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51. Evaluation of the performance of Dutch Lipid Clinic Network score in an Italian FH population: The LIPIGEN study

Author

Casula, Manuela, primary, Olmastroni, Elena, additional, Pirillo, Angela, additional, Catapano, Alberico Luigi, additional, Arca, Marcello, additional, Averna, Maurizio, additional, Bertolini, Stefano, additional, Calandra, Sebastiano, additional, Tarugi, Patrizia, additional, Pellegatta, Fabio, additional, Angelico, Francesco, additional, Bartuli, Andrea, additional, Biasucci, Giacomo, additional, Biolo, Gianni, additional, Bonanni, Luca, additional, Bonomo, Katia, additional, Borghi, Claudio, additional, Bossi, Antonio Carlo, additional, Branchi, Adriana, additional, Carubbi, Francesca, additional, Cipollone, Francesco, additional, Citroni, Nadia, additional, Federici, Massimo, additional, Ferri, Claudio, additional, Fiorenza, Anna Maria, additional, Giaccari, Andrea, additional, Giorgino, Francesco, additional, Guardamagna, Ornella, additional, Iannuzzi, Arcangelo, additional, Iughetti, Lorenzo, additional, Lupattelli, Graziana, additional, Lupi, Alessandro, additional, Mandraffino, Giuseppe, additional, Marcucci, Rossella, additional, Maroni, Lorenzo, additional, Miccoli, Roberto, additional, Mombelli, Giuliana, additional, Muntoni, Sandro, additional, Pecchioli, Valerio, additional, Pederiva, Cristina, additional, Pipolo, Antonio, additional, Pisciotta, Livia, additional, Pujia, Arturo, additional, Purrello, Francesco, additional, Repetti, Elena, additional, Rubba, Paolo, additional, Sabbà, Carlo, additional, Sampietro, Tiziana, additional, Sarzani, Riccardo, additional, Tagliabue, Milena Paola, additional, Trenti, Chiara, additional, Vigna, Giovanni Battista, additional, Werba, Josè Pablo, additional, Zambon, Sabina, additional, Zenti, Maria Grazia, additional, Minicocci, Ilenia, additional, Noto, Davide, additional, Fortunato, Giuliana, additional, Banderali, Giuseppe, additional, Benso, Andrea, additional, Bigolin, Paola, additional, Bonora, Enzo, additional, Bruzzi, Patrizia, additional, Bucci, Marco, additional, Buonuomo, Paola Sabrina, additional, Capra, Maria Elena, additional, Cardolini, Iris, additional, Cefalù, Baldassarre, additional, Cervelli, Nazzareno, additional, Chiariello, Giuseppe, additional, Cocci, Guido, additional, Colombo, Emanuela, additional, Cremonini, Anna Laura, additional, D'Addato, Sergio, additional, D'Erasmo, Laura, additional, Dal Pino, Beatrice, additional, De Sanctis, Luisa, additional, De Vita, Emanuele, additional, Del Ben, Maria, additional, Di Costanzo, Alessia, additional, Di Taranto, Maria Donata, additional, Fasano, Tommaso, additional, Gentile, Luigi, additional, Gentile, Marco, additional, Ghirardello, Omar, additional, Grigore, Liliana, additional, Lussu, Milena, additional, Meregalli, Giancarla, additional, Moffa, Simona, additional, Montalcini, Tiziana, additional, Morgia, Valeria, additional, Nascimbeni, Fabio, additional, Pasta, Andrea, additional, Pavanello, Chiara, additional, Saitta, Antonino, additional, Scicali, Roberto, additional, Siepi, Donatella, additional, Spagnolli, Walter, additional, Spina, Rossella, additional, Sticchi, Elena, additional, Suppressa, Patrizia, additional, Vigo, Lorenzo, additional, Vinci, Pierandrea, additional, Casula, Manuela, additional, Manzato, Enzo, additional, Tragni, Elena, additional, and Zampoleri, Veronica, additional

Published
2018
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52. Epidemiology of cardiovascular risk factors in two population-based studies

Author

Olmastroni, Elena, primary, Shlyakhto, Evgeny V., additional, Konradi, Aleksandra O., additional, Rotar, Oxana P., additional, Alieva, Asiiat S., additional, Boyarinova, Maria A., additional, Baragetti, Andrea, additional, Grigore, Liliana, additional, Pellegatta, Fabio, additional, Tragni, Elena, additional, Catapano, Alberico L., additional, and Casula, Manuela, additional

Published
2018
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53. Myeloid apolipoprotein E controls dendritic cell antigen presentation and T cell activation

Author

Bonacina, Fabrizia, primary, Coe, David, additional, Wang, Guosu, additional, Longhi, Maria P., additional, Baragetti, Andrea, additional, Moregola, Annalisa, additional, Garlaschelli, Katia, additional, Uboldi, Patrizia, additional, Pellegatta, Fabio, additional, Grigore, Liliana, additional, Da Dalt, Lorenzo, additional, Annoni, Andrea, additional, Gregori, Silvia, additional, Xiao, Qingzhong, additional, Caruso, Donatella, additional, Mitro, Nico, additional, Catapano, Alberico L., additional, Marelli-Berg, Federica M., additional, and Norata, Giuseppe D., additional

Published
2018
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54. PCSK9 deficiency reduces insulin secretion and promotes glucose intolerance: the role of the low-density lipoprotein receptor

Author

Da Dalt, Lorenzo, primary, Ruscica, Massimiliano, additional, Bonacina, Fabrizia, additional, Balzarotti, Gloria, additional, Dhyani, Ashish, additional, Di Cairano, Eliana, additional, Baragetti, Andrea, additional, Arnaboldi, Lorenzo, additional, De Metrio, Simona, additional, Pellegatta, Fabio, additional, Grigore, Liliana, additional, Botta, Margherita, additional, Macchi, Chiara, additional, Uboldi, Patrizia, additional, Perego, Carla, additional, Catapano, Alberico Luigi, additional, and Norata, Giuseppe Danilo, additional

Published
2018
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55. Automatic identification of variables in epidemiological datasets using logic regression

Author

Cardiovasculaire Epi Team 5, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Lorenz, Matthias W., Abdi, Negin Ashtiani, Scheckenbach, Frank, Pflug, Anja, Bülbül, Alpaslan, Catapano, Alberico L., Agewall, Stefan, Ezhov, Marat, Bots, Michiel L., Kiechl, Stefan, Orth, Andreas, Norata, Giuseppe D., Empana, Jean Philippe, Lin, Hung Ju, McLachlan, Stela, Bokemark, Lena, Ronkainen, Kimmo, Amato, Mauro, Schminke, Ulf, Srinivasan, Sathanur R., Lind, Lars, Kato, Akihiko, Dimitriadis, Chrystosomos, Przewlocki, Tadeusz, Okazaki, Shuhei, Stehouwer, C. D.A., Lazarevic, Tatjana, Willeit, Peter, Yanez, David N., Steinmetz, Helmuth, Sander, Dirk, Poppert, Holger, Desvarieux, Moise, Ikram, M. Arfan, Bevc, Sebastjan, Staub, Daniel, Sirtori, Cesare R., Iglseder, Bernhard, Engström, Gunnar, Tripepi, Giovanni, Beloqui, Oscar, Lee, Moo Sik, Friera, Alfonsa, Xie, Wuxiang, Grigore, Liliana, Plichart, Matthieu, Su, Ta Chen, Robertson, Christine, Schmidt, Caroline, Tuomainen, Tomi Pekka, Veglia, Fabrizio, Völzke, Henry, Nijpels, Giel, Jovanovic, Aleksandar, Willeit, Johann, Sacco, Ralph L., Franco, Oscar H., Hojs, Radovan, Uthoff, Heiko, Hedblad, Bo, Park, Hyun Woong, Suarez, Carmen, Zhao, Dong, Catapano, Alberico, Ducimetiere, Pierre, Chien, Kuo Liong, Price, Jackie F., Bergström, Göran, Kauhanen, Jussi, Tremoli, Elena, Dörr, Marcus, Berenson, Gerald, Papagianni, Aikaterini, Kablak-Ziembicka, Anna, Kitagawa, Kazuo, Dekker, Jaqueline M., Stolic, Radojica, Polak, Joseph F., Sitzer, Matthias, Bickel, Horst, Rundek, Tatjana, Hofman, Albert, Ekart, Robert, Frauchiger, Beat, Castelnuovo, Samuela, Rosvall, Maria, Zoccali, Carmine, Landecho, Manuel F., Bae, Jang Ho, Gabriel, Rafael, Liu, Jing, Baldassarre, Damiano, Kavousi, Maryam, Cardiovasculaire Epi Team 5, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Lorenz, Matthias W., Abdi, Negin Ashtiani, Scheckenbach, Frank, Pflug, Anja, Bülbül, Alpaslan, Catapano, Alberico L., Agewall, Stefan, Ezhov, Marat, Bots, Michiel L., Kiechl, Stefan, Orth, Andreas, Norata, Giuseppe D., Empana, Jean Philippe, Lin, Hung Ju, McLachlan, Stela, Bokemark, Lena, Ronkainen, Kimmo, Amato, Mauro, Schminke, Ulf, Srinivasan, Sathanur R., Lind, Lars, Kato, Akihiko, Dimitriadis, Chrystosomos, Przewlocki, Tadeusz, Okazaki, Shuhei, Stehouwer, C. D.A., Lazarevic, Tatjana, Willeit, Peter, Yanez, David N., Steinmetz, Helmuth, Sander, Dirk, Poppert, Holger, Desvarieux, Moise, Ikram, M. Arfan, Bevc, Sebastjan, Staub, Daniel, Sirtori, Cesare R., Iglseder, Bernhard, Engström, Gunnar, Tripepi, Giovanni, Beloqui, Oscar, Lee, Moo Sik, Friera, Alfonsa, Xie, Wuxiang, Grigore, Liliana, Plichart, Matthieu, Su, Ta Chen, Robertson, Christine, Schmidt, Caroline, Tuomainen, Tomi Pekka, Veglia, Fabrizio, Völzke, Henry, Nijpels, Giel, Jovanovic, Aleksandar, Willeit, Johann, Sacco, Ralph L., Franco, Oscar H., Hojs, Radovan, Uthoff, Heiko, Hedblad, Bo, Park, Hyun Woong, Suarez, Carmen, Zhao, Dong, Catapano, Alberico, Ducimetiere, Pierre, Chien, Kuo Liong, Price, Jackie F., Bergström, Göran, Kauhanen, Jussi, Tremoli, Elena, Dörr, Marcus, Berenson, Gerald, Papagianni, Aikaterini, Kablak-Ziembicka, Anna, Kitagawa, Kazuo, Dekker, Jaqueline M., Stolic, Radojica, Polak, Joseph F., Sitzer, Matthias, Bickel, Horst, Rundek, Tatjana, Hofman, Albert, Ekart, Robert, Frauchiger, Beat, Castelnuovo, Samuela, Rosvall, Maria, Zoccali, Carmine, Landecho, Manuel F., Bae, Jang Ho, Gabriel, Rafael, Liu, Jing, Baldassarre, Damiano, and Kavousi, Maryam

