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6. Association between Non-HDL-C/HDL-C Ratio and Carotid Intima–Media Thickness in Post-Menopausal Women

Author

Iannuzzi, Arcangelo, primary, Giallauria, Francesco, additional, Gentile, Marco, additional, Rubba, Paolo, additional, Covetti, Giuseppe, additional, Bresciani, Alessandro, additional, Aliberti, Emilio, additional, Cuomo, Gilanluigi, additional, Panico, Camilla, additional, Tripaldella, Maria, additional, Giusti, Maria Ausilia, additional, Mattina, Alessandro, additional, and Iannuzzo, Gabriella, additional

Published
2021
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7. Abstract 12066: The Long-Term Safety and Efficacy of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia

Author

Raal, Frederick J, primary, Rosenson, Robert S, additional, Reeskamp, Rens, additional, Kastelein, John J, additional, Rubba, Paolo, additional, Duell, Bart, additional, Koseki, Masahiro, additional, Stroes, Erik S, additional, Ali, Shazia, additional, Banerjee, Poulabi, additional, Chan, KuoChen, additional, Khilla, Nagwa, additional, McGinniss, Jennifer, additional, Pordy, Robert, additional, Zhang, Yi, additional, and Gaudet, Daniel, additional

Published
2021
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8. Abstract 12027: Low-Density Lipoprotein Cholesterol in Patients With Homozygous Familial Hypercholesterolemia Who Participated in Sequential Studies of Alirocumab and Evinacumab

Author

Raal, Frederick J, primary, Rosenson, Robert S, additional, Kolovou, Genovefa, additional, Harada-shiba, Mariko, additional, Mitchenko, Olena, additional, Rubba, Paolo, additional, ali, shazia, additional, Banerjee, Poulabi, additional, Khilla, Nagwa, additional, McGinniss, Jennifer, additional, pordy, robert, additional, and Blom, Dirk J, additional

Published
2021
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9. Carotid Atherosclerosis, Ultrasound and Lipoproteins

Author

Iannuzzi, Arcangelo, primary, Rubba, Paolo, additional, Gentile, Marco, additional, Mallardo, Vania, additional, Calcaterra, Ilenia, additional, Bresciani, Alessandro, additional, Covetti, Giuseppe, additional, Cuomo, Gianluigi, additional, Merone, Pasquale, additional, Di Lorenzo, Anna, additional, Alfieri, Roberta, additional, Aliberti, Emilio, additional, Giallauria, Francesco, additional, Di Minno, Matteo Nicola Dario, additional, and Iannuzzo, Gabriella, additional

Published
2021
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10. Efficacy and Safety of Alirocumab in Adults With Homozygous Familial Hypercholesterolemia: The ODYSSEY HoFH Trial

Author

Blom, Dirk J., Harada-Shiba, Mariko, Rubba, Paolo, Gaudet, Daniel, Kastelein, John J. P., Charng, Min-Ji, Pordy, Robert, Donahue, Stephen, Ali, Shazia, Dong, Yuping, Khilla, Nagwa, Banerjee, Poulabi, Baccara-Dinet, Marie, Rosenson, Robert S., ACS - Atherosclerosis & ischemic syndromes, Vascular Medicine, and ACS - Pulmonary hypertension & thrombosis

Subjects
low-density lipoprotein, lipoprotein(a), proprotein convertase subtilisin/kexin type 9 inhibitor, lipids (amino acids, peptides, and proteins), homozygous familial hypercholesterolemia
Abstract

Background: Homozygous familial hypercholesterolemia (HoFH) is characterized by extremely elevated low-density lipoprotein–cholesterol (LDL-C) levels and early onset atherosclerotic cardiovascular disease despite treatment with conventional lipid-lowering treatment. Objectives: This study was designed to assess LDL-C reduction with the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab in adult patients with HoFH. Methods: This randomized, double-blind, placebo-controlled, parallel-group, phase 3 study evaluated efficacy and safety of alirocumab 150 mg every 2 weeks. The primary endpoint was percent reduction from baseline in LDL-C versus placebo after 12 weeks of treatment. Results: Patients (N = 69) were randomized 2:1 to alirocumab or placebo. At baseline, background lipid-lowering treatment included 67 patients receiving statin (59 patients on high-intensity statin); 50 patients on ezetimibe; 10 patients on lomitapide; and 10 patients undergoing apheresis. Mean baseline LDL-C was 259.6 mg/dl in the placebo group and 295.0 mg/dl in the alirocumab group. At week 12, the least squares mean difference in LDL-C percent change from baseline was −35.6% (alirocumab [−26.9%] vs. placebo [8.6%]; p < 0.0001). Reductions (least squares mean difference) in other atherogenic lipids at week 12 were: apolipoprotein B, −29.8%; non–high-density lipoprotein cholesterol, −32.9%; total cholesterol, −26.5%; and lipoprotein(a), −28.4% (all p < 0.0001). No serious adverse events, permanent treatment discontinuations, or deaths due to treatment-emergent adverse events were reported during the double-blind treatment period. Conclusions: In the largest randomized controlled interventional trial in HoFH patients to date, alirocumab resulted in significant and clinically meaningful reductions in LDL-C at week 12. Alirocumab was generally well tolerated, with a safety profile comparable to that of placebo. (Study in Participants With Homozygous Familial Hypercholesterolemia [HoFH] [ODYSSEY HoFH] NCT03156621.)

Published
2020

11. Association between Very Low-Density Lipoprotein Cholesterol (VLDL-C) and Carotid Intima-Media Thickness in Postmenopausal Women Without Overt Cardiovascular Disease and on LDL-C Target Levels

Author

Gentile, Marco, primary, Iannuzzi, Arcangelo, additional, Giallauria, Francesco, additional, D’Andrea, Antonello, additional, Venturini, Elio, additional, Pacileo, Mario, additional, Covetti, Giuseppe, additional, Panico, Camilla, additional, Mattiello, Amalia, additional, Vitale, Giuseppe, additional, Sarullo, Filippo Maria, additional, Rubba, Paolo, additional, Vigorito, Carlo, additional, Panico, Salvatore, additional, and Iannuzzo, Gabriella, additional

Published
2020
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12. A Real-World Experience of Clinical, Biochemical and Genetic Assessment of Patients with Homozygous Familial Hypercholesterolemia

Author

Di Taranto, Maria Donata, primary, Giacobbe, Carola, additional, Buonaiuto, Alessio, additional, Calcaterra, Ilenia, additional, Palma, Daniela, additional, Maione, Giovanna, additional, Iannuzzo, Gabriella, additional, Di Minno, Matteo Nicola Dario, additional, Rubba, Paolo, additional, and Fortunato, Giuliana, additional

Published
2020
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13. Different Effects of Antihypertensive Regimens Based on Fosinopril or Hydrochlorothiazide With or Without Lipid Lowering by Pravastatin on Progression of Asymptomatic Carotid Atherosclerosis: Principal Results of PHYLLIS—A Randomized Double-Blind Trial

Author

Zanchetti, Alberto, Crepaldi, Gaetano, Bond, M Gene, Gallus, Giuseppe, Veglia, Fabrizio, Mancia, Giuseppe, Ventura, Alessandro, Baggio, Giovannella, Sampieri, Lorena, Rubba, Paolo, Sperti, Giovanni, and Magni, Alberto

Published
2004
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19. Familial hypercholesterolemia: The Italian Atherosclerosis Society Network (LIPIGEN)

