boniardi Marco, De Biase Anna Maria, Vallerio Paola, Bonacina Edgardo, Mancia Giuseppe, Loli Paola, Giannattasio Cristina
  
  Abstract
  
  Pheochromocytoma is a tumor arising from neuroectodermal chromaffin tissues in the adrenal gland or extra-adrenal paraganglia (paragangliomas). The prevalence of the tumor is 0.1%-0.6% in the hypertensive population, of which 10%-20% are malignant. Pheochromocytoma produces, stores, and secretes catecholamines, as well as leads to hypertensive crisis, arrhythmia, angina, and acute myocardial infarction without coronary artery diseases. We report a case of acute coronary syndrome (ACS) with a final diagnosis of multiple endocrine neoplasia with pheochromocytoma and medullary thyroid carcinoma (MTC).
  
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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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• [Syncope: an untreated symptom with a lifesaving intervention].
  G Ital Cardiol (Rome)

  2015 Sep;16(9):517-8. doi: 10.1714/1988.21532.
  
  Giupponi Luca, De Chiara Benedetta, Spanò Francesca, Giannattasio Cristina, Taglieri Corrado, Moreo Antonella
  
  Abstract
  
  We report the case of a 61-year-old woman referred to our center for cardiac evaluation after a syncope, with echocardiographic findings of a papillary fibroelastoma on the edge of the non-coronary aortic cusp. The three-dimensional transesophageal approach provided a unique understanding of the size and shape of the mass and it favorably directed the surgeon towards treatment with conservative surgery.
  
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• Differential incremental value of ultrasound carotid intima-media thickness, carotid plaque, and cardiac calcium to predict angiographic coronary artery disease across Framingham risk score strata in the APRES multicentre study.
  Eur Heart J Cardiovasc Imaging

  2016 Sep;17(9):991-1000. doi: 10.1093/ehjci/jev222.
  
  Gaibazzi Nicola, Rigo Fausto, Facchetti Rita, Carerj Scipione, Giannattasio Cristina, Moreo Antonella, Mureddu Gian Francesco, Salvetti Massimo, Grolla Elisabetta, Faden Giacomo, Cesana Francesca, Faggiano Pompilio
  
  Abstract
  
  AIMS:
  According to recent data, more accurate selection of patients undergoing coronary angiography for suspected coronary artery disease (CAD) is needed. From the Active PREvention Study multicentre prospective study, we further analyse whether carotid intima-media thickness (cIMT), carotid plaques (cPL), and echocardiographic cardiac calcium score (eCS) have incremental discriminatory and reclassification predictive value for CAD over clinical risk score in subjects undergoing coronary angiography, specifically depending on their low, intermediate, or high class of clinical risk.
  
  METHODS AND RESULTS:
  In eight centres, 445 subjects without history of prior CAD but with chest pain of recent onset and/or a positive/inconclusive stress test for ischaemia prospectively underwent clinically indicated elective coronary angiography after cardiac and carotid ultrasound assessments with measurements of cIMT, cPL, and eCS. The study population was divided into subjects at low (10%), intermediate (10-20%), and high (>20%) Framingham risk score (FRS). Ultrasound parameters were tested for their incremental value to predict CAD over FRS, in each pre-test risk category. No significant difference could be appreciated between the discrimination value of FRS and Diagnostic Imaging for Coronary Artery Disease score for the presence of CAD. eCS or cPL demonstrated significant incremental prediction over FRS, consistently in the three FRS categories (P < 0.01); this applied to both discrimination and reclassification, with the exception of high-risk subjects, in whom cPL was apparently not incremental over FRS, and eCS was only of borderline significance for better discrimination.
  
  CONCLUSIONS:
  Ultrasound eCS and cPL assessments were significant predictors of angiographic CAD in patients without prior CAD but with signs or symptoms suspect for CAD, independently and incrementally to FRS, across all pre-test risk probability strata, although in high-risk subjects, only eCS maintained an incremental value. The use of cIMT was not significantly incrementally useful in any FRS risk category.
  
  Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.
  
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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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• [The conundrum of therapeutic management in acute myocardial infarction complicated by endoventricular thrombosis: moving between different risks].
  G Ital Cardiol (Rome)

  ;16(7-8):437-41. doi: 10.1714/1954.21248.
  
  Varrenti Marisa, Morici Nuccia, De Chiara Benedetta, Oreglia Jacopo Andrea, Pedrotti Patrizia, Giannattasio Cristina, Klugmann Silvio, Roghi Alberto
  
  Abstract
  
  Coronary artery disease is a rare entity in young patients and accurate assessment of its prevalence is difficult. Although coronary artery disease is frequently a silent process, it may also acutely present with myocardial infarction (MI). One of the most feared complications of MI is left ventricular thrombus formation. Transthoracic echocardiography is recommended for all patients with MI, and cardiac magnetic resonance should be considered because of its higher sensitivity if thrombus cannot clearly be demonstrated. The optimal treatment is based on anticoagulant therapy that should be started early and maintained for 3-4 months after the index event. We report the case of a 35-year-old male patient with anterior MI, complicated by left ventricular thrombus formation, extensive edema, microvascular obstruction and hemorrhagic core of the apical septum on cardiac magnetic resonance assessment.
  
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• Changes in Dietary Behavior among Coronary and Hypertensive Patients: A Longitudinal Investigation Using the Health Action Process Approach.
  Appl Psychol Health Well Being

  2015 Nov;7(3):316-39. doi: 10.1111/aphw.12050.
  
  Steca Patrizia, Pancani Luca, Greco Andrea, D'Addario Marco, Magrin Maria Elena, Miglioretti Massimo, Sarini Marcello, Scrignaro Marta, Vecchio Luca, Cesana Francesca, Giannattasio Cristina, Fattirolli Francesco, Zanettini Renzo
  
  Abstract
  
  BACKGROUND:
  Cardiovascular diseases (CVDs) are a major cause of worldwide morbidity and mortality. Nutrition plays an important role in the primary, secondary, and tertiary prevention of CVDs. The present longitudinal study used the Health Action Process Approach (HAPA) to investigate changes in dietary behavior in coronary patients (CPs) affected by acute coronary syndrome and hypertensive patients (HPs) affected by essential arterial hypertension.
  
  METHODS:
  CPs (N = 250) and HPs (N = 246) completed a questionnaire during three measurement points (baseline, 6-month follow-up, and 12-month follow-up). Statistical analyses included a repeated measures ANOVA and a multi-sample structural equation model.
  
  RESULTS:
  HPs showed no changes in dietary behavior, whereas CPs improved their nutrition at 6 months and then maintained the healthier diet. The multi-sample analysis indicated equivalence of the HAPA model for both patient populations.
  
  CONCLUSIONS:
  These findings provide further evidence for the generalisability of the HAPA model, shedding light on dietary behavior among CVD patients and particularly on hypertensive patients which has received little attention. Moreover, the equivalence of the model suggests that the process of change is almost identical for individuals who are at high risk for a coronary event (i.e. HPs) and individuals who have already had the event (i.e. CPs).
  
  © 2015 The International Association of Applied Psychology.
  
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• The impact of age and risk factors on carotid and carotid-femoral pulse wave velocity.
  J Hypertens

  2015 Jul;33(7):1446-51. doi: 10.1097/HJH.0000000000000582.
  
  Kozakova Michaela, Morizzo Carmela, Guarino Daniela, Federico Giovanni, Miccoli Mario, Giannattasio Cristina, Palombo Carlo
  
  Abstract
  
  OBJECTIVE:
  Segmental carotid-femoral pulse-wave velocity (PWV) is a gold standard method for arterial stiffness assessment; recently, a local carotid PWV measurement by ultrasound has been developed. The present study compared the impact of age and established risk factors on carotid and carotid-femoral PWV.
  
  METHODS:
  Three hundred and seven volunteers (167 men; age from 15 to 78 years) free of cardiovascular disease, diabetes, antihypertensive and lipid-lowering treatment underwent sequential measurement of carotid and carotid-femoral PWV.
  
  RESULTS:
  In the entire study population, both carotid and carotid-femoral PWV were independently associated mainly with age and blood pressure. In individuals more than 50 years old (N?=?132, 80 men), carotid-femoral PWV, but not carotid PWV, was also associated with high-density lipoprotein (HDL)-cholesterol and fasting glucose. The annual increase in carotid and carotid-femoral PWV was similar (0.087?±?0.004 and 0.090?±?0.005? m/s, respectively; P?=?0.69). Carotid PWV increased with age more rapidly in women than in men (0.099?±?0.005 vs. 0.076?±?0.005? m/s per year, P?
  CONCLUSION:
  In apparently healthy population, both carotid and carotid-femoral PWV were influenced above all by age and blood pressure. Other established cardiovascular risk factors had a limited impact only on carotid-femoral PWV of older individuals. The age-related increase in carotid and carotid-femoral PWV seemed to follow different patterns; increase in carotid PWV showed age-sex interaction, being steeper in women, whereas increase in carotid-femoral PWV was more prominent in older individuals.
  
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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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• 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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• Paroxysmal supraventricular tachycardia as first manifestation of right atrial hemangioma during endovascular treatment of intracranial arteriovenous fistulas.
  Oncotarget

  2015 Jun;6(16):14060-4.
  
  Spanò Francesca, Cereda Alberto, Moreo Antonella, Bonacina Edgardo, Peritore Angelica, Roghi Alberto, Giannattasio Cristina, Pedrotti Patrizia
  
  Abstract
  
  We report the description of a cardiac mass occupying almost the entire right atrium in a young man who developed paroxysmal supraventricular tachycardia during endovascular treatment of intracranial arteriovenous fistulas. The mass was detected at echocardiographic examination, its tissue characteristics were defined with cardiac magnetic resonance and it was successfully surgically removed. The histopathological findings were consistent with a mixed type cavernous-capillary hemangioma of the heart. The intriguing co-existence of cardiac hemangioma and cerebral arteriovenous fistulas, to the best of our knowledge, has not been previously reported in English Literature.
  