Published
2017

56. Familial hypercholesterolemia: The Italian Atherosclerosis Society Network (LIPIGEN)

Author

Averna, Maurizio, primary, Cefalù, Angelo B., additional, Casula, Manuela, additional, Noto, Davide, additional, Arca, Marcello, additional, Bertolini, Stefano, additional, Calandra, Sebastiano, additional, Catapano, Alberico L., additional, Tarugi, Patrizia, additional, Averna, Maurizio, additional, Catapano, Alberico Luigi, additional, Pellegatta, Fabio, additional, Angelico, Francesco, additional, Bartuli, Andrea, additional, Biasucci, Giacomo, additional, Biolo, Gianni, additional, Bonanni, Luca, additional, Bonomo, Katia, additional, Borghi, Claudio, additional, Bossi, Antonio Carlo, additional, Branchi, Adriana, additional, Carubbi, Francesca, additional, Cipollone, Francesco, additional, Citroni, Nadia, additional, Federici, Massimo, additional, Ferri, Claudio, additional, Fiorenza, Anna Maria, additional, Giaccari, Andrea, additional, Giorgino, Francesco, additional, Guardamagna, Ornella, additional, Iannuzzi, Arcangelo, additional, Iughetti, Lorenzo, additional, Lupattelli, Graziana, additional, Mandraffino, Giuseppe, additional, Marcucci, Rossella, additional, Mombelli, Giuliana, additional, Muntoni, Sandro, additional, Pecchioli, Valerio, additional, Pederiva, Cristina, additional, Pipolo, Antonio, additional, Pisciotta, Livia, additional, Pujia, Arturo, additional, Purrello, Francesco, additional, Repetti, Elena, additional, Rubba, Paolo, additional, Sabbà, Carlo, additional, Sampietro, Tiziana, additional, Sarzani, Riccardo, additional, Tagliabue, Milena Paola, additional, Trenti, Chiara, additional, Vigna, Giovanni Battista, additional, Werba, Josè Pablo, additional, Zambon, Sabina, additional, Zenti, Maria Grazia, additional, Montali, Anna, additional, Fortunato, Giuliana, additional, Grigore, Liliana, additional, Del Ben, Maria, additional, Maranghi, Marianna, additional, Barbagallo, Carlo M., additional, Buonuomo, Paola Sabrina, additional, Capra, Maria Elena, additional, Vinci, Pierandrea, additional, D'Addato, Sergio, additional, Galbiati, Stella, additional, Nascimbeni, Fabio, additional, Bucci, Marco, additional, Spagnoli, Walter, additional, Cardolini, Iris, additional, Cervelli, Nazzareno, additional, Emanuela, Colombo, additional, Vinsin, A. Sun, additional, Laviola, Luigi, additional, Bello, Francesca, additional, Chiariello, Giuseppe, additional, Predieri, Barbara, additional, Siepi, Donatella, additional, Saitta, Antonino, additional, Giusti, Betti, additional, Pavanello, Chiara, additional, Lussu, Milena, additional, Prati, Lucia, additional, Banderali, Giuseppe, additional, Balleari, Giulia, additional, Montalcini, Tiziana, additional, Scicali, Roberto, additional, Gentile, Luigi, additional, Gentile, Marco, additional, Suppressa, Patrizia, additional, Sbrana, Francesco, additional, Cocci, Guido, additional, Benso, Andrea, additional, Negri, Emanuele Alberto, additional, Ghirardello, Omar, additional, Lorenzo, Vigo, additional, Zambon, Alberto, additional, Enzo, Bonora, additional, Minicocci, Ilenia, additional, Spina, Rossella, additional, Orlando, Camilla, additional, Di Taranto, Maria Donata, additional, Chiodo, Lorenzo, additional, Garlaschelli, Katia, additional, Manzato, Enzo, additional, and Tragni, Elena, additional

Published
2017
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57. Spectrum of mutations in Italian patients with familial hypercholesterolemia: New results from the LIPIGEN study

Author

Pirillo, Angela, primary, Garlaschelli, Katia, additional, Arca, Marcello, additional, Averna, Maurizio, additional, Bertolini, Stefano, additional, Calandra, Sebastiano, additional, Tarugi, Patrizia, additional, Catapano, Alberico L., additional, Catapano, Alberico Luigi, additional, Pellegatta, Fabio, additional, Angelico, Francesco, additional, Bartuli, Andrea, additional, Biasucci, Giacomo, additional, Biolo, Gianni, additional, Bonanni, Luca, additional, Bonomo, Katia, additional, Borghi, Claudio, additional, Bossi, Antonio Carlo, additional, Branchi, Adriana, additional, Carubbi, Francesca, additional, Cipollone, Francesco, additional, Citroni, Nadia, additional, Federici, Massimo, additional, Ferri, Claudio, additional, Fiorenza, Anna Maria, additional, Giaccari, Andrea, additional, Giorgino, Francesco, additional, Guardamagna, Ornella, additional, Iannuzzi, Arcangelo, additional, Iughetti, Lorenzo, additional, Lupattelli, Graziana, additional, Mandraffino, Giuseppe, additional, Marcucci, Rossella, additional, Mombelli, Giuliana, additional, Muntoni, Sandro, additional, Pecchioli, Valerio, additional, Pederiva, Cristina, additional, Pipolo, Antonio, additional, Pisciotta, Livia, additional, Pujia, Arturo, additional, Purrello, Francesco, additional, Repetti, Elena, additional, Rubba, Paolo, additional, Sabbà, Carlo, additional, Sampietro, Tiziana, additional, Sarzani, Riccardo, additional, Tagliabue, Milena Paola, additional, Trenti, Chiara, additional, Vigna, Giovanni Battista, additional, Werba, Josè Pablo, additional, Zambon, Sabina, additional, Zenti, Maria Grazia, additional, Montali, Anna, additional, Noto, Davide, additional, Fortunato, Giuliana, additional, Grigore, Liliana, additional, Del Ben, Maria, additional, Maranghi, Marianna, additional, Cefalù, A. Baldassarre, additional, Buonuomo, Paola Sabrina, additional, Capra, Maria Elena, additional, Vinci, Pierandrea, additional, D'Addato, Sergio, additional, Galbiati, Stella, additional, Nascimbeni, Fabio, additional, Bucci, Marco, additional, Spagnoli, Walter, additional, Cardolini, Iris, additional, Cervelli, Nazzareno, additional, Emanuela, Colombo, additional, Sun, Vinsin A., additional, Laviola, Luigi, additional, Bello, Francesca, additional, Chiariello, Giuseppe, additional, Predieri, Barbara, additional, Siepi, Donatella, additional, Saitta, Antonino, additional, Giusti, Betti, additional, Pavanello, Chiara, additional, Lussu, Milena, additional, Prati, Lucia, additional, Banderali, Giuseppe, additional, Balleari, Giulia, additional, Montalcini, Tiziana, additional, Scicali, Roberto, additional, Gentile, Luigi, additional, Gentile, Marco, additional, Suppressa, Patrizia, additional, Sbrana, Francesco, additional, Cocci, Guido, additional, Benso, Andrea, additional, Negri, Emanuele Alberto, additional, Ghirardello, Omar, additional, Lorenzo, Vigo, additional, Zambon, Alberto, additional, Enzo, Bonora, additional, Minicocci, Ilenia, additional, Spina, Rossella, additional, Orlando, Camilla, additional, Di Taranto, Maria Donata, additional, Casula, Manuela, additional, Chiodo, Lorenzo, additional, Manzato, Enzo, additional, and Tragni, Elena, additional

Published
2017
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63. Characterization of metabolic syndrome in PLIC cohort

Author

Casula, Manuela, primary, Chiodo, Lorenzo, additional, Baragetti, Andrea, additional, Garlaschelli, Katia, additional, Grigore, Liliana, additional, Norata, Giuseppe Danilo, additional, Pellegatta, Fabio, additional, Redaelli, Laura, additional, Tidone, Cristina, additional, Tragni, Elena, additional, and Catapano, Alberico Luigi, additional

Published
2017
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68. PCSK9 deficiency reduces insulin secretion and promotes glucose intolerance: the role of the low-density lipoprotein receptor.