Author

Averna, Maurizio, Cefalã¹, Angelo B., Casula, Manuela, Noto, Davide, Arca, Marcello, Bertolini, Stefano, Calandra, Sebastiano, Catapano, Alberico L., Tarugi, Patrizia, Catapano, Alberico Luigi, 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, Mandraffino, Giuseppe, Marcucci, Rossella, Mombelli, Giuliana, Muntoni, Sandro, Pecchioli, Valerio, Pederiva, Cristina, Pipolo, Antonio, Pisciotta, Livia, Pujia, Arturo, Purrello, Francesco, Repetti, Elena, Rubba, Paolo, SabbÃ&nbsp, Carlo, Sampietro, Tiziana, Sarzani, Riccardo, Tagliabue, Milena Paola, Trenti, Chiara, Vigna, Giovanni Battista, Werba, Josà Pablo, Zambon, Sabina, Zenti, Maria Grazia, Montali, Anna, Fortunato, Giuliana, Grigore, Liliana, Del Ben, Maria, Maranghi, Marianna, Barbagallo, Carlo M., Buonuomo, Paola Sabrina, Capra, Maria Elena, Vinci, Pierandrea, D'Addato, Sergio, Galbiati, Stella, Nascimbeni, Fabio, Bucci, Marco, Spagnoli, Walter, Cardolini, Iris, Cervelli, Nazzareno, Emanuela, Colombo, Vinsin, A. Sun, Laviola, Luigi, Bello, Francesca, Chiariello, Giuseppe, Predieri, Barbara, Siepi, Donatella, Saitta, Antonino, Giusti, Betti, Pavanello, Chiara, Lussu, Milena, Prati, Lucia, Banderali, Giuseppe, Balleari, Giulia, Montalcini, Tiziana, Scicali, Roberto, Gentile, Luigi, Gentile, Marco, Suppressa, Patrizia, Sbrana, Francesco, Cocci, Guido, Benso, Andrea, Negri, Emanuele Alberto, Ghirardello, Omar, Lorenzo, Vigo, Zambon, Alberto, Enzo, Bonora, Minicocci, Ilenia, Spina, Rossella, Orlando, Camilla, Di Taranto, Maria Donata, Chiodo, Lorenzo, Garlaschelli, Katia, Manzato, Enzo, Tragni, Elena, Averna, M., Cefalu', A., Casula, M., Noto, D., Arca, M., Bertolini, S., Calandra, S., Catapano, A., Tarugi, P., Pellegatta, F., Angelico, F., Bartuli, A., Biasucci, G., Biolo, G., Bonanni, L., Bonomo, K., Borghi, C., Bossi, A., Branchi, A., Carubbi, F., Cipollone, F., Citroni, N., Federici, M., Ferri, C., Fiorenza, A., Giaccari, A., Giorgino, F., Guardamagna, O., Iannuzzi, A., Iughetti, L., Lupattelli, G., Mandraffino, G., Marcucci, R., Mombelli, G., Muntoni, S., Pecchioli, V., Pederiva, C., Pipolo, A., Pisciotta, L., Pujia, A., Purrello, F., Repetti, E., Rubba, P., Sabbã , C., Sampietro, T., Sarzani, R., Tagliabue, M., Trenti, C., Vigna, G., Werba, J., Zambon, S., Zenti, M., Montali, A., Fortunato, G., Grigore, L., Del Ben, M., Maranghi, M., Cefalã¹, A., Barbagallo, C., Buonuomo, P., Capra, M., Vinci, P., D'Addato, S., Galbiati, S., Nascimbeni, F., Bucci, M., Spagnoli, W., Cardolini, I., Cervelli, N., Emanuela, C., Vinsin, A., Laviola, L., Bello, F., Chiariello, G., Predieri, B., Siepi, D., Saitta, A., Giusti, B., Pavanello, C., Lussu, M., Prati, L., Banderali, G., Balleari, G., Montalcini, T., Scicali, R., Gentile, L., Gentile, M., Suppressa, P., Sbrana, F., Cocci, G., Benso, A., Negri, E., Ghirardello, O., Lorenzo, V., Zambon, A., Enzo, B., Minicocci, I., Spina, R., Orlando, C., Di Taranto, M., Chiodo, L., Garlaschelli, K., Manzato, E., Tragni, E., Averna, Maurizio, Cefalã¹, Angelo B., Casula, Manuela, Noto, Davide, Arca, Marcello, Bertolini, Stefano, Calandra, Sebastiano, Catapano, Alberico L., Tarugi, Patrizia, Catapano, Alberico Luigi, 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, Mandraffino, Giuseppe, Marcucci, Rossella, Mombelli, Giuliana, Muntoni, Sandro, Pecchioli, Valerio, Pederiva, Cristina, Pipolo, Antonio, Pisciotta, Livia, Pujia, Arturo, Purrello, Francesco, Repetti, Elena, Rubba, Paolo, Sabbã , Carlo, Sampietro, Tiziana, Sarzani, Riccardo, Tagliabue, Milena Paola, Trenti, Chiara, Vigna, Giovanni Battista, Werba, Josã Pablo, Zambon, Sabina, Zenti, Maria Grazia, Montali, Anna, Fortunato, Giuliana, Grigore, Liliana, DEL BELLO, Francesca, Maranghi, Marianna, Barbagallo, Carlo M., Buonuomo, Paola Sabrina, Capra, Maria Elena, Vinci, Pierandrea, D'Addato, Sergio, Galbiati, Stella, Nascimbeni, Fabio, Bucci, Marco, Spagnoli, Walter, Cardolini, Iri, Cervelli, Nazzareno, Emanuela, Colombo, Vinsin, A. Sun, Laviola, Luigi, Bello, Francesca, Chiariello, Giuseppe, Predieri, Barbara, Siepi, Donatella, Saitta, Antonino, Giusti, Betti, Pavanello, Chiara, Lussu, Milena, Prati, Lucia, Banderali, Giuseppe, Balleari, Giulia, Montalcini, Tiziana, Scicali, Roberto, Gentile, Luigi, Gentile, Marco, Suppressa, Patrizia, Sbrana, Francesco, Cocci, Guido, Benso, Andrea, Negri, Emanuele Alberto, Ghirardello, Omar, Lorenzo, Vigo, Zambon, Alberto, Enzo, Bonora, Minicocci, Ilenia, Spina, Rossella, Orlando, Camilla, Di Taranto, Maria Donata, Chiodo, Lorenzo, Garlaschelli, Katia, Manzato, Enzo, Tragni, Elena, Cefalù, Angelo B., Sabbà, Carlo, Werba, Josè Pablo, Del Ben, Maria, and Colombo, Emanuela

Subjects
0301 basic medicine, Candidate gene, Genetic testing, Settore MED/09 - Medicina Interna, Databases, Factual, DNA Mutational Analysis, Disease, Familial hypercholesterolemia, 030204 cardiovascular system & hematology, 0302 clinical medicine, Dyslipidemias, National network, Internal Medicine, Cardiology and Cardiovascular Medicine, Risk Factors, Prospective Studies, Program Development, Prospective cohort study, medicine.diagnostic_test, General Medicine, Prognosis, Cholesterol, Phenotype, Italy, Genetic Markers, medicine.medical_specialty, MEDLINE, Hyperlipoproteinemia Type II, 03 medical and health sciences, Databases, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Factual, Retrospective Studies, business.industry, Settore MED/13 - ENDOCRINOLOGIA, Retrospective cohort study, medicine.disease, Atherosclerosis, Mutation, 030104 developmental biology, Endocrinology, Dyslipidemia, Genetic marker, business
Abstract

Background and aims: Primary dyslipidemias are a heterogeneous group of disorders characterized by abnormal levels of circulating lipoproteins. Among them, familial hypercholesterolemia is the most common lipid disorder that predisposes for premature cardiovascular disease. We set up an Italian nationwide network aimed at facilitating the clinical and genetic diagnosis of genetic dyslipidemias named LIPIGEN (LIpid TransPort Disorders Italian GEnetic Network). Methods: Observational, multicenter, retrospective and prospective study involving about 40 Italian clinical centers. Genetic testing of the appropriate candidate genes at one of six molecular diagnostic laboratories serving as nationwide DNA diagnostic centers. Results and conclusions: From 2012 to October 2016, available biochemical and clinical information of 3480 subjects with familial hypercholesterolemia identified according to the Dutch Lipid Clinic Network (DLCN) score were included in the database and genetic analysis was performed in 97.8% of subjects, with a mutation detection rate of 92.0% in patients with DLCN score >= 6. The establishment of the LIPIGEN network will have important effects on clinical management and it will improve the overall identification and treatment of primary dyslipidemias in Italy. (C) 2017 The Authors. Published by Elsevier Ireland Ltd.