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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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• [A matter of perspective: multimodality imaging of a giant cardiac mass].
  G Ital Cardiol (Rome)

  2015 Mar;16(3):186-7. doi: 10.1714/1820.19830.
  
  Baroni Matteo, Nava Stefano, Vignati Gabriele, Marianeschi Stefano Maria, Giannattasio Cristina, Pedrotti Patrizia
  
  Abstract
  
  A newborn was suspected of having situs inversus with levocardia based on chest X-ray. Echocardiography ruled out this hypothesis but revealed a giant cardiac mass that was confirmed by magnetic resonance imaging. Coronary angiography showed that the right coronary artery ran on the surface of the mass, and only partial debulking surgery was performed to relieve right heart compression. Histological examination classified the mass as cardiac fibroma. Complex diagnostic work-up allowed correct anatomic definition of the mass as well as its relationship with adjacent structures, and helped guide surgical planning.
  
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• Cardiac metastatic melanoma: Imaging diagnostic clues.
  J Cardiol Cases

  2015 Aug;12(2):33-36. doi: 10.1016/j.jccase.2015.03.001.
  
  Pedrotti Patrizia, Musca Francesco, Torre Massimo, Pirola Roberto, De Biase Anna Maria, Fieschi Stefano, Quattrocchi Giuseppina, Roghi Alberto, Giannattasio Cristina
  
  Abstract
  
  A 47-year-old male was admitted to hospital for severe pericardial effusion; he had undergone surgical removal of cutaneous melanoma 10 years before. Echocardiography-guided pericardiocentesis revealed the presence of intramyocardial masses, which were better defined and characterized, together with pericardial involvement, by cardiac magnetic resonance. Pericardial fluid drained was negative for malignant cells, so video-assisted thoracoscopy was performed and pathologic tissue was biopsied, leading to the diagnosis of metastatic melanoma. Multidisciplinary approach and multimodality imaging played a key role in allowing the diagnostic workup in this complex case. < The diagnosis of cardiac metastases is challenging and histologic characterization is necessary to guide therapy. Multimodality imaging and minimally invasive thoracoscopy are key tools to achieve these goals.>.
  
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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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• Multiparametric carotid and cardiac ultrasound compared with clinical risk scores for the prediction of angiographic coronary artery disease: a multicenter prospective study.
  J Hypertens

  2015 Jun;33(6):1291-300. doi: 10.1097/HJH.0000000000000543.
  
  Moreo Antonella, Gaibazzi Nicola, Faggiano Pompilio, Mohammed Moemen, Carerj Scipione, Mureddu Gianfrancesco, Pigazzani Filippo, Muiesan Lorenza, Salvetti Massimo, Cesana Francesca, Faden Giacomo, Facchetti Rita, Giannattasio Cristina, Rigo Fausto
  
  Abstract
  
  OBJECTIVE:
  Cardiovascular risk prediction is deemed fundamental and the assessment of organ damage is emerging as a potentially 'downstream' picture of individual risk. Our aim was to assess the feasibility and value of prediction of coronaropathy [coronary artery disease (CAD)] of integrated cardiovascular ultrasound examination.
  
  METHODS:
  This multicenter study involved eight cardiology centers that enrolled 457 consecutive patients. Blood pressures, carotid intima-media thickness (cIMT), carotid pulse wave velocity (cPWV), semiquantitative score of cardiac calcifications, global myocardial longitudinal strain (GLS), and rest Doppler flow velocity on the left anterior descending (LAD) coronary artery were measured. After coronary angiography, patients were divided in CAD, n?=?273, at least one coronary stenosis higher than 50%, and no CAD, n?=?184.
  
  RESULTS:
  CAD were older (65.9?±?10.7 versus 63.1?±?11.2 years, mean?±?standard deviation, P?=?0.01), and had higher blood pressure (137.0?±?18.8/77.5?±?11.1 versus 130.2?±?17.4/75.1?±?9.7?mmHg, P?
  CONCLUSION:
  In Echo-Lab, Rome, Italy, the integrated cardiovascular ultrasound study is feasible in a high percentage of patients. The combination of three parameters, that is, score of calcium, cIMT, and LAD velocity, has incremental predictive value for obstructive CAD.
  
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• Right anterior mini-thoracotomy direct aortic self-expanding trans-catheter aortic valve implantation: A single center experience.
  Int J Cardiol

  2015 Feb;181():437-42. doi: 10.1016/j.ijcard.2014.11.108.
  
  Bruschi Giuseppe, De Marco Federico, Botta Luca, Barosi Alberto, Colombo Paola, Mauri Silvia, Cannata Aldo, Morici Nuccia, Colombo Tiziano, Fratto Pasquale, Nonini Sandra, Soriano Francesco, Mondino Michele, Giannattasio Cristina, Klugmann Silvio
  
  Abstract
  
  OBJECTIVE:
  Transcatheter aortic valve implantation (TAVI) has been designed to treat elderly patients with severe aortic stenosis at high risk for surgery. These patients are also often affected by severe iliac-femoral arteriopathy, rendering the trans-femoral approach unusable. We report our experience with the direct-aortic approach to treat these patients.
  
  METHODS:
  From May 2008 to November 2013 two hundred and thirty-two patients (131 female, 56%) with severe symptomatic aortic stenosis and no reasonable surgical option due to excessive risk were evaluated for TAVI at our department. Of these patients, 202 were deemed eligible for TAVI. Of this group, 50 underwent CoreValve implantation by the direct aortic approach through a right anterior mini-thoracotmy (28 female, 56%), mean age 81.2±6.9. A combined team of cardiologists, cardiac surgeons with expertise in hybrid procedures, and anesthetists performed all the procedures.
  
  RESULTS:
  Twenty-eight (56%) patients were female and 11 (22%) were redo at TAVI. We used a 23-mm CoreValve Evolute in 3 patients (6%), and the most used valve size was the 29mm in 46% of patients. Mean hemodynamic trans-aortic gradient was less than 5mmHg. The paravalvular regurgitation was ? grade 1 in 46 patients as assessed by peri-procedural transesophageal echocardiography (TEE). Seven patients (7/43, 16%) required a permanent pacemaker implantation; 30-day mortality was 6% (3 patients). Seven patients (14.8%) died during follow-up. Actuarial survival at 2years is 84.7±5.3%.
  
  CONCLUSIONS:
  Transcatheter aortic valve implantation with the direct aortic approach is safe and feasible, offering a new attractive option to treat selected high-risk patients with severe aortic stenosis and peripheral vasculopathy, including those requiring a re-do procedure.
  
  Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
  
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• Ultrasound carotid intima-media thickness, carotid plaque and cardiac calcium incrementally add to the Framingham Risk Score for the prediction of angiographic coronary artery disease: a multicenter prospective study.
  Int J Cardiol

  2014 Dec;177(2):708-10. doi: 10.1016/j.ijcard.2014.09.195.
  
  Gaibazzi Nicola, Rigo Fausto, Facchetti Rita, Carerj Scipione, Giannattasio Cristina, Moreo Antonella, Mureddu Gianfrancesco, Paini Anna, Grolla Elisabetta, Faden Giacomo, Cesana Francesca, Faggiano Pompilio
  
  
  
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• Diagnostic and therapeutic problems of isolated systolic hypertension.
  J Hypertens

  2015 Jan;33(1):33-43. doi: 10.1097/HJH.0000000000000424.
  
  Mancia Giuseppe, Giannattasio Cristina
  
  Abstract
  
  Prevalence of isolated systolic hypertension increases with age, due to progressive elevation of SBP, and is a major risk factor for cardiovascular morbidity and mortality. Extensive research has shown that lowering SBP improves cardiovascular outcomes in patients with isolated systolic hypertension, yet SBP control rates remain largely inadequate regardless of antihypertensive treatment. Arterial stiffness is a major determinant of elevated SBP resulting from structural changes in the vascular system, mediated by neurohormonal alterations that occur with vascular ageing. Clinical data have demonstrated an independent association between arterial stiffness and cardiovascular outcomes. Therefore, arterial stiffness has the potential to be an important therapeutic target in the management of isolated systolic hypertension. Current antihypertensive treatments have limited effects on arterial stiffness, so the development of new treatments addressing neurohormonal alterations central to vascular ageing is important. Such therapies may represent effective strategies in the future management of SBP.
  
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• Renal artery stenosis as the cause of resistant arterial hypertension: an unusual technique for revascularization.
  J Clin Hypertens (Greenwich)

  2014 Jul;16(7):536-7. doi: 10.1111/jch.12331.
  
  De Biase Anna, Varrenti Marisa, Meani Paolo, Cesana Francesca, Pirola Roberto, Giupponi Luca, Alloni Marta, Vallerio Paola, Moreo Antonella, Rampoldi Antonio, Giannattasio Cristina
  
  
  
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• Delayed, severe thrombocytemia after abciximab infusion for primary angioplasty in acute coronary syndromes: Moving between systemic bleeding and stent thrombosis.
  Platelets

  2015 ;26(5):498-500. doi: 10.3109/09537104.2014.898181.
  
  Giupponi Luca, Cantoni Silvia, Morici Nuccia, Sacco Alice, Giannattasio Cristina, Klugmann Silvio, Savonitto Stefano
  
  
  
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• Cardiac magnetic resonance imaging of left ventricular apical hypoplasia in two complex congenital clinical syndromes.
  Circ J

  2014 ;78(6):1507-9.
  
  Baroni Matteo, Pedrotti Patrizia, Nava Stefano, Giannattasio Cristina, Roghi Alberto
  
  
  
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• Similarities and differences between renal sympathetic denervation and carotid baroreceptor stimulation.
  Curr Vasc Pharmacol

  2014 Jan;12(1):63-8.
  
  Grassi Guido, Seravalle Gino, Brambilla Gianmaria, Cesana Francesca, Giannattasio Cristina, Mancia Giuseppe
  
  Abstract
  
  The two novel approaches recently introduced for the treatment of resistant hypertension, i.e. carotid baroreceptor stimulation and renal denervation, share a number of similarities but are also characterized by important differences. The similarities include the evidence that both interventions have as common pathophysiological background the state of sympathetic overdrive characterizing essential hypertension. In addition both procedures 1) are invasive, 2) exert in the short-term period clearcut blood pressure lowering effects and 3) still face a number of open questions, particularly related to the long-term blood pressure lowering effects, impact on end-organ damage and on cardiovascular events. The differences include the fact that two procedures act on distinct targets that trigger sympathetic activation and consequently blood pressure increase. In addition, only in the case of carotid baroreceptor stimulation the blood pressure effects can be easily assessed immediately following the implantation. Finally, the economic costs, metabolic effects and impact on vagal modulation of heart rate are different between the two interventions. This paper will provide a comparison of the background, effects and outcome of renal denervation and carotid baroreceptor stimulation, stressing whenever possible the clinical implications of the main features of the two interventions.
  
