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2. Antihypertensive treatment changes and related clinical outcomes in older hospitalized patients

Author

Sebastiano, Cicco, D'Abbondanza, Marco, Proietti, Marco, Vincenzo, Zaccone, Chiara, Pes, Federica, Caradio, Mattioli, Massimo, Salvatore, Piano, Alberto Maria Marra, Alessandro, Nobili, Pier Mannuccio Mannucci, Antonello, Pietrangelo, Giorgio, Sesti, Elena, Buzzetti, Andrea, Salzano, Antonio, Cimellaro, Francesco, Perticone, Francesco, Violi, Gino Roberto Corazza, Salvatore, Corrao, Alessandra, Marengoni, Francesco, Salerno, Matteo, Cesari, Mauro, Tettamanti, Luca, Pasina, Carlotta, Franchi, Alessio, Novella, Gabriella, Miglio, Alessia Antonella Galbussera, Ilaria, Ardoino, Prisco, Domenico, Elena, Silvestri, Giacomo, Emmi, Alessandra, Bettiol, Irene, Mattioli, Gianni, Biolo, Michela, Zanetti, Giacomo, Bartelloni, Michele, Zaccari, Massimiliano, Chiuch, Massimo, Vanoli, Giulia, Grignani, Edoardo Alessandro Pulixi, Pirro, Matteo, Lupattelli, Graziana, Bianconi, Vanessa, Alcidi, Riccardo, Giotta, Alessia, Massimo, R Mannarino, Domenico, Girelli, Fabiana, Busti, Giacomo, Marchi, Mario, Barbagallo, Ligia, Dominguez, Vincenza, Beneduce, Federica, Cacioppo, Giuseppe, Natoli, Salvatore, Mularo, Massimo, Raspanti, Christiano, Argano, Federica, Cavallaro, Marco, Zoli, Maria Laura Matacena, Giuseppe, Orio, Eleonora, Magnolfi, Serafini, Giovanni, Angelo, Simili, Mattia, Brunori, Ilaria, Lazzari, Cappellini, MARIA DOMENICA, Giovanna, Fabio, Margherita Migone De Amicis, Giacomo De Luca, Natalia, Scaramellini, Valeria Di Stefano, Simona, Leoni, Sonia, Seghezzi, Alessandra Danuto Di Mauro, Diletta, Maira, Marta, Mancarella, Tiziano, Lucchi, Paolo Dionigi Rossi, Marta, Clerici, Alessandra Danuta Di Mauro, Giulia, Bonini, Conti, Federica, Silvia, Prolo, Maddalena, Fabrizi, Miriana, Martelengo, Giulia, Vigani, Antonio Di Sabatino, Emanuela, Miceli, Marco Vincenzo Lenti, Martina, Pisati, Lavinia, Pitotti, Donatella, Padula, Valentina, Antoci, Ginevra, Cambiè, Roberto, Pontremoli, Valentina, Beccati, Giulia, Nobili, Giovanna, Leoncini, Jacopo, Alberto, Federico, Cattaneo, Luigi, Anastasio, Lucia, Sofia, Carbone, LUIGI MARIA, Francesco, Cipollone, Maria Teresa Guagnano, Ilaria, Rossi, Emanuele, Valeriani, Damiani, D'Ardes, Lucia, Esposito, Simona, Sestili, Ermanno, Angelucci, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Giuseppe, Delitala, Maria, Berria, Alessandro, Delitala, Maurizio, Muscaritoli, Alessio, Molfino, Enrico, Petrillo, Antonella, Giorgi, Christian, Gracin, Giovanni, Imbimbo, Giuseppe, Zuccalà, Gabriella, D'Aurizio, Giuseppe, Romanelli, Andrea, Volpini, Daniela, Lucente, Francesca, Manzoni, Annalisa, Pirozzi, Alberto, Zucchelli, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Chiara, Dell'Unto, Giuseppe, Bellelli, Maurizio, Corsi, Cesare, Antonucci, Chiara, Sidoli, Giulia, Principato, Alessandra, Bonfanti, Hajnalka, Szabo, Mazzola, Paolo, Piazzoli, Andrea, Franco, Arturi, Elena, Succurro, Bruno, Tassone, Federica, Giofrè, Maria Grazia Serra, Maria Antonietta Bleve, Antonio, Brucato, Teresa