El genoma humano y las pruebas genéticas: su aplicación y las consecuencias en el ámbito laboral

Trabajo final de graduación de 139 páginas en formato pdfLa problemática que se aborda en el presente trabajo puede parecer para algunos desprevenidos como un tema exageradamente futurista; empero, la realidad demuestra que los impresionantes avances en el campo de la genética, obligan, hoy mismo, a comenzar por debatir sobre las consecuencias jurídicas que estos avances científicos permiten. El plan inicial para cartografiar el genoma humano completo, se previó estaría listo en el año 2005, a la fecha está concluido, por lo cual, el Derecho y sus diferentes ramas, en este caso especialmente la materia laboral, debe reconocer tal situación y normar las prácticas que se vendrán, conforme al principio de prevención, y sobre la base cimentadora de los principios cristianos de justicia social. Las noticias sobre los descubrimientos realizados en torno al genoma humano han generado expectativas para el mejoramiento de la salud y han venido deparando cambios de gran impacto social, moral y jurídico, ya que, sus posibilidades las perciben los ciudadanos, de manera ambivalente. Conviene distinguir entre los innegables conflictos que se plantean y que pueden afectar importantes derechos ya reconocidos y el miedo a la ciencia que subyace detrás de algunos fantasmas del inconsciente colectivo.Universidad Estatal a Distancia de Costa Ric

Spatial variability of the relationships of runoff and sediment yield with weather types throughout the Mediterranean basin

Este artículo contiene 16 páginas, 6 figuras, 2 tablas.Soil degradation by water is a serious environmental problem worldwide, with specific climatic factors being the major causes. We investigated the relationships between synoptic atmospheric patterns (i.e. weather types, WTs) and runoff, erosion and sediment yield throughout the Mediterranean basin by analyzing a large database of natural rainfall events at 68 research sites in 9 countries. Principal Component Analysis (PCA) was used to identify spatial relationships of the different WTs including three hydro-sedimentary variables: rainfall, runoff, and sediment yield (SY, used to refer to both soil erosion measured at plot scale and sediment yield registered at catchment scale). The results indicated 4 spatial classes of rainfall and runoff: (a) northern sites dependent on North (N) and North West (NW) flows; (b) eastern sites dependent on E and NE flows; (c) southern sites dependent on S and SE flows; and, finally, (d) western sites dependent on W and SW flows. Conversely, three spatial classes are identified for SY characterized by: (a) N and NE flows in northern sites (b) E flows in eastern sites, and (c) Wand SW flows in western sites. Most of the rainfall, runoff and SY occurred during a small number of daily events, and just a few WTs accounted for large percentages of the total. Our results confirm that characterization by WT improves understanding of the general conditions under which runoff and SY occur, and provides useful information for understanding the spatial variability of runoff, and SY throughout the Mediterranean basin. The approach used here could be useful to aid of the design of regional water management and soil conservation measures.This research was supported by projects funded by the MINECOFEDER: CGL2014-52135-C3-3-R, CGL2014-59946-R, CGL2015-65569- R, CGL2015-64284-C2-2-R, and PCIN-2017-061/AEI. When this manuscript was first submitted Estela Nadal-Romero and Damià Vericat received a “Ramón y Cajal” postdoctoral contract (RYC-2013-14371 and RYC‐2010‐06264, Spanish Ministry of Economy and Competitiveness, MEC). Damià Vericat is now a Serra Húnter Fellow at the University of Lleida. María Fernández-Raga received a “José Castillejo” postdoctoral grant (Spanish Ministry of Education, Culture and Sports). Carla Ferreira was supported by a post-doctoral research grant from the Portuguese Science and Technology Foundation (SFRH/ BPD/120093/2016). Mariano Moreno-de las Heras received a Juan de la Cierva postdoctoral contract (IJCI-2015-26463) from the MEC. José Andrés López-Tarazón received a Vicenç Mut postdoctoral fellowship from the Autonomous Balearic Government (CAIB PD/038/2016). José Andrés López-Tarazón and Ramon Batalla also acknowledge the Secretariat for Universities and Research of the Department of the Economy and Knowledge of the Autonomous Government of Catalonia for supporting the Consolidated Research Group 2014 SGR 645 (RIUSFluvial Dynamics Research Group), and the CERCA Programme. This paper has benefited from the Lab and Field Data Pool created within the framework of the COST action CONNECTEUR (ES1306).Peer reviewe

Analysis of the spatial variability of the relationships between rainfall, runoff, erosion and sediment yield and synoptic atmospheric patterns around the Mediterranean basin

Trabajo presentado en TERRAenVISION Environmental Issues Today: Scientific Solutions for Societal Issues, celebrado en Barcelona (España) del 27 de enero al 2 de febrero de 2018This contribution results from international collaborative efforts of different research groups around the Mediterranean basin focusing on soil conservation and water management. We will present the most complete database of runoff and soil erosion information and analyze the records from 68 locations, including more than 22458 detail events between 1985-2015. Soil conservation and water planning are two of the most challenging problems around the Mediterranean basin due to climate conditions and human activity. We believe that future advances on understanding soil degradation by water should be developed under global approaches. In this contribution, we will present an analysis of atmospheric conditions, expressed by weather types and the resulted rainfall, runoff, and erosion and sediment yield around the Mediterranean basin. The weather types compile daily information about the different air masses responsible for rainfall, runoff and eventually erosion and sediment yield, and their analyses let us know the synchrony of the response at different sites around the Mediterranean basin. The analyses of the global dataset display different spatial patterns for rainfall, runoff, and sediment yield, related to different atmospheric patterns. This research will be a valuable tool for understanding the evolution of these environmental variables, and therefore it will allow future planning to design regional water management and soil conservation measuresPeer reviewe