Published
2017

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

Author

Pirillo, Angela, Garlaschelli, Katia, Arca, Marcello, Averna, Maurizio, Bertolini, Stefano, Calandra, Sebastiano, Tarugi, Patrizia, Catapano, Alberico L., Catapano, Alberico Luigi, 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, Mandraffino, Giuseppe, Marcucci, Rossella, Mombelli, Giuliana, Muntoni, Sandro, Pecchioli, Valerio, Pederiva, Cristina, Pipolo, Antonio, Pisciotta, Livia, Pujia, Arturo, Purrello, Francesco, Repetti, Elena, Rubba, Paolo, SabbÃ&nbsp, Carlo, Sampietro, Tiziana, Sarzani, Riccardo, Tagliabue, Milena Paola, Trenti, Chiara, Vigna, Giovanni Battista, Werba, Josà Pablo, Zambon, Sabina, Zenti, Maria Grazia, Montali, Anna, Noto, Davide, Fortunato, Giuliana, Grigore, Liliana, Del Ben, Maria, Maranghi, Marianna, Cefalã¹, A. Baldassarre, Buonuomo, Paola Sabrina, Capra, Maria Elena, Vinci, Pierandrea, D'Addato, Sergio, Galbiati, Stella, Nascimbeni, Fabio, Bucci, Marco, Spagnoli, Walter, Cardolini, Iris, Cervelli, Nazzareno, Emanuela, Colombo, Sun, Vinsin A., Laviola, Luigi, Bello, Francesca, Chiariello, Giuseppe, Predieri, Barbara, Siepi, Donatella, Saitta, Antonino, Giusti, Betti, Pavanello, Chiara, Lussu, Milena, Prati, Lucia, Banderali, Giuseppe, Balleari, Giulia, Montalcini, Tiziana, Scicali, Roberto, Gentile, Luigi, Gentile, Marco, Suppressa, Patrizia, Sbrana, Francesco, Cocci, Guido, Benso, Andrea, Negri, Emanuele Alberto, Ghirardello, Omar, Lorenzo, Vigo, Zambon, Alberto, Enzo, Bonora, Minicocci, Ilenia, Spina, Rossella, Orlando, Camilla, Di Taranto, Maria Donata, Casula, Manuela, Chiodo, Lorenzo, Manzato, Enzo, Tragni, Elena, Pirillo, Angela, Garlaschelli, Katia, Arca, Marcello, Averna, Maurizio, Bertolini, Stefano, Calandra, Sebastiano, Tarugi, Patrizia, Catapano, Alberico L., Catapano, Alberico Luigi, 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, Mandraffino, Giuseppe, Marcucci, Rossella, Mombelli, Giuliana, Muntoni, Sandro, Pecchioli, Valerio, Pederiva, Cristina, Pipolo, Antonio, Pisciotta, Livia, Pujia, Arturo, Purrello, Francesco, Repetti, Elena, Rubba, Paolo, Sabbã , Carlo, Sampietro, Tiziana, Sarzani, Riccardo, Tagliabue, Milena Paola, Trenti, Chiara, Vigna, Giovanni Battista, Werba, Josã Pablo, Zambon, Sabina, Zenti, Maria Grazia, Montali, Anna, Noto, Davide, Fortunato, Giuliana, Grigore, Liliana, DEL BELLO, Francesca, Maranghi, Marianna, Cefalã¹, A. Baldassarre, Buonuomo, Paola Sabrina, Capra, Maria Elena, Vinci, Pierandrea, D'Addato, Sergio, Galbiati, Stella, Nascimbeni, Fabio, Bucci, Marco, Spagnoli, Walter, Cardolini, Iri, Cervelli, Nazzareno, Emanuela, Colombo, Sun, Vinsin A., Laviola, Luigi, Bello, Francesca, Chiariello, Giuseppe, Predieri, Barbara, Siepi, Donatella, Saitta, Antonino, Giusti, Betti, Pavanello, Chiara, Lussu, Milena, Prati, Lucia, Banderali, Giuseppe, Balleari, Giulia, Montalcini, Tiziana, Scicali, Roberto, Gentile, Luigi, Gentile, Marco, Suppressa, Patrizia, Sbrana, Francesco, Cocci, Guido, Benso, Andrea, Negri, Emanuele Alberto, Ghirardello, Omar, Lorenzo, Vigo, Zambon, Alberto, Enzo, Bonora, Minicocci, Ilenia, Spina, Rossella, Orlando, Camilla, Di Taranto, Maria Donata, Casula, Manuela, Chiodo, Lorenzo, Manzato, Enzo, Tragni, Elena, Sabbà, Carlo, Werba, Josè Pablo, Del Ben, Maria, Cefalù, A. Baldassarre, DI BELLO, Francesca, Pirillo, A., Garlaschelli, K., Arca, M., Averna, M., Bertolini, S., Calandra, S., Tarugi, P., Catapano, A., Pellegatta, F., Angelico, F., Bartuli, A., Biasucci, G., Biolo, G., Bonanni, L., Bonomo, K., Borghi, C., Bossi, A., Branchi, A., Carubbi, F., Cipollone, F., Citroni, N., Federici, M., Ferri, C., Fiorenza, A., Giaccari, A., Giorgino, F., Guardamagna, O., Iannuzzi, A., Iughetti, L., Lupattelli, G., Mandraffino, G., Marcucci, R., Mombelli, G., Muntoni, S., Pecchioli, V., Pederiva, C., Pipolo, A., Pisciotta, L., Pujia, A., Purrello, F., Repetti, E., Rubba, P., Sabbã , C., Sampietro, T., Sarzani, R., Tagliabue, M., Trenti, C., Vigna, G., Werba, J., Zambon, S., Zenti, M., Montali, A., Noto, D., Fortunato, G., Grigore, L., Del Ben, M., Maranghi, M., Cefalu', A., Buonuomo, P., Capra, M., Vinci, P., D'Addato, S., Galbiati, S., Nascimbeni, F., Bucci, M., Spagnoli, W., Cardolini, I., Cervelli, N., Emanuela, C., Sun, V., Laviola, L., Bello, F., Chiariello, G., Predieri, B., Siepi, D., Saitta, A., Giusti, B., Pavanello, C., Lussu, M., Prati, L., Banderali, G., Balleari, G., Montalcini, T., Scicali, R., Gentile, L., Gentile, M., Suppressa, P., Sbrana, F., Cocci, G., Benso, A., Negri, E., Ghirardello, O., Lorenzo, V., Zambon, A., Enzo, B., Minicocci, I., Spina, R., Orlando, C., Di Taranto, M., Casula, M., Chiodo, L., Manzato, E., Tragni, E., and Colombo, Emanuela

Subjects
0301 basic medicine, Apolipoprotein E, Candidate gene, Settore MED/09 - Medicina Interna, Databases, Factual, Apolipoprotein B, DNA Mutational Analysis, Familial hypercholesterolemia, 030204 cardiovascular system & hematology, Compound heterozygosity, PCSK9, 0302 clinical medicine, Risk Factors, Receptors, Genetics, Homozygote, Autosomal dominant trait, Pathogenic variants, General Medicine, Prognosis, APOB, LDLR, Cholesterol, Phenotype, Italy, Autosomal Recessive Hypercholesterolemia, Apolipoprotein B-100, lipids (amino acids, peptides, and proteins), Proprotein Convertase 9, Cardiology and Cardiovascular Medicine, Preliminary Data, Genetic Markers, Familial hypercholesterolemiaLDLRPCSK9APOBPathogenic variants, Heterozygote, Biology, Pathogenic variant, LDL, Hyperlipoproteinemia Type II, 03 medical and health sciences, Databases, medicine, Internal Medicine, Humans, Genetic Predisposition to Disease, Factual, Settore MED/13 - ENDOCRINOLOGIA, medicine.disease, Atherosclerosis, 030104 developmental biology, Receptors, LDL, Mutation, biology.protein
Abstract

Background Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by elevated plasma levels of LDL-cholesterol that confers an increased risk of premature atherosclerotic cardiovascular disease. Early identification and treatment of FH patients can improve prognosis and reduce the burden of cardiovascular mortality. Aim of this study was to perform the mutational analysis of FH patients identified through a collaboration of 20 Lipid Clinics in Italy (LIPIGEN Study). Methods We recruited 1592 individuals with a clinical diagnosis of definite or probable FH according to the Dutch Lipid Clinic Network criteria. We performed a parallel sequencing of the major candidate genes for monogenic hypercholesterolemia (LDLR, APOB, PCSK9, APOE, LDLRAP1, STAP1). Results A total of 213 variants were detected in 1076 subjects. About 90% of them had a pathogenic or likely pathogenic variants. More than 94% of patients carried pathogenic variants in LDLR gene, 27 of which were novel. Pathogenic variants in APOB and PCSK9 were exceedingly rare. We found 4 true homozygotes and 5 putative compound heterozygotes for pathogenic variants in LDLR gene, as well as 5 double heterozygotes for LDLR/APOB pathogenic variants. Two patients were homozygous for pathogenic variants in LDLRAP1 gene resulting in autosomal recessive hypercholesterolemia. One patient was found to be heterozygous for the ApoE variant p.(Leu167del), known to confer an FH phenotype. Conclusions This study shows the molecular characteristics of the FH patients identified in Italy over the last two years. Full phenotypic characterization of these patients and cascade screening of family members is now in progress.

Published
2017

21. Dietary and circulating antioxidant vitamins in relation to carotid plaques in middle-aged women

Author

Iannuzzi, Arcangelo, Celentano, Egidio, Panico, Salvatore, Galasso, Rocco, Covetti, Giuseppe, Sacchetti, Lucia, Zarrilli, Federica, De Michele, Mario, and Rubba, Paolo

Subjects
Carotid artery -- Physiological aspects, Atherosclerosis -- Health aspects, Atherosclerotic plaque -- Physiological aspects, Vitamin E -- Health aspects, Antioxidants -- Health aspects, Food/cooking/nutrition, Health
Abstract

Background: The results of the few studies conducted on the relation between antioxidant vitamins and carotid atherosclerosis have been inconclusive. Objective: We evaluated the association between preclinical carotid atherosclerosis, as determined by high-resolution B-mode ultrasound, and both the intake amounts and plasma concentrations of antioxidant vitamins. Design: Among 5062 participants in Progetto Arena, a population-based study on the etiology of cardiovascular disease and cancer in women, 310 women were examined by B-mode ultrasound to detect early signs of carotid atherosclerosis. The participants answered a food-frequency questionnaire, and their plasma concentrations of vitamin E, vitamin A, and carotenoids were measured. None of the women took vitamin supplements. Results: The occurrence of atherosclerotic plaques at the carotid bifurcation was inversely associated with tertiles of vitamin E intake; the test for a linear trend across tertiles was significant (P < 0.05). Similarly, the ratio of plasma vitamin E to plasma cholesterol was inversely related to the presence of plaques at the carotid bifurcation; the test for a linear trend across tertiles was significant (P < 0.02). No association was found between the intake of other antioxidant vitamins (vitamins A and C and carotenoids) or their plasma concentrations and the presence of carotid plaques. Conclusions: An inverse association was found between both the intake amount and plasma concentration of vitamin E and preclinical carotid atherosclerosis in middle-aged women. This association was independent of other cardiovascular risk factors, was not related to vitamin supplements, and supports the hypothesis that low vitamin E intake is a risk factor for early atherosclerosis. KEY WORDS Vitamin E, antioxidants, carotid arteries, carotid bifurcation, atherosclerosis, ultrasound, Progetto Atena, women