Author

Dalt, Lorenzo Da, Ruscica, Massimiliano, Bonacina, Fabrizia, Balzarotti, Gloria, Dhyani, Ashish, Cairano, Eliana Di, Baragetti, Andrea, Arnaboldi, Lorenzo, Metrio, Simona De, Pellegatta, Fabio, Grigore, Liliana, Botta, Margherita, Macchi, Chiara, Uboldi, Patrizia, Perego, Carla, Catapano, Alberico Luigi, and Norata, Giuseppe Danilo

Abstract

Aims PCSK9 loss of function genetic variants are associated with lower low-density lipoprotein cholesterol but also with higher plasma glucose levels and increased risk of Type 2 diabetes mellitus. Here, we investigated the molecular mechanisms underlying this association. Methods and results Pcsk9 KO, WT, Pcsk9/Ldlr double KO (DKO), Ldlr KO, albumin AlbCre+/Pcsk9LoxP/LoxP (liver-selective Pcsk9 knock-out mice), and AlbCre-/Pcsk9LoxP/LoxP mice were used. GTT, ITT, insulin and C-peptide plasma levels, pancreas morphology, and cholesterol accumulation in pancreatic islets were studied in the different animal models. Glucose clearance was significantly impaired in Pcsk9 KO mice fed with a standard or a high-fat diet for 20 weeks compared with WT animals; insulin sensitivity, however, was not affected. A detailed analysis of pancreas morphology of Pcsk9 KO mice vs. controls revealed larger islets with increased accumulation of cholesteryl esters, paralleled by increased insulin intracellular levels and decreased plasma insulin, and C-peptide levels. This phenotype was completely reverted in Pcsk9/Ldlr DKO mice implying the low-density lipoprotein receptor (LDLR) as the proprotein convertase subtilisin/kexin Type 9 (PCSK9) target responsible for the phenotype observed. Further studies in albumin AlbCre+/Pcsk9LoxP/LoxP mice, which lack detectable circulating PCSK9, also showed a complete recovery of the phenotype, thus indicating that circulating, liver-derived PCSK9, the principal target of monoclonal antibodies, does not impact beta-cell function and insulin secretion. Conclusion PCSK9 critically controls LDLR expression in pancreas perhaps contributing to the maintenance of a proper physiological balance to limit cholesterol overload in beta cells. This effect is independent of circulating PCSK9 and is probably related to locally produced PCSK9. View large Download slide View large Download slide [ABSTRACT FROM AUTHOR]

Published
2019
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69. Normative values for carotid intima media thickness and its progression : Are they transferrable outside of their cohort of origin?

Author

Liao, Ximing, Norata, Giuseppe D., Polak, Joseph F., Stehouwer, Coen D. A., Catapano, Alberico, Rundek, Tatjana, Ezhov, Marat, Sander, Dirk, Thompson, Simon G., Lorenz, Matthias W., Balakhonova, Tatyana, Safarova, Maya, Grigore, Liliana, Empana, Jean-Philippe, Lin, Hung-Ju, McLachlan, Stela, Bokemark, Lena, Ronkainen, Kimmo, Schminke, Ulf, Lind, Lars, Willeit, Peter, Yanez, David N., Steinmetz, Helmuth, Poppert, Holger, Desvarieux, Moise, Ikram, M. Arfan, Johnsen, Stein Harald, Iglseder, Bernhard, Friera, Alfonsa, Xie, Wuxiang, Plichart, Matthieu, Su, Ta-Chen, Srinivasan, Sathanur R., Schmidt, Caroline, Tuomainen, Tomi-Pekka, Volzke, Henry, Nijpels, Giel, Willeit, Johann, Franco, Oscar H., Suarez, Carmen, Zhao, Dong, Ducimetiere, Pierre, Chien, Kuo-Liong, Robertson, Christine, Bergstrom, Goran, Kauhanen, Jussi, Dorr, Marcus, Dekker, Jaqueline M., Kiechl, Stefan, Sitzer, Matthias, Bickel, Horst, Sacco, Ralph L., Hofman, Albert, Mathiesen, Ellisiv B., Gabriel, Rafael, Liu, Jing, Berenson, Gerald, Kavousi, Maryam, Price, Jackie F., Liao, Ximing, Norata, Giuseppe D., Polak, Joseph F., Stehouwer, Coen D. A., Catapano, Alberico, Rundek, Tatjana, Ezhov, Marat, Sander, Dirk, Thompson, Simon G., Lorenz, Matthias W., Balakhonova, Tatyana, Safarova, Maya, Grigore, Liliana, Empana, Jean-Philippe, Lin, Hung-Ju, McLachlan, Stela, Bokemark, Lena, Ronkainen, Kimmo, Schminke, Ulf, Lind, Lars, Willeit, Peter, Yanez, David N., Steinmetz, Helmuth, Poppert, Holger, Desvarieux, Moise, Ikram, M. Arfan, Johnsen, Stein Harald, Iglseder, Bernhard, Friera, Alfonsa, Xie, Wuxiang, Plichart, Matthieu, Su, Ta-Chen, Srinivasan, Sathanur R., Schmidt, Caroline, Tuomainen, Tomi-Pekka, Volzke, Henry, Nijpels, Giel, Willeit, Johann, Franco, Oscar H., Suarez, Carmen, Zhao, Dong, Ducimetiere, Pierre, Chien, Kuo-Liong, Robertson, Christine, Bergstrom, Goran, Kauhanen, Jussi, Dorr, Marcus, Dekker, Jaqueline M., Kiechl, Stefan, Sitzer, Matthias, Bickel, Horst, Sacco, Ralph L., Hofman, Albert, Mathiesen, Ellisiv B., Gabriel, Rafael, Liu, Jing, Berenson, Gerald, Kavousi, Maryam, and Price, Jackie F.

Abstract

Background The clinical use of carotid intima media thickness (cIMT) requires normal values, which may be subject to variation of geographical factors, ethnicity or measurement details. The influence of these factors has rarely been studied. The aim of this study was to determine whether normative cIMT values and their association with event risk are generalizable across populations. Design Meta-analysis of individual participant data. Method From 22 general population cohorts from Europe, North America and Asia we selected subjects free of cardiovascular disease. Percentiles of cIMT and cIMT progression were assessed separately for every cohort. Cox proportional hazards models for vascular events were used to estimate hazard ratios for cIMT in each cohort. The estimates were pooled across Europe, North America and Asia, with random effects meta-analysis. The influence of geography, ethnicity and ultrasound protocols on cIMT values and on the hazard ratios was examined by meta-regression. Results Geographical factors, ethnicity and the ultrasound protocol had influence neither on the percentiles of cIMT and its progression, nor on the hazard ratios of cIMT for vascular events. Heterogeneity for percentiles of cIMT and cIMT progression was too large to create meaningful normative values. Conclusions The distribution of cIMT values is too heterogeneous to define universal or regional population reference values. CIMT values vary widely between different studies regardless of ethnicity, geographic location and ultrasound protocol. Prediction of vascular events with cIMT values was more consistent across all cohorts, ethnicities and regions.

Published
2016
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71. Epicardial Adipose Tissue (EAT) Thickness Is Associated with Cardiovascular and Liver Damage in Nonalcoholic Fatty Liver Disease

Author

Fracanzani, Anna Ludovica, primary, Pisano, Giuseppina, additional, Consonni, Dario, additional, Tiraboschi, Silvia, additional, Baragetti, Andrea, additional, Bertelli, Cristina, additional, Norata, Giuseppe Danilo, additional, Dongiovanni, Paola, additional, Valenti, Luca, additional, Grigore, Liliana, additional, Tonella, Tatiana, additional, Catapano, Alberico, additional, and Fargion, Silvia, additional

Published
2016
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72. Carotid Intima-Media Thickness Progression and Risk of Vascular Events in People With Diabetes: Results From the PROG-IMT Collaboration

Author

Cardiovasculaire Epi Team 5, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Lorenz, Matthias W., Price, Jackie F., Robertson, Christine, Bots, Michiel L., Polak, Joseph F., Poppert, Holger, Kavousi, Maryam, Doerr, Marcus, Stensland, Eva, Ducimetiere, Pierre, Ronkainen, Kimmo, Kiechl, Stefan, Sitzer, Matthias, Rundek, Tatjana, Lind, Lars, Liu, Jing, Bergstrom, Goran, Grigore, Liliana, Bokemark, Lena, Friera, Alfonsa, Yanez, David, Bickel, Horst, Ikram, M. Arfan, Voelzke, Henry, Johnsen, Stein Harald, Empana, Jean Philippe, Tuomainen, Tomi-Pekka, Willeit, Peter, Steinmetz, Helmuth, Desvarieux, Moise, Xie, Wuxiang, Schmidt, Caroline, Norata, Giuseppe D., Suarez, Carmen, Sander, Dirk, Hofman, Albert, Schminke, Ulf, Mathiesen, Ellisiv, Plichart, Matthieu, Kauhanen, Jussi, Willeit, Johann, Sacco, Ralph L., McLachlan, Stela, Zhao, Dong, Fagerberg, Bjorn, Catapano, Alberico L., Gabriel, Rafael, Franco, Oscar H., Buelbuel, Alpaslan, Scheckenbach, Frank, Pflug, Anja, Gao, Lu, Thompson, Simon G., Cardiovasculaire Epi Team 5, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Lorenz, Matthias W., Price, Jackie F., Robertson, Christine, Bots, Michiel L., Polak, Joseph F., Poppert, Holger, Kavousi, Maryam, Doerr, Marcus, Stensland, Eva, Ducimetiere, Pierre, Ronkainen, Kimmo, Kiechl, Stefan, Sitzer, Matthias, Rundek, Tatjana, Lind, Lars, Liu, Jing, Bergstrom, Goran, Grigore, Liliana, Bokemark, Lena, Friera, Alfonsa, Yanez, David, Bickel, Horst, Ikram, M. Arfan, Voelzke, Henry, Johnsen, Stein Harald, Empana, Jean Philippe, Tuomainen, Tomi-Pekka, Willeit, Peter, Steinmetz, Helmuth, Desvarieux, Moise, Xie, Wuxiang, Schmidt, Caroline, Norata, Giuseppe D., Suarez, Carmen, Sander, Dirk, Hofman, Albert, Schminke, Ulf, Mathiesen, Ellisiv, Plichart, Matthieu, Kauhanen, Jussi, Willeit, Johann, Sacco, Ralph L., McLachlan, Stela, Zhao, Dong, Fagerberg, Bjorn, Catapano, Alberico L., Gabriel, Rafael, Franco, Oscar H., Buelbuel, Alpaslan, Scheckenbach, Frank, Pflug, Anja, Gao, Lu, and Thompson, Simon G.