NEOTROPICAL CARNIVORES: a data set on carnivore distribution in the Neotropics

Mammalian carnivores are considered a key group in maintaining ecological health and can indicate potential ecological integrity in landscapes where they occur. Carnivores also hold high conservation value and their habitat requirements can guide management and conservation plans. The order Carnivora has 84 species from 8 families in the Neotropical region: Canidae; Felidae; Mephitidae; Mustelidae; Otariidae; Phocidae; Procyonidae; and Ursidae. Herein, we include published and unpublished data on native terrestrial Neotropical carnivores (Canidae; Felidae; Mephitidae; Mustelidae; Procyonidae; and Ursidae). NEOTROPICAL CARNIVORES is a publicly available data set that includes 99,605 data entries from 35,511 unique georeferenced coordinates. Detection/non-detection and quantitative data were obtained from 1818 to 2018 by researchers, governmental agencies, non-governmental organizations, and private consultants. Data were collected using several methods including camera trapping, museum collections, roadkill, line transect, and opportunistic records. Literature (peer-reviewed and grey literature) from Portuguese, Spanish and English were incorporated in this compilation. Most of the data set consists of detection data entries (n = 79,343; 79.7%) but also includes non-detection data (n = 20,262; 20.3%). Of those, 43.3% also include count data (n = 43,151). The information available in NEOTROPICAL CARNIVORES will contribute to macroecological, ecological, and conservation questions in multiple spatio-temporal perspectives. As carnivores play key roles in trophic interactions, a better understanding of their distribution and habitat requirements are essential to establish conservation management plans and safeguard the future ecological health of Neotropical ecosystems. Our data paper, combined with other large-scale data sets, has great potential to clarify species distribution and related ecological processes within the Neotropics. There are no copyright restrictions and no restriction for using data from this data paper, as long as the data paper is cited as the source of the information used. We also request that users inform us of how they intend to use the data

NEOTROPICAL XENARTHRANS: a data set of occurrence of xenarthran species in the Neotropics

Xenarthrans—anteaters, sloths, and armadillos—have essential functions for ecosystem maintenance, such as insect control and nutrient cycling, playing key roles as ecosystem engineers. Because of habitat loss and fragmentation, hunting pressure, and conflicts with domestic dogs, these species have been threatened locally, regionally, or even across their full distribution ranges. The Neotropics harbor 21 species of armadillos, 10 anteaters, and 6 sloths. Our data set includes the families Chlamyphoridae (13), Dasypodidae (7), Myrmecophagidae (3), Bradypodidae (4), and Megalonychidae (2). We have no occurrence data on Dasypus pilosus (Dasypodidae). Regarding Cyclopedidae, until recently, only one species was recognized, but new genetic studies have revealed that the group is represented by seven species. In this data paper, we compiled a total of 42,528 records of 31 species, represented by occurrence and quantitative data, totaling 24,847 unique georeferenced records. The geographic range is from the southern United States, Mexico, and Caribbean countries at the northern portion of the Neotropics, to the austral distribution in Argentina, Paraguay, Chile, and Uruguay. Regarding anteaters, Myrmecophaga tridactyla has the most records (n = 5,941), and Cyclopes sp. have the fewest (n = 240). The armadillo species with the most data is Dasypus novemcinctus (n = 11,588), and the fewest data are recorded for Calyptophractus retusus (n = 33). With regard to sloth species, Bradypus variegatus has the most records (n = 962), and Bradypus pygmaeus has the fewest (n = 12). Our main objective with Neotropical Xenarthrans is to make occurrence and quantitative data available to facilitate more ecological research, particularly if we integrate the xenarthran data with other data sets of Neotropical Series that will become available very soon (i.e., Neotropical Carnivores, Neotropical Invasive Mammals, and Neotropical Hunters and Dogs). Therefore, studies on trophic cascades, hunting pressure, habitat loss, fragmentation effects, species invasion, and climate change effects will be possible with the Neotropical Xenarthrans data set. Please cite this data paper when using its data in publications. We also request that researchers and teachers inform us of how they are using these data

Relation of Lipoprotein(a) Levels to Incident Type 2 Diabetes and Modification by Alirocumab Treatment