Published
2002

27. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events

Author

Robinson, Jg, Farnier, M, Krempf, M, Bergeron, J, Luc, G, Averna, M, Stroes, Es, Langslet, G, Raal, Fj, El Shahawy, M, Koren, Mj, Lepor, Ne, Lorenzato, C, Pordy, R, Chaudhari, U, Kastelein, Jj, Caccavo, A, Codutti, O, Gelersztein, E, Vico, M, Zaidman, C, Majul, C, Balthazar, Y, Capiau, L, Vrolix, M, Vermeersch, P, Gotchev, D, Todorov, G, Tumbev, H, Tzekova, M, Gronkova, N, Dimov, B, Nikolaeva, A, Devedzhiev, T, Mincheva, V, D'Ignazio, G, Dzongowski, P, Elliott, T, Hart, R, Hoag, G, Martinho, V, O'Mahony, M, Tellier, G, Pandey, S, Heaton, K, Constance, C, Phaneuf, Dc, Shu, D, Narvaez, Nc, Cañon, Co, Cardenas, Sp, Loayza, Ms, de Salazar, Dm, Lopez, Rb, Gomez, Ji, Mendoza, Ja, Cure, Cc, Ceska, R, Zidkova, E, Jansky, P, Egstrup, K, Klausen, Ib, Lomholdt, J, Gislason, G, Torp Pedersen, C, Poulsen, S, Kuusela, M, Kekki, S, Nieminen, S, Tuomilehto, J, Boye, A, Bruckert, E, Cadinot, D, Lejay, D, Revol, T, Schaupp, T, Bonnet, J, Paillard, F, Moulin, P, Junggeburth, J, Isermann, B, Zühlke, M, Züchner, D, Theis, E, Stößel, J, König, Hj, Rinke, A, Piechatzek, R, Contzen, C, Lappo, M, Himpel Boenninghoff, Aa, Meissner, G, Maus, O, Degtyareva, E, Schulze, Ed, Horacek, T, Marten, I, Becher, P, Matoltsy, A, Nyirati, G, Paragh, G, Zilahi, Z, Nagy, K, Kanakaridisz, N, Beke, E, Biro, J, Schnabel, R, Elias, M, Gavish, D, Francis, A, Nseir, W, Zimlichman, R, Pozzi, C, Lembo, G, Bucci, M, Mezzetti, A, De Pellegrin, Am, Salvioni, A, De Cesare, N, Briones, Ir, Campos, Pf, Rosas, El, Espinosa, Ev, Salazar, Ma, Ruiz, Ab, Furusho, Lc, Olvera, I, Stroes, E, van den Berg, R, Basart, D, Köse, V, Kentgens, S, Peeters, M, Hoogendijk, J, Voors Pette, C, Agous, I, van Kempen, W, Lingan, Gr, Kooy, A, Troquay, R, Herrman, J, Hoivik, H, Norheim, P, Risberg, K, Høivik, Ho, Elle, S, Derezinski, T, Miekus, P, Ogorek, M, Szymkowiak, K, Cesar, M, Gawron, A, Dabrowska, M, Blach, E, Konieczny, M, Sidor, M, Matias, F, da Silva, Pm, Carvalho, D, Mendonca, I, Andor, M, Andrei, L, Podoleanu, C, Pop, C, Chizhov, P, Chumakova, G, Goloschekin, B, Libov, I, Paltsman, Z, Strutinskiy, A, Koziolova, N, Breedt, J, Ebrahim, I, Ellis, G, Fulat, M, van Rensburg, Dj, Raal, F, van Dyk, C, Vally, T, van der Walt, E, Kotzé, H, Landman, C, Tayob, M, Caixas, A, García, Lr, Fernandez Cruz, A, Gil Extremera, B, Grijalvo, Om, Plana, N, Fuentes, F, Valdivielso, P, Fraile, B, Borgencrantz, B, Larnefeldt, H, Tengmark, Bo, Eriksson, M, Olsson Önerud, Å, Amalyan, W, Dyadyk, O, Koval, O, Kushnir, M, Svintsitskiy, A, Kovalyov, O, Bondarchuk, O, Tashchuk, V, Barna, O, Prokhorov, O, Karpenko, O, Stanciu, D, Pawa, R, Balaji, H, Doig, F, Harvey, P, Ranganath, L, Massalski, W, Hassanin, H, Timmis, H, Pavel Knox, I, Abdulhakim, E, Oyesile, B, Horvathova, V, Donnachie, H, Kondagunta, V, Shaw, H, Thomas, H, Kadr, H, Gunstone, A, Lip, G, Ellery, A, Kerrane, J, Sarker, A, Wong, Yk, Soran, H, Maw, K, Andersen, J, Blair Britt, L, Huffman, C, Kivitz, A, Marple, R, Patron, A, Schear, M, Allegar, N, Awasty, V, Casanova, R, Chaykin, L, Cohen, L, Collins, H, Collins, G, Elkin, G, Reyes, H, Feld, L, Fuller, G, Glover, R, Greenwald, J, Herrod, J, Kaye, W, Kimmel, M, Kolettis, E, Lakin, G, Lorch, D, Palatnik, M, Patel, R, Reichman, A, Rohlf, J, Shockey, G, Shore, K, Radin, D, Alvarado, O, Bellingar, B, Egelhof, R, Mcknight, T, Plevin, S, Pritchard, J, Reddy, R, Velazquez, F, Bolster, E, Broker, R, Butuk, D, Cheung, D, Cohen, K, Golden, G, Murray, A, Naccarato, T, Uusinarkaus, K, Pudi, K, Graff, A, Blumberg, V, Dunn, F, Toth, P, Anspach, R, Chuang, R, Meli, J, Nevins, B, Wayne, J, Schmidt, L, Levinsky, D, Rubino, J, Shealy, N, Torres, D, West, J, Jain, R, Vardi, G, Singh, N, Thew, S, Lo, E, Heitner, J, Gerber, J, Malik, A, Weinstein, D, Prashad, R, Koren, M, Ghitis, A, David, W, Reis, G, Kinzfogl, G, Haught, H, Kantaros, L, O'Dea, D, Weiss, D, Kassas, S, Hunter, J, Mollod, M, Khan, N, Henderson, D, Gatien, L, Schramm, R, Madder, R, Voyce, S, Nadar, V, Stich, M, Kumar, M, Black, R, Treasure, C, Lebeis, M, Mccullough, P, Lepor, N, Moriarty, P, Waxler, A, Talreja, D, Gen, M, Dohad, S, East, C, Conrad, G, Asbill, B, Roberts, J, Robinson, J, Zarich, S, Davis, B, Krolick, M, Sherman, H, Thompson, P., RUBBA, PAOLO OSVALDO FEDERICO, Robinson, Jg, Farnier, M, Krempf, M, Bergeron, J, Luc, G, Averna, M, Stroes, E, Langslet, G, Raal, Fj, El Shahawy, M, Koren, Mj, Lepor, Ne, Lorenzato, C, Pordy, R, Chaudhari, U, Kastelein, Jj, Caccavo, A, Codutti, O, Gelersztein, E, Vico, M, Zaidman, C, Majul, C, Balthazar, Y, Capiau, L, Vrolix, M, Vermeersch, P, Gotchev, D, Todorov, G, Tumbev, H, Tzekova, M, Gronkova, N, Dimov, B, Nikolaeva, A, Devedzhiev, T, Mincheva, V, D'Ignazio, G, Dzongowski, P, Elliott, T, Hart, R, Hoag, G, Martinho, V, O'Mahony, M, Tellier, G, Pandey, S, Heaton, K, Constance, C, Phaneuf, Dc, Shu, D, Narvaez, Nc, Cañon, Co, Cardenas, Sp, Loayza, M, de Salazar, Dm, Lopez, Rb, Gomez, Ji, Mendoza, Ja, Cure, Cc, Ceska, R, Zidkova, E, Jansky, P, Egstrup, K, Klausen, Ib, Lomholdt, J, Gislason, G, Torp Pedersen, C, Poulsen, S, Kuusela, M, Kekki, S, Nieminen, S, Tuomilehto, J, Boye, A, Bruckert, E, Cadinot, D, Lejay, D, Revol, T, Schaupp, T, Bonnet, J, Paillard, F, Moulin, P, Junggeburth, J, Isermann, B, Zühlke, M, Züchner, D, Theis, E, Stößel, J, König, Hj, Rinke, A, Piechatzek, R, Contzen, C, Lappo, M, Himpel Boenninghoff, Aa, Meissner, G, Maus, O, Degtyareva, E, Schulze, Ed, Horacek, T, Marten, I, Becher, P, Matoltsy, A, Nyirati, G, Paragh, G, Zilahi, Z, Nagy, K, Kanakaridisz, N, Beke, E, Biro, J, Schnabel, R, Elias, M, Gavish, D, Francis, A, Nseir, W, Zimlichman, R, Pozzi, C, Lembo, G, Bucci, M, Mezzetti, A, Rubba, PAOLO OSVALDO FEDERICO, De Pellegrin, Am, Salvioni, A, De Cesare, N, Briones, Ir, Campos, Pf, Rosas, El, Espinosa, Ev, Salazar, Ma, Ruiz, Ab, Furusho, Lc, Olvera, I, van den Berg, R, Basart, D, Köse, V, Kentgens, S, Peeters, M, Hoogendijk, J, Voors Pette, C, Agous, I, van Kempen, W, Lingan, Gr, Kooy, A, Troquay, R, Herrman, J, Hoivik, H, Norheim, P, Risberg, K, Høivik, Ho, Elle, S, Derezinski, T, Miekus, P, Ogorek, M, Szymkowiak, K, Cesar, M, Gawron, A, Dabrowska, M, Blach, E, Konieczny, M, Sidor, M, Matias, F, da Silva, Pm, Carvalho, D, Mendonca, I, Andor, M, Andrei, L, Podoleanu, C, Pop, C, Chizhov, P, Chumakova, G, Goloschekin, B, Libov, I, Paltsman, Z, Strutinskiy, A, Koziolova, N, Breedt, J, Ebrahim, I, Ellis, G, Fulat, M, van Rensburg, Dj, Raal, F, van Dyk, C, Vally, T, van der Walt, E, Kotzé, H, Landman, C, Tayob, M, Caixas, A, García, Lr, Fernandez Cruz, A, Gil Extremera, B, Grijalvo, Om, Plana, N, Fuentes, F, Valdivielso, P, Fraile, B, Borgencrantz, B, Larnefeldt, H, Tengmark, Bo, Eriksson, M, Olsson Önerud, Å, Amalyan, W, Dyadyk, O, Koval, O, Kushnir, M, Svintsitskiy, A, Kovalyov, O, Bondarchuk, O, Tashchuk, V, Barna, O, Prokhorov, O, Karpenko, O, Stanciu, D, Pawa, R, Balaji, H, Doig, F, Harvey, P, Ranganath, L, Massalski, W, Hassanin, H, Timmis, H, Pavel Knox, I, Abdulhakim, E, Oyesile, B, Horvathova, V, Donnachie, H, Kondagunta, V, Shaw, H, Thomas, H, Kadr, H, Gunstone, A, Lip, G, Ellery, A, Kerrane, J, Sarker, A, Wong, Yk, Soran, H, Maw, K, Andersen, J, Blair Britt, L, Huffman, C, Kivitz, A, Marple, R, Patron, A, Schear, M, Allegar, N, Awasty, V, Casanova, R, Chaykin, L, Cohen, L, Collins, H, Collins, G, Elkin, G, Reyes, H, Feld, L, Fuller, G, Glover, R, Greenwald, J, Herrod, J, Kaye, W, Kimmel, M, Kolettis, E, Lakin, G, Lorch, D, Palatnik, M, Patel, R, Reichman, A, Rohlf, J, Shockey, G, Shore, K, Radin, D, Alvarado, O, Bellingar, B, Egelhof, R, Mcknight, T, Plevin, S, Pritchard, J, Reddy, R, Velazquez, F, Bolster, E, Broker, R, Butuk, D, Cheung, D, Cohen, K, Golden, G, Murray, A, Naccarato, T, Uusinarkaus, K, Pudi, K, Graff, A, Blumberg, V, Dunn, F, Toth, P, Anspach, R, Chuang, R, Meli, J, Nevins, B, Wayne, J, Schmidt, L, Levinsky, D, Rubino, J, Shealy, N, Torres, D, West, J, Jain, R, Vardi, G, Singh, N, Thew, S, Lo, E, Heitner, J, Gerber, J, Malik, A, Weinstein, D, Prashad, R, Koren, M, Ghitis, A, David, W, Reis, G, Kinzfogl, G, Haught, H, Kantaros, L, O'Dea, D, Weiss, D, Kassas, S, Hunter, J, Mollod, M, Khan, N, Henderson, D, Gatien, L, Schramm, R, Madder, R, Voyce, S, Nadar, V, Stich, M, Kumar, M, Black, R, Treasure, C, Lebeis, M, Mccullough, P, Lepor, N, Moriarty, P, Waxler, A, Talreja, D, Gen, M, Dohad, S, East, C, Conrad, G, Asbill, B, Roberts, J, Robinson, J, Zarich, S, Davis, B, Krolick, M, Sherman, H, and Thompson, P.

