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1. Rationale and design of the CV-PREVITAL study: an Italian multiple cohort randomised controlled trial investigating innovative digital strategies in primary cardiovascular prevention

Author: Baldassarre, D, Iacoviello, L, Baetta, R, Roncaglioni, M, Condorelli, G, Remuzzi, G, Gensini, G, Frati, L, Ricciardi, W, Conaldi, P, Uccelli, A, Blandini, F, Bosari, S, Scambia, G, Fini, M, Di Malta, A, Amato, M, Veglia, F, Bonomi, A, Klersy, C, Colazzo, F, Pengo, M, Gorini, F, Auteri, L, Ferrante, G, Baviera, M, Ambrosio, G, Catapano, A, Gialluisi, A, Malavazos, A, Castelvecchio, S, Corsi-Romanelli, M, Cardani, R, La Rovere, M, Agnese, V, Pane, B, Prati, D, Spinardi, L, Liuzzo, G, Arbustini, E, Volterrani, M, Visconti, M, Werba, J, Genovese, S, Bilo, G, Invitti, C, Di Blasio, A, Lombardi, C, Faini, A, Rosa, D, Ojeda-Fernandez, L, Foresta, A, De Curtis, A, Di Castelnuovo, A, Scalvini, S, Pierobon, A, Gorini, A, Valenti, L, Luzi, L, Racca, A, Bandi, M, Tremoli, E, Menicanti, L, Parati, G, Pompilio, G, Colombo, G, Vavassori, C, Biondi, M, Frigerio, B, Ravani, A, Sansaro, D, Coggi, D, Romandini, A, Giroli, M, Giuliani, M, Bonmi, A, Rondinelli, M, Trudu, C, Cinieri, C, Monturano, M, Colazo, F, Inviti, C, Di Blasi, A, Torlasco, C, Gilardini, L, Soranna, D, Zambon, A, Perger, E, Zanotti, L, Badano, L, Cova, L, Gentilini, D, Grappiolo, L, Condoreli, G, Ferante, G, Papa, L, Savevski, V, Ieva, F, Romano, I, Remzzi, G, Ojeda, L, Clerici, F, Palumbo, A, Genini, G, Catpano, A, Mattioli, R, Longhi, E, Mantovani, L, Madotto, F, Bonaccio, M, Gianfagna, F, Ghulam, A, Magnacca, S, Noro, F, Costanzo, S, Esposito, S, Orlandi, S, Persichillo, M, Bracone, F, Panzera, T, Ruggiero, E, Parisi, R, Franciosa, S, Morelli, M, De Rita, F, Cerletti, C, de Gaetano, G, Donati, M, Mencanti, L, Romanelli, M, Cerri, A, Dubini, C, Trevisan, M, Renna, L, Milani, V, Boveri, S, Giubbilini, P, Ramputi, L, Baroni, I, De Angeli, G, Riciardi, W, Olmetti, F, Bussotti, M, Gaetano, C, Baiardi, P, Bachetti, T, Balbi, M, Comini, L, Lorenzoni, M, Olivares, A, Traversi, E, Garre, C, Sideri, R, Clemenza, F, Gentile, G, Caruana, G, Cuscino, N, Di Gesaro, G, Greco, A, Loddo, I, Tuzzolino, F, Ucelli, A, Palombo, D, Spinella, G, Mozzetta, G, Ameri, P, Zoppoli, G, Finotello, A, Porto, I, Pratesi, G, Bladini, F, Spnardi, L, Clerici, M, Pelusi, S, Bianco, C, Carpani, R, Periti, G, Margarita, S, Lanza, G, Severino, A, Pedicino, D, D'Amario, D, D'Aiello, A, Vinci, R, Bonanni, A, Brecciaroli, M, Filomia, S, Pastorino, R, Boccia, S, Urbani, A, Sanguinetti, M, Santoliquido, A, Proto, L, Tarquini, D, Grimaldi, M, Leonardi, S, Elia, A, Currao, A, Urtis, M, Di Toro, A, Giuliani, L, Caminiti, G, Marcolongo, F, Sposato, B, Guadagni, F, Morsella, V, Marziale, A, Protti, G, Baldassarre D., Iacoviello L., Baetta R., Roncaglioni M. C., Condorelli G., Remuzzi G., Gensini G., Frati L., Ricciardi W., Conaldi P. G., Uccelli A., Blandini F., Bosari S., Scambia G., Fini M., Di Malta A., Amato M., Veglia F., Bonomi A., Klersy C., Colazzo F., Pengo M., Gorini F., Auteri L., Ferrante G., Baviera M., Ambrosio G., Catapano A., Gialluisi A., Malavazos A. E., Castelvecchio S., Corsi-Romanelli M. M., Cardani R., La Rovere M. T., Agnese V., Pane B., Prati D., Spinardi L., Liuzzo G., Arbustini E., Volterrani M., Visconti M., Werba J. P., Genovese S., Bilo G., Invitti C., Di Blasio A., Lombardi C., Faini A., Rosa D., Ojeda-Fernandez L., Foresta A., De Curtis A., Di Castelnuovo A., Scalvini S., Pierobon A., Gorini A., Valenti L., Luzi L., Racca A., Bandi M., Tremoli E., Menicanti L., Parati G., Pompilio G., Colombo G., Vavassori C., Biondi M. L., Frigerio B., Ravani A., Sansaro D., Coggi D., Romandini A., Giroli M., Giuliani M., Bonmi A., Rondinelli M., Trudu C., Cinieri C., Monturano M., Colazo F., Inviti C., Di Blasi A., Torlasco C., Gilardini L., Soranna D., Zambon A., Perger E., Zanotti L., Badano L., Cova L., Gentilini D., Grappiolo L., Condoreli G., Ferante G., Papa L., Savevski V., Ieva F., Romano I., Remzzi G., Ojeda L., Clerici F., Palumbo A., Genini G. F., Catpano A., Mattioli R., Longhi E., Mantovani L. G., Madotto F., Bonaccio M., Gianfagna F., Ghulam A., Magnacca S., Noro F., Costanzo S., Esposito S., Orlandi S., Persichillo M., Bracone F., Panzera T., Ruggiero E., Parisi R., Franciosa S., Morelli M., De Rita F., Cerletti C., de Gaetano G., Donati M. B., Mencanti L., Romanelli M. M. C., Cerri A., Dubini C., Trevisan M. B., Renna L. V., Milani V., Boveri S., Giubbilini P., Ramputi L., Baroni I., De Angeli G., Riciardi W., Olmetti F., Bussotti M., Gaetano C., Baiardi P., Bachetti T., Balbi M., Comini L., Lorenzoni M., Olivares A., Traversi E., Garre C., Sideri R., Clemenza F., Gentile G., Caruana G., Cuscino N., Di Gesaro G., Greco A., Loddo I., Tuzzolino F., Ucelli A., Palombo D., Spinella G., Mozzetta G., Ameri P., Zoppoli G., Finotello A., Porto I., Pratesi G., Bladini F., Spnardi L., Clerici M., Pelusi S., Bianco C., Carpani R., Periti G., Margarita S., Lanza G. A., Severino A., Pedicino D., D'Amario D., D'Aiello A., Vinci R., Bonanni A., Brecciaroli M., Filomia S., Pastorino R., Boccia S., Urbani A., Sanguinetti M., Santoliquido A., Proto L., Tarquini D., Grimaldi M. C., Leonardi S., Elia A., Currao A., Urtis M., Di Toro A., Giuliani L., Caminiti G., Marcolongo F., Sposato B., Guadagni F., Morsella V., Marziale A., Protti G., Baldassarre, D, Iacoviello, L, Baetta, R, Roncaglioni, M, Condorelli, G, Remuzzi, G, Gensini, G, Frati, L, Ricciardi, W, Conaldi, P, Uccelli, A, Blandini, F, Bosari, S, Scambia, G, Fini, M, Di Malta, A, Amato, M, Veglia, F, Bonomi, A, Klersy, C, Colazzo, F, Pengo, M, Gorini, F, Auteri, L, Ferrante, G, Baviera, M, Ambrosio, G, Catapano, A, Gialluisi, A, Malavazos, A, Castelvecchio, S, Corsi-Romanelli, M, Cardani, R, La Rovere, M, Agnese, V, Pane, B, Prati, D, Spinardi, L, Liuzzo, G, Arbustini, E, Volterrani, M, Visconti, M, Werba, J, Genovese, S, Bilo, G, Invitti, C, Di Blasio, A, Lombardi, C, Faini, A, Rosa, D, Ojeda-Fernandez, L, Foresta, A, De Curtis, A, Di Castelnuovo, A, Scalvini, S, Pierobon, A, Gorini, A, Valenti, L, Luzi, L, Racca, A, Bandi, M, Tremoli, E, Menicanti, L, Parati, G, Pompilio, G, Colombo, G, Vavassori, C, Biondi, M, Frigerio, B, Ravani, A, Sansaro, D, Coggi, D, Romandini, A, Giroli, M, Giuliani, M, Bonmi, A, Rondinelli, M, Trudu, C, Cinieri, C, Monturano, M, Colazo, F, Inviti, C, Di Blasi, A, Torlasco, C, Gilardini, L, Soranna, D, Zambon, A, Perger, E, Zanotti, L, Badano, L, Cova, L, Gentilini, D, Grappiolo, L, Condoreli, G, Ferante, G, Papa, L, Savevski, V, Ieva, F, Romano, I, Remzzi, G, Ojeda, L, Clerici, F, Palumbo, A, Genini, G, Catpano, A, Mattioli, R, Longhi, E, Mantovani, L, Madotto, F, Bonaccio, M, Gianfagna, F, Ghulam, A, Magnacca, S, Noro, F, Costanzo, S, Esposito, S, Orlandi, S, Persichillo, M, Bracone, F, Panzera, T, Ruggiero, E, Parisi, R, Franciosa, S, Morelli, M, De Rita, F, Cerletti, C, de Gaetano, G, Donati, M, Mencanti, L, Romanelli, M, Cerri, A, Dubini, C, Trevisan, M, Renna, L, Milani, V, Boveri, S, Giubbilini, P, Ramputi, L, Baroni, I, De Angeli, G, Riciardi, W, Olmetti, F, Bussotti, M, Gaetano, C, Baiardi, P, Bachetti, T, Balbi, M, Comini, L, Lorenzoni, M, Olivares, A, Traversi, E, Garre, C, Sideri, R, Clemenza, F, Gentile, G, Caruana, G, Cuscino, N, Di Gesaro, G, Greco, A, Loddo, I, Tuzzolino, F, Ucelli, A, Palombo, D, Spinella, G, Mozzetta, G, Ameri, P, Zoppoli, G, Finotello, A, Porto, I, Pratesi, G, Bladini, F, Spnardi, L, Clerici, M, Pelusi, S, Bianco, C, Carpani, R, Periti, G, Margarita, S, Lanza, G, Severino, A, Pedicino, D, D'Amario, D, D'Aiello, A, Vinci, R, Bonanni, A, Brecciaroli, M, Filomia, S, Pastorino, R, Boccia, S, Urbani, A, Sanguinetti, M, Santoliquido, A, Proto, L, Tarquini, D, Grimaldi, M, Leonardi, S, Elia, A, Currao, A, Urtis, M, Di Toro, A, Giuliani, L, Caminiti, G, Marcolongo, F, Sposato, B, Guadagni, F, Morsella, V, Marziale, A, Protti, G, Baldassarre D., Iacoviello L., Baetta R., Roncaglioni M. C., Condorelli G., Remuzzi G., Gensini G., Frati L., Ricciardi W., Conaldi P. G., Uccelli A., Blandini F., Bosari S., Scambia G., Fini M., Di Malta A., Amato M., Veglia F., Bonomi A., Klersy C., Colazzo F., Pengo M., Gorini F., Auteri L., Ferrante G., Baviera M., Ambrosio G., Catapano A., Gialluisi A., Malavazos A. E., Castelvecchio S., Corsi-Romanelli M. M., Cardani R., La Rovere M. T., Agnese V., Pane B., Prati D., Spinardi L., Liuzzo G., Arbustini E., Volterrani M., Visconti M., Werba J. P., Genovese S., Bilo G., Invitti C., Di Blasio A., Lombardi C., Faini A., Rosa D., Ojeda-Fernandez L., Foresta A., De Curtis A., Di Castelnuovo A., Scalvini S., Pierobon A., Gorini A., Valenti L., Luzi L., Racca A., Bandi M., Tremoli E., Menicanti L., Parati G., Pompilio G., Colombo G., Vavassori C., Biondi M. L., Frigerio B., Ravani A., Sansaro D., Coggi D., Romandini A., Giroli M., Giuliani M., Bonmi A., Rondinelli M., Trudu C., Cinieri C., Monturano M., Colazo F., Inviti C., Di Blasi A., Torlasco C., Gilardini L., Soranna D., Zambon A., Perger E., Zanotti L., Badano L., Cova L., Gentilini D., Grappiolo L., Condoreli G., Ferante G., Papa L., Savevski V., Ieva F., Romano I., Remzzi G., Ojeda L., Clerici F., Palumbo A., Genini G. F., Catpano A., Mattioli R., Longhi E., Mantovani L. G., Madotto F., Bonaccio M., Gianfagna F., Ghulam A., Magnacca S., Noro F., Costanzo S., Esposito S., Orlandi S., Persichillo M., Bracone F., Panzera T., Ruggiero E., Parisi R., Franciosa S., Morelli M., De Rita F., Cerletti C., de Gaetano G., Donati M. B., Mencanti L., Romanelli M. M. C., Cerri A., Dubini C., Trevisan M. B., Renna L. V., Milani V., Boveri S., Giubbilini P., Ramputi L., Baroni I., De Angeli G., Riciardi W., Olmetti F., Bussotti M., Gaetano C., Baiardi P., Bachetti T., Balbi M., Comini L., Lorenzoni M., Olivares A., Traversi E., Garre C., Sideri R., Clemenza F., Gentile G., Caruana G., Cuscino N., Di Gesaro G., Greco A., Loddo I., Tuzzolino F., Ucelli A., Palombo D., Spinella G., Mozzetta G., Ameri P., Zoppoli G., Finotello A., Porto I., Pratesi G., Bladini F., Spnardi L., Clerici M., Pelusi S., Bianco C., Carpani R., Periti G., Margarita S., Lanza G. A., Severino A., Pedicino D., D'Amario D., D'Aiello A., Vinci R., Bonanni A., Brecciaroli M., Filomia S., Pastorino R., Boccia S., Urbani A., Sanguinetti M., Santoliquido A., Proto L., Tarquini D., Grimaldi M. C., Leonardi S., Elia A., Currao A., Urtis M., Di Toro A., Giuliani L., Caminiti G., Marcolongo F., Sposato B., Guadagni F., Morsella V., Marziale A., and Protti G.
Abstract: Introduction Prevention of cardiovascular disease (CVD) is of key importance in reducing morbidity, disability and mortality worldwide. Observational studies suggest that digital health interventions can be an effective strategy to reduce cardiovascular (CV) risk. However, evidence from large randomised clinical trials is lacking. Methods and analysis The CV-PREVITAL study is a multicentre, prospective, randomised, controlled, open-label interventional trial designed to compare the effectiveness of an educational and motivational mobile health (mHealth) intervention versus usual care in reducing CV risk. The intervention aims at improving diet, physical activity, sleep quality, psycho-behavioural aspects, as well as promoting smoking cessation and adherence to pharmacological treatment for CV risk factors. The trial aims to enrol approximately 80 000 subjects without overt CVDs referring to general practitioners' offices, community pharmacies or clinics of Scientific Institute for Research, Hospitalization and Health Care (Italian acronym IRCCS) affiliated with the Italian Cardiology Network. All participants are evaluated at baseline and after 12 months to assess the effectiveness of the intervention on short-term endpoints, namely improvement in CV risk score and reduction of major CV risk factors. Beyond the funded life of the study, a long-term (7 years) follow-up is also planned to assess the effectiveness of the intervention on the incidence of major adverse CV events. A series of ancillary studies designed to evaluate the effect of the mHealth intervention on additional risk biomarkers are also performed. Ethics and dissemination This study received ethics approval from the ethics committee of the coordinating centre (Monzino Cardiology Center; R1256/20-CCM 1319) and from all other relevant IRBs and ethics committees. Findings are disseminated through scientific meetings and peer-reviewed journals and via social media. Partners are informed about the study's
Published: 2023

