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7. Lipoprotein-associated phospholipase A2 is increased in patients with impaired bone density

Author

Kotaška Karel, Kolářová Jitka, Jedličková Blanka, Čepová Jana, Kotaška Jan, and Průša Richard

Subjects
lipoprotein-associated phospholipase a2, osteocalcin, bone metabolism, Biochemistry, QD415-436
Abstract

Background: Increased levels of lipoprotein-associated phospholipase A2 are associated with atherosclerosis, and may contribute to cardiac disease. The aim of this study was to analyze serum levels of lipoprotein phospholipase A2 (Lp-PLA2) in patients with impaired bone resorption and correlate the findings with markers of bone metabolism (osteocalcin) and other biochemical markers (cholesterol, low density lipoprotein, triacylglycerols). Methods: Serum Lp-PLA2 was measured by a turbidimetric method in a group of currently treated 85 patients with impaired bone resorption and in a control group of 46 healthy individuals. Serum triacylglycerols was measured by the electrochemiluminescence immunoassay. Cholesterol, low density lipoprotein and triacylglycerols were measured by commercially available enzymatic assays. Bone density was investigated by dual energy X-ray densitometry performed on the lower spine and hips. Results: Concentrations of LP-PLA2 were significantly elevated in the patients with bone resorption compared to the control group of healthy individuals (225 ng/mL vs. 192 ng/mL, p< 0.001) with the highest difference in patients with a T score below -2.5 SD (227 vs. 192 ng/mL). Serum levels of Lp-PLA2 also negatively correlated with decreased levels of serum osteocalcin in patients, and a significant difference in Lp-PLA2 (p= 0.02) levels was observed between the control group and group with low levels of osteocalcin. Elevated Lp-PLA2 levels were significantly associated with the therapeutic procedures used, but not with age, gender and concentration of lipids. Conclusions: Lipoprotein-associated phospholipase A2 seems to play an important role also in bone metabolism.

Published
2014

9. Fluvastatin in the first-line therapy of acute coronary syndrome: results of the multicenter, randomized, double-blind, placebo-controlled trial (the FACS-trial)

Author

Telekes Peter, Holm Frantisek, Slaby Josef, Aschermann Ondrej, Wiendl Martin, Kettner Jiri, Kvapil Milan, Mates Martin, Hajek Petr, Macek Milan, Kukacka Jiri, Vejvoda Jiri, Alan David, Ostadal Petr, Horak David, Blasko Peter, Zemanek David, Veselka Josef, and Cepova Jana

Subjects
Medicine (General), R5-920
Abstract

Abstract Background Statins have been proved to be effective in reduction of mortality and morbidity when started in the early secondary prevention in stabilized patients after acute coronary syndrome (ACS). The safety and efficacy of statin administration directly in the first-line therapy in unstable ACS patients is not clear. The aim of our study was, therefore, to assess the effect of statin treatment initiated immediately at hospital admission of patients with ACS. Methods The trial was stopped prematurely after enrollment of one hundred and fifty-six patients with ACS that were randomized at admission to fluvastatin 80 mg (N = 78) or placebo (N = 78). Study medication was administered immediately after randomization and then once daily for 30 days; all patients were then encouraged to continue in open-label statin therapy and at the end of one-year follow-up 75% in the fluvastatin group and 78% in the placebo group were on statin therapy. Results We did not demonstrate any difference between groups in the level of C-reactive protein, interleukin 6, and pregnancy-associated plasma protein A on Day 2 and Day 30 (primary endpoint). Fluvastatin-therapy, however, significantly reduced one-year occurrence of major adverse cardiovascular events (11.5% vs. 24.4%, odds ratio (OR) 0.40, 95% CI 0.17-0.95, P = 0.038). This difference was caused mainly by reduction of recurrent symptomatic ischemia (7.7% vs. 20.5%, OR 0.32, 95% CI 0.12-0.88, P = 0.037). Conclusions This study failed to prove the effect of fluvastatin given as first-line therapy of ACS on serum markers of inflammation and plaque instability. Fluvastatin therapy was, however, safe and it may reduce cardiovascular event rate that supports immediate use of a statin in patients admitted for ACS. Trial registration NCT00171275

Published
2010
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10. Fluvastatin in the therapy of acute coronary syndrome: Rationale and design of a multicenter, randomized, double-blind, placebo-controlled trial (The FACS Trial)[ISRCTN81331696]

Author

Slaby Josef, Nemecek Eduard, Aschermann Ondrej, Wiendl Martin, Kettner Jiri, Kvapil Milan, Veselka Josef, Blasko Peter, Mates Martin, Vejvoda Jiri, Hajek Petr, Alan David, Ostadal Petr, Holm Frantisek, Rac Marek, Macek Milan, and Cepova Jana

Subjects
statin, fluvastatin, acute coronary syndrome, C-reactive protein, interleukin 6, pregnancy-associated plasma protein A, Medicine (General), R5-920
Abstract