Published
2015

28. Identification and in vitro characterization of two new PCSK9 Gain of Function variants found in patients with Familial Hypercholesterolemia

Author

Di Taranto, Maria Donata, primary, Benito-Vicente, Asier, additional, Giacobbe, Carola, additional, Uribe, Kepa Belloso, additional, Rubba, Paolo, additional, Etxebarria, Aitor, additional, Guardamagna, Ornella, additional, Gentile, Marco, additional, Martín, Cesar, additional, and Fortunato, Giuliana, additional

Published
2017
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33. An improved method on stimulated T-lymphocytes to functionally characterize novel and known LDLR mutations

Author

Romano M, Di Taranto MD, Mirabelli P, Iannuzzi A, Gentile M, Raia M, D'AGOSTINO, MARIA NICOLETTA, MAROTTA, GENNARO, DI NOTO, ROSA, DEL VECCHIO, LUIGI, RUBBA, PAOLO OSVALDO FEDERICO, FORTUNATO, GIULIANA, Romano, M, DI TARANTO, MARIA DONATA, Mirabelli, P, D'Agostino, MARIA NICOLETTA, Iannuzzi, A, Marotta, Gennaro, Gentile, M, Raia, M, DI NOTO, Rosa, DEL VECCHIO, Luigi, Rubba, PAOLO OSVALDO FEDERICO, and Fortunato, Giuliana

Abstract

The main causes of familial hypercholesterolemia (FH) are mutations in LDL receptor (LDLR) gene. Functional studies are necessary to demonstrate the LDLR function impairment caused by mutations and would be useful as a diagnostic tool if they allow discrimination between FH patients and controls. In order to identify the best method to detect LDLR activity, we compared continuous Epstein-Barr virus (EBV)-transformed B-lymphocytes and mitogen stimulated T-lymphocytes. In addition, we characterized both novel and known mutations in the LDLR gene. T-lymphocytes and EBV-transformed B-lymphocytes were obtained from peripheral blood of 24 FH patients and 24 control subjects. Functional assays were performed by incubation with fluorescent LDL followed by flow cytometry analysis. Residual LDLR activity was calculated normalizing fluorescence for the mean fluorescence of controls. With stimulated T-lymphocytes we obtained a better discrimination capacity between controls and FH patients compared with EBV-transformed B-lymphocytes as demonstrated by receiver operating characteristic (ROC) curve analysis (the areas under the curve are 1.000 and 0.984 respectively; P < 0.0001 both). The characterization of LDLR activity through T-lymphocytes is more simple and faster than the use of EBV-transformed B-lymphocytes and allows a complete discrimination between controls and FH patients. Therefore the evaluation of residual LDLR activity could be helpful not only for mutation characterization but also for diagnostic purposes.

Published
2011

35. Nutritional recommendations for the prevention of ischemic stroke

Author

Rotilio G, Berni Canani R, Barba G, Branca F, Cairella G, Dilaghi B, Fieschi C, Garbagnati F, Gentile MG, Gensini GF, Gualtieri A, Inzitari D, La Massa M, Luisi ML, Mancia G, Marcelli M, Masini ML, Mastrilli F, Paolucci S, Pratesi L, Sacchetti ML, Salvia A, Scalfi L, Scognamiglio U, Siani A, Strazzullo P, Italian Working Group on Nutrition, Stroke P.r.e.v.e.n.t.i.o.n., RUBBA, PAOLO OSVALDO FEDERICO, Rotilio, G, Berni Canani, R, Barba, G, Branca, F, Cairella, G, Dilaghi, B, Fieschi, C, Garbagnati, F, Gentile, Mg, Gensini, Gf, Gualtieri, A, Inzitari, D, La Massa, M, Luisi, Ml, Mancia, G, Marcelli, M, Masini, Ml, Mastrilli, F, Paolucci, S, Pratesi, L, Rubba, PAOLO OSVALDO FEDERICO, Sacchetti, Ml, Salvia, A, Scalfi, L, Scognamiglio, U, Siani, A, Strazzullo, P, Italian Working Group on, Nutrition, and Stroke, P. r. e. v. e. n. t. i. o. n.