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• Impact of blood glucose variability on carotid artery intima media thickness and distensibility in type 1 diabetes mellitus.
  Blood Press

  2013 Dec;22(6):355-61. doi: 10.3109/08037051.2013.791413.
  
  Cesana Francesca, Giannattasio Cristina, Nava Stefano, Soriano Francesco, Brambilla Gianmaria, Baroni Matteo, Meani Paolo, Varrenti Marisa, Paleari Felice, Gamba Pierluigi, Facchetti Rita, Alloni Marta, Grassi Guido, Mancia Giuseppe
  
  Abstract
  
  AIMS:
  Diabetes mellitus is characterized by structural and functional alterations of the large- and medium-size arteries. Whether blood glucose variability, i.e. the glycemic oscillations occurring during the 24-h period, represents a risk factor for vascular alterations additional to and independent on HbA1c in type 1 diabetes mellitus is still undefined. The present study was carried out with the aim at investigating the impact of different measures of blood glucose variability on arterial structure and function. We studied 17 non-complicated type 1 diabetic patients (11 males, six females) with an age of 40.8 ± 7.6 years (mean ± SD). In each patient, 24-h glucose profile was obtained by continuous glucose monitoring system and glucose variability was expressed as mean ± SD of 24-h blood glucose levels, mean amplitude of glycemic excursions and postprandial hyperglycemic spikes. Arterial structure and function was measured as carotid IMT and stiffness.
  
  MAJOR FINDINGS:
  The different approaches to assessing blood glucose variability well correlated between and with HbA1c. Carotid IMT and stiffness showed significant correlations with age, blood pressure, heart rate and daily insulin intake but a non- significant correlation with blood glucose variability.
  
  PRINCIPAL CONCLUSION:
  Thus, in type 1 diabetes mellitus, measures of glycemic variability are useful in predicting both actual and long-lasting glycemic control. In absence of diabetes-related complications and of any intima-media thickness alterations, the major predictors of arterial distensibility are represented by traditional risk factors beside glycemic 24-h control.
  
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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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• Variant on chromosome 9p is associated with left ventricular mass: results from two cohorts of essential hypertensive individuals.
  J Hypertens

  2012 Nov;30(11):2144-50. doi: 10.1097/HJH.0b013e3283581f7e.
  
  Menni Cristina, Boffi Lucia, Cesana Francesca, Viviani Anselmi Chiara, Nava Stefano, Bertola Francesca, Blasio Anna M Di, Roncarati Roberta, Trimarco Valentina, Marino Marina, Trimarco Bruno, Grassi Guido, Giannattasio Cristina, Mancia Giuseppe
  
  Abstract
  
  OBJECTIVES:
  It is well known that among hypertensive patients, an increased left ventricular mass (LVM) is a powerful predictor of cardiovascular morbidity and mortality. However, the mechanisms underlying LVM in hypertension are not completely understood, as the absolute value of blood pressure and other risk factors associated do not predict alone a definite LVM progression. Recently, the 9p21 chromosomal region has been consistently associated with coronary heart disease.
  
  METHODS AND RESULTS:
  We examined the association of 384 single nucleotide polymorphisms (SNPs) in the short arm of chromosome 9 with LVM in 821 hypertensive individuals from northern Italy. We identified a SNP (rs894379) in the intronic region of the centlein, centrosomal protein (CNTLN) gene on chromosome 9p22, whose minor allele G is associated with an increased LVM. We performed a follow-up validation analysis for the top SNP in 1038 hypertensive individuals from southern Italy. We then combined the results and found a nominal association for rs894379 (? ?= ?2.46, P ?=? 0.0026).
  
  CONCLUSION:
  We describe a new variant associated with echocardiography LVM. This result, though it needs to be further investigated, may improve our understanding of the genetic determination of this prognostically relevant trait.
  
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• Blood pressure control in Italian essential hypertensives treated by general practitioners.
  Am J Hypertens

  2012 Nov;25(11):1182-7. doi: 10.1038/ajh.2012.108.
  
  Giannattasio Cristina, Cairo Matteo, Cesana Francesca, Alloni Marta, Sormani Paola, Colombo Giulia, Grassi Guido, Mancia Giuseppe
  
  Abstract
  
  BACKGROUND:
  Adequate control of blood pressure (BP) is limited worldwide. This has serious consequences for public health because in hypertensive patients, uncontrolled BP is associated with a higher incidence of cardiovascular events, particularly stroke. The aim of this study was to investigate BP control in a cohort of treated patients with diagnosed hypertension, who were under general practitioner care in Italy.
  
  METHODS:
  Data were collected by 2,643 physicians on 8,572 individual Italian patients. Office BP was measured 5 min after seating each patient and then 3-5 min later. For each patient, data such as medical history of patients, physical examination data, antihypertensive drug usage, and self-BP measurement frequency were obtained.
  
  RESULTS:
  Male prevalence was 48.4%, and mean age was 64.3 ± 10.5 years. Based on the second measurement, BP control (<140/90 mm Hg) was observed in 33.5% of all patients (34.2% in men and 33.4% in women). BP control was much lower for systolic BP than for diastolic BP (35.9 vs. 61.3%, P < 0.0001); moreover, BP control was much more common in patients who were engaged in self-BP measurement (61.2 vs. 38.8%, P < 0.0001). A stricter BP control recommended by the guidelines of the European Society of Hypertension (ESH) and European Society of Cardiology (ESC) (<130/80 mm Hg) was observed in only 5.5% of diabetic patients.
  
  CONCLUSIONS:
  In treated Italian hypertensives effective BP control remains uncommon largely due to the failure to appropriately reduce the systolic BP. The stricter values recommended by the ESH/ESC guidelines for diabetic patients are achieved only by a small fraction of hypertensive diabetic population.
  
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• Radiofrequency-based carotid wall tracking: a comparison between two different systems.
  J Hypertens

  2012 Aug;30(8):1614-9. doi: 10.1097/HJH.0b013e328354dd44.
  
  Palombo Carlo, Kozakova Michaela, Guraschi Nicola, Bini Giacomo, Cesana Francesca, Castoldi Giovanna, Stella Andrea, Morizzo Carmela, Giannattasio Cristina
  
  Abstract
  
  OBJECTIVES:
  A direct measurement of carotid stiffness implies an accurate assessment of changes in carotid diameter and pressure during cardiac cycle. Radiofrequency-based wall-tracking systems (WTS) are capable to track arterial wall movement with adequate spatial and temporal resolution, and to provide carotid pressure estimate from calibrated distension waveforms. The aim of the present study was to compare the values of carotid distension and beta-stiffness index acquired in the same population by two commercially available WTS, in order to determine whether their measures can be pooled in clinical studies. In addition, a local carotid pulse pressure (PP) obtained from calibrated distension waveforms was compared with that obtained from pressure waveforms.
  
  METHODS:
  In 105 patients, right common carotid artery (CCA) systo-diastolic excursions were assessed during the same session and by the same operator both by WTS implemented in Esaote system (QAS, MyLab) and in Aloka system (E-track; Alpha 10). In 78 patients, carotid PP was also estimated by applanation tonometry.
  
  RESULTS:
  Despite comparable blood pressure and heart rate values during the two acquisitions, CCA distension was significantly lower (363 ± 162 vs. 458 ± 176 ?m, P < 0.0001) and beta-stiffness index (11.9 ± 5.5 vs. 9.4 ± 3.8, P < 0.0001) higher with Esaote as compared to Aloka. PP obtained from calibrated pressure and distension waveforms was comparable (42.6 ± 11.4 vs. 43.0 ± 10.7 mmHg, P = 0.51).
  
  CONCLUSIONS:
  The values of carotid distension and stiffness obtained by two different WTS are not interchangeable and cannot be merged into a common database. Calibrated distension curves may provide an acceptable estimate of local carotid pressure.
  
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• Tissue Doppler, triplane echocardiography, and speckle tracking echocardiography: different ways of measuring longitudinal myocardial velocity and deformation parameters. A comparative clinical study.
  Echocardiography

  2012 Apr;29(4):428-37. doi: 10.1111/j.1540-8175.2011.01618.x.
  
  Fontana Antonella, Zambon Antonella, Cesana Francesca, Giannattasio Cristina, Trocino Giuseppe
  
  Abstract
  
  AIMS:
  The aim of our study was to compare global and segmental longitudinal myocardial velocity and deformation obtained from three different echocardiographic techniques of postprocessing analysis (two-dimensional tissue Doppler imaging (2D TDI), triplane tissue Doppler imaging (3D TDI), and speckle tracking echocardiography (STE)), in a group of consecutive subjects referred to echocardiography with different clinical indications, and to assess their reproducibility.
  
  METHODS AND RESULTS:
  Standard echocardiograms with high frame rate gray-scale images and color coded TDI apical views, and a single beat TDI triplane apical section of the left ventricle were acquired at two different times. Longitudinal velocity and deformation parameters were obtained in postprocessing in 103 subjects from TDI and STE derived curves, and absolute values were compared to test the variability of the three techniques. All the measures were repeated twice, for a test-retest study. The times to peak velocity and deformation were similar by TDI and STE; other parameters showed significant difference (P < 0.05), both for global and segmental analysis. Reproducibility (expressed by the coefficient of variation and the coefficient of correlation r, in a large part of cases > 0.9) was acceptable, meaning that measures obtained at two different times did not differ significantly in between.
  
  CONCLUSION:
  TDI and speckle tracking are both feasible and reproducible. Myocardial velocity and deformation parameters obtained with them are significantly different. STE is the most reproducible technique, whereas TDI based measurements are lower reproducible. STE can easily be used during clinical follow up for its feasibility and high reproducibility.
  