De Falco, Enrica, Negro, Martino, Brenna, Lucia, Trotta, Giovanni Lorenzo Squintani, Maria Luisa Randi, Fabrizio, Fabris, Irene, Bertozzi, Giulia, Bogoni, Maria Victoria Rabuini, Tancredi, Prandini, Francesco, Ratti, Chiara, Zurlo, Lorenzo, Cerruti, Elisabetta, Cosi, Roberto, Manfredini, Fabio, Fabbian, Benedetta, Boari, Alfredo De Giorgi, Ruana, Tiseo, Giuseppe, Paolisso, Maria Rosaria Rizzo, Claudia, Catalano, Irene Di Meo, Claudio, Borghi, Enrico, Strocchi, Eugenia, Ianniello, Mario, Soldati, Silvia, Schiavone, Alessio, Bragagni, Francesca Giulia Leoni, Valeria De Sando, Sara, Scarduelli, Michela, Cammarosano, Ilenia, Pareo, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Giovanni Michele De Vincenzo, Alessio, Comitangelo, Emanuele, Amoruso, Carlo, Custodero, Giuseppe, Re, Andrea, Schilardi, Francesca, Loparco, Luigi, Fenoglio, Andrea, Falcetta, Alessia Valentina Giraudo, Salvatore, D'Aniano, Anna, L Fracanzani, Silvia, Tiraboschi, Annalisa, Cespiati, Giovanna, Oberti, Giordano, Sigon, Felice, Cinque, Flora, Peyvandi, Raffaella, Rossio, Giulia, Colombo, Pasquale, Agosti, Erica, Pagliaro, Eleonora, Semproni, Canetta, Ciro, Valter, Monzani, Valeria, Savojardo, Giuliana, Ceriani, Christian, Folli, Giada, Pallini, Fabrizio, Montecucco, Luciano, Ottonello, Lara, Caserza, Giulia, Vischi, Salam, Kassem, Luca, Liberale, Nicola Lucio Liberato, Tiziana, Tognin, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Renzo, Rozzini, Lina, Falanga, Maria Stella Pisciotta, Francesco Baffa Bellucci, Stefano, Buffelli, Camillo, Ferrandina, Francesca, Mazzeo, Elena, Spazzini, Giulia, Cono, Giulia, Cesaroni, Giuseppe, Montrucchio, Paolo, Peasso, Edoardo, Favale, Cesare, Poletto, Carl, Margaria, Maura, Sanino, Ludovica, Perri, Luigina, Guasti, Francesca, Rotunno, Luana, Castiglioni, Andrea, Maresca, Alessandro, Squizzato, Leonardo, Campiotti, Alessandra, Grossi, Roberto Davide Diprizio, Francesco, Dentali, Bertolotti, Marco, Chiara, Mussi, Giulia, Lancellotti, Maria Vittoria Libbra, Matteo, Galassi, Yasmine, Grassi, Alessio, Greco, Elena, Bigi, Pellegrini, Elisa, Laura, Orlandi, Giulia, Dondi, Lucia, Carulli, Angela, Sciacqua, Maria, Perticone, Rosa, Battaglia, Raffaele, Maio, Aleandra, Scozzafava, Valentino, Condoleo, Tania, Falbo, Lidia, Colangelo, Marco, Filice, Elvira, Clausi, Vincenzo, Stanghellini, Eugenio, Ruggeri, Sara Del Vecchio, Ilaria, Benzoni, Andrea, Salvi, Leonardi, Roberto, Giampaolo, Damiani, Gianluca, Moroncini, William, Capeci, Giuseppe Pio Martino, Biondi, Lorenzo, Pietro, Pettinari, Monica, Ormas, Emanuele, Filippini, Devis, Benfaremo, Roberto, Romiti, Riccardo, Ghio, Anna Dal Col, Salvatore, Minisola, Luciano, Colangelo, Mirella, Cilli, Giancarlo, Labbadia, Antonella, Afeltra, Benedetta, Marigliano, Maria Elena Pipita, Pietro, Castellino, Luca, Zanoli, Alfio, Gennaro, Agostino, Gaudio, Samuele, Pignataro, Francesca, Mete, Miriam, Gino, Guido, Moreo, Gloria, Pina, Alberto, Ballestrero, Fabio, Ferrando, Roberta, Gonella, Domenico, Cerminara, Paolo, Setti, Chiara, Traversa, Camilla, Scarsi, Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Gabriella, Gruden, Franco, Berti, Giuseppe, Famularo, Patrizia, Tarsitani, Roberto, Castello, Michela, Pasino, Marcello