Abstract Background Activation of inflammatory pathways plays an important contributory role in coronary plaque instability and subsequent rupture, which can lead to the development of acute coronary syndrome (ACS). Elevated levels of serum inflammatory markers such as C-reactive protein (CRP) represent independent risk factors for further cardiovascular events. Recent evidence indicates that in addition to lowering cholesterol levels, statins also decrease levels of inflammatory markers. Previous controlled clinical trials reporting the positive effects of statins in participants with ACS were designed for very early secondary prevention. To our knowledge, no controlled trials have evaluated the potential benefits of statin therapy, beginning immediately at the time of hospital admission. A previous pilot study performed by our group focused on early initiation of cerivastatin therapy. We demonstrated a highly significant reduction in levels of inflammatory markers (CRP and interleukin-6). Based on these preliminary findings, we are conducting a clinical trial to evaluate the efficacy of another statin, fluvastatin, as an early intervention in patients with ACS. Methods The FACS-trial (Fluvastatin in the therapy of Acute Coronary Syndrome) is a multicenter, randomized, double-blind, placebo-controlled study evaluating the effects of fluvastatin therapy initiated at the time of hospital admission. The study will enroll 1,000 participants admitted to hospital for ACS (both with and without ST elevation). The primary endpoint for the study is the influence of fluvastatin therapy on levels of inflammatory markers (CRP and interleukin-6) and on pregnancy associated plasma protein A (PAPP-A). A combined secondary endpoint is 30-day and one-year occurrence of death, nonfatal myocardial infarction, recurrent symptomatic ischemia, urgent revascularization, and cardiac arrest. Conclusion The primary objective of the FACS trial is to demonstrate that statin therapy, when started immediately after hospital admission for ACS, results in reduction of inflammation and improvement of prognosis. This study may contribute to new knowledge regarding therapeutic strategies for patients suffering from ACS and may offer additional clinical indications for the use of statins.