  © 2012, Wiley Periodicals, Inc.
  
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• Early alterations in left ventricular diastolic function in normotensive diabetic patients.
  Blood Press

  2012 Apr;21(2):110-5. doi: 10.3109/08037051.2012.625670.
  
  Capra Anna, Galderisi Maurizio, Giannattasio Cristina, Innelli Pasquale, Facchetti Rita, Cesana Francesca, Alloni Marta, Carugo Stefano, Grassi Guido, de Divitiis Oreste, Mancia Giuseppe
  
  Abstract
  
  In diabetes mellitus, structural and functional alterations of the heart can be already present at the time of first diagnosis. However, how early these alterations may occur has never been fully clarified. The present study aimed at investigating cardiac functional abnormalities in uncomplicated hypertensive or normotensive patients with a recent diagnosis of diabetes mellitus. We studied 40 diabetics (24 normotensives and 16 hypertensives) by means of routine echocardiography plus pulse tissue Doppler analysis. Data were compared with those obtained in healthy age- and sex-matched controls. Left ventricular remodelling was more evident in hypertensive diabetics than in normotensive diabetics vs controls. Diastolic function was altered in diabetic patients only when detected by pulse tissue Doppler analysis and not by conventional transmitral Doppler evaluation. Normotensive patients with type 2 diabetes with little or no evidence at standard echocardiography of alterations in cardiac structure and function, already displayed an alteration in diastolic function when the evaluation was based on the tissue Doppler approach. Patients with type 2 diabetes combined to hypertension showed more evident functional cardiac alterations at echocardiography. These findings support the conclusion that cardiac abnormalities are very early phenomena in type 2 diabetes.
  
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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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• Impact of body mass index and waist circumference on the long-term risk of diabetes mellitus, hypertension, and cardiac organ damage.
  Hypertension

  2011 Dec;58(6):1029-35. doi: 10.1161/HYPERTENSIONAHA.111.175125.
  
  Bombelli Michele, Facchetti Rita, Sega Roberto, Carugo Stefano, Fodri Danilo, Brambilla Gianmaria, Giannattasio Cristina, Grassi Guido, Mancia Giuseppe
  
  Abstract
  
  Obesity is associated with a higher risk of developing diabetes mellitus (DM), hypertension (HT), and left ventricular hypertrophy (LVH). The present study assessed in the general population the impact of body weight and visceral obesity on the development of alterations in glucose metabolism and cardiac structure, as well as of elevation in blood pressure. In 1412 subjects randomly selected and representative of the general population of Monza, we assessed twice (in 1990/1991 and 2000/2001) body mass index (BMI); waist circumference; office, home, and 24-hour ambulatory (24-hour) blood pressure, fasting glycemia, and left ventricular mass (echocardiography). New-onset high-risk conditions were DM; impaired fasting glucose; office, home, and 24-hour HT; and LVH. The incidence of new-onset DM; impaired fasting glucose; office, home, and 24-hour HT; and LVH increased progressively from the quintile with the lowest to the quintile with the highest BMI values. Adjusting for confounders, the risk of developing new-onset DM; impaired fasting glucose; office, home, and 24-hour HT; and LVH increased significantly for an increase of 1 kg/m(2) of BMI and 1 cm of waist circumference (respectively, 8.4% [P<0.01], 9.5% [P<0.0001], 4.2% [P<0.0001], 3.9% [P<0.001], 2.5% [P<0.05], and 5.1% [P<0.001] for BMI and 3.2% [P<0.001], 3.5% [P<0.0001], 1.8% [P<0.0001], 1.5% [P<0.0001], 1.4% [P<0.001], and 2.6% [P<0.0001]). These data provide evidence that an increase in BMI and waist circumference is associated with a linearly increased adjusted risk of developing conditions with high cardiovascular risk, such as DM, impaired fasting glucose, in- and out-of-office HT, and LVH.
  
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• Prevalence of 'borderline' values of cardiovascular risk factors in the clinical practice of general medicine in Italy: results of the BORDERLINE study.
  High Blood Press Cardiovasc Prev

  2011 Jun;18(2):43-51. doi: 10.2165/11593420-000000000-00000.
  
  Tocci Giuliano, Ferrucci Andrea, Passerini Jasmine, Averna Maurizio, Bellotti Paolo, Bruno Graziella, Cosentino Francesco, Crepaldi Gaetano, Giannattasio Cristina, Modena Maria Grazia, Nati Giulio, Tiengo Antonio, Trimarco Bruno, Vanuzzo Diego, Volpe Massimo
  
  Abstract
  
  INTRODUCTION:
  The prevalence of patients with 'borderline' levels of cardiovascular risk factors has been rarely investigated, being often reported in studies evaluating abnormal values of these parameters. The BORDERLINE study represents a pilot experience to primarily identify the prevalence of 'high-normal' conditions, such as pre-hypertension, lipid and glucose levels in the upper range of normality in the setting of general practice in Italy.
  
  AIM:
  The aim of this study was to evaluate the prevalence of patients with 'borderline' values of cardiovascular risk factors in Italy.
  
  METHODS:
  Involved physicians were asked to evaluate the first 20 outpatients, consecutively seen in June 2009. Data were collected in a study-designed case-report form, in which physicians identified thresholds rather than reported absolute values of several clinical parameters. High-normal values were defined as follows: blood pressure (BP) 130-140/85-90?mmHg; total cholesterol 180-200?mg/dL; low-density lipoprotein cholesterol (LDL-C) 130-150?mg/dL; high-density lipoprotein cholesterol (HDL-C) 30-40?mg/dL in males and 40-50?mg/dL in females; triglycerides 130-150?mg/dL and fasting glucose 100-110?mg/dL.
  
  RESULTS:
  Fifty-three Italian physicians provided valuable clinical data on 826 individual outpatients, among which 692 (83.7%, 377 women, mean age 60.9?±?13.2 years, body mass index 26.6?±?5.0?kg/m2) were included in the present analysis. Prevalence of borderline values of systolic BP and total cholesterol levels were at least comparable with those in the normal limits of the corresponding parameters, whereas prevalence of borderline diastolic BP, LDL-C, HDL-C, triglycerides and fasting glucose levels was significantly lower than that of normal values, but higher than that of abnormal values of the corresponding parameters.
  
  CONCLUSIONS:
  Using this sample of healthy subjects in the setting of general practice in Italy, our results demonstrated a relatively high prevalence of borderline values of cardiovascular risk factors, which was at least comparable with that of normal, but significantly higher than that of abnormal thresholds. These preliminary findings may prompt more extensive investigations in the area of 'borderline' cardiovascular risk. This information may, in fact, potentially enable the design of more effective prevention strategies in the future to limit the burden of cardiovascular disease in the general population in Italy. Received for publication 4 March 2011; accepted for publication 20 April 2011.
  
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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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• Association between ADRA1A gene and the metabolic syndrome: candidate genes and functional counterpart in the PAMELA population.
  J Hypertens

  2011 Jun;29(6):1121-7. doi: 10.1097/HJH.0b013e328346d72c.
  
  Grassi Guido, Padmanabhan Sandosh, Menni Cristina, Seravalle Gino, Lee Wai K, Bombelli Michele, Brambilla Gianmaria, Quarti-Trevano Fosca, Giannattasio Cristina, Cesana Giancarlo, Dominiczak Anna, Mancia Giuseppe
  
  Abstract
  
  OBJECTIVES:
  There is currently uncertainty about whether metabolic syndrome has a common underlying process. We performed a gene-centric association study of metabolic syndrome in 98 major cardiometabolic genes in the large, well phenotyped Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) study. We followed this with functional studies to elucidate a possible mechanism for the top association signal.
  
  METHODS:
  From the PAMELA cohort, we sampled 1407 individuals with information on the metabolic syndrome (ATPIII criteria). We analyzed 1324 tagging single-nucleotide polymorphisms (SNPs) in 98 candidate genes selected, based on known pathways involved in sympathetic nervous system, oxidative stress, renin-angiotensin system and sodium balance.
  
  RESULTS:
  The SNP rs17055869 near the alpha-1A-adrenoreceptor gene (ADRA1A) showed the strongest association with metabolic syndrome (odds ratio 1.7, CI 1.3-2.2; P = 0.00007, P = 0.000098 after permutation). In order to determine a functional basis for this association, we examined in a subgroup of metabolic syndrome patients whether the allelic distribution of the above-mentioned gene is different according to the different degree of the metabolic syndrome-related sympathetic activation, directly assessed by the gold standard method to assess neuroadrenergic drive, that is microneurographic recording of efferent postganglionic muscle sympathetic nerve traffic. All metabolic syndrome patients with a lesser degree of sympathetic activation were homozygous for the major allele (C), whereas those with a very pronounced sympathetic overdrive had an over-representation of the minor T allele (P < 0.0001).
  
  CONCLUSION:
  Thus, the rs17055869 SNP near the 3' end of ADRA1A is significantly associated with metabolic syndrome and it may be involved in determining a greater level of sympathetic activation in metabolic syndrome patients.
  
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• Endothelium in polycythemia secondary to obstructive lung disease.
  J Appl Physiol (1985)

  2011 May;110(5):1158-9. doi: 10.1152/japplphysiol.00202.2011.
  
  Mancia Giuseppe, Giannattasio Cristina
  
  
  
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• Ultrasonographic backscatter of the carotid artery wall in patients with HIV infection: a pilot study.
  Blood Press

  2010 Dec;19(6):344-50. doi: 10.3109/08037051.2010.506997.
  
  Giannattasio Cristina, Failla Monica, Squillace Nicola, Dolara Alberto, Cesana Francesca, Sabbatini Francesca, Bandera Alessandra, Facchetti Rita, Dozio Dario, Gori Andrea, Mancia Giuseppe
  
  Abstract
  
  AIMS:
  The aim of our study was to measure carotid intima-media thickness (cIMT) and risk factors associated with its development and progression, and to evaluate arterial wall characteristics through integrated backscatter analysis (IBS) in HIV patients.
  
  METHODS:
  Perspective cohort study enrolling 44 HIV patients treated with antiretroviral drugs who underwent standard B Mode cIMT measurement and tissue characterization of carotid wall by means of dedicated software by acoustic densitometry, at time 0 and 2 years later.
  