Published
2015

75. Homozygous familial hypobetalipoproteinemia: Two novel mutations in the splicing sites of apolipoprotein B gene and review of the literature

Author

Cefalù, Angelo B., primary, Norata, Giuseppe D., additional, Ghiglioni, Daniele G., additional, Noto, Davide, additional, Uboldi, Patrizia, additional, Garlaschelli, Katia, additional, Baragetti, Andrea, additional, Spina, Rossella, additional, Valenti, Vincenza, additional, Pederiva, Cristina, additional, Riva, Enrica, additional, Terracciano, Luigi, additional, Zoja, Alexa, additional, Grigore, Liliana, additional, Averna, Maurizio R., additional, and Catapano, Alberico L., additional

Published
2015
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76. The Mission of Universities in the Processes of Research - Innovation and Development of Entrepreneurial Culture

Author

GRIGORE Liliana Nicoleta, CANDIDATU Camelia, and BLIDEANU Dana Constanţa

Subjects
jel:I23, jel:L26, jel:H75, academic research, entrepreneurial culture, research and innovation, partnership universities – industry – business environment, strategic mission of the university
Abstract

The article reveals the importance of academic research in the context of new requirements of the knowledge economy. The strategic mission of universities should focus on defining the elements of "a culture of research": the accumulation of knowledge, the renewal of learning methods, the enlargement of research capacity, the growth in revenues resulting from research activities, the strengthening of the links between institutions that develop research in order to meet the challenges arising from the responsibilities to the society and from pointing out the international status of the university. In the analytical approach the authors have put emphasis on the imperative of establishing a cooperative relationship between academic, industry and business environments in order to achieve the general objectives - related to social and economic development at national and regional level - as well as the specific ones - related to the progress of the education, research and innovation fields. The study presents a number of European initiatives aimed to contribute, on the one hand, to the achievement of the university strategic mission in the research domain, and on the other hand, to the defining and development of an entrepreneurial culture. These initiatives are achieved through the integration of academic activities (training, skill development, and insertion of all categories of professionals in research) with activities from the industry and business areas in some specific structures such as business incubators, industrial and research parks, "universities – business" foundations, and research networks.

Published
2009

78. Combination therapy in cholesterol reduction: focus on ezetimibe and statins

Author

Grigore,Liliana, Norata,Giuseppe Danilo, Catapano,Alberico L, Grigore,Liliana, Norata,Giuseppe Danilo, and Catapano,Alberico L

Abstract

Liliana Grigore1, Giuseppe Danilo Norata1,2, Alberico L Catapano1,21Department of Pharmacological Sciences, University of Milan, Milan, Italy; 2Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello B, ItalyAbstract: Although widely used in lipid lowering therapy, HMG CoA reductase inhibitors (even when administered at high doses) are frequently insufficient to achieve guideline-recommended LDL-C goals for many patients with hypercholesterolemia in everyday clinical practice. Many patients do not achieve LDL-C goal on the initial dose of statin and the majority of these patients does not reach their goal after 6 months. As a consequence, a wide therapeutic gap exists between target LDL-C levels and those typically achieved in clinical practice. A recent and more effective therapeutic hypocholesterolemic strategy is to treat the two main sources of cholesterol simultaneously (production of cholesterol, mainly in the liver, and absorption of cholesterol in the intestine) with a complementary mechanism of action, by co-administering ezetimibe, a novel agent inhibiting cholesterol absorption, with a statin, which inhibits cholesterol production in the liver. Ezetimibe can be effectively and safely co-administered with any dose of any statin and, compared with the single inhibition of cholesterol production, afforded by statins alone, provides consistently greater reductions in LDL-C through dual inhibition of both cholesterol production and absorption. We summarize the pivotal role of both the liver and intestine in the overall balance of cholesterol in the body and describe the clinical impact and relevance of using ezetimibe either alone or co-administered with statins in controlling elevated levels of plasma LDL cholesterol.Keywords: hypercholesterolemia, cholesterol absorption, cholesterol biosynthesis, ezetimibe, HMG CoA reductase inhibitors, LDL-C

Published
2008

80. -374 T/A RAGE Polymorphism Is Associated with Chronic Kidney Disease Progression in Subjects Affected by Nephrocardiovascular Disease

Author

Baragetti, Ivano, primary, Norata, Giuseppe Danilo, additional, Sarcina, Cristina, additional, Baragetti, Andrea, additional, Rastelli, Francesco, additional, Buzzi, Laura, additional, Grigore, Liliana, additional, Garlaschelli, Katia, additional, Pozzi, Claudio, additional, and Catapano, Alberico Luigi, additional

Published
2013
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82. Effector Memory T cells Are Associated With Atherosclerosis in Humans and Animal Models

Author

Ammirati, Enrico, primary, Cianflone, Domenico, additional, Vecchio, Viviana, additional, Banfi, Michela, additional, Vermi, Anna C., additional, De Metrio, Monica, additional, Grigore, Liliana, additional, Pellegatta, Fabio, additional, Pirillo, Angela, additional, Garlaschelli, Katia, additional, Manfredi, Angelo A., additional, Catapano, Alberico L., additional, Maseri, Attilio, additional, Palini, Alessio G., additional, and Norata, Giuseppe D., additional

Published
2012
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83. Association between OLR1 K167N SNP and Intima Media Thickness of the Common Carotid Artery in the General Population

Author

Predazzi, Irene Marta, primary, Norata, Giuseppe Danilo, additional, Vecchione, Lucia, additional, Garlaschelli, Katia, additional, Amati, Francesca, additional, Grigore, Liliana, additional, Cutuli, Lucia, additional, Pirillo, Angela, additional, Tramontana, Simona, additional, Romeo, Francesco, additional, Novelli, Giuseppe, additional, and Catapano, Alberico Luigi, additional

Published
2012
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85. Circulating CD4 + CD25 hi CD127 lo Regulatory T-Cell Levels Do Not Reflect the Extent or Severity of Carotid and Coronary Atherosclerosis

Author

Ammirati, Enrico, primary, Cianflone, Domenico, additional, Banfi, Michela, additional, Vecchio, Viviana, additional, Palini, Alessio, additional, De Metrio, Monica, additional, Marenzi, Giancarlo, additional, Panciroli, Claudio, additional, Tumminello, Gabriele, additional, Anzuini, Angelo, additional, Palloshi, Altin, additional, Grigore, Liliana, additional, Garlaschelli, Katia, additional, Tramontana, Simona, additional, Tavano, Davide, additional, Airoldi, Flavio, additional, Manfredi, Angelo A., additional, Catapano, Alberico Luigi, additional, and Norata, Giuseppe Danilo, additional

Published
2010
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86. Effects of PCSK9 variants on common carotid artery intima media thickness and relation to ApoE alleles

Author

Norata, Giuseppe Danilo, primary, Garlaschelli, Katia, additional, Grigore, Liliana, additional, Raselli, Sara, additional, Tramontana, Simona, additional, Meneghetti, Fiorella, additional, Artali, Roberto, additional, Noto, Davide, additional, Cefalù, Angelo Baldassare, additional, Buccianti, Gherardo, additional, Averna, Maurizio, additional, and Catapano, Alberico Luigi, additional

Published
2010
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91. Effect of treatment with pravastatin or ezetimibe on endothelial function in patients with moderate hypercholesterolemia.

Author

Grigore, Liliana, Raselli, Sara, Garlaschelli, Katia, Redaelli, Laura, Norata, Giuseppe, Pirillo, Angela, and Catapano, Alberico

Subjects
*STATINS (Cardiovascular agents), *CLINICAL trials, *ENDOTHELIUM, *HYPERCHOLESTEREMIA, *RESEARCH funding, *T-test (Statistics), *PRAVASTATIN, *PRE-tests & post-tests, *DATA analysis software, *EZETIMIBE, *DESCRIPTIVE statistics, *PHARMACODYNAMICS, *THERAPEUTICS
Abstract

Background/Aim: Statin treatment improves endothelial function. It is matter of debate, however, if this effect of statins is due to their action on low-density lipoprotein cholesterol (LDL-C) or to other non-lipidic (pleiotropic) effects. The aim of this study was to evaluate whether the effect of pravastatin on endothelial function is mediated by pleiotropic effects. We therefore compared the effect of pravastatin and ezetimibe, a cholesterol absorption inhibitor, at doses yielding similar reductions in LDL-C and examined the effect of the two treatments on flow-mediated dilation (FMD) in hypercholesterolemic subjects. Methods: A total of 33 moderately hypercholesterolemic patients were randomized into three treatment groups to receive ezetimibe 10 mg/day ( n = 10), pravastatin 10 mg/day ( n = 13) or no treatment (control, n = 10) for 6 weeks. To assess endothelial function, we determined FMD of the brachial artery non-invasively by high-resolution ultrasound before and after treatment. Results: Ezetimibe and pravastatin treatment reduced LDL-C (mean ± standard error) to a similar extent (−20.6 ± 4.1 vs. −24.1 ± 4.0 %, respectively; P = 0.4771), while no decrease was observed in the control group. FMD increased significantly after treatment with ezetimibe (from 11.4 ± 5.7 to 16.8 ± 3.6 %; P = 0.022) and with pravastatin (from 13.7 ± 4.9 to 17.5 ± 4.4 %; P = 0.0466), but not in the control group. There were no differences in the endothelial function changes between the two treatment groups. Conclusions: In this study, two treatments that lower cholesterol via different mechanisms improved endothelial function to a similar extent, suggesting that the observed effect can be explained by the reduction of cholesterol levels. [ABSTRACT FROM AUTHOR]

Published
2013
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92. THE ROLE OF KNOWLEDGE IN THE INTERNATIONALIZATION PROCESS OF SMALL AND MEDIUM ENTERPRISES.

