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Are all people with diabetes and cardiovascular risk factors or microvascular complications at very high risk? Findings from the Risk and Prevention Study

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Abstract

Aims

To verify whether it is possible, in people with diabetes mellitus (DM) considered at very high cardiovascular (CV) risk, stratify this risk better and identify significant modifiable risk factor (including lifestyle habits) to help patients and clinicians improve CV prevention.

Methods

People with DM and microvascular diseases or one or more CV risk factors (hypertension, hyperlipidemia, smoking, poor dietary habits, overweight, physical inactivity) included in the Risk and Prevention study were selected. We considered the combined endpoint of non-fatal acute myocardial infarction and stroke and CV death. A multivariate Cox proportional analysis was carried out to identify relevant predictors. We also used the RECPAM method to identify subgroups of patients at higher risk.

Results

In our study, the rate of major CV events was lower than expected (5 % in 5 years). Predictors of CV events were age, male, sex, heart failure, previous atherosclerotic disease, atrial fibrillation, insulin treatment, high HbA1c, heart rate and other CV diseases while being physically active was protective. RECPAM analysis indicated that history of atherosclerotic diseases and a low BMI defined worse prognosis (HR 4.51 95 % CI 3.04–6.69). Among subjects with no previous atherosclerotic disease, men with HbA1c more than 8 % were at higher CV risk (HR 2.77; 95 % CI 1.86–4.14) with respect to women.

Conclusions

In this population, the rate of major CV events was lower than expected. This prediction model could help clinicians identify people with DM at higher CV risk and support them in achieving goals of physical activity and HbA1c.

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Acknowledgments

We thank F. Clerici, A. Palumbo and G. Sgaroni for their help in the conduction of the study and J.D. Baggott (all from IRCCS—Istituto di Ricerche Farmacologiche “Mario Negri”) for kindly editing the manuscript.

Authors’ contributions

Fausto Avanzini, Irene Marzona, Maria Carla Roncaglioni, Antonio Nicolucci and Marta Baviera participated in the conception and design of the study and data interpretation. Mauro Tettamanti and Giuseppe Lucisano did the statistical analyses. Fausto Avanzini, Maria Carla Roncaglioni and Irene Marzona wrote the first draft of the report. All authors contributed to writing and have seen and approved the final version.

Funding

Società Prodotti Antibiotici (SPA), Pfizer and Sigma Tau supported the study with an unrestricted grant.

Risk & Prevention Collaborative Group are as follows:

Steering Committee M. Tombesi (chairman), G. Tognoni (co-chairman), E. Massa, W. Marrocco, M. Micalella, V. Caimi, P. Longoni, F. Avanzini, M.G. Franzosi.

Scientific and Organizing Secretariat

M.C. Roncaglioni (coordinator), I. Marzona, M. Baviera, L. Monesi, I. Pangrazzi, S. Barlera, V. Milani, E. Nicolis, C. Casola, F. Clerici, A. Palumbo, G. Sgaroni. IRCCS-Istituto di Ricerche Farmacologiche “Mario Negri,” Via Giuseppe La Masa 19, 20156 Milan, Italy and R. Marchioli, M.G. Silletta (coordinators), R. Pioggiarella, M. Scarano, RM. Marfisi, A. Flamminio, L. Macino, B. Ferri, C. Pera, A. Polidoro. Fondazione Mario Negri Sud, Via Nazionale, 66030 S. Maria Imbaro (CH), Italy.

The Rischio and Prevenzione study is sponsored by the Rischio and Prevenzione Collaborative Group which therefore has full responsibility for the formulation of the protocol, the conduction of the study and the utilization of the results.