Published
2005
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11. 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. Cooremans, Masatsune Ogura, Tevfik Sabuncu, Ruy D Arjona Villicaña, Andrea Giaccari, Xuesong Fan, Auryan Szalat, Sanjaya Dissanayake, Etienne Khoury, Anja Vogt, Hermann Toplak, Alexis Baass, Isabel Palma, Gaelle Sablon, Dana A. Hay, Ya Yang, Margus Viigimaa, Erik S.G. Stroes, Dror Harats, Konstantin Krychtiuk, Zesen Liu, Aleksandra Parczewska, Yves Cottin, Yichen Qu, Mathilde Di-Fillipo, Agnieszka Konopka, Lamija Pojskic, Guadalupe J. Dominguez, Ahmet Temizhan, Roberto C. Chacon, Ibrahim E. Dural, Qiang Yong, G. Kees Hovingh, Kang Meng, Sandra Kutkiene, Julie Lemale, Reinhold Innerhofer, Alexandros D. Tselepis, Handrean Soran, Wolfgang König, Bassam Atallah, Olena Mitchenko, Jana Cepova, Eduardo M. Rodriguez, Ulrich Laufs, Norhidayah Rosman, Alena Lubasova, V. Durlach, Frederick J. Raal, Elyor Khodzhiboboev, Cristina Pederiva, Hui Yuan, Ashraf Reda, Fahad Alnouri, Konstantinos Tziomalos, Thanh T. Le, Jana Sirotiakova, Régis Hankard, Hector E.A. Cazares, Betsabel Rodriguez, Lenka Pavlickova, Assen Goudev, Julius Katzmann, Diana Boger, Wael Almahmeed, Katarina T. Podkrajsek, Sabina Zambon, Fahri Bayram, Nadia Citroni, Samir Rafla, Vincent Rigalleau, Aleksandr B. Shek, Hani Sabbour, Berenice G. Guzman, Shoshi Shpitzen, Eric Tarantino, Ahmed Bendary, Fedya Nikolov, Jean Bergeron, Stefan Kopf, Iva Rasulic, Gerald F. Watts, Muhammad I.A. Hafidz, Mehmet B. Yilmaz, Kathrin Biolik, Ira A. Haack, Robert A. Hegele, Sonia Dulong, Bartosz Wasąg, Osama Sanad, Susana Correia, Zhenjia Wang, Dana Biedermann, Christel König, Helena Podzimkova, Ihab Daoud, Mohammad Alghamdi, Dražen Perica, László Márk, Iosif Koutagiar, Volkan Dogan, Vladimir Blaha, Chandrashekhar K. Ponde, Katerina Valoskova, Amer A. Jabbar, Azhari Rosman, Sazzli Kasim, Mesut Demir, Ulugbek I. Nizamov, Aldo Ferreira-Hermosillo, Dilek Yesilbursa, Atef Elbahry, Arshad Abdulrasheed, Omer A. Elamin, Vasileios Athyros, Joanna Lewek, Gergely Nagy, Ursula Kassner, Jian Jiao, Klaus G. Parhofer, Charlotte Nzeyimana, Marcin Pajkowski, Stanislav Zemek, Jose J.C. Macías, Cornelius Müller, G. Sfikas, Leopoldo Pérez de Isla, Yulia Ragino, Fahad Al-Zadjali, Abdul Rais Sanusi, Anna Rita Roscini, Jean Ferrières, Selim Jambart, Jean Pierre Rabes, Laura Schreier, Hofit Cohen, Olivier S. Descamps, N. Lalic, Christine Stumpp, Antonio J. Vallejo-Vaz, Jutta Christmann, Manuela Casula, Mariko Harada-Shiba, Olga Lunegova, Ewa Starostecka, Nicolas D. Oca, Alain Carrié, Achilleas Attilakos, Savas Ozer, Andreea Dumitrescu, Jürgen Merke, Urte Aliosaitiene, Evangelos Liberopoulos, Manuel O. De los Rios Ibarra, Maria J. Virtuoso, Alessandro Lupi, Panagiotis Anagnostis, Ruth Agar, Dorota Ferrieres, George Liamis, José Eduardo Krieger, Mariann Harangi, Fouzia Sadiq, Francois Schiele, Saif Kamal, Mária Audikovszky, Peter Baumgartner, Marta Gazzotti, Daniel Gaudet, Ashanty F. Ortega, Marcin Gruchała, Philippe Moulin, Ljiljana Popovic, Luca Bonanni, E. Kiouri, Mika Hori, Chiara Trenti, Elena Repetti, Carlo Sabbà, Sophie Bernard, Alejandro R. Zazueta, Mirac Vural, Jesus R. Gonzalez, C. Stevens, Francesca Carubbi, Wenhui Wen, Sabri Demircan, Kanika I. Dharmayat, Anne Tybjærg-Hansen, Elizabete Terauda, Claudia Zemmrich, Alphonsus Isara, Fabiola L. Sobrevilla, Anell Hernandez Garcia, Ibrahim Sisic, Justin T. I-Shing, Yvonne Winhofer-Stöckl, Luya Wang, Manfred Mayer, Mohanad Al-ageedi, Judith Wiener, Mohammed Al-Kindi, Anis Safura Ramli, Yan Chen, Denis Angoulvant, Aytekin Oguz, K.H. Wolmarans, Claudio Ferri, Tomáš Freiberger, Lubomira Cermakova, Julieta D.M. Portano, Pierre Henri Ducluzeau, Katerina Vonaskova, Levent H. Can, Mario H.F. Andrade, György Paragh, C. Ebenbichler, Karina J.A. Rivera, Alia Khudari, Elisabeth Steinhagen-Thiessen, Ana C. Alves, Victoria Korneva, Sandra Singh, Georgia Anastasiou, Nur S. Hamzan, Massimo Federici, Lale Tokgozoglu, Hector G. Alcala, Oana Moldovan, Giuseppe Mandraffino, Swarup A.V. Shah, Lukas Burda, Ersel Onrat, Manuel de los Reyes Barrera Bustillo, Mirjana Radovic, Arman Postadzhiyan, Nien-Tzu Chang, Aylin Yildirir, Martin Mäser, Bruno Fink, Svetlana Mosteoru, Ulrike Schatz, Luis A.V. Talavera, Magdalena Dusejovska, Richard Ceska, Faisal A. Al-Allaf, T.F. Ashavaid, Gereon Böll, Sona Machacova, Gonzalo C. Vargas, Antonio Gallo, Elina Pantchechnikova, Lukas Tichy, Gersina Rega-Kaun, Moses Elisaf, Branislav Vohnout, Antonio Bossi, Suad Al-Mukhaini, Natasa Rajkovic, Ursa Sustar, Merih Kutlu, Mohamed Sobhy, Britta Otte, Ana M. Medeiros, Borut Jug, Patrick Couture, Rodrigo Alonso, Wolfgang Seeger, Guzal J. Abdullaeva, Ahmet Celik, Nasreen Al-Sayed, Béla Benczúr, Petra E. Khoury, Rafezah Razali, Ma L.R. Osorio, Ruiying Zhang, Monica M.N. Usme, Humberto Garcia Aguilar, Ceyhun Ceyhan, Antje Spens, Christoph J. Binder, Volker Schrader, Terrance C.S. Jin, Neftali E.A. Villa, Aleksandra Michalska-Grzonkowska, Francesco Purrello, Marshima M. Rosli, Vincent Maher, Dilshad Rasul, Ines Colaço, Ornella Guardamagna, Giuliana Mombelli, Khalid F. AlHabib, Fahmi Alkaf, Marianne Benn, Youmna Ghaleb, Arsenio V. Vazquez, Lakshmi L. Reddy, Salih Kilic, Siti Hamimah Sheikh Abdul Kadir, E. Bilianou, Rossella Marcucci, Sandro Muntoni, Kurt Widhalm, Evangelos A. Zacharis, Kuznetsova T. Yu, Eric Bruckert, Antonia Sonntag, Katerina Rehouskova, Josè Pablo Werba, Leobardo Sauque-Reyna, Myra Tilney, Dov Gavishv, A.M. Fiorenza, Zdenka Krejsova, Hong A. Le, Andrey V. Susekov, Isabel Klein, Mai N.T. Nguyen, Andrejs Erglis, Muge Ildizli, Diane Brisson, Salmi Razali, Winfried März, Ovidio Muñiz-Grijalvo, Justyna Borowiec-Wolna, Ingrid Buganova, Ngoc T. Kim, Yue Wu, István Reiber, Jose C.A. Martinez, Pavel Malina, Sandy Elbitar, Stephan Matthias, Ali F. Abdalsahib, Zlatko Fras, Wilson E Sadoh, Lucas Kleemann, Tayfun Sahin, Martin P. Bogsrud, Fabio Pellegatta, Mohamed A. Shafy, Yuntao Li, Martine Paquette, Zuhier Awan, Arturo Pujia, Xiantao Song, Renata Cifkova, Alexandre C. Pereira, Ioannis Skoumas, Roman Cibulka, Tadej Battelino, Mariusz Gąsior, Ghada Kazamel, Lahore S.U. Shah, Eran Leitersdorf, Niki Katsiki, Daniel Elías-López, Khalid Al-Rasadi, Grete Talviste, Sarka Mala, Rocio M. Alvarado, Pavel Kraml, Gerret Paulsen, Angelina Passaro, Zsolt Karányi, Carine Ayoub, Vera Adamkova, Ivo Petrov, Turky H. Almigbal, Rohana Abdul Ghani, Franck Boccara, Brian W. McCrindle, François Martin, Jamshed J. Dalal, Shitong Cheng, Khalid Al-Waili, Chaoyi Zhang, Ramon M. Prado, Lubica Cibickova, Lubomira Fabryova, Tobias Wiesner, Thuhairah Hasrah Abdul Rahman, Tan J. Le, Marcello Arca, Sabine Scholl-Bürgi, Juan R. Saucedo, Georgijs Nesterovics, Carla V.M. Valencia, Alexander Stadelmann, Vasileios Kotsis, Lina Badimon, Shizuya Yamashita, Jose C.M. Oyervides, Lay K. Teh, Susanne Greber-Platzer, Marianne Abifadel, Ruta Meiere, Wibke Reinhard, Pablo Corral, Nina Schmidt, Alain Pradignac, A. David Marais, Marta Jordanova, Marzena Romanowska-Kocejko, Johannes Scholl, Brian Tomlinson, Laura G.G. Herrera, Loukianos S. Rallidis, Pedro Mata, Sameh Emil, Matej Mlinaric, Emile Ferrari, Suraya Abdul Razak, Alexandra Ershova, Andrie G. Panayiotou, Alinna Y.R. Garcia, Kairat Davletov, Katarina Lalic, Doan L. Do, Krzysztof Chlebus, Ricardo A. Carrera, Daniel I.P. Vazquez, Nikolaos Sakkas, Liyuan Xu, Mays Altaey, Aysa Hacioglu, Alexandro J. Martagon, Marta Żarczyńska-Buchowiecka, Michael Schömig, Jürgen Homberger, Andrea Benso, Bertrand Cariou, Ardon Rubinstein, Omer Gedikli, Emre Durakoglugil, Mei Chong, Bahadir Kirilmaz, Suhaila Abd Muid, Jose M. Salgado, Berenice P. Aparicio, Mutaz Alkhnifsawi, Bruno Vergès, Cécile Yelnik, Goreti Lobarinhas, Zaneta Petrulioniene, Sylvia Asenjo, Aytul B. Yildirim, László Bajnok, 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., Reiner, 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., 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
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12. Spectrophotometric and chromatographic analysis of creatine:creatinine crystals in urine.