Giuseppe Maggio Gian Paolo Ceda, Simonetta, Morganti, Andrea, Artoni, Margherita, Grossi, Stefano Del Giacco, Davide, Firinu, Giulia, Costanzo, Giacomo, Argiolas, Giovanni, Paoletti, Francesca, Losa, Montalto, GIUSEPPE ALBERT, Anna, Licata, Filippo Alessandro Montalto, Francesco, Corica, Giorgio, Basile, Antonino, Catalano, Federica, Bellone, Concetto, Principato, Lorenzo, Malatino, Benedetta, Stancanelli, Valentina, Terranova, Salvatore Di Marca, Rosario Di Quattro, Lara La Malfa, Rossella, Caruso, Mecocci, Patrizia, Ruggiero, Carmelinda, Boccardi, Virginia, Tiziana, Meschi, Andrea, Ticinesi, Antonio, Nouvenne, Pietro, Minuz, Luigi, Fondrieschi, Giandomenico Nigro Imperiale, Sarah, Morellini, Mario, Pirisi, Gian Paolo Fra, Daniele, Sola, Mattia, Bellan, Roberto, Quadri, Erica, Larovere, Marco, Novelli, Emilio, Simeone, Rosa, Scurti, Fabio, Tolloso, Tarquini, Roberto, Alice, Valoriani, Silvia, Dolenti, Giulia, Vannini, Volpi, Riccardo, Pietro, Bocchi, Alessandro, Vignali, Sergio, Harari, Chiara, Lonati, Federico, Napoli, Italia, Aiello, Teresa, Salvatore, Lucio, Monaco, Carmen, Ricozzi, Alberto, Pilotto, Ilaria, Indiano, Federica, Gandolfo, Franco Laghi Pasini, Pier Leopoldo Capecchi, Ranuccio, Nuti, Roberto, Valenti, Martina, Ruvio, Silvia, Cappelli, Alberto, Palazzuoli, Mauro, Bernardi, Silvia Li Bassi, Luca, Santi, Giacomo, Zaccherini, Vittorio, Durante, Daniela, Tirotta, Giovanna, Eusebi, Cattaneo, Marco Natale, Amoruso, MARIA VALENTINA, Paola, Fracasso, Cristina, Fasolino, Moreno, Tresoldi, Enrica, Bozzolo, Sarah, Damanti, Massimo, Porta, Giuseppe, Armentaro, Maria Immacolata Arnone, Milena, Barone, Lorenzo, Bertolino, Sara, Bianco, Nicolò, Binello, Simona, Brancati, Agostino, Buonauro, William, Cordeddu, Curcio, Rosa, Andrea, Dalbeni, Salvatore, D'Agnano, Damiano, D'Ardes, Martina De Feo, Emilia, Donnarumma, Marco, Fei, Carmine Gabriele Gambino, Paolo, Giorgini, Lombardi, Rosa, Giuseppe, Miceli, Paola, Naccarato, Silvia, Noviello, Gaia, Olivieri, Roberta, Parente, Francesca Serena Pignataro, Sonia, Poma, Enrica, Porceddu, Pucci, Giacomo, Marco, Ricchio, Anna, Sabena, Marco, Salice, Claudia, Santarossa, Ambra, Savona, Caterina, Savrié, Roberto, Scicali, Mario, Stabile, Giovanni, Talerico, Michela, Talia, Eliezer Joseph Tassone, Thomas, Teatini, Elisabetta, Tombolini, Matteo, Traversa, Elia, Vettore, Alessandro, Vignal, Luca, Vilardi, Rosanna, Villani, Francesco, Vitale, Cicco, Sebastiano, D Abbondanza, Marco, Proietti, Marco, Zaccone, Vincenzo, Pes, Chiara, Caradio, Federica, Mattioli, Massimo, Piano, Salvatore, Marra, Alberto Maria, Nobili, Alessandro, Mannucci, Pier Mannuccio, Pietrangelo, Antonello, Sesti, Giorgio, Buzzetti, Elena, Salzano, Andrea, Cimellaro, Antonio, Antonio Cimellaro, Salvatore, Corrao, Mario, Barbagallo, Anna, Licata, Giuseppe, Montalto, Paolisso, Giuseppe, Rizzo, Maria Rosaria, and Cimellaro, Antonio - Giovani Internisti Società Italiana di Medicina Interna (GIS-SIMI) and of the REPOSI Investigators