Principal investigators

DAbbatino, M Acquati, G Addorisio, D Adinolfi, L Adreani, M R Agistri, A Agneta, M L Agnolio, N Agostini, G Agostino, A Airò, N Alaimo, M Albano, N Albano, G Alecci, S Alemanno, A Alexanian, M Alfarano, L Alfè, N Alonzo, S Alvino, A Ancora, S Andiloro, E Andreatta, S Angeli, F Angiari, V Angilletti, C Annicchiarico, M Anzivino, R Aprea, A Aprile, E Aprile, I Aprile, L Aprile, V Armellani, M Arnetoli, A Aronica, V Autiero, G Bacca, A M Baccalaro, M Bacci, G Baglio, M Bagnani, A Baiano, A Baldari, L Ballarini, G Banchi, R Bandera, F Bandini, M Baratella, A Barbieri, A Barbieri Vita, M Bardi, M Barlocchi, P Baron, M Bartoli, A Basile, F Basile, S Basile, A Battaggia, A Battaglia, A Baù, G Beconcini, R Beggio, P A Belfiore, M Belicchi, S Bellamoli, C Bellini, M Bellomo, C Benetollo, R Benetti, E Beretta, P Bertalero, F G Bertaso, U Bertolani, G Bettelli, G Biagiotti, S Bianchi, G Bianco, F Biccari, F Bigioli, M Bindi, G Bisanti, E M Bitetti, M P Blasetti, F Blesi, V Boato, S Boga, E Boidi, G Boldrin, A Bollati, L Bolzan, S Bolzonella, P Bonardi, G B Bonato, M Bonci, G Bonfitto, E Bonincontro, F Boninsegna, D Bonissone, L Bono, E Bonollo, M Borghi, N Borioli, M Borsatto, T Bosco, M Bosisio Pioltelli, C Botarelli, S Botassis, F Bottini, C Bottos, G Bova, V Bova, A Bozzani, R M Bozzetto, V T Braga, M Braglia, E Bramati, C Brazzoli, G Breglia, A Brescia, D Briganti, G Brigato, A Brocchi, F A Brosio, E Bruni, E Buscaglia, M D Bussini, A Bussotti, F Buzzaccarini, A Buzzatti, G Caccamo, C Cacciavillani, G Caggiano, V Caimi, F P Calciano, M Calderisi, S Calienno, P Caltagirone, I Calzolari, M Cammisa, M Campanaro, G B Campanella, F Campese, G Canali, D E L Candiani, R Canepa, D Canini, A Canino, E A Cantoro, V Capilupi, P Capotosto, B Cappelli, G Capraro, F A Carafa, Q Carano, V Carcaterra, D Carriero, G Carrozzo, M Cartanese, M Casalena, M Casarola, C Caso, M Casotto, F Castaldi, R Castegnaro, G Castellani, S Castri, E Catalano, N Catinello, G Caturano, R Cavallaro, A M Cavallo, G Cavallo, M T Cavion, G Cavirani, F Cazzaniga, D Cazzetta, V Cecconi, A Cefalo, M Celebrano, A Celora, P Centonze, D Cerati, D Cesaretti, G Checchia, A Checchin, M Cherubini, L Chianese, A Chiappa, M V Chiappa, G Chiariello, G Chiavini, M Chicco, F Chiumeo, A Ciacciarelli, D Ciaci, R Ciancaglini, C Cicale, S Cicale, A Cipolla, A Ciruolo, A L Citeri, G Citterio, M Clerici, E Coazzoli, G Collecchia, F Colletta, I Colombo, P Colorio, S Coluccia, M Comerio, P Comoretto, M Compagni, O Conte, S Contri, A Contrisciani, T Coppetti, F Corasaniti, M T Corradi, A Corsano, A Corsini, N Corti, G Costantini, A Costantino, S Cotroneo, D Cozzi, M G Cravello, E Cristiano, R Cucchi, L Cusmai, G B D’ Errico, P D’Agostino, P D’Agostino, L Dal Bianco, U Dal Mutto, G Dal Pozzo, P Dallapiccola, G Dallatorre, G Dalle Molle, E Dalloni, A D’Aloiso, G D’Amicis, R Danese, D Danieli, G Danisi, M A D’Anna, G Danti, S D’Ascanio, G Davidde, D De Angeli, R De Bastiani, A De Battisti, A De Bellis, A De Bellis, G De Berardinis, F De Carlo, D De Giorgi, R De Gobbi, E De Lorenzis, P De Luca, G De Martini, M De Marzi, D De Matteis, S De Padova, P De Polo, N De Sabato, T De Stefano, M T De Vita, U De Vito, V De Zolt, F Debernardi, A Del Carlo, G Del Re, F Del Zotti, R D’Elia, P Della Giovanna, L Dell’Acqua, R L Dell’Orco, G Demaria, M G Di Benedetto, G Di Chiara, V Di Corcia, O Di Domizio, P Di Donato, S Di Donato, G Di Fermo, M Di Franco, G Di Giovannantonio, G Di Lascio, G Di Lecce, N Di Lorenzo, T Di Maro, Q Di Mattia, E Di Michele, R S Di Modica, D Di Murro, M C Di Noi, V Di Paoli, M Di Santi, A Di Sanzo, C Di Turi, A Diazzi, I Dileo, A P D’Ingianna, A Dolci, G Donà, C Donato, P Donato, A Donini, M E Donna, T V Donvito, L Esposito, N Esposito, M Evangelista, G Faita, M Falco, D A Falcone, F Falorni, A Fanciullacci, L Fanton, L Fasolo, R Fassina, A Fassone, P Fatarella, F Fedele, I Fera, L Fera, S Ferioli, M G Ferlini, R Ferlino, G Ferrante, F N Ferrara, M F Ferrarese, G Ferrari, O Ferrari, A Ferreri, M Ferroni, G Fezzi, C Figaroli, M G Fina, A Fioretta, C Fiorucci, R Firrincieli, M Fischetti, G Fischietti, D C Fiume, G Flecchia, G Forastiere, B Fossati, P L Franceschi, L Franchi, F Franzoso, G Frapporti, G Frasca, A Frisotti, G Fumagalli, D Fusco, P Gabriele, A Gabrieli, D Gagliano, G Galimberti, A Galli, N Gallicchio, F Gallio, T Gallipoli, P Gallo, T Galopin, L Gambarelli, A Garbin, G M Garozzo, R Gasparri, M Gastaldo, E Gatti, P Gazzaniga, N Gennachi, R V Gentile, P Germani, F Gesualdi, E Gherardi, C