Author

Werle J, Buresova K, Cepova J, Bjørklund G, Fortova M, Prusa R, Fernandez C, Dunovska K, Klapkova E, Kizek R, and Kotaska K

Subjects
Humans, Male, Female, Middle Aged, Spectrophotometry methods, Creatinine urine, Creatine urine, Crystallization
Abstract

Creatinine is the end product of the catabolism of creatine and creatine phosphate. Creatine phosphate serves as a reservoir of high-energy phosphate, especially in skeletal and cardiac muscle. Besides typical known changes in serum and urinary creatinine concentrations, rare cases associated with changes in serum and urinary creatine levels have been described in the literature in humans. These cases are mostly linked to an excessive intake of creatine ethyl ester or creatine monohydrate, often resulting in increased urine creatinine concentrations. In addition, it is known that at such elevated creatinine concentrations, creatinine crystallisation may occur in the urine. Analysis of crystals and urinary concrements, often of heterogenous chemical composition, may provide diagnostic and therapeutic hints to the benefit of the patient. The aim of the present work was to analyze urine crystals of unclear composition with microscopic and spectroscopic techniques. On routine microscopic analysis of urine, a preliminary suspicion of uric acid or creatinine crystals was expressed. The crystals were of a cuboid shape and showed polarization effects in microscopy. The dried urine sample was whitish-orange in colour, odourless and dissolved well in water. Protein concentration in dry weight (DW) urine was about 0.3 mg/mg. The measured zinc content in the studied sample was approximately 660 µg/g DW sample and copper content was approximately 64 µg/g DW sample. A lead signal of around 10 µg/g DW sample was also observed. UV-Vis analysis showed a maximum creatine peak around 220 nm, compatible with the spectrum of creatinine with a maximum peak of 230 nm. Using HPLC technique, an extreme high ratio of creatine to creatinine of about 38 was measured, which led to the conclusion of the occurrence of rare creatine crystals in urine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Published
2024
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13. Short-term impact of vitamin K2 supplementation on biochemical parameters and lipoprotein fractions.

Author

Barna M, Dunovska K, Cepova J, Werle J, Prusa R, Bjørklud G, Melichercik P, Kizek R, and Klapkova E

Abstract

This study explored the short-term effects of vitamin K2 (VK2) supplementation on biochemical parameters (vitamin D, vitamin E, vitamin A, alkaline phosphatase, calcium, phosphorus (P), magnesium, metallothionein, triglycerides, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and lipoprotein fractions (albumin, HDL, very low-density lipoprotein (VLDL), LDL, and chylomicrons). A short-term experiment (24 h, six probands) was performed to track changes in VK2 levels after a single-dose intake (360 µg/day). Liquid chromatography-tandem mass spectrometry was used to monitor vitamin K levels (menaquinone-4 (MK-4), menaquinone-7 (MK-7), and vitamin K1 [VK1]) with a limit of detection of 1.9 pg/mL for VK1 and 3.8 pg/mL for the two forms of VK2. Results showed that MK-7 levels significantly increased within 2-6 h post-administration and then gradually declined. MK-4 levels were initially low, showing a slight increase, whereas VK1 levels rose initially and then decreased. Biochemical analyses indicated no significant changes in sodium, chloride, potassium, calcium, magnesium, albumin, or total protein levels. A transient increase in P was observed, peaking at 12 h before returning to baseline. Agarose gel electrophoresis of lipoprotein fractions revealed distinct chylomicron bands and variations in VLDL and HDL mobility, influenced by dietary lipids and VK2 supplementation. These findings suggest effective absorption and metabolism of MK-7 with potential implications for bone metabolism and cardiovascular health., (© 2024 Wiley‐VCH GmbH.)

Published
2024
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14. Electrochemical Sensors and Biosensors for Identification of Viruses: A Critical Review.