  MAJOR FINDINGS:
  Cross-sectional evaluation performed at baseline found that cIMT value correlated significantly with age (r = 0.42, p = 0.005) and systolic blood pressure (r = 0.31, p = 0.04). No correlation was found between cIMT and CD4, HIV-RNA, triglycerides or total cholesterol. There was no difference between the group with versus the group with no protease inhibitors treatment. cIMT progression during 2 years of observation was statistically significant (median, interquartile range [IQR]: 0.005, 0-0.031). No correlation was found between IBS and duration of disease and kind of therapy, whereas a significant association was found between cIMT and IBS (r = 0.33, p = 0.03). No noticeable changes of IBS were observed during 2 years observation.
  
  CONCLUSIONS:
  Classic risk factors greatly affect cIMT than time of HIV infection, duration of antiretroviral therapy exposure and use of protease inhibitors. IBS is a promising technique for the evaluation of arterial wall composition in HIV patients.
  
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• Low anthracyclines doses-induced cardiotoxicity in acute lymphoblastic leukemia long-term female survivors.
  Pediatr Blood Cancer

  2010 Dec;55(7):1343-7. doi: 10.1002/pbc.22637.
  
  Amigoni Maria, Giannattasio Cristina, Fraschini Donatella, Galbiati Marianna, Capra Anna Clara Maria, Madotto Fabiana, Cesana Francesca, Jankovic Momcilo, Masera Giuseppe, Mancia Giuseppe
  
  Abstract
  
  BACKGROUND:
  High dosage anthracyclines in pediatric patients with acute lymphoblastic leukemia (ALL) is associated with cardiotoxicity. However, data on the cardiac effects of lower cumulative doses of these drugs are not conclusive. The aim of this study was to assess the cardiac effects of low cumulative anthracycline doses in long-term survivors of ALL.
  
  PROCEDURE:
  Echocardiograms were performed on 62 long-term ALL survivors, without any overt or sub-clinical signs or symptoms of heart failure. The interval after stopping therapy was 12.6 ± 4.3 years; the mean cumulative dose of anthracyclines was 228.2 ± 42.3 mg/m(2) . Left ventricular (LV) structure and function were studied by echocolor-Doppler. An age, gender and body surface area (BSA) matched group of healthy subjects was used as controls. Cardiac data were analyzed before and after BSA normalization.
  
  RESULTS:
  Long term survivors of ALL, showed a lower LV mass index, interventricular septal and posterior wall thickness, which were independently related to gender and to age at which the ALL diagnosis was made. Data analyzed according to gender showed that abnormalities were confined to the female group. No alterations were observed in the ALL male group versus the corresponding control group. No relationship was observed between the echocardiografic abnormalities and the duration of follow-up or the anthracycline mean dose employed.
  
  CONCLUSIONS:
  In the absence of any signs or symptoms of heart failure, female ALL survivors treated with low cumulative anthracycline doses, showed a reduced LV mass and wall thickness. This suggests that in female ALL survivors an echocardyographic follow-up should be recommended.
  
  Copyright © 2010 Wiley-Liss, Inc.
  
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• Energy-based hemostatic devices in laparoscopic adrenalectomy.
  Langenbecks Arch Surg

  2010 Feb;395(2):111-4. doi: 10.1007/s00423-009-0563-z.
  
  Sartori Paola Vincenza, Romano Fabrizio, Uggeri Fabio, Colombo Giovanni, Caprotti Roberto, Giannattasio Cristina, Scotti Mauro Alessandro, Delitala Alberto, Prada Massimo, Uggeri Franco
  
  Abstract
  
  PURPOSE:
  In literature, few papers compare different hemostatic devices in laparoscopic adrenalectomy. This sequential cohort study analyzes the outcomes of laparoscopic adrenalectomy performed by different hemostatic instruments, to evaluate if any of them has any advantage over the other and as secondary endpoints, the impact of body mass index (BMI) and tumor size on the indication, and the outcome of laparoscopic adrenalectomy.
  
  METHODS:
  Forty-six patients, aged 54.6 +/- 46 years, underwent laparoscopic adrenalectomy over 5 years. Mean BMI was 27 +/- 4.8 kg/m(2). Twenty-four patients had a left tumor, and 22 had a right one. Patients were divided into two groups according to the hemostatic device: Ultracision was used in 26 patients, and Ligasure was used in 20. Groups were well matched for histology, tumor size and site, BMI, gender, and age.
  
  RESULTS:
  Mean operating time was 126.5 +/- 52 min, blood losses were 101 +/- 169 mm, conversion rate was 6.5%, morbidity was 26%, and hospitalization was 5.3 +/- 2.5 days. Groups did not differ for surgical time, blood losses, complications, and conversion rate; BMI and length of surgery were not related. Tumor side and size did not affect surgical time, regardless of the hemostatic tool. Patients submitted to left adrenalectomy bled more (p = 0.007) and had more complications (p = 0.016) than those undergone operation on the right side.
  
  CONCLUSIONS:
  Obesity (BMI > 30) and large masses do not contraindicate laparoscopic adrenalectomy. Left adrenalectomies bleed more and have a higher morbidity. Hemostatic device choice is up to surgeon's preference.
  
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• Left ventricular hypertrophy increases cardiovascular risk independently of in-office and out-of-office blood pressure values.
  J Hypertens

  2009 Dec;27(12):2458-64. doi: 10.1097/HJH.0b013e328330b845.
  
  Bombelli Michele, Facchetti Rita, Carugo Stefano, Madotto Fabiana, Arenare Francesca, Quarti-Trevano Fosca, Capra Anna, Giannattasio Cristina, Dell'Oro Raffaella, Grassi Guido, Sega Roberto, Mancia Giuseppe
  
  Abstract
  
  OBJECTIVES:
  Previous studies have shown that left ventricular hypertrophy (LVH) represents a cardiovascular risk factor independently of clinic blood pressure (BP). The present study was aimed at determining the impact of LVH on the incidence of cardiovascular morbid and fatal events taking into account not only classical risk factors but also home and ambulatory BP values, which have been shown to have an important independent prognostic impact.
  
  METHODS:
  In 1716 patients belonging to the 'Pressioni Arteriose Monitorate E Loro Associazioni' population of Monza, we quantified left ventricular mass index and identified LVH by standard cutoff values. We also measured clinic, home and 24-h ambulatory BPs together with serum glucose and lipids.
  
  RESULTS:
  During a follow-up of 148 months, the rate of fatal and nonfatal (hospitalizations) cardiovascular events as well as of all-cause death was markedly greater (four-fold to five-fold) in patients as compared with those without LVH. In LVH individuals, the increased risk remained significant even when data were adjusted for a large number of other confounding factors including home BP, 24-h mean BP and ambulatory BP. Results were similar when left ventricular mass was indexed by height and body surface area. A 10% increase in left ventricular mass index was associated with a significant increase in cardiovascular risk or all-cause deaths. In multivariate analysis, left ventricular mass index was always an independent predictor of cardiovascular events and death for any cause.
  
  CONCLUSION:
  Our data provide evidence that LVH is an important risk factor even when the contribution of different BPs to risk is fully taken into account.
  
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• Simultaneous measurement of beat-to-beat carotid diameter and pressure changes to assess arterial mechanical properties.
  Hypertension

  2008 Nov;52(5):896-902. doi: 10.1161/HYPERTENSIONAHA.108.116509.
  
  Giannattasio Cristina, Salvi Paolo, Valbusa Filippo, Kearney-Schwartz Anna, Capra Anna, Amigoni Maria, Failla Monica, Boffi Lucia, Madotto Fabiana, Benetos Athanasios, Mancia Giuseppe
  
  Abstract
  
  Use of local arterial distensibility measurements by change in carotid artery diameter divided by pulse pressure has limitations because blood pressure is often taken in a vessel distant or at a time different from where and when change in diameter is taken. In 92 subjects (23 to 91 years of age), carotid artery diameter was continuously measured ecographically, whereas blood pressure was continuously measured simultaneously tonometrically on the contralateral artery, the 2 signals being synchronized via 2 EKGs. Within each cardiac cycle, there was a linear relationship between the changes in vessel diameter and the changes in blood pressure during either the protomesosystole or the diastole after the dicrotic notch. The diastolic slope was displaced upward and steeper than the systolic slope, the pressure-diameter loop showing a hysteresis. Both slopes showed a high reproducibility when data were averaged over a several-second period. There were small differences between consecutive cardiac cycles, suggesting that modulation of arterial mechanical response to continuous changes in intravascular pressure may undergo physiological variations. In the 92 subjects, systolic and diastolic slopes correlated significantly with distensibility values obtained by Reneman formula and exhibited a close inverse relationship with each subject's age and systolic blood pressure, thereby showing the ability to reflect age- and pressure-dependent large artery stiffening. This method may allow precise assessment of man's arterial mechanical properties within each cardiac cycle. This highly dynamic assessment may help to collect information on properties of normal and altered large elastic arteries and the mechanisms involved in disease.
  
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• Long-term risk of diabetes, hypertension and left ventricular hypertrophy associated with the metabolic syndrome in a general population.
  J Hypertens

  2008 Aug;26(8):1602-11. doi: 10.1097/HJH.0b013e328302f10d.
  
  Mancia Giuseppe, Bombelli Michele, Facchetti Rita, Madotto Fabiana, Corrao Giovanni, Trevano Fosca Quarti, Giannattasio Cristina, Grassi Guido, Sega Roberto
  
  Abstract
  
  OBJECTIVES:
  Metabolic syndrome is accompanied by an increased risk of developing diabetes mellitus. Limited or no evidence exists on whether and to what extent metabolic syndrome increases the risk of developing office hypertension, daily-life hypertension and left ventricular hypertrophy.
  
  METHODS:
  In 1412 individuals representative of the population of Monza, plasma glucose, office, home and ambulatory blood pressure, and echocardiographic left ventricular mass index were measured between 1990 and 1992 and 10 years later. New onset diabetes mellitus, new onset office, home and ambulatory hypertension as well as new onset left ventricular hypertrophy were assessed in individuals with and without metabolic syndrome (Adult Treatment Panel criteria) at the first examination.
  