2. Come superare le barriere all'implementazione delle strategie di prevenzione e cura della malattia cardiovascolare aterosclerotica mediante terapia ipolipemizzante

Author: Arca, M, Averna, M, Borghi, C, Lettino, M, Filardi, P, Alberti, A, Bilato, C, Calabrò, P, Carubbi, F, Ciccone, M, Cipollone, F, Citroni, N, De Luca, L, Giaccari, A, Iannuzzo, G, Maloberti, A, Marcucci, R, Spinazzola, P, Pirro, M, Pisciotta, L, Sarullo, F, Sciacqua, A, Suppressa, P, Varbella, F, Werba, J, Zambon, A, Arca M., Averna M., Borghi C., Lettino M., Filardi P. P., Alberti A., Bilato C., Calabrò P., Carubbi F., Ciccone M. M., Cipollone F., Citroni N., De Luca L., Giaccari A., Iannuzzo G., Maloberti A., Marcucci R., Spinazzola P. P., Pirro M., Pisciotta L., Sarullo F., Sciacqua A., Suppressa P., Varbella F., Werba J. P., Zambon A., Arca, M, Averna, M, Borghi, C, Lettino, M, Filardi, P, Alberti, A, Bilato, C, Calabrò, P, Carubbi, F, Ciccone, M, Cipollone, F, Citroni, N, De Luca, L, Giaccari, A, Iannuzzo, G, Maloberti, A, Marcucci, R, Spinazzola, P, Pirro, M, Pisciotta, L, Sarullo, F, Sciacqua, A, Suppressa, P, Varbella, F, Werba, J, Zambon, A, Arca M., Averna M., Borghi C., Lettino M., Filardi P. P., Alberti A., Bilato C., Calabrò P., Carubbi F., Ciccone M. M., Cipollone F., Citroni N., De Luca L., Giaccari A., Iannuzzo G., Maloberti A., Marcucci R., Spinazzola P. P., Pirro M., Pisciotta L., Sarullo F., Sciacqua A., Suppressa P., Varbella F., Werba J. P., and Zambon A.
Abstract: Atherosclerotic cardiovascular diseases remain the main cause of mortality worldwide, due to a poor control of modifiable risk factors for atherosclerosis. High levels of low-density lipoprotein cholesterol represent the most relevant actor in the development of atherosclerotic cardiovascular diseases, as well as the main target promuovoof prevention strategies. Although lipid-lowering treatments were shown to be effective for cardiovascular prevention, several barriers (e.g. clinician reluctance to prescribe an intensive treatment, poor adherence of patients to therapy, high pharmacotherapy burden of high-risk patients and the fear for adverse events potentially associated with statins) still prevent therapy optimization. Such issues will be addressed in this review article, taking into account possible strategies for their solution, through an integrated approach including both management interventions and a larger use of the available pharmacologic options.
Published: 2023

3. Reported muscle symptoms during statin treatment amongst Italian dyslipidaemic patients in the real‐life setting: the PROSISA Study

Author: Casula, M., Gazzotti, M., Bonaiti, F., Oimastroni, E., Arca, M., Averna, M., Zambon, A., Catapano, A. L., Montali, A., Giammanco, A., Biolo, G., Vinci, P., Borghi, C., D'Addato, S., Bossi, A. C., Meregalli, G., Branchi, A., Squiccimarro, G., Cavalot, F., Ramadori, L., Cipollone, F., Bucci, M., Del Ben, M., Angelico, F., Fiorenza, A. M., Colombo, E., Grigore, L., Zampoleri, V., Lupattelli, G., Gandolfo, V., Mandraffino, G., Savarino, F., Mombelli, G., Pavanello, C., Pisciotta, L., Pasta, A., Purrello, F., Scicali, R., Rubba, P., Fortunato, G., Sabba, C., Suppressa, P., Sarzani, R., Di Pentima, C., Vigna, G. B., Colangiulo, A., Werba, J. P., Vigo, L. M., Zambon, S., Previato, L., Zenti, M. G., Maneschi, C., Casula, M., Gazzotti, M., Bonaiti, F., Oimastroni, E., Arca, M., Averna, M., Zambon, A., Catapano, A. L., Montali, A., Giammanco, A., Biolo, G., Vinci, P., Borghi, C., D'Addato, S., Bossi, A. C., Meregalli, G., Branchi, A., Squiccimarro, G., Cavalot, F., Ramadori, L., Cipollone, F., Bucci, M., Del Ben, M., Angelico, F., Fiorenza, A. M., Colombo, E., Grigore, L., Zampoleri, V., Lupattelli, G., Gandolfo, V., Mandraffino, G., Savarino, F., Mombelli, G., Pavanello, C., Pisciotta, L., Pasta, A., Purrello, F., Scicali, R., Rubba, P., Fortunato, G., Sabba, C., Suppressa, P., Sarzani, R., Di Pentima, C., Vigna, G. B., Colangiulo, A., Werba, J. P., Vigo, L. M., Zambon, S., Previato, L., Zenti, M. G., Maneschi, C., Casula M, Gazzotti M, Bonaiti F, OImastroni E, Arca M, Averna M, Zambon A, Catapano AL, PROSISA Study Group, Borghi C, Casula M., Gazzotti M., Bonaiti F., OImastroni E., Arca M., Averna M., Zambon A., Catapano A.L., Montali A., Giammanco A., Biolo G., Vinci P., Borghi C., D'Addato S., Bossi A.C., Meregalli G., Branchi A., Squiccimarro G., Cavalot F., Ramadori L., Cipollone F., Bucci M., Del Ben M., Angelico F., Fiorenza A.M., Colombo E., Grigore L., Zampoleri V., Lupattelli G., Gandolfo V., Mandraffino G., Savarino F., Mombelli G., Pavanello C., Pisciotta L., Pasta A., Purrello F., Scicali R., Rubba P., Fortunato G., Sabba C., Suppressa P., Sarzani R., Di Pentima C., Vigna G.B., Colangiulo A., Werba J.P., Vigo L.M., Zambon S., Previato L., Zenti M.G., and Maneschi C.
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Settore MED/09 - Medicina Interna, adverse effects, myopathy, statin-associated muscle symptoms, statins, 030204 cardiovascular system & hematology, Medication Adherence, 03 medical and health sciences, 0302 clinical medicine, Muscular Diseases, Internal medicine, adverse effect, Internal Medicine, medicine, Prevalence, Humans, statin‐associated muscle symptoms, Adverse effect, Dechallenge, Creatine Kinase, Dyslipidemias, Female, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Italy, Middle Aged, Retrospective Studies, business.industry, Retrospective cohort study, Odds ratio, Original Articles, Confidence interval, Discontinuation, 030104 developmental biology, Concomitant, Cohort, Original Article, business, statin-associated muscle symptom
Abstract: Aim: Statin-associated muscle symptoms (SAMS) are a major determinant of poor treatment adherence and/or discontinuation, but a definitive diagnosis of SAMS is challenging. The PROSISA study was an observational retrospective study aimed to assess the prevalence of reported SAMS in a cohort of dyslipidaemic patients. Methods: Demographic/anamnestic data, biochemical values and occurrence of SAMS were collected by 23 Italian Lipid Clinics. Adjusted logistic regression was performed to estimate odds ratio (OR) and 95% confidence intervals for association between probability of reporting SAMS and several factors. Results: Analyses were carried out on 16717 statin-treated patients (mean±SD, age 60.5±12.0years; 52.1% men). During statin therapy, 9.6% (N=1599) of patients reported SAMS. Women and physically active subjects were more likely to report SAMS (OR 1.23 [1.10–1.37] and OR 1.35 [1.14–1.60], respectively), whist age≥65 (OR 0.79 [0.70–0.89]), presence of type 2 diabetes mellitus (OR 0.62 [0.51–0.74]), use of concomitant nonstatin lipid-lowering drugs (OR 0.87 [0.76–0.99]), use of high-intensity statins (OR 0.79 [0.69–0.90]) and use of potential interacting drugs (OR 0.63 [0.48–0.84]) were associated with lower probability of reporting SAMS. Amongst patients reporting SAMS, 82.2% underwent dechallenge (treatment interruption) and/or rechallenge (change or restart of statin therapy), with reappearance of muscular symptoms in 38.4% (3.01% of the whole cohort). Conclusions: The reported prevalence of SAMS was 9.6% of the whole PROSISA cohort, but only a third of patients still reported SAMS after dechallenge/rechallenge. These results emphasize the need for a better management of SAMS to implement a more accurate diagnosis and treatment re-evaluation.
Published: 2020