Author

Hosnedlova B, Werle J, Cepova J, Narayanan VHB, Vyslouzilova L, Fernandez C, Parikesit AA, Kepinska M, Klapkova E, Kotaska K, Stepankova O, Bjorklund G, Prusa R, and Kizek R

Abstract

Due to their life cycle, viruses can disrupt the metabolism of their hosts, causing diseases. If we want to disrupt their life cycle, it is necessary to identify their presence. For this purpose, it is possible to use several molecular-biological and bioanalytical methods. The reference selection was performed based on electronic databases (2020-2023). This review focused on electrochemical methods with high sensitivity and selectivity (53% voltammetry/amperometry, 33% impedance, and 12% other methods) which showed their great potential for detecting various viruses. Moreover, the aforementioned electrochemical methods have considerable potential to be applicable for care-point use as they are portable due to their miniaturizability and fast speed analysis (minutes to hours), and are relatively easy to interpret. A total of 2011 articles were found, of which 86 original papers were subsequently evaluated (the majority of which are focused on human pathogens, whereas articles dealing with plant pathogens are in the minority). Thirty-two species of viruses were included in the evaluation. It was found that most of the examined research studies (77%) used nanotechnological modifications. Other ones performed immunological (52%) or genetic analyses (43%) for virus detection. 5% of the reports used peptides to increase the method's sensitivity. When evaluable, 65% of the research studies had LOD values in the order of ng or nM. The vast majority (79%) of the studies represent proof of concept and possibilities with low application potential and a high need of further research experimental work.

Published
2024
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15. X-linked adrenoleukodystrophy: phenotype-genotype correlation in hemizygous males and heterozygous females with ABCD1 mutations.

Author

Zemanova M, Chrastina P, Dvorakova L, Reboun M, Vlaskova H, Jahnova H, El-Lababidi N, Cepova J, Honzik T, and Zeman J

Abstract

Objectives: X-linked adrenoleukodystrophy (X-ALD) causes cerebral adrenoleukodystrophy (cALD), myelopathy and/or adrenal insufficiency in males, and myelopathy/peripheral neuropathy in females. These distinct phenotypes are scarcely linked to a specific mutations. The objective herein was to find a link between the phenotype with the genotype mutation, serum very long-chain fatty acids (VLCFA), and the diet with Lorenzo´s and GTO oils in hemizygous males and heterozygous females., Methods: A retrospective study design with follow-up of 45 hemizygous males and 50 heterozygous females carrying mutations in ABCD1 from 35 unrelated families with X-ALD. Mutation analysis was performed by Sanger sequencing of PCR and/or RT-PCR and the severity of missense mutations was evaluated using GERP++ score and CADD score., Results: Twenty-five described and eight novel ABCD1 mutations were identified. Fifteen males and 23 females had severe mutations while 30 males and 27 females had less detrimental ones. cALD developed in 25 males (56%) including nine boys with severe mutations, 10 boys with less detrimental mutations and 6 adults with adrenomyelopathy. Myelopathy and/or adrenal insufficiency developed in 14 males (31%), six were asymptomatic. Adrenal insufficiency developed in two of five boys treated with hematopoietic stem cell transplantation (HSCT). Myelopathy/peripheral neuropathy developed in 26% of females. No correlation was found between the disease severity and the genotype, GERP++ and CADD scores, presence/absence of aberrant ALDP protein or X-inactivation. VLCFA were higher in males than heterozygous females and decreased during Lorenzo´s and GTO oils diet without a clear clinical impact on the disease., Conclusion: The prognosis was unfavourable in most males and significant part of females. Therapy with early HSCT is effective. Thus, the need for early diagnosis with the neonatal screening is crucial.

Published
2021

16. Vancomycin and its crystalline degradation products released from bone grafts and different types of bone cement.

Author

Klapkova E, Nescakova M, Melichercik P, Jahoda D, Dunovska K, Cepova J, and Prusa R

Subjects
Bone Transplantation, Chromatography, High Pressure Liquid, Humans, Methicillin-Resistant Staphylococcus aureus drug effects, Microbial Sensitivity Tests, Anti-Bacterial Agents analysis, Anti-Bacterial Agents metabolism, Bone Cements analysis, Vancomycin analysis, Vancomycin metabolism
Abstract

Vancomycin is often used in orthopedic surgery as a local prophylaxis of bacterial infection. The aim of this work was to compare the release of vancomycin and its biologically inactive crystalline degradation products (CDP-1) during in vitro experiments from different types of local antibiotic delivery systems (bone grafts and bone cements). The concentrations of vancomycin and its crystalline degradation products were determined by high-performance liquid chromatography. Each experiment was performed in a phosphate buffer solution over 21 days. Morselized bone grafts, synthetic bone cements Palacos and Copal, and synthetic bone grafts were tested as local carriers of vancomycin. The highest concentration approximately 670 mg/L of vancomycin was released from synthetic bone grafts Actifuse. Even after 21 days, the concentration of vancomycin was still above the minimum inhibitory concentration (MIC). The maximum concentration of vancomycin released in two experiments with human bone grafts exceeded 600 mg/L during the first day and was still above MIC level 21 days later when the experiment was concluded. By comparing the synthetic bone cements Palacos and Copal, Copal had the average maximum concentration of only 32.4 mg/L and Palacos 35.7 mg/L. The concentration of vancomycin fell below the MIC for vancomycin-resistant Staphylococcus aureus (VRSA) on the seventh day with Palacos and the ninth day with Copal. This study showed the insufficient concentration of released vancomycin from synthetic bone cements at the end of the experiment. For improvement of local prophylaxis, it would be beneficial to increase the amount of vancomycin in bone cements.

Published
2020
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17. LC-MS/MS quantitative analysis of phylloquinone, menaquinone-4 and menaquinone-7 in the human serum of a healthy population.