Ghezzi, M G Ghidini, F Ghionda, L Giacci, D Gialdini, C Giampaolo, R Giancane, A Giannanti, S Giannese, L Giannini, M Giaretta, R Giaretta, L Giavardi, P Giordano, E Giordano, B Giordano, G M Gioria, R Giugliano, E A Grassi, A Greco, L Greco, N Grilletti, N Grimaldi, G Grisetti, G Groppelli, L Gualtieri, M Guarducci, G Guastella, M Guerra, F Guerrini, A Guglielmini, A Guido, P Gulotta, E Iacono, G Iadarola, G Ianiro, V Iarussi, M L Ieluzzi, C Ierardi, F Ingaldi, S Interlandi, M Iocca, A Iorno, E Ioverno, R Iurato, L La Pace, C La Piscopia, R La Selva, M Lafratta, M Lamparelli, G Lanaro, R Lancerotto, M Larcher, M Lassandro, G Lattuada, P Laurino, C Lefons, F Legrottaglie, A Lemma, D Leone, F Leone, A Leso, G Leuzzi, G Levato, L Libardi, N Libralesso, P I Licini, G Licursi, F Lidonnici, C Lillo, L Liveri, A Livio, R A Loiero, M Loison, G Lombardo, T Lombardo, V Lomunno, S Lomuscio, A Lonedo, E Longo, P Longoni, L Lora, A Lotterio, L Lucatello, A Luongo, M Lupoli, C Macchia, G Macri, M Mafessanti, V Maggialetti, A Maggioni, M Magnani, G Maiellaro, A Mancuso, A R Maniglio, G L Mannari, A Manni, B Manocchio, M Mao, A Maranò, E Maraone, D Marascio, P Marcheselli, B Marchetto, S Marchetto, A Marchi, G L Marchi, C Mariano, S Marinacci, S Marinelli, G Marini, VC Marra, F Marrali, C Marseglia, G Martello, C Martino, G Martino, M Martino, C F Marulli, G Maruzzi, A Marzotti, G Mascheroni, P Mascolo, G Masoch, R Masone, E Massa, L Massa, M Massafra, M Massi, D M Massignani, A M Matarese, G Matini, R Mauro, M Mazzi, A Mazzillo, E Mazzocato, N S Mazzoleni, A Mazzone, A Melacci, E Mele, P Meliota, S Menaspà, F Meneghello, G Merola, L Merone, A Metrucci, V Mezzina, A Micchi, A Michielon, N Migliore, G Minero, F Minotta, C Mirandola, S Mistrorigo, L Modafferi, R Moitre, E Mola, C Monachese, C Mongiardini, F Montagna, M Montani, I Montemurno, R Montolli, S Montorsi, M Montresor, M G Monzani, F Morabito, G Mori, A Moro, M F Mosca, F Motti, L Muddolon, M Mugnai, F Muscas, F Naimoli, G Nanci, E Nargi, R Nasorri, G Nastrini, M Negossi, A Negrini, A Negroni, V Neola, F Niccolini, C M Niro, C Nosengo, G Novella, C Nuti, F Obici, C Olita, S S Oliverio, I Olivieri, S Oriente, G Orlando, C Paci, G Pagano, C Pagliara, G Paita, G Paladini, G Paladino, T Palano, A Palatella, P Palermo, M Palmisano, P Pando, P Panessa, F Panigo, G Panozzo, F Panvini, F Panzieri, A Panzino, F Panzitta, N Paoli, R Papagna, M G Papaleo, G Papalia, R Parisi, N Parotti, D Parravicini, P Passarella, G A Pastore, M Patafio, P Pavone, W Pedroli, M Pedroni, G Pelligra, M Pellizzari, A Penati, M Perlot, A Perrone, A Perrone, G Perrone, P Peruzzi, C Peselli, L Petracchini, L Petrera, S Petrone, C Peverelli, F Pianorsi, G P Piazza, G Piazzolla, A Picci, G Pienabarca, T P Pietronigro, P Pignocchino, R Pilone, D Pinto, E Pirovano, D Pirrotta, V Pisante, P Pitotto, L Pittari, A Piva, A Pizzoglio, O R Plantera, W Plebani, S Plessi, D Podrecca, V Poerio, F Poggiani, W Pogliani, L Poli, F G Poloni, R Porcelli, S Porto, L Pranzo, C Prevedello, C Profeta, D Profico, A Punzi, G M Quaglia, M Racano, A Raccone, F Radice, C A Raho, R Raimondi, M Rainò, R Ramponi, A Ramunni, A L Ramunni, F Ravasio, M Ravera, G Re Sartò, G Rebustello, S Regazzoli, C Restelli, M Rezzonico, F Ricchiuto, S Rigo, G Rigon, R Rigon, O V Rinaldi, M Rinaldi, P G Risplendente, M Rispoli, R Riundi, M G Riva, A L Rizzi, D Rizzi, L D Rizzo, L Rocchi, B Rondinone, B Rosa, F Rosati, F Roselli, A Rossetti, C Rossetti, R Rossi, P R Rossi, A Rossi, C L Rossi, A Rossitto, R Ruffini, A Ruffo, S Ruggio, M Ruo, B Russo, L Russo, R Russo, S Russo, U Russo, V Russo, G Ruta, F Sacchi, F Sacco Botto, A Saia, G Salladini, S Salmoiraghi, F Saluzzo, C Salvatore, E Salvatori, G Salvio, P Sandri, T Sandrini, V Sangermano, N Santoni, A D Saracino, A Saracino, P Sarasin, C Sardo Infirri, B Sarrì, G Sartori, N Sartori, C Sauro, M Scaglioni, C Scalfi, A M Scamardella, G Scandale, L Scandone, G Scannavini, R Scarati, A Scardi, F M Scarpa, P Scazzi, A Schifone, G Schiroso, G Scigliano, A Scilla, M Sciortino, G Scolaro, E Scollo, G Scorretti, R Sellitti, A Selmo, G Selvaggio, A Sempio, F Seren, L Serio, C Serra, L Serra, D Siciliano, A Sideri, M Sighele, R Signore, F Siliberto, M Silvestro, G Simioni, G Simmini, L Simonato, F Sinchetto, E Sizzano, G Smajato, M Smaldone, G Sola, L Sordillo, C S Sovran, P Spagnul, F Spanò, S Sproviero, A Squintani, L Stella, V Stilo, B Stocchiero, M C Stornello, G 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Pharmacists of the local health units