4. The Role of Registers in Increasing Knowledge and Improving Management of Children and Adolescents Affected by Familial Hypercholesterolemia: the LIPIGEN Pediatric Group

Author: Gazzotti, M, Casula, M, Bertolini, S, Capra, M, Olmastroni, E, Catapano, A, Pederiva, C, Allevi, M, Arca, M, Auricchio, R, Averna, M, Baldera, D, Banderali, G, Bartuli, A, Biasucci, G, Borghi, C, Bruzzi, P, Buganza, R, Buonuomo, P, Calabro, P, Calandra, S, Carubbi, F, Cesaro, A, Cipollone, F, Citroni, N, Covetti, G, Cremonini, A, D'Addato, S, Ben, M, Di Taranto, M, Fortunato, G, Franceschi, R, Galimberti, F, Genovesi, S, Giammanco, A, Grigore, L, Guardamagna, O, Iannuzzi, A, Iannuzzo, G, Lascala, L, Locatelli, F, Iughetti, L, Madaghiele, S, Mandraffino, G, Mannarino, M, Marco, B, Maroni, L, Minicocci, I, Mombelli, G, Muntoni, S, Nascimbeni, F, Parati, G, Passaro, A, Pavanello, C, Pellegatta, F, Perla, F, Generale, M, Pirro, M, Pisciotta, L, Pujia, A, Purrello, F, Rinaldi, E, Sarzani, R, Scicali, R, Suppressa, P, Tarugi, P, Verachtert, S, Vigna, G, Werba, J, Zambon, A, Zambon, S, Zenti, M, Gazzotti M., Casula M., Bertolini S., Capra M. E., Olmastroni E., Catapano A. L., Pederiva C., Allevi M., Arca M., Auricchio R., Averna M., Baldera D., Banderali G., Bartuli A., Biasucci G., Borghi C., Bruzzi P., Buganza R., Buonuomo P. S., Calabro P., Calandra S., Carubbi F., Cesaro A., Cipollone F., Citroni N., Covetti G., Cremonini A., D'Addato S., Ben M. D., Di Taranto M. D., Fortunato G., Franceschi R., Galimberti F., Genovesi S., Giammanco A., Grigore L., Guardamagna O., Iannuzzi A., Iannuzzo G., Lascala L., Locatelli F., Iughetti L., Madaghiele S., Mandraffino G., Mannarino M. R., Marco B., Maroni L., Minicocci I., Mombelli G., Muntoni S., Nascimbeni F., Parati G., Passaro A., Pavanello C., Pellegatta F., Perla F. M., Generale M., Pirro M., Pisciotta L., Pujia A., Purrello F., Rinaldi E., Sarzani R., Scicali R., Suppressa P., Tarugi P., Verachtert S., Vigna G. B., Werba J. P., Zambon A., Zambon S., Zenti M. G., Gazzotti, M, Casula, M, Bertolini, S, Capra, M, Olmastroni, E, Catapano, A, Pederiva, C, Allevi, M, Arca, M, Auricchio, R, Averna, M, Baldera, D, Banderali, G, Bartuli, A, Biasucci, G, Borghi, C, Bruzzi, P, Buganza, R, Buonuomo, P, Calabro, P, Calandra, S, Carubbi, F, Cesaro, A, Cipollone, F, Citroni, N, Covetti, G, Cremonini, A, D'Addato, S, Ben, M, Di Taranto, M, Fortunato, G, Franceschi, R, Galimberti, F, Genovesi, S, Giammanco, A, Grigore, L, Guardamagna, O, Iannuzzi, A, Iannuzzo, G, Lascala, L, Locatelli, F, Iughetti, L, Madaghiele, S, Mandraffino, G, Mannarino, M, Marco, B, Maroni, L, Minicocci, I, Mombelli, G, Muntoni, S, Nascimbeni, F, Parati, G, Passaro, A, Pavanello, C, Pellegatta, F, Perla, F, Generale, M, Pirro, M, Pisciotta, L, Pujia, A, Purrello, F, Rinaldi, E, Sarzani, R, Scicali, R, Suppressa, P, Tarugi, P, Verachtert, S, Vigna, G, Werba, J, Zambon, A, Zambon, S, Zenti, M, Gazzotti M., Casula M., Bertolini S., Capra M. E., Olmastroni E., Catapano A. L., Pederiva C., Allevi M., Arca M., Auricchio R., Averna M., Baldera D., Banderali G., Bartuli A., Biasucci G., Borghi C., Bruzzi P., Buganza R., Buonuomo P. S., Calabro P., Calandra S., Carubbi F., Cesaro A., Cipollone F., Citroni N., Covetti G., Cremonini A., D'Addato S., Ben M. D., Di Taranto M. D., Fortunato G., Franceschi R., Galimberti F., Genovesi S., Giammanco A., Grigore L., Guardamagna O., Iannuzzi A., Iannuzzo G., Lascala L., Locatelli F., Iughetti L., Madaghiele S., Mandraffino G., Mannarino M. R., Marco B., Maroni L., Minicocci I., Mombelli G., Muntoni S., Nascimbeni F., Parati G., Passaro A., Pavanello C., Pellegatta F., Perla F. M., Generale M., Pirro M., Pisciotta L., Pujia A., Purrello F., Rinaldi E., Sarzani R., Scicali R., Suppressa P., Tarugi P., Verachtert S., Vigna G. B., Werba J. P., Zambon A., Zambon S., and Zenti M. G.
Abstract: Pathology registers can be a useful tool to overcome obstacles in the identification and management of familial hypercholesterolemia since childhood. In 2018, the LIPIGEN pediatric group was constituted within the Italian LIPIGEN study to focus on FH subjects under 18 years. This work aimed at discussing its recent progress and early outcomes. Demographic, biochemical, and genetic baseline characteristics were collected, with an in-depth analysis of the genetic defects. The analysis was carried out on 1,602 children and adolescents (mean age at baseline 9.9 ± 4.0 years), and almost the whole cohort underwent the genetic test (93.3%). Overall, the untreated mean value of LDL-C was 220.0 ± 97.2 mg/dl, with an increasing gradient from subjects with a negative (N = 317; mean untreated LDL-C = 159.9 ± 47.7 mg/dl), inconclusive (N = 125; mean untreated LDL-C = 166.4 ± 56.5 mg/dl), or positive (N = 1,053; mean untreated LDL-C = 246.5 ± 102.1 mg/dl) genetic diagnosis of FH. In the latter group, the LDL-C values presented a great variability based on the number and the biological impact of involved causative variants. The LIPIGEN pediatric group represents one of the largest cohorts of children with FH, allowing the deepening of the characterization of their baseline and genetic features, providing the basis for further longitudinal investigations for complete details.
Published: 2022

5. Response to “The Effect of Green Tea With Exceptionally High Catechin Content on Nadolol Plasma Concentration”

Author: Misaka, S, Yatabe, J, Müller, F, Takano, K, Glaeser, H, Yatabe, M S, Onoue, S, Werba, J P, Watanabe, H, Yamada, S, Fromm, M F, and Kimura, J
Published: 2014
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6. Green Tea Ingestion Greatly Reduces Plasma Concentrations of Nadolol in Healthy Subjects

Author: Misaka, S, Yatabe, J, Müller, F, Takano, K, Kawabe, K, Glaeser, H, Yatabe, M S, Onoue, S, Werba, J P, Watanabe, H, Yamada, S, Fromm, M F, and Kimura, J
Published: 2014
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7. Evaluation of the performance of Dutch Lipid Clinic Network score in an Italian FH population: The LIPIGEN study