Author

Dunovska K, Klapkova E, Sopko B, Cepova J, and Prusa R

Abstract

A novel application of the liquid chromatography method combined with the triple quadrupole tandem mass spectrometry method was developed for the quantification of vitamin K 1 and two forms of vitamin K 2 (menaquinone-4, menaquinone-7) in human serum. Total chromatography time for each run was 9 min. Time required for the sample pretreatment procedures was approximately 4 h. The coefficients of variation (CVs) of intra-assay were 10.4%, 3.2 % and 2.3% for vitamin K 1 in three levels of quality control samples; were 14.3%, 3.2% and 6.7% for menaquinone-4; and were 11.1%, 6.0% and 7.0% for menaquinone-7. The inter-assay CVs were 12.8%, 11.3% and 7.4% for vitamin K 1 ; were 15.2%, 9.2% and 8.7% for menaquinone-4; and were 13.2%,11.1% and 7.2% for menaquinone-7. No interference was found between K 1 , menaquinone-4 and menaquinone-7, nor any deuterated internal standards. This method was then used to determine reference values for Caucasian populations of central European origin. Samples were measured from 191 healthy volunteers (51.2 ± 16.2 years (mean ± SD)) and the values concerning K 1 were 0.044-1.357 ng/mL for women and 0.030-1.214 ng/mL for men. The values for menaquinone-4 and menaquinone-7 did not exhibit any differences between women and men, and were 0.050-1.598 and 0.074-0.759 ng/mL, respectively., Competing Interests: The authors declare that they have no competing interests., (© 2019 Dunovska et al.)

Published
2019
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18. Determination of vitamins K 1 , MK-4, and MK-7 in human serum of postmenopausal women by HPLC with fluorescence detection.

Author

Klapkova E, Cepova J, Dunovska K, and Prusa R

Subjects
Female, Humans, Time Factors, Vitamin K 2 classification, Chromatography, High Pressure Liquid methods, Fluorescence, Postmenopause blood, Vitamin K 1 blood, Vitamin K 2 blood
Abstract

Background: New high-performance liquid chromatography (HPLC) method was developed for the determination of vitamin K 1 and two forms of vitamin K 2 (MK-4 and MK-7) in human serum, and the levels of vitamin K were determined in 350 samples of postmenopausal women., Methods: Vitamin K was determined by HPLC with fluorescence detection after postcolumn zinc reduction. The detection was performed at 246 nm (excitation) and 430 nm (emission). The internal standard and 2 mL of ethanol were added to 500 μL of serum. The mixture was extracted with 4 mL of hexane, and solid phase extraction was then used., Results: The HLPC method was fully validated. The intra- and interday accuracy and precision were evaluated on two QC samples by multiple analysis, and CV were less than 10%. The limit of quantification for MK-4 was found at 0.04 ng/mL, for K 1 0.03 ng/mL, and for MK-7 0.03 ng/mL. The mean recoveries of the corresponding compounds were 98%-110%. Serum levels of MK-4, K 1 , and MK-7 in postmenopausal women with osteoporosis were 0.890 ± 0.291 ng/mL, 0.433 ± 0.394 ng/mL, and 1.002 ± 1.020 ng/mL, respectively (mean ± SD). Serum levels of MK-4, K 1 , and MK-7 in postmenopausal women without osteoporosis were 0.825 ± 0.266 ng/mL, 0.493 ± 0.399 ng/mL, and 1.186 ± 1.076 ng/mL, respectively (mean ± SD)., Conclusion: New HPLC method for the determination of vitamins K 1 , MK-4, and MK-7 in serum was evaluated and validated. This method is highly specific and sensitive with the low limit of quantification., (© 2018 Wiley Periodicals, Inc.)

Published
2018
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19. A Comparison of Four Methods (Immunochemistry and HPLC) for Determination of 25-(OH)-Vitamin D in Postmenopausal Women.

Author

Klapkova E, Cepova J, Pechova M, Dunovska K, Kotaska K, and Prusa R

Subjects
Biomarkers blood, Female, Humans, Luminescent Measurements, Predictive Value of Tests, Reproducibility of Results, Spectrophotometry, Ultraviolet, Vitamin D blood, 25-Hydroxyvitamin D 2 blood, Calcifediol blood, Chromatography, High Pressure Liquid, Fluorescent Antibody Technique, Direct, Fluorescent Antibody Technique, Indirect, Postmenopause blood, Vitamin D analogs & derivatives
Abstract

Background: Three immunochemical methods for the determination of 25-(OH)-vitamin D and validated HPLC method for the determination of 25-(OH)-vitamin D3 and 25-(OH)-vitamin D2 were compared. 62 patient samples from postmenopausal women were measured and the results obtained by all these methods were compared., Methods: We used three chemiluminescent assays for determination of 25-(OH)-vitamin D. 25-(OH)-vitamin D3 and 25-(OH)-vitamin D2 were determined by HPLC with UV detection (Agilent 1200). The chemiluminescent assays were performed using the Abbott Architect i4000SR analyzer (Abbott Laboratories, Germany), the ADVIA Centaur (Siemens, USA), and the Liaison XL (DiaSorin Inc, USA). The statistical evaluation was done using GraphPad Prism 6.0., Results: The data were tested by Tukey's multiple comparison test. All methods showed significant differences in comparison with the immunochemical method from DiaSorin (p < 0.001 for Abbott, p < 0.05 for Siemens, and p < 0.0001 for HPLC). The comparison of the immunochemical method from Siemens with HPLC was also significant, p < 0.05. The mean of DiaSorin measurements was 38% lower than the mean of HPLC measurements. The non-significant difference was shown by the comparison of Abbott with HPLC and also Abbott with Siemens. Means for the 25-(OH)-vitamin D methods used were: Abbott 70.2 ± 24.2 nmol/L, Siemens 67.6 ± 27.9 nmol/L, DiaSorin 53.5 ± 17.1, and HPLC 82.4 ± 40.0 nmol/L., Conclusions: The comparison of the DiaSorin immunochemical assay with other tested methods showed the greatest deviation. The mean of DiaSorin measurements was 38% lower than the mean of HPLC measurements. According to the results of the DiaSorin method, most patients treated with vitamin D would not achieve the optimal level of 25-(OH)-vitamin D and this could negatively affect the clinical decision.