  RESULTS:
  New onset diabetes mellitus, hypertension and left ventricular hypertrophy were all much more frequent in individuals with metabolic syndrome than in those without. In patients with metabolic syndrome, the adjusted risk of new onset diabetes mellitus was five to six times greater (P < 0.001), that of new onset office, home or ambulatory hypertension 3.5, 2.9 and 3.2 times greater (P < 0.001), respectively, and that of new onset left ventricular hypertrophy 2.6 times greater (P < 0.001). The most important predictors of new onset diabetes mellitus, hypertension and left ventricular hypertrophy were the baseline blood glucose, blood pressure and left ventricular mass index, respectively, with an independent contribution, in each condition, from other metabolic syndrome components. The metabolic syndrome as such did not have an additional predictive value.
  
  CONCLUSION:
  In the general population, metabolic syndrome is associated with a marked increase in the risk not only of new onset diabetes mellitus but also of new onset office and daily-life hypertension, and left ventricular hypertrophy. This may account for the increased rate of cardiovascular morbidity and mortality exhibited with this condition in long-term studies.
  
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• Increased arterial stiffness in normoglycemic normotensive offspring of type 2 diabetic parents.
  Hypertension

  2008 Feb;51(2):182-7. doi: 10.1161/HYPERTENSIONAHA.107.097535.
  
  Giannattasio Cristina, Failla Monica, Capra Anna, Scanziani Elisabetta, Amigoni Maria, Boffi Lucia, Whistock Christine, Gamba Pierluigi, Paleari Felice, Mancia Giuseppe
  
  Abstract
  
  Diabetes is associated with a reduction of arterial distensibility. Limited information exists regarding whether or how early this appears in the course of the disease. We studied 54 normoglycemic, normotensive, healthy offspring of 2 parents with type 2 diabetes mellitus and 55 age- and sex-matched healthy control subjects. Carotid diastolic diameter and systodiastolic change were measured by echo tracking (Wall Track System) and wall thickness by echocolor Doppler (Sonos 5500, Philips). Pulse pressure was measured by a semiautomatic device positioned on the brachial artery and arterial distensibility calculated by Reneman formula. Blood pressure, blood glucose, glycohemoglobin, and insulin sensitivity (homeostasis model assessment index) were normal or only slightly elevated and by and large similar in the 2 groups. Compared with control subjects, offspring of diabetic parents showed similar carotid diameters at diastole and a reduced increase in carotid diameter at systole (-16%), a reduced carotid artery distensibility (-30%), and an increased pulse pressure (+21.8%), all differences being statistically significant (P<0.05) and persisting in subgroups with elevated or normal body mass index values (<25 and >or=25 kg/m(2)). Carotid artery wall thickness was not different between the 2 groups. Thus, subjects with predisposition to diabetes show carotid artery stiffening even in the absence of blood pressure alterations, as well as substantial alterations of glucose metabolism, body mass index, and changes in carotid wall thickness. This suggests that, in diabetes, alterations in arterial mechanical properties represent an early phenomenon, which may occur in the absence of metabolic and blood pressure alterations.
  
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• HIV and metabolic syndrome: a comparison with the general population.
  J Acquir Immune Defic Syndr

  2007 Aug;45(4):426-31.
  
  Bonfanti Paolo, Giannattasio Cristina, Ricci Elena, Facchetti Rita, Rosella Elena, Franzetti Marzia, Cordier Laura, Pusterla Luigi, Bombelli Michele, Sega Roberto, Quirino Tiziana, Mancia Giuseppe
  
  Abstract
  
  OBJECTIVE:
  To compare the prevalence of metabolic syndrome (MS) in HIV-positive patients with that from a sample of a general Italian population.
  
  DESIGN:
  Cross-sectional study.
  
  METHODS:
  A total of 1263 HIV-infected patients 18 years of age or older were recruited in 18 centers for infectious diseases in northern and central Italy. Controls were 2051 subjects aged 25 to 74 years representative of the residents of Monza, a town in Milan province, who were enrolled in the Pressioni Arteriose Monitorate E Loro Associazioni study.
  
  RESULTS:
  The prevalence of MS in the HIV group was 20.8%, whereas in the control group, it was only 15.8%, with the difference being statistically significant. The age- and gender-adjusted risk of having MS in HIV-infected patients was twice as great as that in controls. Compared with controls, HIV-infected patients had a greater prevalence of the impaired fasting glucose, increased plasma triglycerides, and reduced high-density lipoprotein cholesterol components. MS prevalence was similar in treated and never-treated HIV-infected patients, and so were the various MS components.
  
  CONCLUSIONS:
  The risk of MS is greater in HIV-infected patients compared with the general population because of a greater prevalence of lipid and glucose abnormalities. The prevalence of MS and its components is similar in treated and untreated HIV-positive patients.
  
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• Effects of prostaglandin E1alpha cyclodextrin [corrected] treatment on endothelial dysfunction in patients with systemic sclerosis.
  J Hypertens

  2007 Apr;25(4):793-7.
  
  Giannattasio Cristina, Pozzi MariaRosa, Gardinali Marco, Gradinali Marco, Montemerlo Elisabetta, Citterio Francesca, Maestroni Silvia, Fantini Elena, Failla Monica, Robuschi Maria, Bianco Salvatore, Mancia Giuseppe
  
  Abstract
  
  OBJECTIVE:
  Systemic sclerosis (SSc) is characterized by an altered nitric oxide (NO): endothelin I ratio and by endothelial dysfunction.
  
  AIMS:
  To verify the effects of prostaglandin E1 (PGE1) alpha-cyclodestrin treatment on endothelial function, quantified as flow-mediated dilation (FMD) of the radial artery.
  
  METHODS:
  In 16 women with SSc (age 57 +/- 2.7 years, means +/- SE) in whom a diagnosis of SSc had been made several years earlier (7.1 +/- 1.2 years), FMD was evaluated by an echotracking technique on the radial artery, using trinitroglycerin vasodilation as a non-endothelial measure of the vessel's ability to increase its diameter maximally. FMD was evaluated after 4 months washout period and after 4 months cyclic infusion of PGE1 alpha-cyclodestrin. Expired NO was measured at the same time.
  
  RESULTS:
  PGE1 alpha-cyclodestrin cyclic infusions did not modify systolic and diastolic blood pressure, heart rate or trinitroglycerin radial artery vasodilation. On the other hand, it induced a marked and significant increase in FMD of the radial artery, which was also accompanied by an increase in blood flow and expired NO.
  
  CONCLUSIONS:
  Endothelial dysfunction and reduced FMD associated with SSc are improved by cyclic treatment with PGE1 alpha-cyclodestrin. This effect occurs together with a concomitant increase in expired NO, suggesting its direct positive influence on endothelial function. It may also partly explain the clinical beneficial effect of the drug in SSc.
  
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• Relationship between arterial distensibility and coronary atherosclerosis in angina patients.
  J Hypertens

  2007 Mar;25(3):593-8.
  
  Giannattasio Cristina, Capra Anna, Facchetti Rita, Viscardi Luigina, Bianchi Francesca, Failla Monica, Colombo Virgilio, Grieco Antonio, Mancia Giuseppe
  
  Abstract
  
  OBJECTIVE:
  Arterial stiffening is associated with an increased risk of cardiovascular disease. However, limited evidence exists on whether it also relates to subclinical atherosclerosis, thereby providing a non-invasive marker of the overall cardiovascular status. The aim of the present study was to provide information on arterial stiffening in angina patients in whom angiographic evaluation allowed quantification of coronary atherosclerosis.
  
  METHODS:
  We studied 101 patients with angina from a large number admitted to our hospital for coronary angiography. In each patient, radial (RA), subdiaphragmatic aorta (AO) and carotid (CA) distensibility (Dist) were measured by an ultrasonic device, following ultrasonic exclusion of atherosclerotic lesions at these specific sites. Patients were classified into three groups according to the angiographic findings: (i) no significant coronary lesions (lumen obstruction < 50%, group A); (ii) one (group B); and (iii) two or three (group C) coronary vessels with hemodynamic significant plaques (lumen obstruction > 50%).
  
  RESULTS:
  Age, male prevalence, previous cardiovascular disease and interventions were progressively greater or more common from group A to C, whereas several other risk factors (plasma glucose, serum cholesterol, smoking, history of hypertension, etc.) did not differ between the three groups or between the group with single vessel (B) versus the group with multivessel disease (C). CA and AO Dist decreased progressively from group A to C with a significant relationship in the group as a whole between distensibility values and the number of diseased vessels. The progressive decrease in AO Dist from group A to C remained significant after adjustment for variables that showed between-group differences (such as gender, age and systolic blood pressure) and the ROC curve showed it to be a more sensitive and specific marker of coronary atherosclerosis than CA Dist. RA Dist was similar in the three groups and showed no relationship with the number of diseased vessels in the group as a whole.
  
  CONCLUSION:
  In patients with angina, AO and CA Dist are related to the severity of coronary atherosclerosis, with the relationship being better for alterations in aortic than in carotid mechanical properties. Large elastic artery (and in particular aortic) stiffening can thus be considered as a marker of the severity of coronary atherosclerosis, providing non-invasive obtainable information on the need to proceed with further clinical examinations.
  