Subjects
cardiovascular events, older patient, hypertension, antihypertensive drugs, older patients, survival, Clinical Biochemistry, antihypertensive drug, General Medicine, Biochemistry, cardiovascular event
Abstract

Background: Hypertension management in older patients represents a challenge, particularly when hospitalized. Objective: The objective of this study is to investigate the determinants and related outcomes of antihypertensive drug prescription in a cohort of older hospitalized patients. Methods: A total of 5671 patients from REPOSI (a prospective multicentre observational register of older Italian in-patients from internal medicine or geriatric wards) were considered; 4377 (77.2%) were hypertensive. Minimum treatment (MT) for hypertension was defined according to the 2018 ESC guidelines [an angiotensin-converting-enzyme-inhibitor (ACE-I) or an angiotensin-receptor-blocker (ARB) with a calcium-channel-blocker (CCB) and/or a thiazide diuretic; if >80 years old, an ACE-I or ARB or CCB or thiazide diuretic]. Determinants of MT discontinuation at discharge were assessed. Study outcomes were any cause rehospitalization/all cause death, all-cause death, cardiovascular (CV) hospitalization/death, CV death, non-CV death, evaluated according to the presence of MT at discharge. Results: Hypertensive patients were older than normotensives, with a more impaired functional status, higher burden of comorbidity and polypharmacy. A total of 2233 patients were on MT at admission, 1766 were on MT at discharge. Discontinuation of MT was associated with the presence of comorbidities (lower odds for diabetes, higher odds for chronic kidney disease and dementia). An adjusted multivariable logistic regression analysis showed that MT for hypertension at discharge was associated with lower risk of all-cause death, all-cause death/hospitalization, CV death, CV death/hospitalization and non-CV death. Conclusions: Guidelines-suggested MT for hypertension at discharge is associated with a lower risk of adverse clinical outcomes. Nevertheless, changes in antihypertensive treatment still occur in a significant proportion of older hospitalized patients.

Published
2023

3. Sacubitril/valsartan improves medium-term reverse left ventricular remodeling: why wait?

Author

Elisabetta Tombolini, Laura Massironi, Filippo Toriello, Daniela Torta, Federica Valli, Stefano Carugo, Gloria Santangelo, Laura Bosotti, and Francesca Bursi

Subjects
Male, medicine.medical_specialty, Time Factors, Treatment outcome, Time to treatment, Tetrazoles, Ventricular Function, Left, Medium term, Time-to-Treatment, Internal medicine, Medicine, Humans, Protease Inhibitors, Ventricular remodeling, Aged, Retrospective Studies, Aged, 80 and over, Heart Failure, Ventricular function, Ventricular Remodeling, business.industry, Aminobutyrates, Biphenyl Compounds, Retrospective cohort study, Stroke Volume, General Medicine, Recovery of Function, Middle Aged, medicine.disease, Drug Combinations, Treatment Outcome, Cardiology, Valsartan, Female, Neprilysin, Cardiology and Cardiovascular Medicine, business, Angiotensin II Type 1 Receptor Blockers, Sacubitril, Valsartan
Published
2019

4. 18F-FDG PET reveals unique features of large vessel inflammation in patients with Takayasu’s arteritis

Author

Elena Baldissera, Luigi Gianolli, Elena Incerti, Maurizio Papa, Maria Grazia Sabbadini, Maria Picchio, Silvia Sartorelli, Elisabetta Tombolini, Pierpaolo Alongi, Francesco De Cobelli, Federico Fallanca, Justin C Mason, Enrico Tombetti, Angelo A. Manfredi, Incerti, Elena, Tombetti, Enrico, Fallanca, Federico, Baldissera, Elena M., Alongi, Pierpaolo, Tombolini, Elisabetta, Sartorelli, Silvia, Sabbadini, MARIA GRAZIA, Papa, Maurizio, DE COBELLI, Francesco, Mason, Justin C., Gianolli, Luigi, Manfredi, ANGELO ANDREA M. A., and Picchio, Maria