Author

Grigore, Liliana, Stǎnculescu, Anca Maria, Gagea, Andreea Mihaela, and Grigore, Ana-Maria

Subjects
SMALL business, GLOBALIZATION, KNOWLEDGE-based theory of the firm, RESOURCE-based theory of the firm, COMPETITIVE advantage in business, BUSINESS intelligence, KNOWLEDGE base, BUSINESS planning, BUSINESS development
Abstract

The article analyses the role knowledge plays in the internationalization process of small and medium enterprises. Small and medium enterprises are considered from a knowledge-based view, an extension of the resource-based view of the firm, with knowledge as the most strategically significant resource of a firm and the basis for building and sustaining competitive advantage in nowadays complex, dynamic environment. Knowledge may be thus viewed as an essential determinant of small and medium enterprises internationalization processes. The assigned models of small and medium enterprises internationalization refer to this role, and an examination of the different approaches allows for an integrated view of the ways in which knowledge may determine, influence and support small and medium enterprises internationalization. Small and medium enterprises internationalization strategy development implies several specific phases which are analyzed in order to identify the knowledge necessities for internationalizing small and medium enterprises. Knowledge is then object of certain knowledge processes which include knowledge acquirement, through creation or acquisition, use, handling and development, and revaluation, that are further analyzed according to their specificity related to small and medium enterprises internationalization. A special focus is placed on the process of knowledge acquirement, as the main premise of the internationalization process. These considerations are applied in the case of Romanian small and medium enterprises, providing proposals regarding possible ways of integrating knowledge in the process of internationalization and facilitating their access to knowledge. [ABSTRACT FROM AUTHOR]

Published
2009

94. Carotid intima-media thickness progression and risk of vascular events in people with diabetes: results from the PROG-IMT collaboration

Author

Lorenz, Matthias W, Price, Jackie F, Robertson, Christine, Bots, Michiel L, Polak, Joseph F, Poppert, Holger, Kavousi, Maryam, Dörr, Marcus, Stensland, Eva, Ducimetiere, Pierre, Ronkainen, Kimmo, Kiechl, Stefan, Sitzer, Matthias, Rundek, Tatjana, Lind, Lars, Liu, Jing, Bergström, Göran, Grigore, Liliana, Bokemark, Lena, Friera, Alfonsa, Yanez, David, Bickel, Horst, Ikram, M Arfan, Völzke, Henry, Johnsen, Stein Harald, Empana, Jean Philippe, Tuomainen, Tomi-Pekka, Willeit, Peter, Steinmetz, Helmuth, Desvarieux, Moise, Xie, Wuxiang, Schmidt, Caroline, Norata, Giuseppe D, Suarez, Carmen, Sander, Dirk, Hofman, Albert, Schminke, Ulf, Mathiesen, Ellisiv, Plichart, Matthieu, Kauhanen, Jussi, Willeit, Johann, Sacco, Ralph L, McLachlan, Stela, Zhao, Dong, Fagerberg, Björn, Catapano, Alberico L, Gabriel, Rafael, Franco, Oscar H, Bülbül, Alpaslan, Scheckenbach, Frank, Pflug, Anja, Gao, Lu, and Thompson, Simon G

Subjects
Adult, Aged, 80 and over, Male, Carotid Artery, Common, Middle Aged, Atherosclerosis, Carotid Intima-Media Thickness, 3. Good health, Diabetes Mellitus, Type 2, Risk Factors, cardiovascular system, Disease Progression, Humans, Female, cardiovascular diseases, Cooperative Behavior, Diabetic Angiopathies, Aged, Proportional Hazards Models
Abstract

OBJECTIVE: Carotid intima-media thickness (CIMT) is a marker of subclinical organ damage and predicts cardiovascular disease (CVD) events in the general population. It has also been associated with vascular risk in people with diabetes. However, the association of CIMT change in repeated examinations with subsequent CVD events is uncertain, and its use as a surrogate end point in clinical trials is controversial. We aimed at determining the relation of CIMT change to CVD events in people with diabetes. RESEARCH DESIGN AND METHODS: In a comprehensive meta-analysis of individual participant data, we collated data from 3,902 adults (age 33-92 years) with type 2 diabetes from 21 population-based cohorts. We calculated the hazard ratio (HR) per standard deviation (SD) difference in mean common carotid artery intima-media thickness (CCA-IMT) or in CCA-IMT progression, both calculated from two examinations on average 3.6 years apart, for each cohort, and combined the estimates with random-effects meta-analysis. RESULTS: Average mean CCA-IMT ranged from 0.72 to 0.97 mm across cohorts in people with diabetes. The HR of CVD events was 1.22 (95% CI 1.12-1.33) per SD difference in mean CCA-IMT, after adjustment for age, sex, and cardiometabolic risk factors. Average mean CCA-IMT progression in people with diabetes ranged between -0.09 and 0.04 mm/year. The HR per SD difference in mean CCA-IMT progression was 0.99 (0.91-1.08). CONCLUSIONS: Despite reproducing the association between CIMT level and vascular risk in subjects with diabetes, we did not find an association between CIMT change and vascular risk. These results do not support the use of CIMT progression as a surrogate end point in clinical trials in people with diabetes.

95. Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration

Author

Lorenz, Matthias W, Gao, Lu, Ziegelbauer, Kathrin, Norata, Giuseppe Danilo, Empana, Jean Philippe, Schmidtmann, Irene, Lin, Hung-Ju, McLachlan, Stela, Bokemark, Lena, Ronkainen, Kimmo, Amato, Mauro, Schminke, Ulf, Srinivasan, Sathanur R, Lind, Lars, Okazaki, Shuhei, Stehouwer, Coen DA, Willeit, Peter, Polak, Joseph F, Steinmetz, Helmuth, Sander, Dirk, Poppert, Holger, Desvarieux, Moise, Ikram, M Arfan, Johnsen, Stein Harald, Staub, Daniel, Sirtori, Cesare R, Iglseder, Bernhard, Beloqui, Oscar, Engström, Gunnar, Friera, Alfonso, Rozza, Francesco, Xie, Wuxiang, Parraga, Grace, Grigore, Liliana, Plichart, Matthieu, Blankenberg, Stefan, Su, Ta-Chen, Schmidt, Caroline, Tuomainen, Tomi-Pekka, Veglia, Fabrizio, Völzke, Henry, Nijpels, Giel, Willeit, Johann, Sacco, Ralph L, Franco, Oscar H, Uthoff, Heiko, Hedblad, Bo, Suarez, Carmen, Izzo, Raffaele, Zhao, Dong, Wannarong, Thapat, Catapano, Alberico, Ducimetiere, Pierre, Espinola-Klein, Christine, Chien, Kuo-Liong, Price, Jackie F, Bergström, Göran, Kauhanen, Jussi, Tremoli, Elena, Dörr, Marcus, Berenson, Gerald, Kitagawa, Kazuo, Dekker, Jacqueline M, Kiechl, Stefan, Sitzer, Matthias, Bickel, Horst, Rundek, Tatjana, Hofman, Albert, Mathiesen, Ellisiv B, Castelnuovo, Samuela, Landecho, Manuel F, Rosvall, Maria, Gabriel, Rafael, De Luca, Nicola, Liu, Jing, Baldassarre, Damiano, Kavousi, Maryam, De Groot, Eric, Bots, Michiel L, Yanez, David N, Thompson, Simon G, and PROG-IMT Study Group

Subjects
Male, Cardiovascular Diseases, Risk Factors, cardiovascular system, Humans, Female, cardiovascular diseases, Middle Aged, Prognosis, Carotid Intima-Media Thickness, Intersectoral Collaboration, 3. Good health, Aged
Abstract

AIMS: Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk. METHODS AND RESULTS: From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C. CONCLUSIONS: We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.

96. Progression of conventional cardiovascular risk factors and vascular disease risk in individuals: insights from the PROG-IMT consortium

Author

Bahls, Martin, Lorenz, Matthias W, Dörr, Marcus, Gao, Lu, Kitagawa, Kazuo, Tuomainen, Tomi-Pekka, Agewall, Stefan, Berenson, Gerald, Catapano, Alberico L, Norata, Giuseppe D, Bots, Michiel L, Van Gilst, Wiek, Asselbergs, Folkert W, Brouwers, Frank P, Uthoff, Heiko, Sander, Dirk, Poppert, Holger, Hecht Olsen, Michael, Empana, Jean Philippe, Schminke, Ulf, Baldassarre, Damiano, Veglia, Fabrizio, Franco, Oscar H, Kavousi, Maryam, De Groot, Eric, Mathiesen, Ellisiv B, Grigore, Liliana, Polak, Joseph F, Rundek, Tatjana, Stehouwer, Coen DA, Skilton, Michael R, Hatzitolios, Apostolos I, Savopoulos, Christos, Ntaios, George, Plichart, Matthieu, McLachlan, Stela, Lind, Lars, Willeit, Peter, Steinmetz, Helmuth, Desvarieux, Moise, Ikram, M Arfan, Johnsen, Stein Harald, Schmidt, Caroline, Willeit, Johann, Ducimetiere, Pierre, Price, Jackie F, Bergström, Göran, Kauhanen, Jussi, Kiechl, Stefan, Sitzer, Matthias, Bickel, Horst, Sacco, Ralph L, Hofman, Albert, Völzke, Henry, and Thompson, Simon G