Author: Casula, M., Olmastroni, E., Pirillo, A., Catapano, A. L., Averna, M., Bertolini, Stefania, Calandra, S., Tarugi, P., Pellegatta, F., Angelico, F., Bartuli, A., Biasucci, G., Biolo, G., Bonanni, L., Bonomo, K., Borghi, C., Bossi, A. C., Branchi, A., Carubbi, F., Cipollone, F., Citroni, N., Federici, Marco, Ferri, C., Fiorenza, A. M., Giaccari, Andrea, Giorgino, F., Guardamagna, O., Iannuzzi, A., Iughetti, L., Lupattelli, G., Lupi, Alessandro, Mandraffino, G., Marcucci, R., Maroni, L., Miccoli, R., Mombelli, Gaia, Muntoni, S., Pecchioli, V., Pederiva, C., Pipolo, A., Pisciotta, L., Pujia, A., Purrello, F., Repetti, E., Rubba, P., Sabba, C., Sampietro, T., Sarzani, R., Tagliabue, M. P., Trenti, C., Vigna, G. B., Werba, J. P., Zambon, S., Zenti, M. G., Minicocci, I., Noto, D., Fortunato, G., Banderali, G., Benso, A., Bigolin, P., Bonora, E., Bruzzi, P., Bucci, M., Buonuomo, Paola Sabrina, Capra, M. E., Cardolini, I., Cefalu, B., Cervelli, N., Chiariello, Giovanni Alfonso, Cocci, G., Colombo, E., Cremonini, A. L., D'Addato, S., D'Erasmo, L., Dal Pino, B., De Sanctis, L., De Vita, E., Del Ben, M., Di Costanzo, A., Di Taranto, M. D., Fasano, T., Gentile, L., Gentile, Marino, Ghirardello, O., Grigore, L., Lussu, M., Meregalli, G., Moffa, Simona, Montalcini, T., Morgia, V., Nascimbeni, F., Pasta, A., Pavanello, C., Saitta, A., Scicali, R., Siepi, D., Spagnolli, W., Spina, R., Sticchi, E., Suppressa, P., Vigo, L., Vinci, P., Manzato, E., Tragni, E., Zampoleri, V., Arca, M., Bertolini S., Federici M., Giaccari A. (ORCID:0000-0002-7462-7792), Lupi A., Mombelli G., Buonuomo P. S., Chiariello G., Gentile M., Moffa S., Casula, M., Olmastroni, E., Pirillo, A., Catapano, A. L., Averna, M., Bertolini, Stefania, Calandra, S., Tarugi, P., Pellegatta, F., Angelico, F., Bartuli, A., Biasucci, G., Biolo, G., Bonanni, L., Bonomo, K., Borghi, C., Bossi, A. C., Branchi, A., Carubbi, F., Cipollone, F., Citroni, N., Federici, Marco, Ferri, C., Fiorenza, A. M., Giaccari, Andrea, Giorgino, F., Guardamagna, O., Iannuzzi, A., Iughetti, L., Lupattelli, G., Lupi, Alessandro, Mandraffino, G., Marcucci, R., Maroni, L., Miccoli, R., Mombelli, Gaia, Muntoni, S., Pecchioli, V., Pederiva, C., Pipolo, A., Pisciotta, L., Pujia, A., Purrello, F., Repetti, E., Rubba, P., Sabba, C., Sampietro, T., Sarzani, R., Tagliabue, M. P., Trenti, C., Vigna, G. B., Werba, J. P., Zambon, S., Zenti, M. G., Minicocci, I., Noto, D., Fortunato, G., Banderali, G., Benso, A., Bigolin, P., Bonora, E., Bruzzi, P., Bucci, M., Buonuomo, Paola Sabrina, Capra, M. E., Cardolini, I., Cefalu, B., Cervelli, N., Chiariello, Giovanni Alfonso, Cocci, G., Colombo, E., Cremonini, A. L., D'Addato, S., D'Erasmo, L., Dal Pino, B., De Sanctis, L., De Vita, E., Del Ben, M., Di Costanzo, A., Di Taranto, M. D., Fasano, T., Gentile, L., Gentile, Marino, Ghirardello, O., Grigore, L., Lussu, M., Meregalli, G., Moffa, Simona, Montalcini, T., Morgia, V., Nascimbeni, F., Pasta, A., Pavanello, C., Saitta, A., Scicali, R., Siepi, D., Spagnolli, W., Spina, R., Sticchi, E., Suppressa, P., Vigo, L., Vinci, P., Manzato, E., Tragni, E., Zampoleri, V., Arca, M., Bertolini S., Federici M., Giaccari A. (ORCID:0000-0002-7462-7792), Lupi A., Mombelli G., Buonuomo P. S., Chiariello G., Gentile M., and Moffa S.
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

8. BDNFVal66met polymorphism: A potential bridge between depression and thrombosis

Author: Amadio, P, Colombo, G, Tarantino, E, Gianellini, S, Ieraci, A, Brioschi, M, Banfi, C, Werba, J, Parolari, A, Lee, F, Tremoli, E, Barbieri, S, Amadio P., Colombo G. I., Tarantino E., Gianellini S., Ieraci A., Brioschi M., Banfi C., Werba J. P., Parolari A., Lee F. S., Tremoli E., Barbieri S. S., Amadio, P, Colombo, G, Tarantino, E, Gianellini, S, Ieraci, A, Brioschi, M, Banfi, C, Werba, J, Parolari, A, Lee, F, Tremoli, E, Barbieri, S, Amadio P., Colombo G. I., Tarantino E., Gianellini S., Ieraci A., Brioschi M., Banfi C., Werba J. P., Parolari A., Lee F. S., Tremoli E., and Barbieri S. S.
Abstract: Aims Epidemiological studies strongly suggest a link between stress, depression, and cardiovascular diseases (CVDs); the mechanistic correlation, however, is poorly understood. A single-nucleotide polymorphism in the BDNF gene (BDNFVal66Met), associated with depression and anxiety, has been proposed as a genetic risk factor for CVD. Using a knock-in mouse carrying the BDNFVal66Met human polymorphism, which phenocopies psychiatric-related symptoms found in humans, we investigated the impact of this SNP on thrombosis. Methods and results BDNFMet/Met mice displayed a depressive-like phenotype concomitantly with hypercoagulable state and platelet hyperreactivity. Proteomic analysis of aorta secretome from BDNFMet/Met and wild-type (WT) mice showed differential expression of proteins involved in the coagulation and inflammatory cascades. The BDNF Met allele predisposed to carotid artery thrombosis FeCl3-induced and to death after collagen/epinephrine injection. Interestingly, transfection with BDNFMet construct induced a prothrombotic/proinflammatory phenotype in WT cells. SIRT1 activation, using resveratrol and/or CAY10591, prevented thrombus formation and restored the physiological levels of coagulation and of platelet markers in BDNFMet/Met mice and/or cells transfected with the Met allele. Conversely, inhibition of SIRT1 by sirtinol and/or by specific siRNA induced the prothrombotic/proinflammatory phenotype inWT mice and cells. Finally, we found that BDNF Met homozygosity is associated with increased risk of acute myocardial infarction (AMI) in humans. Conclusion Activation of platelets, alteration in coagulation pathways, and changes in vessel wall protein expression in BDNFMet/Met mice recapitulate well the features occurring in the anxiety/depression condition. Furthermore, our data suggest that the BDNFVal66Met polymorphism contribute to the individual propensity for arterial thrombosis related to AMI.
Published: 2017

9. Common carotid intima-media thickness measurement. A method to improve accuracy and precision.

Author: Baldassarre, D, primary, Werba, J P, additional, Tremoli, E, additional, Poli, A, additional, Pazzucconi, F, additional, and Sirtori, C R, additional
Published: 1994
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10. P330 A CASE OF SEVERE AORTIC STENOSIS IN A YOUNG PATIENT WITH BICUSPID AORTIC VALVE, FAMILIAL HYPERCHOLESTEROLEMIA AND CALCIFICATION AT THE SINOTUBULAR JUNCTION

Author: Brusamolino, M, Muratori, M, Apostolo, A, Mapelli, M, Bonalumi, G, Nanci, G, Werba, J, Pepi, M, Mantegazza, V, Calligaris, G, Formenti, A, Agrifoglio, M, and Agostoni, P
Published: 2022
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11. Marked neointimal lipoprotein lipase increase in distinct models of proclivity to atherosclerosis: a feature independent of endothelial layer integrity

Author: Werba, J. P., Martinez, V., Abulafia, D. P., Levy, R., Magarinos, G., Rey, R. H., Baetta, R., Soma, M. R., Anel, A. D., and Cuniberti, L. A.
Published: 2001
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12. Dose-Related Increase of HDL-cholesterol Levels after N-acetylcysteine in Man

Author: Franceschini, G., Werba, J. P., Safa, O., Gikalov, I., and Sirtori, C. R.
Abstract: Changes in plasma lipid-lipoprotein levels were evaluated in 10 hyperlipidemic patients during treatment with progressive doses (from 1200 mg day^-1 to 3600 mg day^-1) of N-acetylcysteine (NAC). Plasma total cholesterol and triglyceride levels, as well as those of lipoprotein (a) did not change to an appreciable extent, even with the highest dosage. However, the HDL-cholesterol levels showed a significant, dose-related rise, the mean absolute increase, with the highest NAC dose, being of approximately 10 mg dl^-1 (16.2%). The rise of HDL-cholesterol was independent of changes in other lipid-lipoprotein parameters, suggesting a possible direct effect of NAC on the HDL system. Copyright 1993, 1999 Academic Press
Published: 1993
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13. Determination of bezafibrate, ciprofibrate and fenofibric acid in human plasma by high-performance liquid chromatography

Author: Masnatta, L. D., Cuniberti, L. A., Rey, R. H., and Werba, J. P.
Published: 1996
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14. The effect of green tea on simvastatin tolerability

Author: Werba, J. P., Giroli, M., Cavalca, V., Nava, M. C., ELENA TREMOLI, and Bo, L. D.

15. Plasma triglycerides and lipoprotein(a): inverse relationship in a hyperlipidemic Italian population

Author: Werba, J. P., Safa, O., Gianfranceschi, G., and Michelagnoli, S.
Published: 1993
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16. Drug control of reverse cholesterol transport

Author: Franceschini, G., Werba, J. P., and Calabresi, L.
Published: 1994
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17. LDL-cholesterol control in the primary prevention of cardiovascular diseases: An expert opinion for clinicians and health professionals

Author: Poli, Andrea, Catapano, Alberico L, Corsini, Alberto, Manzato, Enzo, Werba, José Pablo, Catena, Gabriele, Cetin, Irene, Cicero, Arrigo F G, Cignarella, Andrea, Colivicchi, Furio, Consoli, Agostino, Landi, Francesco, Lucarelli, Maurizio, Manfellotto, Dario, Marrocco, Walter, Parretti, Damiano, Perrone Filardi, Pasquale, Pirillo, Angela, Sesti, Giorgio, Volpe, Massimo, Marangoni, Franca, Poli, A., Catapano, A. L., Corsini, A., Manzato, E., Werba, J. P., Catena, G., Cetin, I., Cicero, A. F. G., Cignarella, A., Colivicchi, F., Consoli, A., Landi, F., Lucarelli, M., Manfellotto, D., Marrocco, W., Parretti, D., Perrone Filardi, P., Pirillo, A., Sesti, G., Volpe, M., and Marangoni, F.
Subjects: Primary prevention, Cardiovascular disease, Cardiovascular risk, LDL-cholesterol, Risk factors, Settore BIO/14 - Farmacologia, Settore MED/40 - Ginecologia e Ostetricia
Abstract: Aims: Although adequate clinical management of patients with hypercholesterolemia without a history of known cardiovascular disease is essential for prevention, these subjects are often disregarded. Furthermore, the scientific literature on primary cardiovascular prevention is not as rich as that on secondary prevention; finally, physicians often lack adequate tools for the effective management of subjects in primary prevention and have to face some unsolved relevant issues. This document aims to discuss and review the evidence available on this topic and provide practical guidance. Data synthesis: Available algorithms and risk charts represent the main tool for the assessment of cardiovascular risk in patients in primary prevention. The accuracy of such an estimate can be substantially improved considering the potential contribution of some additional risk factors (C-reactive protein, lipoprotein(a), family history of cardiovascular disease) and conditions (environmental pollution, sleep quality, socioeconomic status, educational level) whose impact on the cardiovascular risk has been better understood in recent years. The availability of non-invasive procedures to evaluate subclinical atherosclerosis may help to identify subjects needing an earlier intervention. Unveiling the presence of these conditions will improve cardiovascular risk estimation, granting a more appropriate intervention. Conclusions: The accurate assessment of cardiovascular risk in subjects in primary prevention with the use of algorithms and risk charts together with the evaluation of additional factors will allow physicians to approach each patient with personalized strategies, which should translate into an increased adherence to therapy and, as a consequence, a reduced cardiovascular risk.
Published: 2022