M Altomonte, N. Anelli, F Angiò, P Annale, S Antonacci, R Anzilotta, F Bano, O Basadonna, L Beduschi, P Becagli, G Bellotti, C Blotta, G Bruno, A Cappuccini, S Caramatti, M P Cariolato, M Castellana, L Castellani, R Catania, A Chielli, A Chinellato, A Ciaccia, E Clerici, A Cocci, G Costanzo, F D’Ercole, G De Stefano, F Decè, N Di Cicco, A Di Marco, C Donati Sarti, E Draghi, G Dusi, V Esposito, L Ferraro, A Ferretti, E Ferri, L Foggetti, A Foglia, E Fonzi, G Frau, M R Fuoco, G Furci, L Gallo, V Garra, A Giannini, A Gris, R Iacovino, R Interrigi, R Joppi, B Laner, G La Fortezza, A La Padula, M R Lista, G Lupi, D Maffei, G Maggioni, L Magnani, E Marrazzo, L Marcon, V Marinò, A Maroni, C Martinelli, E Mastandrea, F Mastropierro, A T Meo, P Mero, E Minesso, V Moschetta, E Mosele, C Nanni, A Negretti, C Nisticò, A Orsini, M Osti, M C Pacilli, C Pennestre, G Picerno, K Piol, L Pivano, E Pizzuti, L Poggi, I Poidomani, M Pozzetto, M L Presti, R Ravani, V Recalenda, F Romagnuolo, S Rossignoli, E Rossin, C Sabatella, F Sacco, F Sanità, E Sansone, F Servadei, M T Sisto, A Sorio, A Sorrentino, E Spinelli, A Spolaor, A Squillacioti, P Stella, A Talerico, C Todisco, M Vadino, C Zuliani.

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Correspondence to Irene Marzona.

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The R&P Study has been reviewed by the appropriate ethics committees and has therefore been performed in accordance with the ethical standards laid down in an appropriate version of the 1964 Declaration of Helsinki.

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This study involved human participants and the protocol was approved by the Italian Regulatory Authorities and by the Local Ethic Committees.

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All patients provided informed consent before enrollment.

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Managed by Massimo Porta.

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Marzona, I., Avanzini, F., Lucisano, G. et al. Are all people with diabetes and cardiovascular risk factors or microvascular complications at very high risk? Findings from the Risk and Prevention Study. Acta Diabetol 54, 123–131 (2017). https://doi.org/10.1007/s00592-016-0899-0

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