none1691siOBJECTIVE: In observational data, lower levels of lipoprotein(a) have been associated with greater prevalence of type 2 diabetes. Whether pharmacologic lowering of lipoprotein(a) influences incident type 2 diabetes is unknown. We determined the relationship of lipoprotein(a) concentration with incident type 2 diabetes and effects of treatment with alirocumab, a PCSK9 inhibitor. RESEARCH DESIGN AND METHODS: In the ODYSSEY OUTCOMES trial alirocumab was compared with placebo in patients with acute coronary syndrome. Incident diabetes was determined from laboratory, medication, and adverse event data. RESULTS: Among 13,480 patients without diabetes at baseline, 1,324 developed type 2 diabetes over a median 2.7 years. Median baseline lipoprotein(a) was 21.9 mg/dL. With placebo, 10 mg/dL lower baseline lipoprotein(a) was associated with hazard ratio 1.04 (95% CI 1.02-1.06, P < 0.001) for incident type 2 diabetes. Alirocumab reduced lipoprotein(a) by a median 23.2% with greater absolute reductions from higher baseline levels and no overall effect on incident type 2 diabetes (hazard ratio 0.95, 95% CI 0.85-1.05). At low baseline lipoprotein(a) levels, alirocumab tended to reduce incident type 2 diabetes, while at high baseline lipoprotein(a) alirocumab tended to increase incident type 2 diabetes compared with placebo (treatment-baseline lipoprotein(a) interaction P = 0.006). In the alirocumab group, a 10 mg/dL decrease in lipoprotein(a) from baseline was associated with hazard ratio 1.07 (95% CI 1.03-1.12; P = 0.0002) for incident type 2 diabetes. CONCLUSIONS: In patients with acute coronary syndrome, baseline lipoprotein(a) concentration associated inversely with incident type 2 diabetes. Alirocumab had neutral overall effect on incident type 2 diabetes. However, treatment-related reductions in lipoprotein(a), more pronounced from high baseline levels, were associated with increased risk of incident type 2 diabetes. Whether these findings pertain to other therapies that reduce lipoprotein(a) is undetermined.restrictedSchwartz G.G.; Szarek M.; Bittner V.A.; Bhatt D.L.; Diaz R.; Goodman S.G.; Jukema J.W.; Loy M.; Manvelian G.; Pordy R.; White H.D.; Steg P.G. ODYSSEY OUTCOMES Committees and Investigators: Gregory G Schwartz, Philippe Gabriel Steg, Deepak L Bhatt, Vera A Bittner, Rafael Diaz, Shaun G Goodman, Robert A Harrington, J Wouter Jukema, Michael Szarek, Harvey D White, Andreas M Zeiher, Pierluigi Tricoci, Matthew T Roe, Kenneth W Mahaffey, Jay M Edelberg, Corinne Hanotin, Guillaume Lecorps, Angèle Moryusef, Robert Pordy, William J Sasiela, Jean-François Tamby, Philip E Aylward, Heinz Drexel, Peter Sinnaeve, Mirza Dilic, Renato D Lopes, Nina N Gotcheva, Juan-Carlos Prieto, Huo Yong, Patricio López-Jaramillo, Ivan Pećin, Zeljko Reiner, Petr Ostadal, Margus Viigimaa, Markku S Nieminen, Vakhtang Chumburidze, Nikolaus Marx, Nicolas Danchin, Evangelos Liberopoulos, Pablo Carlos Montenegro Valdovinos, Hung-Fat Tse, Robert Gabor Kiss, Denis Xavier, Doron Zahger, Marco Valgimigli, Takeshi Kimura, Hyo Soo Kim, Sang-Hyun Kim, Andrejs Erglis, Aleksandras Laucevicius, Sasko Kedev, Khalid Yusoff, Gabriel Arturo Ramos López, Marco Alings, Sigrun Halvorsen, Roger M Correa Flores, Andrzej Budaj, Joao Morais, Maria Dorobantu, Yuri Karpov, Arsen D Ristic, Terrance Chua, Jan Murin, Zlatko Fras, Anthony J Dalby, José Tuñón, H Asita de Silva, Emil Hagström, Ulf Landmesser, Chern-En Chiang, Piyamitr Sritara, Sema Guneri, Alexander Parkhomenko, Kausik K Ray, Patrick M Moriarty, Robert Vogel, Bernard Chaitman, Sheryl F Kelsey, Anders G Olsson, Jean-Lucien Rouleau, Maarten L Simoons, Karen Alexander, Chiara Meloni, Robert Rosenson, Eric J G Sijbrands, Pierluigi Tricoci, John H Alexander, Luciana Armaganijan, Akshay Bagai, Maria Cecilia Bahit, J Matthew Brennan, Shaun Clifton, Adam D DeVore, Shalonda Deloatch, Sheila Dickey, Keith Dombrowski, Grégory Ducrocq, Zubin Eapen, Patricia Endsley, Arleen Eppinger, Robert W Harrison, Connie Ng Hess, Mark A Hlatky, Joseph Dedrick Jordan, Joshua W Knowles, Bradley J Kolls, David F Kong, Sergio Leonardi, Linda Lillis, David J Maron, Jill Marcus, Robin Mathews, Rajendra H Mehta, Robert J Mentz, Humberto Graner Moreira, Chetan B Patel, Sabrina Bernardez-Pereira, Lynn Perkins, Thomas J Povsic, Etienne Puymirat, William Schuyler Jones, Bimal R Shah, Matthew W Sherwood, Kenya