18. Global perspective of familial hypercholesterolaemia: a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)

Author: Jie Lin, Snejana Tisheva, Ishwar C. Verma, Francesco Cipollone, Liam R. Brunham, Florentina Predica, Perla A.C. Gonzalez, Jocelyne Inamo, André R. Miserez, Belma Pojskic, Michel Farnier, Avishay Ellis, Katia Bonomo, Ibrahim Al-Zakwani, Maria Grazia Zenti, Humberto A. Lopez, Khairul Shafiq Ibrahim, Erkin M. Mirrakhimov, Alexey Meshkov, Jose P. de Moura, Muthukkaruppan Annamalai, Raul D. Santos, F. Paillard, Maria Del Ben, Jan Lacko, Miguel T. Rico, Ximena Reyes, Laura E.G. de Leon, Noor Shafina Mohd Nor, Ulrich Julius, Mohammed A. Batais, Dieter Böhm, Ta-Chen Su, Takuya Kobayashi, Magdalena Chmara, Marco Gebauer, Marcos M. Lima-Martínez, Ravshanbek D. Kurbanov, Daisaku Masuda, Amro El-Hadidy, Melanie Schüler, Francisco Fuentes, Florian J. Mayer, Helena Vaverkova, F. Ulrich Beil, Juraj Bujdak, Mario Stoll, Isabelle Ruel, Elena Dorn, Thomas M. Stulnig, Abubaker Elfatih, Rano B. Alieva, Jiri Vesely, Valérie Carreau, Cristina M. Sibaja, Sophie Béliard, Olivier Ziegler, Adriana Branchi, Daniel Schurr, G.B. John Mancini, Tai E. Shyong, Eric L.T. Siang, Mafalda Bourbon, Zerrin Yigit, Meral Kayıkçıoğlu, Jacques Genest, Wei Yu, Michal Vrablík, Shavkat U. Hoshimov, Dan Gaita, Antonio Pipolo, Ashraf H.A. AlQudaimi, Walter Speidl, Gianfranco Parati, Zaliha Ismail, Victoria M. Zubieta, René Valéro, Tomas Salek, Hana Halamkova, Gustavs Latkovskis, Nicole Allendorf-Ostwald, Agnes Perrin, Vladimir Soska, Anastasia Garoufi, Francisco Araujo, Nacu C. Portilla, Thomas Segiet, Charalambos Koumaras, Hila Knobler, Fatih Sivri, Hani Altaradi, Ivan Pećin, Long Jiang, Alexander Dressel, Marlena Woś, Jana Franekova, D. Agapakis, Quitéria Rato, Dirk J. Blom, Marcin A. Bartlomiejczyk, Krzysztof Dyrbuś, Maurizio Averna, Phivos Symeonides, Yung A. Chua, Asim Rana, András Nagy, Juan C.G. Cuellar, Alexander Jäkel, Maya Safarova, Neama Luqman, Amalia-Despoina Koutsogianni, Patrick Tounian, Jose A. Alvarez, Ada Cuevas, Corinna Richter, Sybil Charrieres, Vitaliy Zafiraki, Michalis Doumas, Angela Lux, Thanh Huong Truong, Elaine Chow, José Luis Díaz-Díaz, Jesus R.H. Almada, Sabine Füllgraf-Horst, Gustavo G. Retana, Claudio Borghi, Gianni Biolo, Ivajlo Tzvetkov, Patrícia Pais, Mehmet Akbulut, Kumiko Nagahama, Oner Ozdogan, Frank Leistikow, Jianxun He, Alexander R.M. Lyons, Poranee Ganokroj, Luis E.S. Mendia, Ann-Cathrin Koschker, Gabriela A.G. Ramirez, Dainus Gilis, Karin Balinth, José Ramiro Cruz, Paolo Calabrò, Alberico L. Catapano, Emmanouil Skalidis, Hamida Al-Barwani, Genovefa Kolovou, Carolyn S.P. Lam, Yoto Yotov, Yaacov Henkin, Gabriella Iannuzzo, Aimi Z. Razman, Alma B.M. Rodriguez, Hans Dieplinger, Darlington E. Obaseki, Ursulo J. Herrera, Arcangelo Iannuzzi, Christoph Säly, Elena Olmastroni, Francisco G. Padilla, S.A. Nazli, Ioanna Gouni-Berthold, Miriam Kozárová, Urh Groselj, Igor Shaposhnik, Lorenzo Iughetti, Nawal Rwaili, Cinthia E. Jannes, Andrea Bartuli, Mikhail Voevoda, Marat V. Ezhov, Yanyu Duan, Alper Sonmez, Mustafa Yenercag, Ariane Sultan, Natasza Gilis-Malinowska, Tavintharan Subramaniam, Mohamed Ashraf, Jing Pang, Kota Matsuki, Tao Jiang, Gerald Klose, Eduardo A.R. Rodriguez, Lucie Solcova, Riccardo Sarzani, Mahmoud Traina, Alejandra Vázquez Cárdenas, Gordon A. Francis, Adolat V. Ziyaeva, Ronen Durst, Maciej Banach, Francisco Silva, Heribert Schunkert, Børge G. Nordestgaard, Ziyou Liu, Ahmad Bakhtiar Md Radzi, Hana Rosolova, Andrea Bäßler, Abdulhalim Jamal Kinsara, Noël Peretti, Victor Gurevich, Margarita T. Tamayo, Abdullah Tuncez, Florian Höllerl, Ljubica Stosic, Jianguang Qi, Anja Kirschbaum, Jitendra P.S. Sawhney, Michael Scholl, Kausik K. Ray, Mohamed Bendary, Hapizah Nawawi, Adrienne Tarr, Barbora Nussbaumerova, B.C. Brice, Kurt Huber, Noor Alicezah Mohd Kasim, A. Rahman A. Jamal, Vaclava Palanova, Giacomo Biasucci, Pucong Ye, Eva Cubova, Roopa Mehta, Rüdiger Schweizer, Veronica Zampoleri, Jacek Jóźwiak, Alyaa Al-Khateeb, Jing Hong, Katarina Raslova, Kirsten B. Holven, Tatiana Rozkova, Reinhold Busch, Alexander Klabnik, Konrad Hein, Eloy A.Z. Carrillo, Robin Urbanek, Livia Pisciotta, Fatma Y. Coskun, Jose J.G. Garcia, Valerio Pecchioli, Azra D. Nalbantic, Weerapan Khovidhunkit, Jernej Kovac, Michaela Kadurova, Mohammed Al-Jarallah, Vita Saripo, Christos V. Rizos, Jie Peng, Ang L. Chua, Dorothee Deiss, Nor A.A. Murad, Aneta Stróżyk, See Kwok, Gökhan Alici, Gillian J. Pilcher, John J.P. Kastelein, Dmitry Duplyakov, Calin Lengher, Milena Budikova, C. Azzopardi, Christina Antza, Luis E.V. Arroyo, Khalid Al-Jumaily, Ahmad Al-Sarraf, Carlos A. Aguilar-Salinas, Erkayim Bektasheva, Arta Upena-RozeMicena, Qian Wang, Xumin Wang, Leah Leavit, Radzi Rahmat, Selim Topcu, Željko Reiner, Lorenzo Maroni, Matija Cevc, Elizabeth R. 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R.B., Kurbanov R.D., Hoshimov S.U., Nizamov U.I., Ziyaeva A.V., Abdullaeva G.J., Do D.L., Nguyen M.N.T., Kim N.T., Le T.T., Le H.A., Tokgozoglu L., Catapano A.L., Ray K.K., Vallejo-Vaz, A. J., Stevens, C. A. T., Lyons, A. R. M., Dharmayat, K. I., Freiberger, T., Hovingh, G. K., Mata, P., Raal, F. J., Santos, R. D., Soran, H., Watts, G. F., Abifadel, M., Aguilar-Salinas, C. A., Alhabib, K. F., Alkhnifsawi, M., Almahmeed, W., Alnouri, F., Alonso, R., Al-Rasadi, K., Al-Sarraf, A., Al-Sayed, N., Araujo, F., Ashavaid, T. F., Banach, M., Beliard, S., Benn, M., Binder, C. J., Bogsrud, M. P., Bourbon, M., Chlebus, K., Corral, P., Davletov, K., Descamps, O. S., Durst, R., Ezhov, M., Gaita, D., Genest, J., Groselj, U., Harada-Shiba, M., Holven, K. B., Kayikcioglu, M., Khovidhunkit, W., Lalic, K., Latkovskis, G., Laufs, U., Liberopoulos, E., Lima-Martinez, M. M., Lin, J., Maher, V., Marais, A. D., Marz, W., Mirrakhimov, E., Miserez, A. R., Mitchenko, O., Nawawi, H., Nordestgaard, B. G., Panayiotou, A. G., Paragh, G., Petrulioniene, Z., Pojskic, B., Postadzhiyan, A., Raslova, K., Reda, A., Sadiq, F., Sadoh, W. E., Schunkert, H., Shek, A. B., Stoll, M., Stroes, E., Su, T. -C., Subramaniam, T., Susekov, A. V., Tilney, M., Tomlinson, B., Truong, T. H., Tselepis, A. D., Tybjaerg-Hansen, A., Vazquez Cardenas, A., Viigimaa, M., Wang, L., Yamashita, S., Kastelein, J. J. P., Bruckert, E., Vohnout, B., Schreier, L., Pang, J., Ebenbichler, C., Dieplinger, H., Innerhofer, R., Winhofer-Stockl, Y., Greber-Platzer, S., Krychtiuk, K., Speidl, W., Toplak, H., Widhalm, K., Stulnig, T., Huber, K., Hollerl, F., Rega-Kaun, G., Kleemann, L., Maser, M., Scholl-Burgi, S., Saly, C., Mayer, F. J., Sablon, G., Tarantino, E., Nzeyimana, C., Pojskic, L., Sisic, I., Nalbantic, A. D., Jannes, C. E., Pereira, A. C., Krieger, J. E., Petrov, I., Goudev, A., Nikolov, F., Tisheva, S., Yotov, Y., Tzvetkov, I., Baass, A., Bergeron, J., Bernard, S., Brisson, D., Brunham, L. R., Cermakova, L., Couture, P., Francis, G. A., Gaudet, D., Hegele, R. A., Khoury, E., Mancini, G. B. J., Mccrindle, B. W., Paquette, M., Ruel, I., Cuevas, A., Asenjo, S., Wang, X., Meng, K., Song, X., Yong, Q., Jiang, T., Liu, Z., Duan, Y., Hong, J., Ye, P., Chen, Y., Qi, J., Li, Y., Zhang, C., Peng, J., Yang, Y., Yu, W., Wang, Q., Yuan, H., Cheng, S., Jiang, L., Chong, M., Jiao, J., Wu, Y., Wen, W., Xu, L., Zhang, R., Qu, Y., He, J., Fan, X., Wang, Z., Chow, E., Pecin, I., Perica, D., Symeonides, P., Vrablik, M., Ceska, R., Soska, V., Tichy, L., Adamkova, V., Franekova, J., Cifkova, R., Kraml, P., Vonaskova, K., Cepova, J., Dusejovska, M., Pavlickova, L., Blaha, V., Rosolova, H., Nussbaumerova, B., Cibulka, R., Vaverkova, H., Cibickova, L., Krejsova, Z., Rehouskova, K., Malina, P., Budikova, M., Palanova, V., Solcova, L., Lubasova, A., Podzimkova, H., Bujdak, J., Vesely, J., Jordanova, M., Salek, T., Urbanek, R., Zemek, S., Lacko, J., Halamkova, H., Machacova, S., Mala, S., Cubova, E., Valoskova, K., Burda, L., Bendary, A., Daoud, I., Emil, S., Elbahry, A., Rafla, S., Sanad, O., Kazamel, G., Ashraf, M., Sobhy, M., El-Hadidy, A., Shafy, M. A., Kamal, S., Bendary, M., Talviste, G., Angoulvant, D., Boccara, F., Cariou, B., Carreau, V., Carrie, A., Charrieres, S., Cottin, Y., Di-Fillipo, M., Ducluzeau, P. H., Dulong, S., Durlach, V., Farnier, M., Ferrari, E., Ferrieres, D., Ferrieres, J., Gallo, A., Hankard, R., Inamo, J., Lemale, J., Moulin, P., Paillard, F., Peretti, N., Perrin, A., Pradignac, A., Rabes, J. P., Rigalleau, V., Sultan, A., Schiele, F., Tounian, P., Valero, R., Verges, B., Yelnik, C., Ziegler, O., Haack, I. A., Schmidt, N., Dressel, A., Klein, I., Christmann, J., Sonntag, A., Stumpp, C., Boger, D., Biedermann, D., Usme, M. M. N., Beil, F. U., Klose, G., Konig, C., Gouni-Berthold, I., Otte, B., Boll, G., Kirschbaum, A., Merke, J., Scholl, J., Segiet, T., Gebauer, M., Predica, F., Mayer, M., Leistikow, F., Fullgraf-Horst, S., Muller, C., Schuler, M., Wiener, J., Hein, K., Baumgartner, P., Kopf, S., Busch, R., Schomig, M., Matthias, S., Allendorf-Ostwald, N., Fink, B., Bohm, D., Jakel, A., Koschker, A. -C., Schweizer, R., Vogt, A., Parhofer, K., Konig, W., Reinhard, W., Bassler, A., Stadelmann, A., Schrader, V., Katzmann, J., Tarr, A., Steinhagen-Thiessen, E., Kassner, U., Paulsen, G., Homberger, J., Zemmrich, C., Seeger, W., Biolik, K., Deiss, D., Richter, C., Pantchechnikova, E., Dorn, E., Schatz, U., Julius, U., Spens, A., Wiesner, T., Scholl, M., Rizos, C. V., Sakkas, N., Elisaf, M., Skoumas, I., Tziomalos, K., Rallidis, L., Kotsis, V., Doumas, M., Athyros, V., Skalidis, E., Kolovou, G., Garoufi, A., Bilianou, E., Koutagiar, I., Agapakis, D., Kiouri, E., Antza, C., Katsiki, N., Zacharis, E., Attilakos, A., Sfikas, G., Koumaras, C., Anagnostis, P., Anastasiou, G., Liamis, G., Koutsogianni, A. -D., Karanyi, Z., Harangi, M., Bajnok, L., Audikovszky, M., Mark, L., Benczur, B., Reiber, I., Nagy, G., Nagy, A., Reddy, L. L., Shah, S. A. V., Ponde, C. K., Dalal, J. J., Sawhney, J. P. S., Verma, I. C., Altaey, M., Al-Jumaily, K., Rasul, D., Abdalsahib, A. F., Jabbar, A. A., Al-ageedi, M., Agar, R., Cohen, H., Ellis, A., Gavishv, D., Harats, D., Henkin, Y., Knobler, H., Leavit, L., Leitersdorf, E., Rubinstein, A., Schurr, D., Shpitzen, S., Szalat, A., Casula, M., Zampoleri, V., Gazzotti, M., Olmastroni, E., Sarzani, R., Ferri, C., Repetti, E., Sabba, C., Bossi, A. C., Borghi, C., Muntoni, S., Cipollone, F., Purrello, F., Pujia, A., Passaro, A., Marcucci, R., Pecchioli, V., Pisciotta, L., Mandraffino, G., Pellegatta, F., Mombelli, G., Branchi, A., Fiorenza, A. M., Pederiva, C., Werba, J. P., Parati, G., Carubbi, F., Iughetti, L., Iannuzzi, A., Iannuzzo, G., Calabro, P., Averna, M., Biasucci, G., Zambon, S., Roscini, A. R., Trenti, C., Arca, M., Federici, M., Del