Subjects
Surgical critical care, medicine.medical_specialty, Nutrition and Dietetics, food, ischemic stroke, nutrients, nutrition, prevention, recommendations, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), Brain Ischemia, Nutrition Policy, Stroke, Italy, Risk Factors, Stroke prevention, Family medicine, Ischemic stroke, Practice Guidelines as Topic, medicine, Physical therapy, Humans, Nutritional Physiological Phenomena, Cardiology and Cardiovascular Medicine, Nutrition
Abstract

The Italian Working Group on Nutrition and Stroke Prevention G. Rotilio 1,2, R. Berni Canani 2, G. Barba 3, E Branca 4,17, G. Cairella 5,17, B. Dilaghi 6, C. Fieschi 7, E Garbagnati 2, M.G. Gentile 8,17, G.E Gensini 6, A. Gualtieri 7, D. Inzitari 9, M. La Massa 9, M.L.E. Luisi 1°, 17, G. Mancia n, M. Marcelli 12,17, M.L. Masini 13, E Mastrilli 14, S. Paolucci 14 , L. Pratesi 14, P. Rubba 15 , M.L. Sacchetti 7 , A. Salvia 14 , L. Scalfi 16,17, U. Scognamiglio 2, A. Siani 3,17, p. Strazzul1015 1Department of Biology, Tor Vergata University of Rome, 2Centre of Research on Nutrition and Rehabilitation (CeSAR), IRCCS Fondazione S. Lucia, Rome, 3Institute of Food Sciences, CNR, Avellino, 4National Institute for Research on Food and Nutrition (1NRAN), Rome, 5Department of Prevention Nutrition Unit ASL RMB, Rome, 6Department of Medical and Surgical Critical Care, Section of Clinical Medicine and Cardiology, A.O.U. Careggi, Florence, 7Department of Neurology, University "La Sapienza", Rome, 8Clincal Nutrition Unit, Niguarda Hospital, Milan, 9Department of Neurological and Psychiatric Sciences, University of Florence, 1°Don Carlo Gnocchi Foundation, IRCCS Florence, 11Department of Clinical Medicine, Prevention and Applied Biotechnologies, University of Milano-Bicocca, Monza, 12Clinical Nutrition Unit A.O.S. Giovanni Addolorata, Rome, 13Dietetic Unit A.O.U. Careggi, Florence, 14IRCCS Fondazione S. Lucia, Rome, 15Department of Clinical and Experimental Medicine, Federico 1I University of Naples, 16Department of Food Science, Federico II University of Naples, and 17Italian Society of Human Nutrition (SINU)

Published
2004

36. Refinement of Variant Selection for the LDL Cholesterol Genetic Risk Score in the Diagnosis of the Polygenic Form of Clinical Familial Hypercholesterolemia and Replication in Samples from 6 Countries

Author

Futema, Marta, primary, Shah, Sonia, primary, Cooper, Jackie A, primary, Li, KaWah, primary, Whittall, Ros A, primary, Sharifi, Mahtab, primary, Goldberg, Olivia, primary, Drogari, Euridiki, primary, Mollaki, Vasiliki, primary, Wiegman, Albert, primary, Defesche, Joep, primary, D'Agostino, Maria N, primary, D'Angelo, Antonietta, primary, Rubba, Paolo, primary, Fortunato, Giuliana, primary, Waluś-Miarka, Małgorzata, primary, Hegele, Robert A, primary, Aderayo Bamimore, Mary, primary, Durst, Ronen, primary, Leitersdorf, Eran, primary, Mulder, Monique T, primary, Roeters van Lennep, Jeanine E, primary, Sijbrands, Eric J G, primary, Whittaker, John C, primary, Talmud, Philippa J, primary, and Humphries, Steve E, primary

Published
2015
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37. Efficacy and safety of rosuvastatin in the management of dyslipidemia

Author

Rubba, Paolo

Subjects
nutritional and metabolic diseases, lipids (amino acids, peptides, and proteins), Vascular Health and Risk Management
Abstract

Paolo Rubba, Gennaro Marotta, Marco GentileDepartment of Clinical and Experimental Medicine, Federico II University of Naples, ItalyAbstract: Rosuvastatin is a synthetic statin that represents an advance in the pharmacologic and clinical properties of statins. Relative to other statins, rosuvastatin possesses a greater number of binding interactions with HMG-CoA reductase and has a high affinity for the active site of the enzyme. As with other statins, serious adverse effects with rosuvastatin therapy are uncommon and primarily involve effects on the liver and skeletal muscle. The risk increases with increasing dosages and coadministration with other drugs interacting with the same metabolic pathway. The degree of LDL reduction is important to achieve the treatment goals suggested by international guidelines. Among the most potent statins, rosuvastatin is capable of getting the majority of patients to their LDL cholesterol goals. In addition, rosuvastatin has been found effective in reducing small-dense LDL, C-reactive protein and in increasing HDL cholesterol levels. Controlled clinical trials using vascular end-points have been performed. In particular, a study demonstrated that rosuvastatin therapy could slow progression and/or cause regression of carotid intima-media thickness over 2 years in middle-aged individuals with a low Framingham risk score (FRS) and mild to moderate subclinical atherosclerosis. A primary prevention study (JUPITER) was stopped before the programmed end of the study, because of excess benefit for high-risk individuals receiving rosuvastatin treatment. It is suggested that pronounced LDL reduction, in association with significant HDL cholesterol increase, are the bases of a marked preventive action of rosuvastatin. The results from JUPITER support the use of rosuvastatin for primary cardiovascular prevention, in overweight men and women, with near to normal LDL cholesterol and high CRP. There is now evidence of benefit from rosuvastatin treatment for a wide segment of the general population at intermediate cardiovascular risk. In absolute numbers, this segment represents the main source of cardiovascular events: on the basis of JUPITER results, it is expected that treatment target and potential candidates to statin therapy will be revaluated and redefined.Keywords: cardiovascular prevention, cholesterol, high-density lipoprotein, C-reactive protein, vascular end-point, overweight

Published
2009

38. An improved method on stimulated T-lymphocytes to functionally characterize novel and known LDLR mutations

Author

Romano, Maria, primary, Di Taranto, Maria Donata, additional, Mirabelli, Peppino, additional, D’Agostino, Maria Nicoletta, additional, Iannuzzi, Arcangelo, additional, Marotta, Gennaro, additional, Gentile, Marco, additional, Raia, Maddalena, additional, Di Noto, Rosa, additional, Del Vecchio, Luigi, additional, Rubba, Paolo, additional, and Fortunato, Giuliana, additional

Published
2011
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41. Reply

Author

Ciardullo, Anna V., primary, Panico, Salvatore, additional, Iannuzzi, Arcangelo, additional, Rubba, Paolo, additional, and Berrino, Franco, additional

Published
2002
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42. Low Circulating Folate and Vitamin B 6 Concentrations

Author

Robinson, Killian, primary, Arheart, Kristopher, additional, Refsum, Helga, additional, Brattström, Lars, additional, Boers, Godfried, additional, Ueland, Per, additional, Rubba, Paolo, additional, Palma-Reis, Roberto, additional, Meleady, Raymond, additional, Daly, Leslie, additional, Witteman, Jacqueline, additional, and Graham, Ian, additional

Published
1998
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43. Association between Non-HDL-C/HDL-C Ratio and Carotid Intima–Media Thickness in Post-Menopausal Women.

Author

Iannuzzi, Arcangelo, Giallauria, Francesco, Gentile, Marco, Rubba, Paolo, Covetti, Giuseppe, Bresciani, Alessandro, Aliberti, Emilio, Cuomo, Gilanluigi, Panico, Camilla, Tripaldella, Maria, Giusti, Maria Ausilia, Mattina, Alessandro, and Iannuzzo, Gabriella

Subjects
CAROTID intima-media thickness, POSTMENOPAUSE, CAROTID artery, SYSTOLIC blood pressure, LOW density lipoproteins
Abstract

Atherogenic lipoproteins (particularly, very low-density lipoproteins, VLDL) are associated with subclinical atherosclerosis. The present study aims at evaluating whether routinely analysed lipid parameters are associated with carotid intima–media thickness, a proxy for subclinical atherosclerosis. Lipid parameters from 220 post-menopausal women undergoing ultrasound investigation of the carotid arteries were analysed. Forty-five percent of women showed subclinical atherosclerosis on carotid ultrasound. The mean carotid intima–media thickness was 1.26 ± 0.38 mm. The mean value of the non-HDL-C/HDL-C ratio was 3.1 ± 1.2. Univariate analysis showed a significant association between non-HDL-C/HDL-C ratio and intima–media thickness (r = 0.21, p = 0.001). After adjusting for cardiovascular risk factors (age, systolic blood pressure, smoking, body mass index Homeostasis model assessment: insulin resistance and high-sensitivity C-Reactive-Protein), multivariate analysis showed a significant association between non-HDL-C/HDL-C ratio and intima–media thickness (β = 0.039, p = 0.04). Logistic regression analysis showed that the highest tertile of the non-HDL-C/HDL-C ratio was associated with the presence of carotid plaques (OR = 3.47, p = 0.003). Finally, a strong correlation between non-HDL-C/HDL-C ratio and cholesterol bound to VLDL (r = 0.77, p < 0.001) has been found. Non-HDL-C/HDL-C ratio is associated with the presence of carotid atherosclerosis in post-menopausal women and is strongly correlated to VLDL-C levels. [ABSTRACT FROM AUTHOR]

Published
2022
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44. Increased Carotid Intima-Media Thickness and Stiffnessin Obese Children.