Subjects
Takayasu's arteritis, Radiology, Nuclear Medicine and Imaging, PROGNOSIS, DISEASE-ACTIVITY, Systemic inflammation, 030218 nuclear medicine & medical imaging, 0302 clinical medicine, Disease activity, Prospective cohort study, medicine.diagnostic_test, Radiology, Nuclear Medicine & Medical Imaging, WALL, General Medicine, Takayasu’s arteriti, Nuclear Medicine & Medical Imaging, Radiology, medicine.symptom, Vasculitis, Life Sciences & Biomedicine, MRI, CT, Vasculiti, medicine.medical_specialty, 0299 Other Physical Sciences, IMPROVEMENT, Standardized uptake value, DIAGNOSIS, Lesion, 03 medical and health sciences, MANAGEMENT, medicine, Arterial graft, Radiology, Nuclear Medicine and imaging, Arteritis, 030203 arthritis & rheumatology, Science & Technology, Arterial grafts, business.industry, Takayasu’s arteritis, 1103 Clinical Sciences, Magnetic resonance imaging, medicine.disease, FDG PET/CT, EMISSION-TOMOGRAPHY, PET/MRI, Nuclear medicine, business
Abstract

Purpose: The object of this study was to assess whether18F-fluorodeoxyglucose PET/CT (FDG PET/CT) provides novel information in patients with Takayasu’s arteritis (TA) in addition to that provided by current activity assessment, to analyse the effects of possible confounders, such as arterial grafts, and to verify whether PET/CT could be informative in lesions

Published
2017
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5. FDG Uptake by Prosthetic Arterial Grafts in Large Vessel Vasculitis Is Not Specific for Active Disease

Author

Jaita Mukherjee, Emyr Humphreys, Silvia Sartorelli, Elena Incerti, Elena Baldissera, Adil Al-Nahhas, Francesco De Cobelli, Jacqueline Andrews, Enrico Tombetti, Federico Fallanca, Julian Nash, Elisabetta Tombolini, Tara Barwick, Maurizio Papa, Maria Grazia Sabbadini, Maria Picchio, A. Salerno, Taryn Youngstein, Justin C Mason, Angelo A. Manfredi, Luigi Gianolli, Giuseppe A. Ramirez, Youngstein, Taryn, Tombetti, Enrico, Mukherjee, Jaita, Barwick, Tara D., Al-Nahhas, Adil, Humphreys, Emyr, Nash, Julian, Andrews, Jacqueline, Incerti, Elena, Tombolini, Elisabetta, Salerno, Annalaura, Sartorelli, Silvia, Ramirez, Giuseppe A., Papa, Maurizio, Sabbadini, Maria Grazia, Gianolli, Luigi, De Cobelli, Francesco, Fallanca, Federico, Baldissera, Elena, Manfredi, Angelo A., Picchio, Maria, Mason, Justin C., National Institute for Health Research, and Imperial College Healthcare NHS Trust- BRC Funding

Subjects
Male, Radiology, Nuclear Medicine and Imaging, Cardiac & Cardiovascular Systems, Time Factors, positron emission tomography, Periprosthetic, 030204 cardiovascular system & hematology, large-vessel vasculitis, Magnetic resonance angiography, Tertiary Care Centers, 0302 clinical medicine, Interquartile range, Positron Emission Tomography Computed Tomography, INFECTION, London, Prospective Studies, medicine.diagnostic_test, Radiology, Nuclear Medicine & Medical Imaging, TAKAYASU ARTERITIS, Arteries, Middle Aged, Treatment Outcome, Italy, Female, Radiology, Vasculitis, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, medicine.drug, Adult, medicine.medical_specialty, Adolescent, PET-CT, Standardized uptake value, DIAGNOSIS, 1102 Cardiovascular Medicine And Haematology, Takayasu arteriti, 03 medical and health sciences, Blood Vessel Prosthesis Implantation, Young Adult, POSITRON-EMISSION-TOMOGRAPHY, INFLAMMATION, Fluorodeoxyglucose F18, Predictive Value of Tests, medicine, MANAGEMENT, Humans, Radiology, Nuclear Medicine and imaging, Arteritis, AORTIC-WALL, large-vessel vasculiti, 030203 arthritis & rheumatology, Fluorodeoxyglucose, MR angiography, Science & Technology, business.industry, DIAMETER, F-18-FDG UPTAKE, 1103 Clinical Sciences, medicine.disease, Blood Vessel Prosthesis, Cross-Sectional Studies, Cardiovascular System & Hematology, arterial graft, Cardiovascular System & Cardiology, Radiopharmaceuticals, business, Magnetic Resonance Angiography
Abstract