Subjects
lipids (amino acids, peptides, and proteins), 610 Medicine & health, 360 Social problems & social services, 3. Good health
Abstract

AIMS Averaged measurements, but not the progression based on multiple assessments of carotid intima-media thickness, (cIMT) are predictive of cardiovascular disease (CVD) events in individuals. Whether this is true for conventional risk factors is unclear. METHODS AND RESULTS An individual participant meta-analysis was used to associate the annualised progression of systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with future cardiovascular disease risk in 13 prospective cohort studies of the PROG-IMT collaboration (n = 34,072). Follow-up data included information on a combined cardiovascular disease endpoint of myocardial infarction, stroke, or vascular death. In secondary analyses, annualised progression was replaced with average. Log hazard ratios per standard deviation difference were pooled across studies by a random effects meta-analysis. In primary analysis, the annualised progression of total cholesterol was marginally related to a higher cardiovascular disease risk (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.00 to 1.07). The annualised progression of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol was not associated with future cardiovascular disease risk. In secondary analysis, average systolic blood pressure (HR 1.20 95% CI 1.11 to 1.29) and low-density lipoprotein cholesterol (HR 1.09, 95% CI 1.02 to 1.16) were related to a greater, while high-density lipoprotein cholesterol (HR 0.92, 95% CI 0.88 to 0.97) was related to a lower risk of future cardiovascular disease events. CONCLUSION Averaged measurements of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol displayed significant linear relationships with the risk of future cardiovascular disease events. However, there was no clear association between the annualised progression of these conventional risk factors in individuals with the risk of future clinical endpoints.

97. Twelve Variants Polygenic Score for Low-Density Lipoprotein Cholesterol Distribution in a Large Cohort of Patients With Clinically Diagnosed Familial Hypercholesterolemia With or Without Causative Mutations

Author

Olmastroni, E., Gazzotti, M., Arca, M., Averna, M., Pirillo, A., Catapano, A. L., Casula, M., Marcello, A., Maurizio, A., Stefano, B., Sebastiano, C., Luigi, C. A., Patrizia, T., Fabio, P., Andrea, B., Giacomo, B., Gianni, B., Luca, B., Katia, B., Claudio, B., Carlo, B. A., Adriana, B., Paolo, C., Francesca, C., Francesco, C., Nadia, C., Maria, D. B., Massimo, F., Claudio, F., Maria, F. A., Andrea, G., Ornella, G., Arcangelo, I., Gabriella, I., Lorenzo, I., Graziana, L., Alessandro, L., Giuseppe, M., Rossella, M., Lorenzo, M., Giuliana, M., Sandro, M., Valerio, P., Cristina, P., Antonio, P., Livia, P., Arturo, P., Francesco, P., Elena, R., Carlo, S., Riccardo, S., Chiara, T., Battista, V. G., Pablo, W. J., Sabina, Z., Grazia, Z. M., Alessia, D. C., Giuliana, F., Rossella, S., Davide, B., Giuseppe, B., Francesco, B., Guglielmo, B., Sandra, B., Patrizia, B., Marco, B., Sabrina, B. P., Elena, C. M., Iris, C., Baldassarre, C. A., Maria, C., Emanuela, C., Giuseppe, C., Laura, C. A., Ada, C., Sergio, D., Vincenzo, D., Giuseppe, D. C., Chiara, D. P., Fabio, F., Marco, G., Omar, G., Betti, G., Davide, G., Liliana, G., Giulia, M., Giancarla, M., Ilenia, M., Simona, M., Tiziana, M., Fabio, N., Alberto, N. E., Chiara, P., Lucia, P., Rita, R. A., Elena, S., Alon, S., Roberto, S., Patrizia, S., Michele, T., Pierandrea, V., Manuela, C., Enzo, M., Elena, T., Veronic, Z., Olmastroni, Elena, Gazzotti, Marta, Arca, Marcello, Averna, Maurizio, Pirillo, Angela, Catapano, Alberico Luigi, Casula, Manuela, Stefano, Bertolini, Sebastiano, Calandra, Patrizia, Tarugi, Fabio, Pellegatta, Andrea, Bartuli, Andrea, Benso, Giacomo, Biasucci, Gianni, Biolo, Luca, Bonanni, Katia, Bonomo, Claudio, Borghi, Antonio Carlo Bossi, Adriana, Branchi, Paolo, Calabrò, Francesca, Carubbi, Francesco, Cipollone, Nadia, Citroni, Maria Del Ben, Massimo, Federici, Claudio, Ferri, Anna Maria Fiorenza, Andrea, Giaccari, Ornella, Guardamagna, Arcangelo, Iannuzzi, Iannuzzo, Gabriella, Lorenzo, Iughetti, Graziana, Lupattelli, Alessandro, Lupi, Giuseppe, Mandraffino, Rossella, Marcucci, Lorenzo, Maroni, Giuliana, Mombelli, Sandro, Muntoni, Valerio, Pecchioli, Cristina, Pederiva, Antonio, Pipolo, Livia, Pisciotta, Antonio, Pujia, Francesco, Purrello, Elena, Repetti, Carlo, Sabbà, Riccardo, Sarzani, Chiara, Trenti, Giovanni Battista Vigna, Josè Pablo Werba, Sabina, Zambon, Maria Grazia Zenti, Alessia Di Costanzo, Fortunato, Giuliana, Rossella, Spina, Davide, Baldera, Giuseppe, Banderali, Francesco, Baratta, Guglielmo, Beccuti, Sandra, Bertocco, Patrizia, Bruzzi, Marco, Bucci, Paola Sabrina Buonuomo, Maria Elena Capra, Iris, Cardolini, Angelo Baldassarre Cefalù, Maria, Cinquegrani, Emanuela, Colombo, Giuseppe, Covetti, Anna Laura Cremonini, Ada, Cutolo, Sergio, D'Addato, Vincenzo, D'Ambrosio, Giuseppe De Corrado, Chiara Di Pentima, Fabio, Fimiani, Gentile, Marco, Omar, Ghirardello, Betti, Giusti, Davide, Grassi, Liliana, Grigore, Giulia, Massini, Giancarla, Meregalli, Ilenia, Minicocci, Simona, Moffa, Tiziana, Montalcini, Fabio, Nascimbeni, Emanuele Alberto Negri, Chiara, Pavanello, Lucia, Prati, Anna Rita Roscini, Elena, Sani, Alon, Schaffer, Roberto, Scicali, Patrizia, Suppressa, Michele, Tedeschi, Pierandrea, Vinci, Enzo, Manzato, Elena, Tragni, Veronica, Zampoler, and Bertolini Stefano, Calandra Sebastiano, Tarugi Patrizia, Pellegatta Fabio, Bartuli Andrea, Benso Andrea, Biasucci Giacomo, Biolo Gianni, Bonanni Luca, Bonomo Katia, Borghi Claudio, Bossi Antonio Carlo, Branchi Adriana, Calabrò Paolo, Carubbi Francesca, Cipollone Francesco, Citroni Nadia, Del Ben Maria, Federici Massimo, Ferri Claudio, Fiorenza Anna Maria, Giaccari Andrea, Guardamagna Ornella, Iannuzzi Arcangelo, Iannuzzo Gabriella, Iughetti Lorenzo, Lupattelli Graziana, Lupi Alessandro, Mandraffino Giuseppe, Marcucci Rossella, Maroni Lorenzo, Mombelli Giuliana, Muntoni Sandro, Pecchioli Valerio, Pederiva Cristina, Pipolo Antonio, Pisciotta Livia, Pujia Arturo, Purrello Francesco, Repetti Elena, Sabbà Carlo, Sarzani Riccardo, Trenti Chiara, Vigna Giovanni Battista, Werba Josè Pablo, Zambon Sabina, Zenti Maria Grazia. Di Costanzo Alessia, Fortunato Giuliana, Spina Rossella, Baldera Davide, Banderali Giuseppe, Baratta Francesco, Beccuti Guglielmo, Bertocco Sandra, Bruzzi Patrizia, Bucci Marco, Buonuomo Paola Sabrina, Capra Maria Elena, Cardolini Iris, Cefalù Angelo Baldassare, Cinquegrani Maria, Colombo Emanuela, Covetti Giuseppe, Cremonini Anna Laura, Cutolo Ada, D’Addato Sergio, D’Ambrosio Vincenzo, De Corrado Giuseppe, Di Pentima Chiara, Fimiani Fabio, Gentile Marco, Ghirardello Omar, Giusti Betti, Grassi Davide, Grigore Liliana, Massini Giulia, Meregalli Giancarla, Minicocci Ilenia, Moffa Simona, Montalcini Tiziana, Nascimbeni Fabio, Negri Emanuele Alberto, Pavanello Chiara, Prati Lucia, Roscini Anna Rita, Sani Elena, Schaffer Alon, Scicali Roberto, Suppressa Patrizia, Tedeschi Michele, Vinci Pierandrea, Manzato Enzo, Tragni Elena, Zampoleri Veronica

Subjects
Male, Adult, Multifactorial Inheritance, Settore MED/09 - Medicina Interna, familial hypercholesterolemia, molecular diagnosis, polygenic risk score, Cholesterol, LDL, Female, Humans, Middle Aged, Mutation, Gene Regulatory Networks, Hyperlipoproteinemia Type II, LDL, Cholesterol, molecular diagnosi
Abstract