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• Metabolic syndrome in the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study: daily life blood pressure, cardiac damage, and prognosis.
  Hypertension

  2007 Jan;49(1):40-7.
  
  Mancia Giuseppe, Bombelli Michele, Corrao Giovanni, Facchetti Rita, Madotto Fabiana, Giannattasio Cristina, Trevano Fosca Quarti, Grassi Guido, Zanchetti Alberto, Sega Roberto
  
  Abstract
  
  The prevalence of the metabolic syndrome (National Cholesterol Education Program Adult Treatment Panel III criteria) and its relationships with daily life blood pressures, cardiac damage, and prognosis were determined in 2013 subjects from a Northern Italian population aged 25 to 74 years. Home blood pressure, 24-hour blood pressure, and left ventricular mass index (echocardiography) were also measured. Cardiovascular and noncardiovascular deaths were registered over 148 months. Metabolic syndrome was found in 16.2% of the sample, an office blood pressure elevation being the most frequent (95.4%) and the blood glucose abnormality the least frequent (31.5%) component. There was in metabolic syndrome a frequent elevation in home and/or 24-hour average blood pressure, as well as a greater left ventricular mass index and prevalence of left ventricular hypertrophy, which was manifest even when data were adjusted for between-group differences, including blood pressure. The adjusted risk of cardiovascular and all-cause mortality was greater in metabolic syndrome subjects (+71.0% and +37.0%; P<0.05), a further marked increase being observed with left ventricular hypertrophy or "in-office" and "out-of-office" blood pressure elevations. The increased risk was related to the blood pressure and the blood glucose component of metabolic syndrome, with no contribution of the remaining components. Thus, metabolic syndrome is common in a Mediterranean population in which it significantly increases the long-term risk of death. Cardiac abnormalities and increases in home and 24-hour blood pressure are common in metabolic syndrome, and their occurrence further enhances the risk. The contribution of metabolic syndrome components to the risk, however, is unbalanced and mainly related to blood pressure and glucose abnormalities.
  
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• Aortic stiffness as a predictor of coronary atherosclerosis.
  J Hypertens

  2006 Dec;24(12):2347-8.
  
  Giannattasio Cristina
  
  
  
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• Expert consensus document on arterial stiffness: methodological issues and clinical applications.
  Eur Heart J

  2006 Nov;27(21):2588-605.
  
  Laurent Stephane, Cockcroft John, Van Bortel Luc, Boutouyrie Pierre, Giannattasio Cristina, Hayoz Daniel, Pannier Bruno, Vlachopoulos Charalambos, Wilkinson Ian, Struijker-Boudier Harry,
  
  Abstract
  
  In recent years, great emphasis has been placed on the role of arterial stiffness in the development of cardiovascular diseases. Indeed, the assessment of arterial stiffness is increasingly used in the clinical assessment of patients. Although several papers have previously addressed the methodological issues concerning the various indices of arterial stiffness currently available, and their clinical applications, clinicians and researchers still report difficulties in selecting the most appropriate methodology for their specific use. This paper summarizes the proceedings of several meetings of the European Network for Non-invasive Investigation of Large Arteries and is aimed at providing an updated and practical overview of the most relevant methodological aspects and clinical applications in this area.
  
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• Obesity and vascular stiffness: when body fat has an adverse impact on arterial dynamics.
  J Hypertens

  2005 Oct;23(10):1789-91.
  
  Grassi Guido, Giannattasio Cristina
  
  
  
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• Relationship of office, home, and ambulatory blood pressure to blood glucose and lipid variables in the PAMELA population.
  Hypertension

  2005 Jun;45(6):1072-7.
  
  Mancia Giuseppe, Facchetti Rita, Bombelli Michele, Polo Friz Hernan, Grassi Guido, Giannattasio Cristina, Sega Roberto
  
  Abstract
  
  Alterations in blood glucose and cholesterol are more frequently detectable in hypertensive than in normotensive conditions. However, no information exists as to whether this phenomenon involves only office or also home and 24-hour ambulatory blood pressure (ie, when values are representative of daily life). In 2045 subjects enrolled in the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study, we measured home, 24-hour, and office blood pressure. Measurements also included fasting blood glucose and serum total and HDL cholesterol values. Prevalence of diabetes (> or =126 mg/dL or use of antidiabetic drugs), impaired fasting blood glucose (> or =110 to <126 mg/dL), and hypercholesterolemia (serum total cholesterol > or =240 mg/dL or 200 mg/dL) increased progressively from "optimal" to "normal," "high-normal," and "elevated" office systolic or diastolic blood pressure. Fasting blood glucose and total serum cholesterol also increased progressively from the first to the fourth group, with HDL cholesterol values showing a concomitant progressive decrease. This was also the case for quartiles of office, home, and 24-hour blood pressure. In the whole population, there was a positive correlation between serum cholesterol or blood glucose and all blood pressure values (P always <0.0001), with a much smaller and less consistent relationship with heart rate. In a multivariate analysis that included gender, body mass index, age, and antihypertensive treatment, all blood pressure values remained highly significantly related to values of either metabolic variables. Thus, in the PAMELA population, glucose and lipid values are independently related to blood pressure. This is also the case when daily life blood pressure values are considered.
  
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• Different relation between 24-h blood pressure and distensibility at different peripheral arteries. Data from the European Lacidipine Study on Atherosclerosis (ELSA).
  J Hypertens

  2005 Mar;23(3):557-62.
  
  Giannattasio Cristina, Failla Monica, Hennig Michael, Hollweck Regina, Laurent Stephan, Mallion Jean Michel, Reid John, Safar Michel, Bond Gene, Zanchetti Alberto, Mancia Giuseppe
  
  Abstract
  
  INTRODUCTION:
  The European Lacidipine Study on Atherosclerosis (ELSA) has been planned to investigate the effect of reduction in office and ambulatory blood pressure by lacidipine versus atenolol on carotid artery wall thickness in mild to moderate essential hypertensive patients with no metabolic abnormalities. One prespecified sub-study of ELSA focused on measurements of arterial distensibility in the carotid as well as in the radial artery to determine the relationship of functional arterial properties with office versus ambulatory blood pressure (BP) values as well as the correspondence between functional and structural arterial alterations.
  
  METHODS:
  The sub-study was conducted on 124 patients recruited in four centres (Monza-Milan, Paris, Grenoble and Glasgow). BP was measured both by a mercury sphygmomanometer and by 24-h ambulatory monitoring. Common carotid artery wall thickness was measured by certified sonographers as described in the main study. Common carotid and radial artery distensibility were obtained by echotracking techniques, which allowed to relate changes in arterial diameter with systo-diastolic BP changes.
  
  RESULTS:
  Carotid artery wall distensibility showed (1) a negative correlation with office and more so 24-h average systolic BP (r = -0.45 and -0.58, P < 0.008 and 0.001) but not with office or 24-h diastolic BP) and (2) a negative correlation with the corresponding wall thickness (r = -0.47, P < 0.005). In contrast, at the radial artery level distensibility and thickness showed no correlation with each other and with BP. Carotid (but not radial) artery distensibility also correlated with ambulatory systolic BP variability but the correlation was lost after adjustment for age and mean BP values.
  
  CONCLUSION:
  These data suggest that stiffening of large elastic artery is reflected more by ambulatory than office BP elevations, systolic BP being much more important than diastolic. Alterations of large elastic arteries function is related to structural wall changes. Functional and structural properties of middle-size muscle arteries are independent of BP.
  
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• Arterial stiffening influence of sympathetic nerve activity: evidence from hand transplantation in humans.
  Hypertension

  2005 Apr;45(4):608-11.
  
  Giannattasio Cristina, Failla Monica, Lucchina Stefano, Zazzeron Chiara, Scotti Valentina, Capra Anna, Viscardi Luigina, Bianchi Francesca, Vitale Giovanni, Lanzetta Marco, Mancia Giuseppe
  
  Abstract
  
  Studies in animals and humans suggest that sympathetic activity exerts a stiffening influence on large and middle-sized artery walls. We sought to obtain further evidence on this issue by measuring radial artery distensibility in an allotransplanted and thus denervated hand using the contralateral artery as control. In 2 men, blood pressure was measured by a semiautomatic device (Dinamap). Diastolic diameter, systo-diastolic diameter excursion (ultrasound Wall Track system), and distensibility (Reneman formula) of both radial arteries were measured at a level corresponding to 4 cm below the suture of the transplanted hand 40 days after surgery and every 4 weeks for the next 6 months. After surgery, systo-diastolic diameter excursion and distensibility were much greater in the transplanted radial artery than in the contralateral vessel, reaching values similar to the contralateral ones after 4 months, when signs of reinnervation of the transplanted hands had appeared. Radial deinnervation was accompanied by an increased arterial distensibility, which provides further evidence of the sympathetic stiffening effect on arterial wall in humans.
  
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• Endothelial function and dysfunction. Part I: Methodological issues for assessment in the different vascular beds: a statement by the Working Group on Endothelin and Endothelial Factors of the European Society of Hypertension.
  J Hypertens

  2005 Jan;23(1):7-17.
  
  Deanfield John, Donald Ann, Ferri Claudio, Giannattasio Cristina, Halcox Julian, Halligan Sean, Lerman Amir, Mancia Giuseppe, Oliver James J, Pessina Achille C, Rizzoni Damiano, Rossi Gian Paolo, Salvetti Antonio, Schiffrin Ernesto L, Taddei Stefano, Webb David J,
  
  Abstract
  
  An enormous number of studies in the last two decades have been devoted to investigating the role of the endothelium in cardiovascular diseases. Nonetheless, the optimal methodology for investigating the multifaceted aspects of endothelial dysfunction is still under debate. Biochemical markers, molecular genetic tests and invasive and non-invasive tools with and without pharmacological and physiological stimuli have been introduced. Furthermore newer pharmacological tools have been proposed. However, the application of these methodologies should fulfil a number of requirements in order to provide conclusive answers in this area of research. Thus, the most relevant methodological issues in the research on endothelial function and dysfunction are summarized in this paper.
  
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• Arterial stiffness.
  Curr Hypertens Rep

  2004 Oct;6(5):331-2.
  
  Giannattasio Cristina
  
  
  
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• Cardiovascular risk profile and blood pressure control in Italian hypertensive patients under specialist care.
  J Hypertens

  2004 Jan;22(1):51-7.
  
  Mancia Giuseppe, Volpe Roberto, Boros Stefano, Ilardi Maura, Giannattasio Cristina
  
  Abstract
  
  BACKGROUND:
  Information on the association between high hypertension and metabolic risk factors in Italy is limited. Furthermore, data on the rate of blood pressure control in the Italian hypertensive population are restricted to some Italian regions only, and refer usually to surveys performed, in most instances, several years ago.
  
  METHODS:
  In the present study, a total of 4059 essential hypertensive patients were examined consecutively from March to June 2000 by 450 cardiovascular specialists (cardiologists, internists and diabetologists) operating throughout the Italian territory. Analysable data were obtained in 3812 patients.
  