Stringfellow, Darin Sujjavanich, Mustafa Toma, Charlene Trotter, Sean Van Diepen, Matthew D Wilson, Andrew T Yan, Lilia B Schiavi, Marcelo Garrido, Andrés F Alvarisqueta, Sonia A Sassone, Anselmo P Bordonava, Alberto E Alves De Lima, Jorge M Schmidberg, Ernesto A Duronto, Orlando C Caruso, Leonardo P Novaretto, Miguel Angel Hominal, Oscar R Montaña, Alberto Caccavo, Oscar A Gomez Vilamajo, Alberto J Lorenzatti, Luis R Cartasegna, Gustavo A Paterlini, Ignacio J Mackinnon, Guillermo D Caime, Marcos Amuchastegui, Oscar Salomone, Oscar R Codutti, Horacio O Jure, Julio O E Bono, Adrian D Hrabar, Julio A Vallejos, Rodolfo A Ahuad Guerrero, Federico Novoa, Cristian A Patocchi, Cesar J Zaidman, Maria E Giuliano, Ricardo D Dran, Marisa L Vico, Gabriela S Carnero, Pablo N Guzman, Juan C Medrano Allende, Daniela F Garcia Brasca, Miguel H Bustamante Labarta, Sebastian Nani, Eduardo D S Blumberg, Hugo R Colombo, Alberto Liberman, Victorino Fuentealba, Hector L Luciardi, Gabriel D Waisman, Mario A Berli, Ruben O Garcia Duran, Horacio G Cestari, Hugo A Luquez, Jorge A Giordano, Silvia S Saavedra, Gerardo Zapata, Osvaldo Costamagna, Susana Llois, Jonathon H Waites, Nicholas Collins, Allan Soward, Chris L S Hii, James Shaw, Margaret A Arstall, John Horowitz, Daniel Ninio, James F Rogers, David Colquhoun, Romulo E Oqueli Flores, Philip Roberts-Thomson, Owen Raffel, Sam J Lehman, Constantine Aroney, Steven G M Coverdale, Paul J Garrahy, Gregory Starmer, Mark Sader, Patrick A Carroll, Ronald Dick, Robert Zweiker, Uta Hoppe, Kurt Huber, Rudolf Berger, Georg Delle-Karth, Bernhard Frey, Franz Weidinger, Dirk Faes, Kurt Hermans, Bruno Pirenne, Attilio Leone, Etienne Hoffer, Mathias C M Vrolix, Luc De Wolf, Bart Wollaert, Marc Castadot, Karl Dujardin, Christophe Beauloye, Geert Vervoort, Harry Striekwold, Carl Convens, John Roosen, Emanuele Barbato, Marc Claeys, Frank Cools, Ibrahim Terzic, Fahir Barakovic, Zlatko Midzic, Belma Pojskic, Emir Fazlibegovic, Mehmed Kulić, Azra Durak-Nalbantic, Dusko Vulic, Adis Muslibegovic, Boris Goronja, Gilmar Reis, Luciano Sousa, Jose C Nicolau, Flavio E Giorgeto, Ricardo P Silva, Lilia Nigro Maia, Rafael Rech, Paulo R F Rossi, Maria José A G Cerqueira, Norberto Duda, Renato Kalil, Adrian Kormann, José Antonio M Abrantes, Pedro Pimentel Filho, Ana Priscila Soggia, Mayler O N de Santos, Fernando Neuenschwander, Luiz C Bodanese, Yorghos L Michalaros, Freddy G Eliaschewitz, Maria H Vidotti, Paulo E Leaes, Roberto V Botelho, Sergio Kaiser, Euler Roberto Fernandes Manenti, Dalton B Precoma, Jose C Moura Jorge, Pedro G Silva, Jose A Silveira, Wladmir Saporito, Jose A Marin-Neto, Gilson S Feitosa, Luiz Eduardo F Ritt, Juliana A de Souza, Fernando Costa, Weimar K S B Souza, Helder J L Reis, Leandro Machado, José Carlos Aidar Ayoub, Georgi V Todorov, Fedya P Nikolov, Elena S Velcheva, Maria L Tzekova, Haralambi O Benov, Stanislav L Petranov, Haralin S Tumbev, Nina S Shehova-Yankova, Dimitar T Markov, Dimitar H Raev, Mihail N Mollov, Kostadin N Kichukov, Katya A Ilieva-Pandeva, Raya Ivanova, Maryana Gospodinov, Valentina M Mincheva, Petar V Lazov, Bojidar I Dimov, Manohara Senaratne, James Stone, Jan Kornder, Stephen Pearce, Danielle Dion, Daniel Savard, Yves Pesant, Amritanshu Pandey, Simon Robinson, Gilbert Gosselin, Saul Vizel, Gordon Hoag, Ronald Bourgeois, Anne Morisset, Eric Sabbah, Bruce Sussex, Simon Kouz, Paul MacDonald, Ariel Diaz, Nicolas Michaud, David Fell, Raymond Leung, Tycho Vuurmans, Christopher Lai, Frank Nigro, Richard Davies, Gustavo Nogareda, Ram Vijayaraghavan, John Ducas, Serge Lepage, Shamir Mehta, James Cha, Robert Dupuis, Peter Fong, Sohrab Lutchmedial, Josep Rodes-Cabau, Hussein Fadlallah, David Cleveland, Thao Huynh, Iqbal Bata, Adnan Hameed, Cristian Pincetti, Sergio Potthoff, Monica Acevedo, Arnoldo Aguirre, Margarita Vejar, Mario Yañez, Guillermo Araneda, Mauricio Fernandez, Luis Perez, Paola Varleta, Fernando Florenzano, Laura Huidobro, Carlos A Raffo, Claudia Olivares, Leonardo Nahuelpan, Humberto Montecinos, Jiyan Chen, Yugang Dong, Weijian Huang, Jianzhong Wang, Shi'An Huang, Zhuhua Yao, Xiang Li, Lan Cui, Wenhua Lin, Yuemin Sun, Jingfeng Wang, Jianping Li, Xuelian Zhang, Hong Zhu, Dandan Chen, Lan Huang, Shaohong Dong, Guohai Su, Biao Xu, Xi Su, Xiaoshu Cheng, Jinxiu Lin, Wenxia Zong, Huanming Li, Yi Feng, Dingli Xu, Xinchun Yang, Yuannan Ke, Xuefeng