Background A significant proportion of individuals clinically diagnosed with familial hypercholesterolemia (FH), but without any disease-causing mutation, are likely to have polygenic hypercholesterolemia. We evaluated the distribution of a polygenic risk score, consisting of 12 low-density lipoprotein cholesterol (LDL-C)-raising variants (polygenic LDL-C risk score), in subjects with a clinical diagnosis of FH. Methods and Results Within the Lipid Transport Disorders Italian Genetic Network (LIPIGEN) study, 875 patients who were FH-mutation positive (women, 54.75%; mean age, 42.47±15.00 years) and 644 patients who were FH-mutation negative (women, 54.21%; mean age, 49.73±13.54 years) were evaluated. Patients who were FH-mutation negative had lower mean levels of pretreatment LDL-C than patients who were FH-mutation positive (217.14±55.49 versus 270.52±68.59 mg/dL, P

Published
2022

98. Genetically determined hypercholesterolaemia results into premature leucocyte telomere length shortening and reduced haematopoietic precursors

Author

A. Moregola, Fabio Pellegatta, Maurizio Averna, Alberico L. Catapano, V. Zampoleri, Rossella Spina, Angelo Baldassarre Cefalù, Fabrizia Bonacina, Lorenzo Da Dalt, Liliana Grigore, Andrea Baragetti, Giuseppe Danilo Norata, Angela Pirillo, Baragetti, Andrea, Bonacina, Fabrizia, Da Dalt, Lorenzo, Moregola, Annalisa, Zampoleri, Veronica, Pellegatta, Fabio, Grigore, Liliana, Pirillo, Angela, Spina, Rossella, Cefalù', Angelo Baldassare, Averna, Maurizio, Norata, Giuseppe D, and Catapano, Alberico L

Subjects
medicine.medical_specialty, Settore MED/09 - Medicina Interna, Cellular ageing, Epidemiology, Hypercholesterolemia, CD34, Cellular senescence, 030204 cardiovascular system & hematology, Hyperlipoproteinemia Type II, 03 medical and health sciences, Mice, 0302 clinical medicine, Internal medicine, Leukocytes, Medicine, Animals, Humans, Progenitor cell, Haematopoiesi, 030304 developmental biology, Ldl cholesterol, 0303 health sciences, business.industry, Cholesterol, LDL, Telomere, 3. Good health, Haematopoiesis, Increased risk, Endocrinology, medicine.anatomical_structure, CHD, Telomeres, Bone marrow, Cardiology and Cardiovascular Medicine, business, Familial hypercholesterolaemia
Abstract

Aims Leucocyte telomere length (LTL) shortening is a marker of cellular senescence and associates with increased risk of cardiovascular disease (CVD). A number of cardiovascular risk factors affect LTL, but the correlation between elevated LDL cholesterol (LDL-C) and shorter LTL is debated: in small cohorts including subjects with a clinical diagnosis of familial hypercholesterolaemia (FH). We assessed the relationship between LDL-C and LTL in subjects with genetic familial hypercholesterolaemia (HeFH) compared to those with clinically diagnosed, but not genetically confirmed FH (CD-FH), and normocholesterolaemic subjects. Methods and results LTL was measured in mononuclear cells-derived genomic DNA from 206 hypercholesterolaemic subjects (135 HeFH and 71 CD-FH) and 272 controls. HeFH presented shorter LTL vs. controls (1.27 ± 0.07 vs. 1.59 ± 0.04, P = 0.045). In particular, we found shorter LTL in young HeFH as compared to young controls ( Conclusions We found (i) shorter LTL in genetically determined hypercholesterolaemia, (ii) lower circulating haematopoietic precursors in HeFH subjects, and reduced bone marrow resident LT-HSPCs in LDLR-KO mice. We support early cellular senescence and haematopoietic alterations in subjects with FH.

Published
2020

99. Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk – Results from the PROG-IMT collaboration

Author

Sathanur R. Srinivasan, Christine Espinola-Klein, Albert Hofman, Jing Liu, Eric de Groot, Tomi-Pekka Tuomainen, Helmuth Steinmetz, Ta-Chen Su, Carmen Suárez, Maria Rosvall, Stela McLachlan, Raffaele Izzo, Marcus Dörr, Liliana Grigore, Gunnar Engström, Stein Harald Johnsen, David Yanez, Giel Nijpels, Giuseppe Danilo Norata, Fabrizio Veglia, Matthias W. Lorenz, Dong Zhao, Lu Gao, Wuxiang Xie, Damiano Baldassarre, Mauro Amato, Ellisiv B. Mathiesen, Michiel L. Bots, Dirk Sander, Joseph F. Polak, Matthieu Plichart, Holger Poppert, Matthias Sitzer, Ralph L. Sacco, Irene Schmidtmann, Heiko Uthoff, Manuel F. Landecho, Horst Bickel, Gerald S. Berenson, Oscar H. Franco, Bo Hedblad, Kazuo Kitagawa, Daniel Staub, Jackie F. Price, Caroline Schmidt, Alberico L. Catapano, Tatjana Rundek, Thapat Wannarong, M. Arfan Ikram, Kathrin Ziegelbauer, Alfonso Friera, Francesco Rozza, Kimmo Ronkainen, Jacqueline M. Dekker, Peter Willeit, Samuela Castelnuovo, Coen D.A. Stehouwer, Shuhei Okazaki, Pierre Ducimetière, Stefan Blankenberg, Johann Willeit, Oscar Beloqui, Maryam Kavousi, Henry Völzke, Kuo-Liong Chien, Grace Parraga, Bernhard Iglseder, Rafael Gabriel, Lena Bokemark, Stefan Kiechl, Cesare R. Sirtori, Göran Bergström, Jussi Kauhanen, Simon G. Thompson, Nicola De Luca, Lars Lind, Jean Philippe Empana, Moïse Desvarieux, Ulf Schminke, Hung-Ju Lin, Elena Tremoli, Lorenz, Matthias W, Gao, Lu, Ziegelbauer, Kathrin, Norata, Giuseppe Danilo, Empana, Jean Philippe, Schmidtmann, Irene, Lin, Hung-Ju, Mclachlan, Stela, Bokemark, Lena, Ronkainen, Kimmo, Amato, Mauro, Schminke, Ulf, Srinivasan, Sathanur R, Lind, Lar, Okazaki, Shuhei, Stehouwer, Coen D A, Willeit, Peter, Polak, Joseph F, Steinmetz, Helmuth, Sander, Dirk, Poppert, Holger, Desvarieux, Moise, Ikram, M Arfan, Johnsen, Stein Harald, Staub, Daniel, Sirtori, Cesare R, Iglseder, Bernhard, Beloqui, Oscar, Engström, Gunnar, Friera, Alfonso, Rozza, Francesco, Xie, Wuxiang, Parraga, Grace, Grigore, Liliana, Plichart, Matthieu, Blankenberg, Stefan, Su, Ta-Chen, Schmidt, Caroline, Tuomainen, Tomi-Pekka, Veglia, Fabrizio, Völzke, Henry, Nijpels, Giel, Willeit, Johann, Sacco, Ralph L, Franco, Oscar H, Uthoff, Heiko, Hedblad, Bo, Suarez, Carmen, Izzo, Raffaele, Zhao, Dong, Wannarong, Thapat, Catapano, Alberico, Ducimetiere, Pierre, Espinola-Klein, Christine, Chien, Kuo-Liong, Price, Jackie F, Bergström, Göran, Kauhanen, Jussi, Tremoli, Elena, Dörr, Marcu, Berenson, Gerald, Kitagawa, Kazuo, Dekker, Jacqueline M, Kiechl, Stefan, Sitzer, Matthia, Bickel, Horst, Rundek, Tatjana, Hofman, Albert, Mathiesen, Ellisiv B, Castelnuovo, Samuela, Landecho, Manuel F, Rosvall, Maria, Gabriel, Rafael, de Luca, Nicola, Liu, Jing, Baldassarre, Damiano, Kavousi, Maryam, de Groot, Eric, Bots, Michiel L, Yanez, David N, Thompson, Simon G, Lorenz, Matthias W [0000-0002-7565-1751], Apollo - University of Cambridge Repository, General practice, APH - Health Behaviors & Chronic Diseases, Epidemiology and Data Science, Interne Geneeskunde, RS: CARIM - R3.01 - Vascular complications of diabetes and the metabolic syndrome, MUMC+: HVC Pieken Maastricht Studie (9), MUMC+: MA Interne Geneeskunde (3), Epidemiology, Neurology, Radiology & Nuclear Medicine, Pirro, Matteo, and PROG-IMT study group

Subjects
Male, Myocardial Infarction, lcsh:Medicine, PROGRESSION, Cardiovascular Medicine, 030204 cardiovascular system & hematology, Vascular Medicine, Biochemistry, Carotid Intima-Media Thickness, Geographical locations, DISEASE, 0302 clinical medicine, Risk Factors, Germany, Medicine and Health Sciences, Medicine, Cardiac and Cardiovascular Systems, Myocardial infarction, skin and connective tissue diseases, lcsh:Science, ARTERY INTIMA, Stroke, Intersectoral Collaboration, POPULATION, Cardiovascular Diseases/diagnosis, METABOLIC SYNDROME, education.field_of_study, Kardiologi, Multidisciplinary, Agricultural and Biological Sciences(all), VDP::Medical disciplines: 700::Clinical medical disciplines: 750, Hazard ratio, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750, Middle Aged, Prognosis, Predictive value, 3. Good health, Europe, Neurology, Italy, Cardiovascular Diseases, HYPERTENSIVE MEN, Cardiology, cardiovascular system, Female, Research Article, medicine.medical_specialty, High cardiovascular risk, Cerebrovascular Diseases, Science, Population, 030209 endocrinology & metabolism, ATHEROSCLEROSIS RISK, Arbetsmedicin och miljömedicin, 03 medical and health sciences, Carotid intima media thickness (CIMT), Internal medicine, Humans, European Union, ddc:610, cardiovascular diseases, education, Aged, Sweden, Biochemistry, Genetics and Molecular Biology(all), Proportional hazards model, business.industry, lcsh:R, Health Risk Analysis, Correction, Occupational Health and Environmental Health, Atherosclerosis, medicine.disease, Confidence interval, Health Care, Intima-media thickness, MYOCARDIAL-INFARCTION, Medical Biophysics, lcsh:Q, VASCULAR RISK, sense organs, Carotid intima media thickness , Cardiovascular risk, People and places, Metabolic syndrome, business, FOLLOW-UP, 030217 neurology & neurosurgery, Genetics and Molecular Biology(all)
Abstract