OBJECTIVES: This study investigated the incidence and clinical significance of arterial graft-associated uptake of fluorodeoxyglucose in large-vessel vasculitis (LVV). BACKGROUND: The role of (18)F-labeled fluorodeoxyglucose-positron emission tomography/computed tomography ([(18)F]FDG-PET/CT) in the management of LVV remains to be defined. Although [(18)F]FDG uptake at arterial graft sites raises concerns regarding active arteritis or infection, its clinical significance in LVV has never been formally studied. METHODS: An observational prospective study sought to identify patients with Takayasu arteritis (TA) undergoing [(18)F]FDG-PET/CT more than 6 months after graft surgery from a large cohort of patients from 2 tertiary referral centers. [(18)F]FDG uptake by the graft and native arteries was scored on a scale of 0 to 3 relative to hepatic uptake, and periprosthetic maximum standardized uptake value (SUVmax) was calculated. Periprosthetic [(18)F]FDG uptake in active disease was compared with that in inactive disease, and arterial progression was assessed by prospective magnetic resonance angiography (MRA). RESULTS: Twenty-six subjects with TA were enrolled. All were afebrile with negative blood culture. Periprosthetic uptake was significant in 23 of 26 patients, and the mean SUVmax was 4.21 ± 1.46. Median periprosthetic [(18)F]FDG uptake score (3; interquartile range [IQR]: 3 to 3) was higher than in native aorta (1; IQR: 0 to 1; p < 0.001). Graft-specific [(18)F]FDG uptake was unrelated to disease activity. Despite the high frequency of graft-associated [(18)F]FDG uptake, sequential MRAs did not reveal arterial progression in 25 of 26 patients; the 1 remaining case showed minor progression limited to native arteries. Nine patients underwent repeated PET/CT scanning without showing changes in graft-specific uptake, despite increased treatment. CONCLUSIONS: Significant [(18)F]FDG uptake that is confined to arterial graft sites in patients with LVV does not reflect clinically relevant disease activity or progression. To minimize exposure to immunosuppression and in the face of negative blood culture, clinically quiescent arteritis, normal or stably raised C-reactive protein levels, we elected not to escalate treatment and monitor progression with MRA.

Published
2017

6. Chromogranin-A production and fragmentation in patients with Takayasu arteritis

Author

Silvia Sartorelli, Francesco De Cobelli, Elena Baldissera, Maria Grazia Sabbadini, Alessandro Ambrosi, Elisabetta Tombolini, A. Salerno, Chiara Lanzani, Patrizia Rovere-Querini, Maurizio Papa, Barbara Colombo, Angelo Corti, Enrica Bozzolo, Claudia Godi, Angelo A. Manfredi, Maria Chiara Di Chio, Alessandro Del Maschio, Enrico Tombetti, Giulia Benedetti, Tombetti, E, Colombo, B, Di Chio, Mc, Sartorelli, S, Papa, M, Salerno, A, Bozzolo, Ep, Tombolini, E, Benedetti, G, Godi, C, Lanzani, C, ROVERE QUERINI, Patrizia, DEL MASCHIO, Alessandro, Ambrosi, Alessandro, DE COBELLI, Francesco, Sabbadini, MARIA GRAZIA, Baldissera, E, Corti, Angelo, and Manfredi, ANGELO ANDREA M. A.

Subjects
0301 basic medicine, Vascular remodelling, Male, Angiogenesis, 030204 cardiovascular system & hematology, 0302 clinical medicine, Immunology and Allergy, Proton-pump inhibitors, Ultrasonography, biology, Chromogranin A, Middle Aged, Biomarker (medicine), Female, medicine.symptom, Vasculitis, Proton-pump inhibitor, Research Article, Adult, medicine.medical_specialty, Vasculiti, endocrine system, Immunology, Inflammation, Enzyme-Linked Immunosorbent Assay, Vascular Remodeling, Vascular remodelling in the embryo, Takayasu arteriti, 03 medical and health sciences, Young Adult, Rheumatology, Internal medicine, medicine, Humans, Aged, business.industry, Biomarker, medicine.disease, Takayasu Arteritis, Peptide Fragments, 030104 developmental biology, Secretory protein, Endocrinology, biology.protein, business, Biomarkers, Magnetic Resonance Angiography
Abstract