Author

Iannuzzi, Arcangelo, Licenziati, Maria Rosaria, Acampora, Ciro, Salvatore, Vittorio, Auriemma, Lucia, Romano, Maria Luigia, Panico, Salvatore, Rubba, Paolo, and Trevisan, Maurizio

Subjects
CHILDHOOD obesity, METABOLIC disorders in children, NUTRITION disorders in children, VASCULAR diseases, ATHEROSCLEROSIS in children, ATHEROSCLEROSIS prevention
Abstract

Presents information on a study which investigated whether obesity in childhood may cause premature vascular alterations in both sexes. Details of the selection of subjects; Results of statistical analysis; Recommendations for the long-term prevention of atherosclerosis.

Published
2004
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46. Evinacumab for Homozygous Familial Hypercholesterolemia

Author

Gerald Watts, Farrah Deeba, David Sullivan, Paul Donald Bonnitcha, San San Min, Nimalie Jacintha Nanayakkara, Christopher Ebenbichler, Alexander Tschoner, Clemens Engler, Daniel Gaudet, Nathalie Roy, David Blackburn, Jean Bergeron, Hisee Villeneuve, Samir Saheb, Antonio Gallo, Sophia Beliard, Bertrand Dussol, Sophie Morange, Pascale Poullin, Rene Valero, Charalampos Milionis, Sebastian Filippas-Ntekouan, Eleftherios Klouras, Genovefa Kolovou, George Hatzigeorgiou, Spyridon Rammos, Paolo Rubba, Gabriella Iannuzzo, Mariko Harada-Shiba, Cheol Son, Hisashi Makino, Kiminori Hosoda, Kota Matsuki, Kyoko Kohmo, Masaki Matsubara, Masatsune Ogura, Michio Noguchio, Miki Matsuo, Ryo Koezuka, Tamiko Tamanaha, Tsutomu Tomita, Yoko Ohata, Yoshihiko Otsubo, Noriaki Koyanagi, Masaaki Kawashiri, Hayato Tada, Atsushi Nohara, Akihiro Nomura, Hirofumi Okada, Naohiko Fujii, Daisuke Hayashi, Sayoko Yonemoto, Shungo Fukuda, Koji Yanagi, Miwa Ryo, Masahiro Koseki, Makoto Nishida, Takeshi Okada, Erik Stroes, Laurens Reeskamp, Daniela Stols-Goncalves, Eva Hamulyak, Anho H Liem, Jurgen M Akkerhuis, Pieter R Nierop, Bastiaan M van Dalen, Sweder W E van de Poll, Adriana J M van Miltenburg-van Zijl, Marinus J Veerhoek, Frederick Raal, Sindeep Amrat Bhana, Olena Mitchenko, Vadym Romanov, Iryna Chulaevska, Leonid Rudenko, Olena Beregova, Igor Vakaliuk, Iryna Drapchak, Natalia Tymochko, Anna Isayeva, Olena Buriakovska, Maryna Vovchenko, Vira Tseluyko, Nataliya Matviychuk, Larysa Yakovleva, Paul Duell, Jonathan Barton Purnell, Robert Rosenson, Donald Smith, Theresa Halloran, Robert Gottlieb, Peter A McCullough, Zachary P Rosol, Andy Y Lee, Clay M Barbin, Seth J Baum, Reina Mendelson, Melissa Wright, Linda Hemphill, Akl Fahed, Traci Turner, Angela Ellard, Gerald Watts, ., Deeba, Farrah, Sullivan, David, Donald Bonnitcha, Paul, San Min, San, Jacintha Nanayakkara, Nimalie, Ebenbichler, Christopher, Tschoner, Alexander, Engler, Clemen, Gaudet, Daniel, Roy, Nathalie, Blackburn, David, Bergeron, Jean, Villeneuve, Hisee, Saheb, Samir, Gallo, Antonio, Beliard, Sophia, Dussol, Bertrand, Morange, Sophie, Poullin, Pascale, Valero, Rene, Milionis, Charalampo, Filippas-Ntekouan, Sebastian, Klouras, Eleftherio, Kolovou, Genovefa, Hatzigeorgiou, George, Rammos, Spyridon, Rubba, PAOLO OSVALDO FEDERICO, Iannuzzo, Gabriella, Harada-Shiba, Mariko, Son, Cheol, Makino, Hisashi, Hosoda, Kiminori, Matsuki, Kota, Kohmo, Kyoko, Matsubara, Masaki, Ogura, Masatsune, Noguchio, Michio, Matsuo, Miki, Koezuka, Ryo, Tamanaha, Tamiko, Tomita, Tsutomu, Ohata, Yoko, Otsubo, Yoshihiko, Koyanagi, Noriaki, Kawashiri, Masaaki, Tada, Hayato, Nohara, Atsushi, Nomura, Akihiro, Okada, Hirofumi, Fujii, Naohiko, Hayashi, Daisuke, Yonemoto, Sayoko, Fukuda, Shungo, Yanagi, Koji, Ryo, Miwa, Koseki, Masahiro, Nishida, Makoto, Okada, Takeshi, Stroes, Erik, Reeskamp, Lauren, Stols-Goncalves, Daniela, Hamulyak, Eva, H Liem, Anho, M Akkerhuis, Jurgen, R Nierop, Pieter, M van Dalen, Bastiaan, E van de Poll, Sweder W, M van Miltenburg-van Zijl, Adriana J, J Veerhoek, Marinu, Raal, Frederick, Amrat Bhana, Sindeep, Mitchenko, Olena, Romanov, Vadym, Chulaevska, Iryna, Rudenko, Leonid, Beregova, Olena, Vakaliuk, Igor, Drapchak, Iryna, Tymochko, Natalia, Isayeva, Anna, Buriakovska, Olena, Vovchenko, Maryna, Tseluyko, Vira, Matviychuk, Nataliya, Yakovleva, Larysa, Duell, Paul, Barton Purnell, Jonathan, Rosenson, Robert, Smith, Donald, Halloran, Theresa, Gottlieb, Robert, A McCullough, Peter, P Rosol, Zachary, Y Lee, Andy, M Barbin, Clay, J Baum, Seth, Mendelson, Reina, Wright, Melissa, Hemphill, Linda, Fahed, Akl, Turner, Traci, Ellard, Angela, Graduate School, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, Experimental Vascular Medicine, and ACS - Pulmonary hypertension & thrombosis

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Evinacumab, Angiopoietin-like Protein, Disease, Familial hypercholesterolemia, 030204 cardiovascular system & hematology, Hyperlipoproteinemia Type II, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Double-Blind Method, Internal medicine, Anticholesteremic Agent, Medicine, Infusions, Intravenou, 030212 general & internal medicine, Child, Aged, Least-Squares Analysi, business.industry, Cholesterol, Homozygote, Antibodies, Monoclonal, Cholesterol, LDL, General Medicine, Middle Aged, medicine.disease, Endocrinology, Receptors, LDL, Multicenter study, chemistry, Ldl metabolism, Mutation, Female, lipids (amino acids, peptides, and proteins), business, Human, Lipoprotein
Abstract

BACKGROUND: Homozygous familial hypercholesterolemia is characterized by premature cardiovascular disease caused by markedly elevated levels of low-density lipoprotein (LDL) cholesterol. This disorder is associated with genetic variants that result in virtually absent (null-null) or impaired (non-null) LDL-receptor activity. Loss-of-function variants in the gene encoding angiopoietin-like 3 (ANGPTL3) are associated with hypolipidemia and protection against atherosclerotic cardiovascular disease. Evinacumab, a monoclonal antibody against ANGPTL3, has shown potential benefit in patients with homozygous familial hypercholesterolemia. METHODS: In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned in a 2:1 ratio 65 patients with homozygous familial hypercholesterolemia who were receiving stable lipid-lowering therapy to receive an intravenous infusion of evinacumab (at a dose of 15 mg per kilogram of body weight) every 4 weeks or placebo. The primary outcome was the percent change from baseline in the LDL cholesterol level at week 24. RESULTS: The mean baseline LDL cholesterol level in the two groups was 255.1 mg per deciliter, despite the receipt of maximum doses of background lipid-lowering therapy. At week 24, patients in the evinacumab group had a relative reduction from baseline in the LDL cholesterol level of 47.1%, as compared with an increase of 1.9% in the placebo group, for a between-group least-squares mean difference of -49.0 percentage points (95% confidence interval [CI], -65.0 to -33.1; P