Ben, M., Bartuli, A., Giaccari, A., Pipolo, A., Citroni, N., Guardamagna, O., Bonomo, K., Benso, A., Biolo, G., Maroni, L., Lupi, A., Bonanni, L., Zenti, M. G., Matsuki, K., Hori, M., Ogura, M., Masuda, D., Kobayashi, T., Nagahama, K., Al-Jarallah, M., Radovic, M., Lunegova, O., Bektasheva, E., Khodzhiboboev, E., Erglis, A., Gilis, D., Nesterovics, G., Saripo, V., Meiere, R., Upena-RozeMicena, A., Terauda, E., Jambart, S., Khoury, P. E., Elbitar, S., Ayoub, C., Ghaleb, Y., Aliosaitiene, U., Kutkiene, S., Kasim, N. A. M., Nor, N. S. M., Ramli, A. S., Razak, S. A., Al-Khateeb, A., Kadir, S. H. S. A., Muid, S. A., Rahman, T. A., Kasim, S. S., Radzi, A. B. M., Ibrahim, K. S., Razali, S., Ismail, Z., Ghani, R. A., Hafidz, M. I. A., Chua, A. L., Rosli, M. M., Annamalai, M., Teh, L. K., Razali, R., Chua, Y. A., Rosman, A., Sanusi, A. R., Murad, N. A. A., Jamal, A. R. A., Nazli, S. A., Razman, A. Z., Rosman, N., Rahmat, R., Hamzan, N. S., Azzopardi, C., Mehta, R., Martagon, A. J., Ramirez, G. A. G., Villa, N. E. A., Vazquez, A. V., Elias-Lopez, D., Retana, G. G., Rodriguez, B., Macias, J. J. C., Zazueta, A. R., Alvarado, R. M., Portano, J. D. M., Lopez, H. A., Sauque-Reyna, L., Herrera, L. G. G., Mendia, L. E. S., Aguilar, H. G., Cooremans, E. R., Aparicio, B. P., Zubieta, V. M., Gonzalez, P. A. C., Ferreira-Hermosillo, A., Portilla, N. C., Dominguez, G. J., Garcia, A. Y. R., Cazares, H. E. A., Gonzalez, J. R., Valencia, C. V. M., Padilla, F. G., Prado, R. M., De los Rios Ibarra, M. O., Villicana, R. D. A., Rivera, K. J. A., Carrera, R. A., Alvarez, J. A., Martinez, J. C. A., de los Reyes Barrera Bustillo, M., Vargas, G. C., Chacon, R. C., Andrade, M. H. F., Ortega, A. F., Alcala, H. G., de Leon, L. E. G., Guzman, B. G., Garcia, J. J. G., Cuellar, J. C. G., Cruz, J. R. G., Garcia, A. H., Almada, J. R. H., Herrera, U. J., Sobrevilla, F. L., Rodriguez, E. M., Sibaja, C. M., Rodriguez, A. B. M., Oyervides, J. C. M., Vazquez, D. I. P., Rodriguez, E. A. R., Osorio, M. L. R., Saucedo, J. R., Tamayo, M. T., Talavera, L. A. V., Arroyo, L. E. V., Carrillo, E. A. Z., Isara, A., Obaseki, D. E., Al-Waili, K., Al-Zadjali, F., Al-Zakwani, I., Al-Kindi, M., Al-Mukhaini, S., Al-Barwani, H., Rana, A., Shah, L. S. U., Starostecka, E., Konopka, A., Lewek, J., Bartlomiejczyk, M., Gasior, M., Dyrbus, K., Jozwiak, J., Gruchala, M., Pajkowski, M., Romanowska-Kocejko, M., Zarczynska-Buchowiecka, M., Chmara, M., Wasag, B., Parczewska, A., Gilis-Malinowska, N., Borowiec-Wolna, J., Strozyk, A., Wos, M., Michalska-Grzonkowska, A., Medeiros, A. M., Alves, A. C., Silva, F., Lobarinhas, G., Palma, I., de Moura, J. P., Rico, M. T., Rato, Q., Pais, P., Correia, S., Moldovan, O., Virtuoso, M. J., Salgado, J. M., Colaco, I., Dumitrescu, A., Lengher, C., Mosteoru, S., Meshkov, A., Ershova, A., Rozkova, T., Korneva, V., Yu, K. T., Zafiraki, V., Voevoda, M., Gurevich, V., Duplyakov, D., Ragino, Y., Safarova, M., Shaposhnik, I., Alkaf, F., Khudari, A., Rwaili, N., Al-Allaf, F., Alghamdi, M., Batais, M. A., Almigbal, T. H., Kinsara, A., Alqudaimi, A. H. A., Awan, Z., Elamin, O. A., Altaradi, H., Rajkovic, N., Popovic, L., Singh, S., Stosic, L., Rasulic, I., Lalic, N. M., Lam, C., Le, T. J., Siang, E. L. T., Dissanayake, S., I-Shing, J. T., Shyong, T. E., Jin, T. C. S., Balinth, K., Buganova, I., Fabryova, L., Kadurova, M., Klabnik, A., Kozarova, M., Sirotiakova, J., Battelino, T., Kovac, J., Mlinaric, M., Sustar, U., Podkrajsek, K. T., Fras, Z., Jug, B., Cevc, M., Pilcher, G. J., Blom, D. J., Wolmarans, K. H., Brice, B. C., Muniz-Grijalvo, O., Diaz-Diaz, J. L., de Isla, L. P., Fuentes, F., Badimon, L., Martin, F., Lux, A., Chang, N. -T., Ganokroj, P., Akbulut, M., Alici, G., Bayram, F., Can, L. H., Celik, A., Ceyhan, C., Coskun, F. Y., Demir, M., Demircan, S., Dogan, V., Durakoglugil, E., Dural, I. E., Gedikli, O., Hacioglu, A., Ildizli, M., Kilic, S., Kirilmaz, B., Kutlu, M., Oguz, A., Ozdogan, O., Onrat, E., Ozer, S., Sabuncu, T., Sahin, T., Sivri, F., Sonmez, A., Temizhan, A., Topcu, S., Tuncez, A., Vural, M., Yenercag, M., Yesilbursa, D., Yigit, Z., Yildirim, A. B., Yildirir, A., Yilmaz, M. B., Atallah, B., Traina, M., Sabbour, H., Hay, D. A., Luqman, N., Elfatih, A., Abdulrasheed, A., Kwok, S., Oca, N. D., Reyes, X., Alieva, R. B., Kurbanov, R. D., Hoshimov, S. U., Nizamov, U. I., Ziyaeva, A. V., Abdullaeva, G. J., Do, D. L., Nguyen, M. N. T., Kim, N. T., Le, T. T., Le, H. A., Tokgozoglu, L., Catapano, A. L., Ray, K. K., and EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC), Borghi C
Subjects: Male, Settore MED/09 - Medicina Interna, Arterial disease, Cross-sectional study, Adult population, Coronary Disease, Disease, Global Health, Medical and Health Sciences, Doenças Cardio e Cérebro-vasculares, Anticholesteremic Agent, Monoclonal, Prevalence, Registries, Familial Hypercholesterolemia, Humanized, Stroke, 11 Medical and Health Sciences, LS2_9, Studies Collaboration, Anticholesteremic Agents, General Medicine, Heart Disease Risk Factor, Middle Aged, FHSC global registry data, Europe, Treatment Outcome, Lower prevalence, Guidance, lipids (amino acids, peptides, and proteins), Female, Proprotein Convertase 9, Familial hypercholesterolaemia, Life Sciences & Biomedicine, Human, Adult, medicine.medical_specialty, Combination therapy, FHSC global registry, heterozygous familial hypercholesterolaemia, Cardiovascular risk factors, Antibodies, Monoclonal, Humanized, Insights, Antibodies, NO, Hyperlipoproteinemia Type II, Clinician, Medicine, General & Internal, Internal medicine, General & Internal Medicine, Health Sciences, medicine, Humans, EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC), Cross-Sectional Studie, Science & Technology, Global Perspective, business.industry, Cholesterol, LDL, medicine.disease, Cross-Sectional Studies, Heart Disease Risk Factors, Hydroxymethylglutaryl-CoA Reductase Inhibitor, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business
Abstract: Background The European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC) global registry provides a platform for the global surveillance of familial hypercholesterolaemia through harmonisation and pooling of multinational data. In this study, we aimed to characterise the adult population with heterozygous familial hypercholesterolaemia and described how it is detected and managed globally. Methods Using FHSC global registry data, we did a cross-sectional assessment of adults (aged 18 years or older) with a clinical or genetic diagnosis of probable or definite heterozygous familial hypercholesterolaemia at the time they were entered into the registries. Data were assessed overall and by WHO regions, sex, and index versus non-index cases. Findings Of the 61 612 individuals in the registry, 42 167 adults (21 999 [53.6%] women) from 56 countries were included in the study. Of these, 31 798 (75.4%) were diagnosed with the Dutch Lipid Clinic Network criteria, and 35 490 (84.2%) were from the WHO region of Europe. Median age of participants at entry in the registry was 46.2 years (IQR 34.3-58.0); median age at diagnosis of familial hypercholesterolaemia was 44.4 years (32.5-56.5), with 40.2% of participants younger than 40 years when diagnosed. Prevalence of cardiovascular risk factors increased progressively with age and varied by WHO region. Prevalence of coronary disease was 17.4% (2.1% for stroke and 5.2% for peripheral artery disease), increasing with concentrations of untreated LDL cholesterol, and was about two times lower in women than in men. Among patients receiving lipid-lowering medications, 16 803 (81.1%) were receiving statins and 3691 (21.2%) were on combination therapy, with greater use of more potent lipid-lowering medication in men than in women. Median LDL cholesterol was 5.43 mmol/L (IQR 4.32-6.72) among patients not taking lipid-lowering medications and 4.23 mmol/L (3.20-5.66) among those taking them. Among patients taking lipid-lowering medications, 2.7% had LDL cholesterol lower than 1.8 mmol/L; the use of combination therapy, particularly with three drugs and with proprotein convertase subtilisin-kexin type 9 inhibitors, was associated with a higher proportion and greater odds of having LDL cholesterol lower than 1.8 mmol/L. Compared with index cases, patients who were non-index cases were younger, with lower LDL cholesterol and lower prevalence of cardiovascular risk factors and cardiovascular diseases (all p, Pfizer Independent Grant for Learning Change [16157823]; Amgen; Merck Sharp Dohme; Sanofi-Aventis; Daiichi Sankyo; Regeneron; National Institute for Health Research (NIHR) Imperial Biomedical Research Centre, UK; NIHR; Czech Ministry of Health [NU20-02-00261]; Canadian Institutes of Health Research; Austrian Heart Foundation; Tyrolean Regional Government; Gulf Heart Association, The EAS FHSC is an academic initiative that has received funding from a Pfizer Independent Grant for Learning & Change 2014 (16157823) and from investigator-initiated research grants to the European Atherosclerosis Society-Imperial College London from Amgen, Merck Sharp & Dohme, Sanofi-Aventis, Daiichi Sankyo, and Regeneron. KKR acknowledges support from the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre, UK. KID acknowledges support from a PhD Studentship from NIHR under the Applied Health Research programme for Northwest London, UK (the views expressed in this publication are those of the authors and not necessarily those of the National Health Service, the NIHR, or the Department of Health). TF was supported by a grant from the Czech Ministry of Health (NU20-02-00261). JG receives support from the Canadian Institutes of Health Research. The Austrian Familial Hypercholesterolaemia registry has been supported by funds from the Austrian Heart Foundation and the Tyrolean Regional Government. The Gulf Familial Hypercholesterolaemia registry was done under the auspices of the Gulf Heart Association.
Published: 2021