Background Chromogranin-A (CgA) is a secretory protein processed into peptides that regulate angiogenesis and vascular cells activation, migration and proliferation. These processes may influence arterial inflammation and remodelling in Takayasu arteritis (TA). Methods Plasma levels of full-length CgA (CgA439), CgA fragments lacking the C-terminal region (CgA-FRs) and the N-terminal fragment, CgA1–76 (vasostatin-1, VS-1) were analysed in 42 patients with TA and 20 healthy age-matched controls. Vascular remodelling was longitudinally assessed by imaging. CgA peptides were related to markers of systemic and local inflammation, disease activity and vascular remodelling. Results Levels of CgA-FRs and VS-1 were increased in TA. Treatment with proton-pump inhibitors (PPIs) and arterial hypertension partially accounted for CgA levels and high inter-patient variability. CgA439, CgA-FRs and VS-1 levels did not reflect disease activity or extent. Markers of systemic or local inflammation correlated with higher CgA-FRs and VS-1 in normotensive patients and with higher CgA439 in hypertensive patients. Treatment with non-biologic anti-rheumatic agents was associated with increased CgA-FRs and a distinctive regulation of CgA processing. Reduced blood levels of anti-angiogenic CgA peptides were associated with vascular remodelling in the groups of patients on PPIs and with arterial hypertension. Conclusions The plasma levels of CgA fragments are markedly increased in TA as a consequence of disease- and therapy-related variables. Anti-angiogenic forms of CgA may limit vascular remodelling. Given the effect of the various CgA peptides, it is advisable to limit the therapeutic prescriptions that might influence CgA-derived peptide levels to clearly agreed medical indications until further data become available. Electronic supplementary material The online version of this article (doi:10.1186/s13075-016-1082-2) contains supplementary material, which is available to authorized users.

Published
2016

7. SAT0350 Functional Characterisation of Takayasu Arteritis Vascular Lesions by MR and FDG-PET/CT Provides Non-Redundant Information over Clinical Assessment

Author

Enrico Tombetti, Giulia Benedetti, Elena Incerti, A. Salerno, Elena Baldissera, Maurizio Papa, Angelo A. Manfredi, F. De Cobelli, M.G. Sabbadini, Maria Picchio, Luigi Gianolli, and Elisabetta Tombolini

Subjects
medicine.medical_specialty, medicine.diagnostic_test, business.industry, Immunology, Takayasu arteritis, Magnetic resonance imaging, medicine.disease, Systemic inflammation, General Biochemistry, Genetics and Molecular Biology, Lesion, Stenosis, Rheumatology, Contrast-to-noise ratio, Occlusion, medicine, Immunology and Allergy, Clinical significance, Radiology, medicine.symptom, business, Nuclear medicine
Abstract

Background Disease activity (DA) assessment in Takayasu arteritis (TA) is an unresolved enigma as systemic inflammation and current activity measures poorly correlate with arterial progression. Morphological imaging, e.g. with morphological magnetic resonance (MR) sequencies, is the goal standard to evaluate arterial progression after its occurrence, and it is not clear whether functional characterisation of the lesions (e.g. contrast enhancement at MR or fluorodesoxyglucose [FDG] uptake at FDG-PET/CT [PET]) can predict arterial progression before its occlusion. We are prospectively following 60 TA patients with functional and morphological imaging to understand the predictors of arterial progression. Here we present the baseline assessment of the first 47 patients. Objectives to verify if activity measures, and functional lesion characterisation with PET or MR provide independent information. Methods Cross-sectional analysis of 47 TA patients according to ACR criteria followed at our Institution and undergoing closely related MR, PET and clinical evaluation. DA was evaluated with NIH criteria, indian Takayasu activity score (ITAS2010) and physician global assessment (PGA). At MR, arterial lesions were characterized by length, thickness and percentage of stenosis. Contrast to noise ratio (CNR) was calculated, when technically possible. Each vascular lesion uptake large enough to be evaluated by PET was evaluated with a quantitative (SUVmax) method. Per patients and per lesion analyses were performed. Results The median interval between MR and PET was 24 days. TA was active in 25, 17 and 35 patients according to NIH criteria, ITAS2010 and PGA (including active and grumbling disease). In total, MR identified 333 arterial lesions (median lesion N per patient 6, IQR 1–15). At the “per patient” analysis, median CNRmax at MR was 12,43 (IQR 0,00–54,29). CNRmax did not correlate with acute-phase markers nor activity measures, except for ITAS-CRP (rho 0.300, p=0,038). PET showed significant uptake in 18 patients. Meadian SUVmax was 1,19 (IQR 0,00–9,00). SUVmax did not correlate with activity measures. At the “per lesions” analysis, 56 lesions had positive uptake in PET. There was no correlation between the degree of enhancement at MR and of FDG uptake at PET (rho 0,094, p=0,529). Conclusions Current activity measures, mainly based on systemic inflammation, and functional characterisation of the arterial lesions by MR and FDG-PET provide independent information in TA. The prospective part of this study will clarify the clinical relevance and the predictive values for progression of these different pieces of information. Disclosure of Interest None declared