Published
2017
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20. Correlation between common genetic variants and risk factors associated with prediction of cardiovascular diseases in dyslipidemic patients.

Author

Kotaska K, Kolarova J, Kotrcova K, Cepova J, and Prusa R

Subjects
Adult, Aged, Aged, 80 and over, Female, Genetic Predisposition to Disease, Genotype, Humans, Male, Middle Aged, Mutation, Polymorphism, Genetic, Predictive Value of Tests, Risk Factors, Smoking genetics, Young Adult, Cardiovascular Diseases genetics, Dyslipidemias genetics, Genetic Variation, Nitric Oxide Synthase Type III genetics, Peptidyl-Dipeptidase A genetics
Abstract

Aims: The aim of the study was to investigate genetic variants predicting cardiovascular events in patients with dyslipidemia and compare its relationship with common risk factors including hyperlipidemia, metabolic syndrome, history of acute myocardial infarction, thrombosis, obesity, and smoking., Materials and Methods: Five hundred two individuals divided into six groups corresponding with the risk factors and a control group of normolypidemic patients were analyzed for the presence of eight mutations and polymorphisms (endothelial nitric oxide synthase -786T → C and G894T; lymphotoxin A C804A; angiotensin-converting enzyme [ACE] ins/del; human platelet antigen 1 a/b; beta-fibrinogen -455G → A; apolipoprotein B [ApoB] R3500Q; APOE E2/E3/E4) using the ViennaLab CVD Strip assay., Results: ACE deletions are the most frequent genetic variants in risk groups of dyslipidemic patients (from 58% in cardiovascular events to 51% in smokers). We found a strong relationship between genetic variants and risk factors. G894T is significantly associated with smoking (value of odds ratio [OR] = 1.62, p = 0.04), and ACE deletions are negatively associated with cardiovascular events (OR = 0.62, p = 0.03)., Conclusion: Significant associations between genetic variants predicting cardiovascular events and common risk factors in dyslipidemic patients were found.

Published
2012
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21. Alterations in serum selenium levels and their relation to troponin I in acute myocardial infarction.

Author

Kutil B, Ostadal P, Vejvoda J, Kukacka J, Cepova J, Alan D, Krüger A, and Vondrakova D

Subjects
Anticoagulants therapeutic use, Biomarkers blood, Catheter Ablation, Coronary Angiography, Hospitalization, Humans, Myocardial Infarction pathology, Myocardial Infarction therapy, Necrosis, Time Factors, Myocardial Infarction blood, Selenium blood, Troponin I blood
Abstract

Selenium (Se) is an essential trace element with antioxidant function. The aim of the present study was to estimate the alterations of Se serum level during the acute phase of myocardial infarction and its relation to biomarkers of myocardial necrosis. Serum Se levels were measured at admission and after 24 h in 60 consecutive patients with acute coronary syndrome (both with and without ST elevation). Troponin I (TnI) was assessed at admission and then twice daily for 3 days; patients with normal levels were excluded. Fifty-five patients with acute MI (positive TnI) were included into the analysis. During the first day of hospitalization, patients received standard therapy, including acetylsalicylic acid, clopidogrel, and heparin or enoxaparin; all underwent urgent coronary angiography and percutaneous intervention, when appropriate. Mean Se levels at baseline and 24 h later were comparable (67.1 ± 2.1 vs. 67.2 ± 1.8 μg/L, ns). Linear regression has shown significant correlation between baseline Se levels and peak TnI (y = 3.4x - 116, r (2) = 0.13, P = 0.008). Positive correlation was found also between the peak TnI and the difference from baseline to 24 h (y = 2.2x + 115, r (2) = 0.08, P = 0.04). Moreover, close negative correlation was observed between baseline Se levels and the difference from baseline to 24 h (y = -0.9x + 62.7, r (2) = 0.55, P<0.001). Our results have shown marked individual changes in Se levels during the acute phase of MI as well as correlation between Se levels and peak TnI. These results suggest that alterations in serum Se may be related to the extent of myocardial infarction.

Published
2010
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22. Fluvastatin in the first-line therapy of acute coronary syndrome: results of the multicenter, randomized, double-blind, placebo-controlled trial (the FACS-trial).

Author

Ostadal P, Alan D, Vejvoda J, Kukacka J, Macek M, Hajek P, Mates M, Kvapil M, Kettner J, Wiendl M, Aschermann O, Slaby J, Holm F, Telekes P, Horak D, Blasko P, Zemanek D, Veselka J, and Cepova J

Subjects
Acute Coronary Syndrome immunology, Acute Coronary Syndrome mortality, Aged, C-Reactive Protein metabolism, Chi-Square Distribution, Czech Republic, Double-Blind Method, Drug Administration Schedule, Early Termination of Clinical Trials, Fatty Acids, Monounsaturated adverse effects, Female, Fluvastatin, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects, Indoles adverse effects, Inflammation Mediators blood, Interleukin-6 blood, Kaplan-Meier Estimate, Male, Middle Aged, Odds Ratio, Patient Admission, Patient Selection, Placebo Effect, Pregnancy-Associated Plasma Protein-A metabolism, Prospective Studies, Risk Assessment, Sample Size, Time Factors, Treatment Outcome, Acute Coronary Syndrome drug therapy, Fatty Acids, Monounsaturated administration & dosage, Hydroxymethylglutaryl-CoA Reductase Inhibitors administration & dosage, Indoles administration & dosage, Secondary Prevention methods
Abstract