19. Effects of smoking regular or light cigarettes on brachial artery flow-mediated dilation.

Author: Amato M, Frigerio B, Castelnuovo S, Ravani A, Sansaro D, Tremoli E, Squellerio I, Cavalca V, Veglia F, Sirtori CR, Werba JP, and Baldassarre D
Subjects: Adult, Brachial Artery diagnostic imaging, Brachial Artery metabolism, Dose-Response Relationship, Drug, Endothelium, Vascular drug effects, Endothelium, Vascular metabolism, Endothelium, Vascular physiopathology, Female, Humans, Male, Middle Aged, Nicotine adverse effects, Nicotinic Agonists adverse effects, Nitric Oxide metabolism, Oxidative Stress physiology, Smoking metabolism, Ultrasonography, Vasculitis diagnostic imaging, Vasculitis metabolism, Vasculitis physiopathology, Vasodilation drug effects, Brachial Artery physiology, Smoking adverse effects, Smoking physiopathology, Tobacco Products adverse effects, Vasodilation physiology
Abstract: Background and Purpose: To compare the effects of regular cigarettes (RCs) and light cigarettes (LCs) on brachial artery flow-mediated dilation (FMD) and sublingual glyceryl trinitrate-induced dilation (GTN), markers of endothelial dependant and independent function, respectively., Methods: 206 subjects (age 51.5 ± 12.8 yr, 122 men) had their smoking habits recorded and FMD and GTN measured by B-mode ultrasound. Cigarettes were categorized as RCs or LCs according to their content of tar, nicotine and CO. The chronic effect was assessed in current smokers of RCs (n = 85) or LCs (n = 53) and in never smokers (NS; n = 68). The acute effect was assessed in current smokers by measuring FMD before and 10-min after smoking a single regular (n = 29) or light (n = 51) cigarette., Results: FMD was significantly lower in consumers of RCs (6.26%, 95% C.I. 5.58, 6.94) or LCs (5.59%, 95% C.I. 4.74, 6.45) compared to NS (8.68%, 95% C.I. 7.92, 9.44) (both P < 0.0001), but did not differ (P > 0.05) when compared to each other. GTN was similar in the three groups. Analyses adjusted for clinical confounders and for markers involved in oxidative stress, arginine/nitric oxide pathway, and inflammation provided identical results. Smoking a single cigarette, either regular or light, reduced FMD (-0.88% and -1.17%, respectively, both P < 0.05), without significant difference between cigarette type. RCs and LCs produced analogous chronic and acute effects when FMD was calculated with respect to the last 60 s of the low-flow phase (FMD60s)., Conclusions: LCs impair endothelial-dependant vasodilation as much as RCs. Thus, smoking LCs cannot be considered an alternative to the only safe choice of a complete and permanent smoking cessation., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)
Published: 2013
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20. The metabolic syndrome predicts carotid intima-media thickness no better than the sum of individual risk factors in a lipid clinic population.

Author: Baldassarre D, Werba JP, Castelnuovo S, Frigerio B, Amato M, Ravani A, Veglia F, Sirtori CR, and Tremoli E
Subjects: Aged, Atherosclerosis complications, Atherosclerosis diagnostic imaging, Carotid Arteries diagnostic imaging, Dyslipidemias diagnosis, Female, Humans, Male, Middle Aged, Predictive Value of Tests, Risk Factors, Tunica Intima diagnostic imaging, Tunica Media diagnostic imaging, Ultrasonography, Atherosclerosis diagnosis, Metabolic Syndrome diagnosis
Abstract: Objective: To assess whether the diagnosis 'metabolic syndrome' (MS) predicts the degree of subclinical atherosclerosis better than its component parts or the total number of vascular risk factors (VRFs) in patients attending a lipid clinic., Methods: Carotid intima-media thickness (C-IMT) was measured by B-mode ultrasound in 1804 patients (56+/-13 years; 52% women). To investigate whether the increased subclinical carotid atherosclerosis often ascribed to MS may be explained by a real interaction between the components or simply by a sum of VRFs, observed C-IMTs were compared with those predicted by the sum of individual components. Values for C-IMT of MS patients were also compared with those of controls matched for number of VRFs or for SCORE predicted risk (SPR)., Results: Carotid IMT values were significantly higher in patients with MS (n=362) than in those not so diagnosed (IMT(mean), 1.07+/-0.37 vs. 0.95+/-0.33; IMT(max), 1.98+/-0.93mm vs. 1.67+/-0.82mm, both p<0.0001), but were not higher than those predicted by the sum of individual risk factors. The linear regression lines of the correlations between C-IMT and total number of VRFs overlapped in patients with and without MS. In patients with and without MS matched for age, sex and total number of VRFs, or matched for age, sex and SPR the C-IMT differences disappeared., Conclusions: In patients attending a lipid clinic, 'metabolic syndrome' appears not to correlate with C-IMT to a greater extent than what is expected from its component parts or from the patient's total number of VRFs., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)
Published: 2010
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21. Injury produces early rise in lipoprotein lipase activity in rabbit aorta.