Lin, Zheng Zhang, Zeqi Zheng, Zhurong Luo, Yundai Chen, Chunhua Ding, Yi Zhong, Yang Zheng, Xiaodong Li, Daoquan Peng, Shuiping Zhao, Ying Li, Xuebo Liu, Meng Wei, Shaowen Liu, Yihua Yu, Baiming Qu, Weihong Jiang, Yujie Zhou, Xingsheng Zhao, Zuyi Yuan, Ying Guo, Xiping Xu, Xubo Shi, Junbo Ge, Guosheng Fu, Feng Bai, Weiyi Fang, Xiling Shou, Xiangjun Yang, Jian'An Wang, Meixiang Xiang, Yingxian Sun, Qinghua Lu, Ruiyan Zhang, Jianhua Zhu, Yizhou Xu, Zhongcai Fan, Tianchang Li, Chun Wu, Nicolas Jaramillo, Gregorio Sanchez Vallejo, Diana C Luna Botia, Rodrigo Botero Lopez, Dora I Molina De Salazar, Alberto J Cadena Bonfanti, Carlos Cotes Aroca, Juan Diego Higuera, Marco Blanquicett, Sandra I Barrera Silva, Henry J Garcia Lozada, Julian A Coronel Arroyo, Jose L Accini Mendoza, Ricardo L Fernandez Ruiz, Alvaro M Quintero Ossa, Fernando G Manzur Jatin, Aristides Sotomayor Herazo, Jeffrey Castellanos Parada, Rafael Suarez Arambula, Miguel A Urina Triana, Angela M Fernandez Trujillo, Maja Strozzi, Siniša Car, Melita Jerić, Davor Miličić, Martina Lovrić Benčić, Hrvoje Pintarić, Đeiti Prvulović, Jozica Šikić, Viktor Peršić, Dean Mileta, Kresimir Štambuk, Zdravko Babić, Vjekoslav Tomulic, Josip Lukenda, Stanka Mejic-Krstulovic, Boris Starcevic, Jindrich Spinar, David Horak, Zdenek Velicka, Josef Stasek, David Alan, Vilma Machova, Ales Linhart, Vojtech Novotny, Vladimir Kaucak, Richard Rokyta, Robert Naplava, Zdenek Coufal, Vera Adamkova, Ivo Podpera, Jiri Zizka, Zuzana Motovska, Ivana Marusincova, Premysl Svab, Petr Heinc, Jiri Kuchar, Petr Povolny, Jiri Matuska, Steen H Poulsen, Bent Raungaard, Peter Clemmensen, Lia E Bang, Ole May, Morten Bøttcher, Jens D Hove, Lars Frost, Gunnar Gislason, John Larsen, Peter Betton Johansen, Flemming Hald, Peter Johansen, Jørgen Jeppesen, Tonny Nielsen, Kjeld S Kristensen, Piotr Maria Walichiewicz, Jens D Lomholdt, Ib C Klausen, Peter Kaiser Nielsen, Flemming Davidsen, Lars Videbaek, Mai Soots, Veiko Vahula, Anu Hedman, Üllar Soopõld, Kaja Märtsin, Tiina Jurgenson, Arved Kristjan, Juhani K Airaksinen, Saila Vikman, Heikki Huikuri, Pierre Coste, Emile Ferrari, Olivier Morel, Gilles Montalescot, Jacques Machecourt, Gilles Barone-Rochette, Jacques Mansourati, Yves Cottin, Florence Leclercq, Abdelkader Belhassane, Nicolas Delarche, Franck Boccara, Franck Paganelli, Jérôme Clerc, Francois Schiele, Victor Aboyans, Vincent Probst, Jacques Berland, Thierry Lefèvre, Bernard Citron, Irakli Khintibidze, Tamaz Shaburishvili, Zurab Pagava, Ramaz Ghlonti, Zaza Lominadze, George Khabeishvili, Rayyan Hemetsberger, Kemala Edward, Ursula Rauch-Kröhnert, Matthias Stratmann, Karl-Friedrich Appel, Ekkehard Schmidt, Heyder Omran, Christoph Stellbrink, Thomas Dorsel, Emmanouil Lianopoulos, Hans Friedrich Vöhringer, Roger Marx, Andreas Zirlik, Detlev Schellenberg, Thomas Heitzer, Ulrich Laufs, Christian Werner, Nikolaus Marx, Stephan Gielen, Sebastian Nuding, Bernhard Winkelmann, Steffen Behrens, Karsten Sydow, Mahir Karakas, Gregor Simonis, Thomas Muenzel, Nikos Werner, Stefan Leggewie, Dirk Böcker, Rüdiger Braun-Dullaeus, Nicole Toursarkissian, Michael Jeserich, Matthias Weißbrodt, Tim Schaeufele, Joachim Weil, Heinz Völler, Johannes Waltenberger, Mohammed Natour, Susanne Schmitt, Dirk Müller-Wieland, Stephan Steiner, Lothar Heidenreich, Elmar Offers, Uwe Gremmler, Holger Killat, Werner Rieker, Sotiris Patsilinakos, Athanasios Kartalis, Athanassios Manolis, Dimitrios Sionis, Geargios Chachalis, Ioannis Skoumas, Vasilios Athyros, Panagiotis Vardas, Frangkiskos Parthenakis, Dimitrios Alexopoulos, Georgios Hahalis, John Lekakis, Apostolos Hatzitolios, Sergio R Fausto Ovando, Juan L Arango Benecke, Edgar R Rodriguez De Leon, Bryan P Y Yan, David C W Siu, Tibor Turi, Bela Merkely, Imre Ungi, Geza Lupkovics, Lajos Nagy, András Katona, István Édes, Gábor Müller, Iván Horvath, Tibor Kapin, Zsolt Szigeti, József Faluközy, Mukund Kumbla, Manjinder Sandhu, Sharath Annam, Naveen Reddy Proddutur, Reddy Regella, Rajendra K Premchand, Ajaykumar Mahajan, Sudhir Pawar, Atul D Abhyanakar, Prafulla Kerkar, Ravishankar A Govinda, Abraham Oomman, Dhurjati Sinha, Sachin N Patil, Dhiman Kahali, Jitendra Sawhney, Abhijeet B Joshi, Sanjeev Chaudhary, Pankaj Harkut, Santanu Guha, Sanjay Porwal, Srimannarayana Jujjuru, Ramesh B Pothineni, Minguel R Monteiro, Aziz Khan, Shamanna S Iyengar, Jasprakash Singh