AIMS: Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk. METHODS AND RESULTS: From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C. CONCLUSIONS: We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals. The PROG-IMT project, which includes this publication, has been funded by the German Research Foundation (Deutsche Forschungsgemeinschaft, www.dfg.de) under the grants DFG Lo 1569/2-1 and DFG Lo 1569/2-3, received by MWL. The DFG had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Simon Thompson is supported by the British heart Foundation (CH/12/2/29428). Some of the contributing studies were funded by different parties, as listed in the acknowledgement section. Here, too, the funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Sí

Published
2018
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100. Evaluation of the performance of Dutch Lipid Clinic Network score in an Italian FH population: The LIPIGEN study

Author

Casula, M. a., B, Be, Olmastroni, E. a., Pirillo, A. c., Catapano, D, A. L. b., D, Jemail, Author, Lipigen, Group, Averna, M. g., Bertolini, S. h., Calandra, S. i., Tarugi, P. i., Pellegatta, F. k., Angelico, F. f., Bartuli, A. l., Biasucci, G. m., Biolo, G. n., Bonanni, L. o., Bonomo, K. p., Borghi, C. q., Bossi, A. C. r., Branchi, A. s., Carubbi, F. t., Cipollone, F. u., Citroni, N. v., Federici, M. w., Ferri, C. x., Fiorenza, A. M. y., Giaccari, A. z., Giorgino, Aa, F., Guardamagna, Ab, O., Iannuzzi, Ac, A., Iughetti, Ad, L., Lupattelli, Ae, G., Lupi, Af, A., Mandraffino, Giuseppe, Ag, G., Marcucci, Ah, R., Maroni, Ai, L., Miccoli, Aj, R., Mombelli, Ak, G., Muntoni, Al, S., Pecchioli, Am, V., Pederiva, An, C., Pipolo, Ao, A., Pisciotta, Ap, L., Pujia, Aq, A., Purrello, Ar, F., Repetti, As, E., Rubba, At, P., Sabbà, Au, C., Sampietro, Av, T., Sarzani, Aw, R., Tagliabue, M. P., Ax, Trenti, Ay, C., Vigna, G. B., Az, Werba, J. P., Ba, Zambon, Bb, S., Zenti, M. G., Bc, Minicocci, I. f., Noto, D. g., Fortunato, Bd, G., Banderali, An, G., Benso, Ax, A., Bigolin, Bb, P., Bonora, Bc, E., Bruzzi, Ad, P., Bucci, M. u., Buonuomo, P. S. l., Capra, M. E. m., Cardolini, I. w., Cefalù, B. g., Cervelli, N. x., Chiariello, Ac, G., Cocci, Aw, G., Colombo, E. y., Cremonini, A. L., Ap, D'Addato, S. q., D'Erasmo, L. f., Dal, Pino, Av, B., Sanctis, De, Ab, L., Vita, De, Ao, E., Del, Ben, M. f., Costanzo, Di, A. f., Taranto, Di, M. D., Bd, Fasano, Ay, T., Gentile, As, L., At, M., Ghirardello, Az, O., Grigore, L. k., Lussu, Al, M., Meregalli, G. r., Moffa, S. z., Montalcini, Aq, T., Morgia, Nascimbeni, F. t., Pasta, A. h., Pavanello, Ak, C., Saitta, Antonino, Ag, A., Scicali, Ar, R., Siepi, Ae, D., Spagnolli, W. v., Spina, R. g., Sticchi, Ah, E., Suppressa, Au, P., Vigo, Ba, L., Vinci, P. n., Manzato, Bf, E., Tragni, Be, E., Zampoleri, Bg, V., Casula, Manuela, Olmastroni, Elena, Pirillo, Angela, Catapano, Alberico Luigi, Arca, Marcello, Averna, Maurizio, Bertolini, Stefano, Calandra, Sebastiano, Tarugi, Patrizia, Pellegatta, Fabio, Angelico, Francesco, Bartuli, Andrea, Biasucci, Giacomo, Biolo, Gianni, Bonanni, Luca, Bonomo, Katia, Borghi, Claudio, Bossi, Antonio Carlo, Branchi, Adriana, Carubbi, Francesca, Cipollone, Francesco, Citroni, Nadia, Federici, Massimo, Ferri, Claudio, Fiorenza, Anna Maria, Giaccari, Andrea, Giorgino, Francesco, Guardamagna, Ornella, Iannuzzi, Arcangelo, Iughetti, Lorenzo, Lupattelli, Graziana, Lupi, Alessandro, Mandraffino, Giuseppe, Marcucci, Rossella, Maroni, Lorenzo, Miccoli, Roberto, Mombelli, Giuliana, Muntoni, Sandro, Pecchioli, Valerio, Pederiva, Cristina, Pipolo, Antonio, Pisciotta, Livia, Pujia, Arturo, Purrello, Francesco, Repetti, Elena, Rubba, Paolo, Sabbà, Carlo, Sampietro, Tiziana, Sarzani, Riccardo, Tagliabue, Milena Paola, Trenti, Chiara, Vigna, Giovanni Battista, Werba, Josè Pablo, Zambon, Sabina, Zenti, Maria Grazia, Minicocci, Ilenia, Noto, Davide, Fortunato, Giuliana, Banderali, Giuseppe, Benso, Andrea, Bigolin, Paola, Bonora, Enzo, Bruzzi, Patrizia, Bucci, Marco, Buonuomo, Paola Sabrina, Capra, Maria Elena, Cardolini, Iri, Cefalù, Baldassarre, Cervelli, Nazzareno, Chiariello, Giuseppe, Cocci, Guido, Colombo, Emanuela, Cremonini, Anna Laura, D'Addato, Sergio, D'Erasmo, Laura, Dal Pino, Beatrice, De Sanctis, Luisa, De Vita, Emanuele, Del Ben, Maria, Di Costanzo, Alessia, Di Taranto, Maria Donata, Fasano, Tommaso, Gentile, Luigi, Gentile, Marco, Ghirardello, Omar, Grigore, Liliana, Lussu, Milena, Meregalli, Giancarla, Moffa, Simona, Montalcini, Tiziana, Morgia, Valeria, Nascimbeni, Fabio, Pasta, Andrea, Pavanello, Chiara, Saitta, Antonino, Scicali, Roberto, Siepi, Donatella, Spagnolli, Walter, Spina, Rossella, Sticchi, Elena, Suppressa, Patrizia, Vigo, Lorenzo, Vinci, Pierandrea, Manzato, Enzo, Tragni, Elena, Zampoleri, Veronica, D'addato, Sergio, D'erasmo, Laura, Casula, M, Olmastroni, E, Pirillo, A, Catapano, A, Averna, M, Noto, D, Cefalu, B, and Spina, R

Subjects
Male, Settore MED/09 - Medicina Interna, Genetic testing, Predictive Value of Test, Familial hypercholesterolemia, 030204 cardiovascular system & hematology, Decision Support Technique, 0302 clinical medicine, Retrospective Studie, Risk Factors, Cardiovascular Disease, Genetic Marker, Prospective Studies, 030212 general & internal medicine, Age of Onset, Prospective cohort study, education.field_of_study, medicine.diagnostic_test, Middle Aged, Dutch Lipid Clinic Network score, Adult, Biomarkers, Cardiovascular Diseases, Cholesterol, LDL, Female, Genetic Markers, Genetic Predisposition to Disease, Genetic Testing, Humans, Hyperlipoproteinemia Type II, Italy, Phenotype, Predictive Value of Tests, Reproducibility of Results, Retrospective Studies, Risk Assessment, Decision Support Techniques, Mutation, 3. Good health, Cholesterol, Cardiology and Cardiovascular Medicine, Human, medicine.medical_specialty, Population, Reproducibility of Result, Physical examination, LDL, 03 medical and health sciences, Internal medicine, medicine, First-degree relatives, education, business.industry, Risk Factor, Settore MED/13 - ENDOCRINOLOGIA, Biomarker, medicine.disease, Missing data, Dutch Lipid Clinic Network score, Familial hypercholesterolemia, Genetic testing, Prospective Studie, Age of onset, business
Abstract

Background and aims Familial hypercholesterolemia (FH) is an inherited disorder characterized by high levels of blood cholesterol from birth and premature coronary heart disease. Thus, the identification of FH patients is crucial to prevent or delay the onset of cardiovascular events, and the availability of a tool helping with the diagnosis in the setting of general medicine is essential to improve FH patient identification. Methods This study evaluated the performance of the Dutch Lipid Clinic Network (DLCN) score in FH patients enrolled in the LIPIGEN study, an Italian integrated network aimed at improving the identification of patients with genetic dyslipidaemias, including FH. Results The DLCN score was applied on a sample of 1377 adults (mean age 42.9 ± 14.2 years) with genetic diagnosis of FH, resulting in 28.5% of the sample classified as probable FH and 37.9% as classified definite FH. Among these subjects, 43.4% had at least one missing data out of 8, and about 10.0% had 4 missing data or more. When analyzed based on the type of missing data, a higher percentage of subjects with at least 1 missing data in the clinical history or physical examination was classified as possible FH (DLCN score 3–5). We also found that using real or estimated pre-treatment LDL-C levels may significantly modify the DLCN score. Conclusions Although the DLCN score is a useful tool for physicians in the diagnosis of FH, it may be limited by the complexity to retrieve all the essential information, suggesting a crucial role of the clinical judgement in the identification of FH subjects.

Published
2018

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