Author: Werba JP, Cuniberti LA, Laguens RP, Masnatta LD, Rey RH, Levy R, and Pichel RH
Subjects: Animals, Catheterization, Cholesterol metabolism, Male, Rabbits, Time Factors, Aorta injuries, Lipoprotein Lipase metabolism, Wounds and Injuries metabolism
Abstract: The mechanisms following intimal injury predisposing towards atherosclerotic changes have not been fully elucidated. We speculated that a local increase in the enzyme lipoprotein lipase (LPL) might explain a higher susceptibility of the damaged intima to lipid accretion, and so we investigated the effect of balloon endothelial denudation on LPL activity and cholesterol content (LPLa and Cholc, respectively), in aortas from normolipidemic male New Zealand white rabbits. Arteries were obtained from injured and control animals after 2, 6, 8 and 10 weeks to evaluate the shortest period after de-endothelialization necessary to detect LPLa changes. Injury resulted in a 4-fold LPLa rise (P < 0.01), as early as 2 weeks, and the enzymatic activity remained increased throughout the study period. A mild but significant 22% Cholc increase (P < 0.03) was found after 2 weeks of injury, even in this normolipidemic rabbit model. We conclude that physical damage to the intima markedly and soon increases LPLa. This finding might account for the higher lipid accumulation by injured vessels, providing additional support to the hypothesis of LPL as an atherogenic mediator.
Published: 1996
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22. [Repeatability of insulin sensitivity estimation using the Minimal Model and comparison with a modified short low-dose insulin tolerance test].

Author: Rey RH, Masnatta LD, Pirola D, Cuniberti LA, Maceira C, and Werba JP
Subjects: Adult, Glucose administration & dosage, Glucose analysis, Humans, Hyperinsulinism, Insulin administration & dosage, Insulin blood, Middle Aged, Reproducibility of Results, Time Factors, Glucose Tolerance Test methods, Insulin Resistance
Abstract: Hyperinsulinemia and insulin-resistance are metabolic disturbances associated with obesity, essential hypertension, hypertriglyceridemia, glucose intolerance, overt non-insulin dependent diabetes mellitus, polymetabolic syndrome and atherosclerotic disease. The assessment of in vivo insulin sensitivity (SAI in vivo) changes achieved by life style modifications or drug interventions require a reproducible technique. To evaluate the day-to-day intra-individual repeatability of SAI-in vivo, we determined the variation in the SI index (calculated from the Minimal Model of Bergman modified by insulin or MMins) in 11 subjects with a wide range of insulin-resistance. SI (first study) varied from 0.82 to 8.48 x 10(-4) min-1/microU.mL (4.43 +/- 2.85 x 10(-4) min-1/microU.mL mean +/- SD) and highly correlated with SI (second study) (r = 0.89; p = 0.0002). The average interday coefficient of variation was 20.9 +/- 13.9% and was similar in subjects with low or high SI values. We also measured SAI in vivo by assessing the rate of serum glucose decline induced by human cristalline insulin 0.025 U/kg IV dose after a 12-14 hours fasting period (a modified Bonora's method or BBD) in 11 subjects. No subject presented biochemical or symptomatic hypoglycemia. SAI in vivo values determined by BBD varied from 21 a 234 mumol/ml/min (134 +/- 64.8 mumol/ml/min, mean +/- SD). We found a highly significant correlation between SI values obtained from MMins and SAI in vivo assessed by the BBD (r = 0.89, p = 0.0002). Our results suggest that the Mmins is a fairly reproducible procedure and that a BBD is an acceptable option to quantify SAI in vivo, mainly when a fast-execution practice is necessary or cost restrictions are required.
Published: 1996

23. Microsomal enzyme inducers raise plasma high-density lipoprotein cholesterol levels in healthy control subjects but not in patients with primary hypoalphalipoproteinemia.

Author: Franceschini G, Werba JP, D'Acquarica AL, Gianfranceschi G, Michelagnoli S, and Sirtori CR
Subjects: Aged, Analysis of Variance, Apolipoproteins blood, Carrier Proteins blood, Cholesterol Ester Transfer Proteins, Cholesterol Esters blood, Humans, Lipids blood, Male, Middle Aged, Phenytoin pharmacology, Phosphatidylcholine-Sterol O-Acyltransferase blood, Reference Values, Tangier Disease enzymology, Triglycerides blood, Cholesterol, HDL blood, Enzyme Induction physiology, Glycoproteins, Microsomes, Liver enzymology, Tangier Disease blood
Abstract: In this study we compared the ability of phenytoin, a microsomal enzyme inducer, to raise plasma high-density lipoprotein (HDL) levels in normolipidemic subjects and patients with primary hypoalphalipoproteinemia. In healthy control subjects, phenytoin caused a dose-dependent increase of plasma HDL, HDL2, and HDL3 cholesterol levels, up to 40% to 50%. Minor changes were recorded in the plasma concentrations of apolipoprotein (apo) A-I and apo A-II; the plasma level of the cholesteryl ester transfer protein (CETP) decreased by 42%. In contrast, none of the patients with hypoalphalipoproteinemia had changes in plasma HDL, HDL2, or HDL3 cholesterol, apo A-I, apo A-II, or CETP levels. These findings indicate that microsomal enzyme inducers are unsuitable to increase plasma HDL levels in high-risk patients with primary hypoalphalipoproteinemia, and they disclose a new mechanism, that is, decreased CETP-mediated transfer of cholesterol out of HDL, for the HDL-raising effect of microsomal enzyme inducers in healthy individuals.
Published: 1995
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24. Mechanisms of high-density lipoprotein reduction after probucol treatment: changes in plasma cholesterol esterification/transfer and lipase activities.

Author: Chiesa G, Michelagnoli S, Cassinotti M, Gianfranceschi G, Werba JP, Pazzucconi F, Sirtori CR, and Franceschini G
Subjects: Apolipoprotein A-I analysis, Cholesterol Ester Transfer Proteins, Female, Humans, Lipoproteins, HDL blood, Male, Middle Aged, Phosphatidylcholine-Sterol O-Acyltransferase blood, Probucol blood, Carrier Proteins blood, Cholesterol blood, Cholesterol Esters blood, Glycoproteins, Lipase blood, Lipoproteins, HDL drug effects, Probucol pharmacology
Abstract: Probucol treatment results in a significant reduction of plasma high-density lipoprotein (HDL) levels. Since the remodeling of HDL within the plasma compartment is a crucial determinant of HDL levels, the activities of several factors participating in the process, ie, lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), and lipoprotein and hepatic lipases (LPL, HL), were evaluated in 15 hypercholesterolemic patients treated with probucol (1 g/d) for 8 weeks. Drug treatment was associated with significant reductions of HDL cholesterol ([HDL-C] -32%), HDL2-C (-65%), HDL3-C (-22%), apolipoprotein (apo)A-I (-27%), and apo A-II (-11%) levels and with the accumulation of small HDL in plasma. CETP activity increased by 48%, with minor changes in LCAT (-7%), LPL (+4%), and HL (-7%) activities. By linear regression analysis, CETP activity correlated inversely with HDL-C, HDL2-C, and apo A-I levels (r = -.63, -.52, and -.73, respectively) and with HDL particle size. In multivariate analysis, CETP activity was the strongest predictor of HDL-C levels, apo A-I levels, and HDL particle size. The hypothetical mechanism of probucol is a stimulation of CETP activity, resulting in the formation of triglyceride (TG)-enriched HDL. These are acted on by HL, leading to the accumulation of small HDL in plasma.
Published: 1993
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25. Tolerability of fibric acids. Comparative data and biochemical bases.

Author: Sirtori CR, Calabresi L, Werba JP, and Franceschini G
Subjects: Animals, Blood Coagulation drug effects, Chemical and Drug Induced Liver Injury, Cholelithiasis chemically induced, Humans, Microbodies drug effects, Muscular Diseases chemically induced, Clofibric Acid adverse effects, Clofibric Acid analogs & derivatives, Hypolipidemic Agents adverse effects
Abstract: Fibric acids are an established class of drugs for the treatment of hyperlipoproteinaemias. Although they have been in use for 30 years or longer, some doubts remain as to their relative tolerability, both as a class and as single agents. Some side effects, e.g. lithogenicity, may be related to their mode of action, while others, e.g. the acute muscular syndrome, may be linked to the spatial conformation of the molecule. These disadvantages should, however, be weighed against the additional, potentially therapeutic properties shown by these compounds. In particular, effects on maturity onset diabetes and hyperuricaemia, as well as a very interesting fibrinolytic potential, have been described for some of them. A painstaking comparative analysis of the major literature data pertaining to the clinical toxicological profile of these agents allow to conclude that, while belonging to a chemical class, fibric acids show dramatic differences from one another, in terms of side effects and of additional pharmacodynamic activities. Moreover, in the case of lithogenicity for example, considerable differences exist between normo- and hyperlipidaemic subjects. Overall, newer molecules of more sophisticated design have a significantly improved tolerability profile vs the old clofibrate.
Published: 1992
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25 results on '"Werba J. P."'

1. Rationale and design of the CV-PREVITAL study: an Italian multiple cohort randomised controlled trial investigating innovative digital strategies in primary cardiovascular prevention

2. Come superare le barriere all'implementazione delle strategie di prevenzione e cura della malattia cardiovascolare aterosclerotica mediante terapia ipolipemizzante

3. Reported muscle symptoms during statin treatment amongst Italian dyslipidaemic patients in the real‐life setting: the PROSISA Study

4. The Role of Registers in Increasing Knowledge and Improving Management of Children and Adolescents Affected by Familial Hypercholesterolemia: the LIPIGEN Pediatric Group

5. Response to “The Effect of Green Tea With Exceptionally High Catechin Content on Nadolol Plasma Concentration”

6. Green Tea Ingestion Greatly Reduces Plasma Concentrations of Nadolol in Healthy Subjects

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

8. BDNFVal66met polymorphism: A potential bridge between depression and thrombosis

9. Common carotid intima-media thickness measurement. A method to improve accuracy and precision.

10. P330 A CASE OF SEVERE AORTIC STENOSIS IN A YOUNG PATIENT WITH BICUSPID AORTIC VALVE, FAMILIAL HYPERCHOLESTEROLEMIA AND CALCIFICATION AT THE SINOTUBULAR JUNCTION

11. Marked neointimal lipoprotein lipase increase in distinct models of proclivity to atherosclerosis: a feature independent of endothelial layer integrity

12. Dose-Related Increase of HDL-cholesterol Levels after N-acetylcysteine in Man

13. Determination of bezafibrate, ciprofibrate and fenofibric acid in human plasma by high-performance liquid chromatography

14. The effect of green tea on simvastatin tolerability

15. Plasma triglycerides and lipoprotein(a): inverse relationship in a hyperlipidemic Italian population

16. Drug control of reverse cholesterol transport

17. LDL-cholesterol control in the primary prevention of cardiovascular diseases: An expert opinion for clinicians and health professionals

18. Global perspective of familial hypercholesterolaemia: a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)

19. Effects of smoking regular or light cigarettes on brachial artery flow-mediated dilation.

20. The metabolic syndrome predicts carotid intima-media thickness no better than the sum of individual risk factors in a lipid clinic population.

21. Injury produces early rise in lipoprotein lipase activity in rabbit aorta.

22. [Repeatability of insulin sensitivity estimation using the Minimal Model and comparison with a modified short low-dose insulin tolerance test].

23. Microsomal enzyme inducers raise plasma high-density lipoprotein cholesterol levels in healthy control subjects but not in patients with primary hypoalphalipoproteinemia.

24. Mechanisms of high-density lipoprotein reduction after probucol treatment: changes in plasma cholesterol esterification/transfer and lipase activities.

25. Tolerability of fibric acids. Comparative data and biochemical bases.

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25 results on '"Werba J. P."'

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