Grewal, Manoj Chopda, Mahesh C Fulwani, Aparna Patange, Patil Sachin, Vijay K Chopra, Naresh K Goyal, Rituparna Shinde, Gajendra V Manakshe, Nitin Patki, Sumeet Sethi, Vengatesh Munusamy, Sunil Karna, Sunil Thanvi, Srilakshmi Adhyapak, Chandrakant Patil, Ulhas Pandurangi, Rishabh Mathur, Jugal Gupta, Suhas Kalashetti, Ajit Bhagwat, Bagirath Raghuraman, Shiv Kumar Yerra, Prasant Bhansali, Rohidas Borse, Patil Rahul, Srihari Das, Vinay Kumar, Jabir Abdullakutty, Shireesh Saathe, Priya Palimkar, Shireesh Sathe, Shaul Atar, Michael Shechter, Morris Mosseri, Yaron Arbel, Chorin Ehud, Havakuk Ofer, Chaim Lotan, Uri Rosenschein, Amos Katz, Yaakov Henkin, Adi Francis, Marc Klutstein, Eugenia Nikolsky, Robert Zukermann, Yoav Turgeman, Majdi Halabi, Alon Marmor, Ran Kornowski, Michael Jonas, Offer Amir, Yonathan Hasin, Yoseph Rozenman, Shmuel Fuchs, Vered Zvi, Osamah Hussein, Dov Gavish, Zvi Vered, Yoseph Caraco, Mazen Elias, Naveh Tov, Efrat Wolfovitz, Michael Lishner, Nizar Elias, Giancarlo Piovaccari, Annamaria De Pellegrin, Raffaella Garbelotto, Gabriele Guardigli, Valgimigli Marco, Giovanni Licciardello, Carla Auguadro, Filippo Scalise, Claudio Cuccia, Alessandro Salvioni, Giuseppe Musumeci, Michelle Senni, Paolo Calabrò, Salvatore Novo, Pompilio Faggiano, Marco Metra, Nicoletta B De Cesare, Sergio Berti, Claudio Cavallini, Enrico Puccioni, Marcello Galvani, Maurizio Tespili, Piermarco Piatti, Michela Palvarini, Giuseppe De Luca, Roberto Violini, Alessandro De Leo, Zoran Olivari, Pasquale Perrone Filardi, Maurizio Ferratini, Vittorio Racca, Kazuoki Dai, Yuji Shimatani, Haruo Kamiya, Kenji Ando, Yoshihiro Takeda, Yoshihiro Morino, Yoshiki Hata, Kazuo Kimura, Koichi Kishi, Ichiro Michishita, Hiroki Uehara, Toshinori Higashikata, Atsushi Hirayama, Keiji Hirooka, Yasuji Doi, Satoru Sakagami, Shuichi Taguchi, Akihiro Koike, Hiroyuki Fujinaga, Shinji Koba, Ken Kozuma, Tomohiro Kawasaki, Yujiro Ono, Masatoshi Shimizu, Yousuke Katsuda, Atsuyuki Wada, Toshiro Shinke, Takeshi Kimura, Junya Ako, Kenshi Fujii, Toshiyuki Takahashi, Tomohiro Sakamoto, Koichi Nakao, Yutaka Furukawa, Hiroshi Sugino, Ritsu Tamura, Toshiaki Mano, Masaaki Uematsu, Noriaki Utsu, Kashima Ito, Takuya Haraguchi, Katsuhiko Sato, Yasunori Ueda, Akira Nishibe, Kazuteru Fujimoto, Motomaru Masutani, Jung Han Yoon, Hack-Lyoung Kim, Hun Sik Park, In-Ho Chae, Moo Hyun Kim, Myung Ho Jeong, Seungwoon Rha, Chongjin Kim, Hyo-Soo Kim, Hae Young Kim, Taekjong Hong, Seung-Jea Tahk, Youngkwon Kim, Arija Busmane, Natalija Pontaga, Aldis Strelnieks, Iveta Mintale, Iveta Sime, Zaneta Petrulioniene, Roma Kavaliauskiene, Ruta Jurgaitiene, Gintare Sakalyte, Rimvydas Slapikas, Sigute Norkiene, Nerijus Misonis, Aleksandras Kibarskis, Raimondas Kubilius, Stojko Bojovski, Nensi Lozance, Aleksandar Kjovkaroski, Snezana Doncovska, Tiong Kiam Ong, Sazzli Kasim, Oteh Maskon, Balachandran Kandasamy, Houng B Liew, Wan Mohd Izani Wan Mohamed, Armando García Castillo, Jorge Carrillo Calvillo, Pedro Fajardo Campos, Juan Carlos Núñez Fragoso, Edmundo Alfredo Bayram Llamas, Marco Antonio Alcocer Gamba, Jaime Carranza Madrigal, Luis Gerardo González Salas, Enrique López Rosas, Belinda González Díaz, Eduardo Salcido Vázquez, Alfredo Nacoud Ackar, Guillermo Antonio Llamas Esperón, Carlos Rodolfo Martínez Sánchez, María Guerrero De Leon, Rodrigo Suarez Otero, Guillermo Fanghänel Salmón, Jesús Antonio Pérez Ríos, José Angel Garza Ruíz, Robert W Breedveld, Margriet Feenema-Aardema, Alida Borger-Van Der Burg, Pieter A M Hoogslag, Harry Suryapranata, Antonius Oomen, Paulus Van Haelst, Jacobijne J Wiersma, Dirk Basart, Ruud M A Van Der Wal, Peter Zwart, Pascalle Monraats, Henricus Van Kesteren, Ioannis Karalis, Johan Jukema, Gerardus J E Verdel, Bart R G Brueren, Roland P T Troquay, Eric P Viergever, Nadea Y Y Al-Windy, Gerard L Bartels, Jan H Cornel, Walter R M Hermans, Johannes P R Herrman, Robert J Bos, Reginald G E J Groutars, Coenraad C Van Der Zwaan, Refik Kaplan, Raymond Lionarons, Eelko Ronner, Bjorn E Groenemeijer, Patrick N A Bronzwaer, Anho A H Liem, Bernard J W M Rensing, Marcel J J A Bokern, Remco Nijmeijer, Ferry M R J Hersbach, Frank F Willems, Antonius T M Gosselink, Saman Rasoul, John Elliott, Gerard Wilkins, Raewyn Fisher, Douglas Scott, Hamish Hart, Ralph Stewart, Scott Harding, Ian Ternouth, Nicholas Fisher, Samuel Wilson, Denise Aitken, Russell Anscombe, Laura