Published
2020

47. A subgroup analysis of the ODYSSEY APPRISE study: Safety and efficacy of alirocumab in the Italian cohort

Author

Angelo B. Cefalù, Raffaella Garbelotto, Giuliana Mombelli, Matteo Pirro, Paolo Rubba, Marcello Arca, Claudio Borghi, Katia Bonomo, Stefano Gonnelli, Katia Massaroni, Giampaolo Tirone, Maurizio Averna, Francesco Angelico, Francesco Cipollone, Enzo Corghi, Pompilio Faggiano, Cesare Greco, Luigina Guasti, Tiziano Lucchi, Carlo Sabba, Riccardo Sarzani, Pierfranco Terrosu, Alberto Zambon, Cefalu', Angelo B, Garbelotto, Raffaella, Mombelli, Giuliana, Pirro, Matteo, Rubba, Paolo, Arca, Marcello, Borghi, Claudio, Bonomo, Katia, Gonnelli, Stefano, Massaroni, Katia, Tirone, Giampaolo, and Averna, Maurizio

Subjects
Settore MED/09 - Medicina Interna, Nutrition and Dietetics, LDL-C, Endocrinology, Diabetes and Metabolism, Anticholesteremic Agents, Medicine (miscellaneous), alirocumab, Cholesterol, LDL, Antibodies, Monoclonal, Humanized, Hyperlipoproteinemia Type II, heterozygous familial hypercholesterolemia, Treatment Outcome, Italy, Humans, high cardiovascular risk, Cardiology and Cardiovascular Medicine
Abstract

ODYSSEY APPRISE trial evaluated efficacy and safety of alirocumab in 994 patients with hypercholesterolemia and high CV risk in a real-life setting. The aim of the present report is to detail on the Italian cohort enrolled and treated in the trial.The methodology of the of the multinational, single-arm, Phase 3b open-label ODYSSEY APPRISE (Clinicaltrials.gov: NCT02476006) has been previously reported. 255 Italian patients were enrolled and treated according to the trial protocol. Overall mean exposure to alirocumab was 83.3 ± 27.7 weeks. At week 12, LDL-C decreased by 51.3 ± 23.1% and this reduction was overall maintained for the duration of the study. A similar reduction was observed in patients with and without heterozygous familial hypercholesterolemia (HeFH 50.7% ± 23.9 vs. non-FH, 53.6% ± 19.6). LDL-C was reduced below 1.8 mmol/L and/or by ≥ 50% reduction from baseline in 62% of patients overall (61% in HeFH and 67% in non-FH). Alirocumab was similarly well tolerated in the Italian cohort as in the entire study population and the more common treatment emergent adverse events (TEAEs) were influenza, myalgia and nasopharyngitis. The incidence LDL-C levels25 mg/dl and15 mg/dl, was 8.2% and 2.9% respectively.The efficacy and safety of alirocumab in a real-life setting, in the Italian subgroup of patients are consistent with findings in the entire study population and confirm that alirocumab is a beneficial approach to further reduce LDL-C levels in patients at high CV risk on maximally tolerated conventional lipid lowering treatment.NCT02476006.

Published
2021

48. Lipoprotein (a) is an independent predictor of cardiovascular events in Mediterranean women (Progetto Atena)

Author

Salvatore Panico, Amalia Mattiello, Vittorio Simeon, Gabriella Iannuzzo, Marco Gentile, Paolo Rubba, Maria Donata Di Taranto, Gentile, Marco, Simeon, Vittorio, Iannuzzo, Gabriella, Mattiello, Amalia, Donata di Taranto, Maria, Panico, Salvatore, and Rubba, Paolo

Subjects
Adult, Cardiovascular event, Mediterranean climate, medicine.medical_specialty, Epidemiology, Independent predictor, Predictive Value of Tests, Risk Factors, Internal medicine, medicine, Humans, Prospective Studies, Aged, biology, business.industry, Lipoprotein(a), Middle Aged, Italy, Cardiovascular Diseases, Case-Control Studies, biology.protein, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Biomarkers
Abstract

Non presente

Published
2020

49. Identification and in vitro characterization of two new PCSK9 Gain of Function variants found in patients with Familial Hypercholesterolemia

Author

Kepa B. Uribe, Ornella Guardamagna, Maria Donata Di Taranto, Paolo Rubba, Carola Giacobbe, César Martín, Asier Benito-Vicente, Aitor Etxebarria, Marco Gentile, Giuliana Fortunato, Di Taranto, Maria Donata, Benito-Vicente, Asier, Giacobbe, Carola, Uribe, Kepa Belloso, Rubba, Paolo, Etxebarria, Aitor, Guardamagna, Ornella, Gentile, Marco, Martín, Cesar, and Fortunato, Giuliana

Subjects
Male, 0301 basic medicine, Apolipoprotein B, Mutation, Missense, lcsh:Medicine, Familial hypercholesterolemia, 030204 cardiovascular system & hematology, Article, Hyperlipoproteinemia Type II, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, lcsh:Science, Gene, Genetics, Multidisciplinary, biology, PCSK9, lcsh:R, Autosomal dominant trait, medicine.disease, Proprotein convertase, 030104 developmental biology, Amino Acid Substitution, Receptors, LDL, Gain of Function Mutation, Apolipoprotein B-100, LDL receptor, biology.protein, Kexin, Female, lipids (amino acids, peptides, and proteins), lcsh:Q, Proprotein Convertase 9
Abstract

Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by pathogenic variants in genes encoding for LDL receptor (LDLR), Apolipoprotein B and Proprotein convertase subtilisin/kexin type 9 (PCSK9). Among PCSK9 variants, only Gain-of- Function (GOF) variants lead to FH. Greater attention should be paid to the classification of variants as pathogenic. Two hundred sixty nine patients with a clinical suspect of FH were screened for variants in LDLR and the patients without pathogenic variants were screened for variants in PCSK9 and APOB. Functional characterization of PCSK9 variants was performed by assessment of protein secretion, of LDLR activity in presence of PCSK9 variant proteins as well as of the LDLR affinity of the PCSK9 variants. Among 81 patients without pathogenic variants in LDLR, 7 PCSK9 heterozygotes were found, 4 of whom were carriers of variants whose role in FH pathogenesis is still unknown. Functional characterization revealed that two variants (p.(Ser636Arg) and p.(Arg357Cys)) were GOF variants. In Conclusions, we demonstrated a GOF effect of 2 PCSK9 variants that can be considered as FH-causative variants. The study highlights the important role played by functional characterization in integrating diagnostic procedures when the pathogenicity of new variants has not been previously demonstrated.

Published
2017

50. Association between Lp (a) and atherosclerosis in menopausal women without metabolic syndrome

Author

Gabriella Iannuzzo, Amalia Mattiello, Salvatore Panico, Paolo Rubba, Marco Gentile, Arcangelo Iannuzzi, Gennaro Marotta, Gentile, M, Iannuzzo, Gabriella, Mattiello, Amalia, Marotta, Gennaro, Iannuzzi, A, Panico, Salvatore, and Rubba, PAOLO OSVALDO FEDERICO

Subjects
Adult, Blood Glucose, Carotid ultrasound, medicine.medical_specialty, Waist, Clinical Biochemistry, Blood Pressure, 030204 cardiovascular system & hematology, Carotid imt, Carotid Intima-Media Thickness, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Drug Discovery, Odds Ratio, Humans, Medicine, cardiovascular diseases, 030212 general & internal medicine, Aged, Lipoprotein cholesterol, Metabolic Syndrome, business.industry, Biochemistry (medical), Cholesterol, LDL, Odds ratio, Middle Aged, Atherosclerosis, medicine.disease, Intima-media thickness, Multivariate Analysis, cardiovascular system, Cardiology, Female, Menopause, Waist Circumference, Metabolic syndrome, business, Lipoprotein(a), Lipoprotein
Abstract

Aim: The association between Lipoprotein (a) (Lp [a]) and common carotid intima media thickness (IMT) has been evaluated in 222 menopausal women. Material & methods: Lp (a) and IMT were measured, carotid ultrasound examination (B-Mode imaging) was performed and mean max IMT was calculated. Results: Lp (a) was significantly lower in women with metabolic syndrome (MS). In a multivariate analysis Lp (a) showed the following odds ratio (OR; all p < 0.05) of having common carotid IMT (≥1.30 mm): 1.03, adjusted for age, low-density lipoprotein cholesterol (LDL) and waist circumference; 1.02, adjusted for age LDL, homeostatic assessment model (HOMA). In women without MS, after controlling for age, LDL and waist circumference, we found the following OR for increased IMT (≥1.30; OR: 1.03; for Lp [a]); 1.02 adjusted for age, LDL and HOMA (all p < 0.05). In women with MS these relationships were not statistically significant. Conclusion: Lp (a) gives additional information in the risk assessment for atherosclerotic cardiovascular disease, especially in menopausal women without MS.

Published
2016

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