Background: Statins have been proved to be effective in reduction of mortality and morbidity when started in the early secondary prevention in stabilized patients after acute coronary syndrome (ACS). The safety and efficacy of statin administration directly in the first-line therapy in unstable ACS patients is not clear. The aim of our study was, therefore, to assess the effect of statin treatment initiated immediately at hospital admission of patients with ACS., Methods: The trial was stopped prematurely after enrollment of one hundred and fifty-six patients with ACS that were randomized at admission to fluvastatin 80 mg (N = 78) or placebo (N = 78). Study medication was administered immediately after randomization and then once daily for 30 days; all patients were then encouraged to continue in open-label statin therapy and at the end of one-year follow-up 75% in the fluvastatin group and 78% in the placebo group were on statin therapy., Results: We did not demonstrate any difference between groups in the level of C-reactive protein, interleukin 6, and pregnancy-associated plasma protein A on Day 2 and Day 30 (primary endpoint). Fluvastatin-therapy, however, significantly reduced one-year occurrence of major adverse cardiovascular events (11.5% vs. 24.4%, odds ratio (OR) 0.40, 95% CI 0.17-0.95, P = 0.038). This difference was caused mainly by reduction of recurrent symptomatic ischemia (7.7% vs. 20.5%, OR 0.32, 95% CI 0.12-0.88, P = 0.037)., Conclusions: This study failed to prove the effect of fluvastatin given as first-line therapy of ACS on serum markers of inflammation and plaque instability. Fluvastatin therapy was, however, safe and it may reduce cardiovascular event rate that supports immediate use of a statin in patients admitted for ACS., Trial Registration: NCT00171275.

Published
2010
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23. Immediate effect of fluvastatin on lipid levels in acute coronary syndrome.

Author

Ostadal P, Alan D, Vejvoda J, Cepova J, Kukacka J, Blasko P, Martinkovicova L, and Vojacek J

Subjects
Acute Coronary Syndrome blood, Antioxidants therapeutic use, Female, Fluvastatin, Humans, Male, Middle Aged, Treatment Outcome, Acute Coronary Syndrome drug therapy, Cholesterol blood, Cholesterol, HDL blood, Cholesterol, LDL blood, Fatty Acids, Monounsaturated therapeutic use, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Indoles therapeutic use, Triglycerides blood
Abstract

It is widely assumed that acute benefit of statin therapy is mediated especially by non-lipid effects. The immediate influence of statins on lipid levels in patients with acute coronary syndrome (ACS) is, however, not clear. A total of 64 consecutive patients with ACS were randomized at admission to fluvastatin 80 mg (Group 1, N = 32) or standard therapy without statin (Group 2, N = 32). The levels of total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), high-density-lipoprotein cholesterol (HDL-C), and triglycerides (TG) were examined at admission and after 24 h. Baseline characteristics were comparable in both groups. In Group 1, fluvastatin significantly decreased the levels of TC by 14.5%, LDL-C by 17.2%, and HDL-C by 10.0% (P < 0.001); TG were not influenced. In Group 2 only marginal reductions in TC (by 4.1%, P = 0.03) and HDL-C (by 7.5%, P < 0.01) were detected; the levels of LDL-C and TG were not changed. As compared with Group 2, in Group 1 the final levels of TC (P = 0.02) and LDL-C (P = 0.01) were significantly lower. Fluvastatin therapy, when started at admission in patients with ACS, significantly reduces TC and LDL-C already after 24 h. We suggest that the lipid-lowering effect of statins in the therapy of ACS is probably as prompt as non-lipid effects.

Published
2007
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24. Fluvastatin in the therapy of acute coronary syndrome: Rationale and design of a multicenter, randomized, double-blind, placebo-controlled trial (The FACS Trial)[ISRCTN81331696].

Author

Ostadal P, Alan D, Hajek P, Vejvoda J, Mates M, Blasko P, Veselka J, Kvapil M, Kettner J, Wiendl M, Aschermann O, Slaby J, Nemecek E, Holm F, Rac M, Macek M, and Cepova J

Abstract

BACKGROUND: Activation of inflammatory pathways plays an important contributory role in coronary plaque instability and subsequent rupture, which can lead to the development of acute coronary syndrome (ACS). Elevated levels of serum inflammatory markers such as C-reactive protein (CRP) represent independent risk factors for further cardiovascular events. Recent evidence indicates that in addition to lowering cholesterol levels, statins also decrease levels of inflammatory markers. Previous controlled clinical trials reporting the positive effects of statins in participants with ACS were designed for very early secondary prevention. To our knowledge, no controlled trials have evaluated the potential benefits of statin therapy, beginning immediately at the time of hospital admission. A previous pilot study performed by our group focused on early initiation of cerivastatin therapy. We demonstrated a highly significant reduction in levels of inflammatory markers (CRP and interleukin-6). Based on these preliminary findings, we are conducting a clinical trial to evaluate the efficacy of another statin, fluvastatin, as an early intervention in patients with ACS. METHODS: The FACS-trial (Fluvastatin in the therapy of Acute Coronary Syndrome) is a multicenter, randomized, double-blind, placebo-controlled study evaluating the effects of fluvastatin therapy initiated at the time of hospital admission. The study will enroll 1,000 participants admitted to hospital for ACS (both with and without ST elevation). The primary endpoint for the study is the influence of fluvastatin therapy on levels of inflammatory markers (CRP and interleukin-6) and on pregnancy associated plasma protein A (PAPP-A). A combined secondary endpoint is 30-day and one-year occurrence of death, nonfatal myocardial infarction, recurrent symptomatic ischemia, urgent revascularization, and cardiac arrest. CONCLUSION: The primary objective of the FACS trial is to demonstrate that statin therapy, when started immediately after hospital admission for ACS, results in reduction of inflammation and improvement of prognosis. This study may contribute to new knowledge regarding therapeutic strategies for patients suffering from ACS and may offer additional clinical indications for the use of statins.

Published
2005
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