Davidson, Tadeusz Tomala, Ottar Nygård, Jon Arne Sparby, Kjell Andersen, Lars Gullestad, Jarle Jortveit, Peter S Munk, Erlend Gyllensten Singsaas, Ulf Hurtig, Jorge R Calderon Ticona, Julio R Durand Velasquez, Sandra A Negron Miguel, Enrique S Sanabria Perez, Jesus M Carrion Chambilla, Carlos A Chavez Ayala, Reynaldo P Castillo Leon, Rolando J Vargas Gonzales, Jose D Hernandez Zuniga, Luis A Camacho Cosavalente, Jorge E Bravo Mannucci, Javier Heredia Landeo, Nassip C Llerena Navarro, Yudy M Roldan Concha, Víctor E Rodriguez Chavez, Henry A Anchante Hernandez, Carlos A Zea Nunez, Walter Mogrovejo Ramos, Arthur Ferrolino, Rosa Allyn G Sy, Louie Tirador, Rody G Sy, Generoso Matiga, Raul Martin Coching, Alisa Bernan, Gregorio Rogelio, Dante D Morales, Edgar Tan, Dennis Jose Sulit, Adrian Wlodarczak, Krystyna Jaworska, Grzegorz Skonieczny, Lidia Pawlowicz, Pawel Wojewoda, Benita Busz-Papiez, Janusz Bednarski, Aleksander Goch, Pawel Staneta, Elzbieta Dulak, Krzysztof Saminski, Wlodzimierz Krasowski, Wanda Sudnik, Aleksander Zurakowski, Marcin Skorski, Beata Miklaszewicz, Jacek Kubica, Jan Andrzej Lipko, Edyta Kostarska-Srokosz, Marek Piepiorka, Anna Drzewiecka, Ryszard Sciborski, Arkadiusz Stasiewski, Tomasz Blicharski, Leszek Bystryk, Michal Szpajer, Marek Korol, Tomasz Czerski, Ewa Mirek-Bryniarska, Jacek Gniot, Andrzej Lubinski, Jerzy Gorny, Edward Franek, Grzegorz Raczak, Hanna Szwed, Pedro Monteiro, Jose Mesquita Bastos, Helder H Pereira, Dinis Martins, Filipe Seixo, Carlos Mendonça, Ana Botelho, Francisca Caetano, Bogdan Minescu, Octavian Istratoaie, Dan N Tesloianu, Gabriel Cristian, Silviu Dumitrescu, Cristian G C Podoleanu, Mircea C A Constantinescu, Cristina M Bengus, Constantin Militaru, Doina Rosu, Irinel R Parepa, Adrian V Matei, Tom M Alexandru, Mihaela Malis, Ioan Coman, Rodica Stanescu-Cioranu, Doina Dimulescu, Yury Shvarts, Olga Orlikova, Zhanna Kobalava, Olga L Barbarash, Valentin Markov, Nadezhda Lyamina, Alexander Gordienko, Konstantin Zrazhevsky, Alexander Y Vishnevsky, Victor Gurevich, Raisa Stryuk, Nikita V Lomakin, Igor Bokarev, Tatiana Khlevchuk, Sergey Shalaev, Larisa Khaisheva, Petr Chizhov, Inna Viktorova, Natalya Osokina, Vladimir Shchekotov, Evgenia Akatova, Galina Chumakova, Igor Libov, Mikhail I Voevoda, Tatyana V Tretyakova, Evgeny Baranov, Sergey Shustov, Sergey Yakushin, Ivan Gordeev, Niiaz Khasanov, Olga Reshetko, Tatiana Sotnikova, Olga Molchanova, Konstantin Nikolaev, Liudmila Gapon, Elena Baranova, Zaur Shogenov, Elena Kosmachova, Yuriy Karpov, Anton Povzun, Liudmila Egorova, Vadim V Tyrenko, Igor G Ivanov, Masterov Ilya, Sergey Kanorsky, Dragan Simic, Nikola Ivanovic, Goran Davidovic, Nebojsa Tasic, Milika R Asanin, Stevo Stojic, Svetlana R Apostolovic, Stevan Ilic, Biljana Putnikovic Tosic, Aleksandar Stankovic, Aleksandra Arandjelovic, Slavica Radovanovic, Branislava Todic, Jovan Balinovac, Dragan V Dincic, Petar Seferovic, Ana Karadzic, Slobodan Dodic, Sinisa Dimkovic, Tamara Jakimov, Kian-Keong Poh, Hean Yee Ong, Justin Tang I-Shing, Karol Micko, Jan Nociar, Daniel Pella, Peter Fulop, Marian Hranai, Juraj Palka, Juraj Mazur, Ivan Majercák, Andrej Dzupina, František Fazekas, Jozef Gonsorcik, Viliam Bugan, Juraj Selecky, Gabriel Kamensky, Jaroslava Strbova, Rudolf Smik, Andrej Dukat, Peter Olexa, Ivan Žuran, Janez Poklukar, Nataša Černič Šuligoj, Matija Cevc, Henry P Cyster, Naresh Ranjith, Clive Corbett, Junaid Bayat, Ellen Makoali Makotoko, Hendrik du Toit Theron, Ilse E Kapp, Matthys M de V Basson, Hanlie Lottering, Dina Van Aswegen, Louis J Van Zyl, Peter J Sebastian, Thayabran Pillay, Jan A Saaiman, Patrick J Commerford, Soraya Cassimjee, Garda Riaz, Iftikhar O Ebrahim, Mahomed Sarvan, Joseph H Mynhardt, Helmuth Reuter, Rajendran Moodley, Manuel Vida, Angel R Cequier Fillat, Vicente Bodí Peris, Francisco Fuentes Jimenez, Francisco Marín, Jose M Cruz Fernández, Rafael Jesus Hidalgo Urbano, Blas Gil-Extremera, Pablo Toledo, Fernando Worner Diz, David Garcia-Dorado, Andres Iñiguez, José Tuñón Fernández, Jose R Gonzalez-Juanatey, Javier Fernandez Portales, Fernando Civeira Murillo, Laia Matas Pericas, Jose Luis Zamorano, Manuel De Mora Martin, Jordi Bruguera Cortada, Joaquin J Alonso Martin, Jose Maria Serrano Antolin, José R De Berrazueta Fernández, José Antonio Vázquez de Prada, Jose Francisco Díaz Fernández, José Alberto García Lledó, Juan Cosín Sal

Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol

International audienceBackground: Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk.Objectives: In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels.Methods: ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was 13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% CI: 0.72-0.92) and 0.89 (95% CI: 0.75-1.06), with Pinteraction = 0.43.Conclusions: In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402)

Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial

Background After acute coronary syndrome, diabetes conveys an excess risk of ischaemic cardiovascular events. A reduction in mean LDL cholesterol to 1.4-1.8 mmol/L with ezetimibe or statins reduces cardiovascular events in patients with an acute coronary syndrome and diabetes. However, the efficacy and safety of further reduction in LDL cholesterol with an inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) after acute coronary syndrome is unknown. We aimed to explore this issue in a prespecified analysis of the ODYSSEY OUTCOMES trial of the PCSK9 inhibitor alirocumab, assessing its effects on cardiovascular outcomes by baseline glycaemic status, while also assessing its effects on glycaemic measures including risk of new-onset diabetes

Apolipoprotein B, Residual Cardiovascular Risk After Acute Coronary Syndrome, and Effects of Alirocumab.

Background: Apolipoprotein B (apoB) provides an integrated measure of atherogenic risk. Whether apoB levels and apoB lowering hold incremental predictive information on residual risk after acute coronary syndrome beyond that provided by low-density lipoprotein cholesterol is uncertain. Methods: The ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) compared the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome and elevated atherogenic lipoproteins despite optimized statin therapy. Primary outcome was major adverse cardiovascular events (MACE; coronary heart disease death, nonfatal myocardial infarction, fatal/nonfatal ischemic stroke, hospitalization for unstable angina). Associations between baseline apoB or apoB at 4 months and MACE were assessed in adjusted Cox proportional hazards and propensity score–matched models. Results: Median follow-up was 2.8 years. In proportional hazards analysis in the placebo group, MACE incidence increased across increasing baseline apoB strata (3.2 [95% CI, 2.9–3.6], 4.0 [95% CI, 3.6–4.5], and 5.5 [95% CI, 5.0–6.1] events per 100 patient-years in strata 35–<50, and ≤35 mg/dL, respectively). Compared with propensity score–matched patients from the placebo group, treatment hazard ratios for alirocumab also decreased monotonically across achieved apoB strata. Achieved apoB was predictive of MACE after adjustment for achieved low-density lipoprotein cholesterol or non–high-density lipoprotein cholesterol but not vice versa. Conclusions: In patients with recent acute coronary syndrome and elevated atherogenic lipoproteins, MACE increased across baseline apoB strata. Alirocumab reduced MACE across all strata of baseline apoB, with larger absolute reductions in patients with higher baseline levels. Lower achieved apoB was associated with lower risk of MACE, even after accounting for achieved low-density lipoprotein cholesterol or non–high-density lipoprotein cholesterol, indicating that apoB provides incremental information. Achievement of apoB levels as low as ≤35 mg/dL may reduce lipoprotein-attributable residual risk after acute coronary syndrome. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01663402.gov; Unique identifier: NCT01663402.URL: https://www