  RESULTS:
  Blood pressure control by treatment (< 140/90 mmHg) was infrequent (11.9%), this being particularly the case for systolic as compared to diastolic blood pressure (15.1 versus 33.7%). Hypertension was the only risk factor in only 13.7% of the patients, the association with diabetes, hypercholesterolaemia or obesity characterizing the remaining cases. About 60% of the patients fell into the high or very high cardiovascular risk category of the World Health Organization/International Society of Hypertension (WHO/ISH) Guidelines. Compared to low or moderate cardiovascular risk, multiple antihypertensive drug treatment was more frequently used in individuals at high or very high risk. These conditions were frequently underdiagnosed by physicians.
  
  CONCLUSIONS:
  Thus, in Italy, hypertension continues to be a poorly controlled condition. Despite being a Mediterranean country, the occurrence of hypertension is commonly associated with metabolic risk factors and often with a high or very high cardiovascular risk profile. This is not properly identified by specialist physicians.
  
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• Nonpharmacologic treatment of hypertension by respiratory exercise in the home setting.
  Am J Hypertens

  2004 Apr;17(4):370-4.
  
  Meles Ester, Giannattasio Cristina, Failla Monica, Gentile Gaetano, Capra Anna, Mancia Giuseppe
  
  Abstract
  
  BACKGROUND:
  Device-guided breathing exercises at home have a potential to become a nonpharmacologic treatment of high blood pressure (BP). The aim of this study was to evaluate the impact of device-guided breathing exercises on both office and home BP.
  
  METHODS:
  A total of 79 mild hypertensive individuals, either medicated or unmedicated, with BP > 140/90 mm Hg were enrolled. After a 2-week run-in phase, in both the control and treatment groups daily home blood pressure was monitored for 8 weeks. The treatment group also engaged in 15-min daily sessions with device-guided breathing exercises.
  
  RESULTS:
  A total of 47 treatment patients and 26 control subjects completed the study. In the control group both office and home BP showed small nonsignificant reductions. Device-guided breathing exercises reduced mean office BP (systolic/diastolic) by 5.5/3.6 mm Hg (P < .05 for diastolic) and mean home BP by 5.4/3.2 mm Hg (P < .001 for both). Home BP response reached a plateau after 3 weeks.
  
  CONCLUSION:
  Our data show that device-guided breathing exercises have an antihypertensive effect that can be seen in conditions closer to daily life than the setting of the physician's office.
  
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• Effects of heart rate changes on arterial distensibility in humans.
  Hypertension

  2003 Sep;42(3):253-6.
  
  Giannattasio Cristina, Vincenti Antonio, Failla Monica, Capra Anna, Cirò Antonio, De Ceglia Sergio, Gentile Gaetano, Brambilla Roberta, Mancia Giuseppe
  
  Abstract
  
  In rats, an increase in heart rate by pacing is accompanied by progressive large-artery stiffening. Whether this is also the case in humans is unknown. We enrolled 20 patients who were chronically implanted with a pacemaker because of atrioventricular block or sick sinus syndrome. Arterial distensibility was measured by an echo-tracking device. In 10 patients, the evaluation was performed on the radial artery by using continuous finger blood pressure measurements, whereas in the remaining 10 patients, the common carotid artery was studied with a semiautomatic measure of brachial artery blood pressure. Diastolic diameter, systodiastolic diameter change, and distensibility were obtained at baseline (heart rate 63+/-2 beats/min) and after atrial and ventricular sequential pacing at a heart rate of 90 and 110 beats/min. At baseline, the diameter was 7.8+/-0.3 mm in the carotid artery and 2.4+/-0.1 mm in the radial artery; the respective systodiastolic diameter change values were 375.4+/-31.0 and 55.9+/-9.0 (microm) and the distensibility values were 1.4+/-0.1 and 0.7+/-0.1 (1/mm Hg 10-3). Blood pressure and diameter were not significantly modified by increasing heart rate, which markedly modified systodiastolic diameter change and distensibility. In the radial artery, distensibility was reduced by 47% (P<0.05) at a heart rate of 90 beats/min with no further reduction at 110 beats/min. In the carotid artery, distensibility was reduced by 20% at a heart rate of 90 beats/min (P<0.05) with a further reduction at 110 beats/min (45%, P<0.05). These data provide the first evidence in humans that acute increases in heart rate markedly affect arterial distensibility and that this occurs in both large- and middle-size muscle arteries within the range of "normal" heart rate values.
  
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• [Study of arterial distensibility in man. Modulating mechanisms, pathological conditions and effects of treatment].
  Ital Heart J Suppl

  2003 Jun;4(6):467-76.
  
  Giannattasio Cristina, Failla Monica, Corsi Davide, Capra Anna, Meles Ester, Gentile Gaetano, Fantini Elena, Boffi Lucia, Maestroni Silvia, Scotti Valentina, Mancia Giuseppe
  
  Abstract
  
  The reduction of large arterial distensibility has several adverse consequences for the cardiovascular system. This paper reviews the evidence we have obtained by measuring distensibility through quantification of changes in arterial diameter vs blood pressure changes at large elastic and middle size muscle artery sites. Evidence shows that arterial distensibility is reduced in conditions such as hypercholesterolemia, hypertension, diabetes, and congestive heart failure. In some conditions (e.g. hypertension) the alterations are not uniformly distributed in the arteries of different structure and size whereas in others (e.g. diabetes and heart failure) they are widespread. In diabetes evidence is available that distensibility changes occur early in the course of the disease. Evidence is also available that in all above conditions treatment can improve arterial distensibility thereby reversing the initial abnormality. This is due to a variable combination of structural and functional factors. However, technical ability to determine their precise role in distensibility changes in humans is limited.
  
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• How to assess central arterial blood pressure?
  J Hypertens

  2003 Mar;21(3):495-6.
  
  Giannattasio Cristina
  
  
  
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• Arterial distensibility in humans. Modulating mechanisms, alterations in diseases and effects of treatment.
  J Hypertens

  2002 Oct;20(10):1889-99.
  
  Giannattasio Cristina, Mancia Giuseppe
  
  Abstract
  
  Reduction of large artery distensibility has several adverse consequences for the cardiovascular system. This paper reviews the evidence obtained by measuring distensibility through quantification of changes in arterial diameter versus blood pressure changes at large elastic and middle size muscle artery sites. Evidence is available that arterial distensibility is reduced in conditions as varied as hypercholesterolemia, hypertension, diabetes and congestive heart failure. In some conditions (e.g. hypertension) the alterations are not uniformly distributed in arteries of different structure and size whereas in others (e.g. diabetes and heart failure) they are widespread. In diabetes evidence is available that distensibility changes occur early in the course of the disease. Evidence is also available that in all above conditions treatment can improve arterial distensibility thereby reversing the initial abnormality. This appears to be due to a variable combination of structural and functional factors. Technical ability to determine their precise role in distensibility changes in humans is limited, however.
  
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• Effects of hematocrit changes on flow-mediated and metabolic vasodilation in humans.
  Hypertension

  2002 Jul;40(1):74-7.
  
  Giannattasio Cristina, Piperno Alberto, Failla Monica, Vergani Anna, Mancia Giuseppe
  
  Abstract
  
  Endothelial function is noninvasively assessed by measuring nitric oxide-dependent increase in radial artery diameter accompanying the elevation in shear stress induced by increasing blood flow through a short-lasting ischemia of the hand. However, shear stress also depends on blood viscosity, whose changes might thus affect nitric oxide increase in a manner that is not properly reflected by blood flow changes. In 12 subjects with hemochromatosis, we measured ultrasonographically radial artery diameter and blood flow responses to a 4-minute ischemia of the hand. This was done also after removing 500 mL of blood (and concomitantly infusing 500 mL of saline), which significantly (P<0.01) reduced hemoglobin concentration and hematocrit. The increase in blood flow induced by the 4-minute ischemia was similar before and after blood removal (+76% and +80%), which, in contrast, markedly attenuated the accompanying increase in radial artery diameter (+25% versus +13%, P<0.01). Thus, in humans, blood viscosity is involved in the endothelial response to an increase in shear stress. This implies that this response may not be accurately assessed and compared by quantifying the stimulus only through an increase in blood flow.
  
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• Radial, carotid and aortic distensibility in congestive heart failure: effects of high-dose angiotensin-converting enzyme inhibitor or low-dose association with angiotensin type 1 receptor blockade.
  J Am Coll Cardiol

  2002 Apr;39(8):1275-82.
  
  Giannattasio Cristina, Achilli Felice, Failla Monica, Capra Anna, Vincenzi Antonella, Valagussa Franco, Mancia Giuseppe
  
  Abstract
  
  UNLABELLED:
  objectives; The aim of this study was to determine whether in patients with congestive heart failure (CHF) a distensibility (Dist) reduction: 1) similarly occurs in different arteries; 2) is related to CHF severity; and 3) is reversible with treatment. background: Several studies suggest that CHF is accompanied by a reduced arterial Dist.
  
  METHODS:
  We measured diameter in radial artery, carotid artery (CA) and abdominal aorta (AO) by echotracking. Distensibility was obtained by relating it to blood pressure. Data were collected in 30 patients with CHF (New York Heart Association functional class I to III) under standard treatment with diuretic, digitalis and angiotensin-converting enzyme (ACE) inhibitor in whom CHF severity was assessed by maximum oxygen consumption (VO(2)max) percentage and in 30 age- and gender-matched controls. Patients with CHF were then randomized to maintain standard treatment (n = 10), double the ACE inhibitor dose (n = 10) or add an angiotensin II antagonist (n = 10) and restudied after two months.
  
  RESULTS:
  Distensibility was markedly reduced in the CHF group in all three vessels (p < 0.01), CA and AO Dist being related to CHF severity (p < 0.05). After two months, Dist did not change in the group maintained under standard treatment, but it increased significantly (p < 0.05) and similarly when the ACE inhibitor dose was doubled or an angiotensin II antagonist was added.
  
  CONCLUSIONS:
  Congestive heart failure is characterized by a reduction of Dist of large-elastic and middle-sized muscular arteries. The reduction of large-elastic artery Dist is related to the CHF severity. These alterations can be reversed by drugs, effectively interfering with the renin-angiotensin system either at the ACE or at the angiotensin receptor level.
  
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