Published
2016
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8. SAT0335 Differential Modulation of The Chromogranin-A System in Takayasu Arteritis and Systemic Lupus Erythematosus

Author

Silvia Sartorelli, Maurizio Papa, Elisabetta Tombolini, Angelo A. Manfredi, Elena Baldissera, F. De Cobelli, M.G. Sabbadini, Barbara Colombo, Angelo Corti, Enrico Tombetti, M.C. Di Chio, and Giuseppe A. Ramirez

Subjects
Differential modulation, endocrine system, medicine.medical_specialty, Pathology, biology, Angiogenesis, business.industry, Immunology, Takayasu arteritis, Chromogranin A, medicine.disease, Systemic inflammation, Gastroenterology, General Biochemistry, Genetics and Molecular Biology, Pathogenesis, Rheumatology, Internal medicine, Heart failure, medicine, biology.protein, Immunology and Allergy, medicine.symptom, business, Contraindication
Abstract

Background Chromogranin-A (CgA) is a multi-source protein proteolitically processed into a family of peptides with various paracrine and endocrine functions. CgA-derived peptides influence vascular biology and neoangiogenesis: CgA1–439 (CgA439) and vasostatin-1 (VS1, CgA1–76) have anti-angiogenic properties, while fragments lacking the C-terminal domain (CgA-FRs) are pro-angiogenic. The mechanisms regulating vascular events and systemic inflammation in Takayasu Arteritis (TA) and Systemic Lupus Erythematosus (SLE) are poorly characterized. Objectives To evaluate how the CgA system is modulated in TA and SLE Methods 42 consecutive patients (pts) with TA were enrolled and matched with 20 age- and sex- matched SLE pts and 20 healthy subjects (HCs). Exclusion criteria were moderate/severe heart failure or contraindication to MR angiography (MRA). TA pts were longitudinally studied with 2 MRAs (12 months apart). Disease activity was assessed with NIH criteria and SLEDAI in the TA and SLE group, respectively. Arterial progression was defined as the appearance of new lesions or worsening of pre-existing lesions at MRA. CgA peptides and total CgA (CgAtot) were quantified with validated ELISAs. CgA processing was studied by ratios of CgA peptides to CgAtot. The antiangiogenic CgA potential was quantified in TA by summing the ranks of CgA439 and VS1. Results Median age of TA patients (39W, 3M) was 46 (IQR 34–54) years. Median disease duration was 10 (IQR 7–14) years for TA, and 13 (7–21) years for SLE. Twelve TA and 8 SLE pts had active disease. Thirty TA and 10 SLE pts received proton pump inhibitors (PPI), which are known to increase CgA levels. Nine TA pts (8 treated with PPIs) underwent arterial progression. Serum CgA-FR were significantly higher in TA pts than in SLE pts (p Conclusions A selective processing of CgA is evident in SLE, whose molecular bases are unknown. TA associates with a greater increase in CgA-FR levels than SLE during PPI therapy. CgA peptides do not correlate with disease activity. Antiangiogenic CgA potential is reduced in TA pts on PPI undergoing progression, underlining the importance of angiogenesis in arterial remodelling and suggesting an involvement of CgA peptides in TA pathogenesis. Disclosure of Interest None declared

Published
2016
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