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

none724siBackground 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<0.001).Interpretation Familial hypercholesterolaemia is diagnosed late. Guideline-recommended LDL cholesterol concentrations are infrequently achieved with single-drug therapy. Cardiovascular risk factors and presence of coronary disease were lower among non-index cases, who were diagnosed earlier. Earlier detection and greater use of combination therapies are required to reduce the global burden of familial hypercholesterolaemia. Copyright (C) 2021 Elsevier Ltd. All rights reserved.mixedVallejo-Vaz, Antonio J.; Stevens, Christophe A.T.; Lyons, Alexander R.M.; Dharmayat, Kanika I.; Freiberger, Tomas; Hovingh, G. Kees; Mata, Pedro; Raal, Frederick J.; Santos, Raul D.; Soran, Handrean; Watts, Gerald F.; Abifadel, Marianne; Aguilar-Salinas, Carlos A.; Alhabib, Khalid F.; Alkhnifsawi, Mutaz; Almahmeed, Wael; Alnouri, Fahad; Alonso, Rodrigo; Al-Rasadi, Khalid; Al-Sarraf, Ahmad; Al-Sayed, Nasreen; Araujo, Francisco; Ashavaid, Tester F.; Banach, Maciej; Béliard, Sophie; Benn, Marianne; Binder, Christoph J.; Bogsrud, Martin P.; Bourbon, Mafalda; Chlebus, Krzysztof; Corral, Pablo; Davletov, Kairat; Descamps, Olivier S.; Durst, Ronen; Ezhov, Marat; Gaita, Dan; Genest, Jacques; Groselj, Urh; Harada-Shiba, Mariko; Holven, Kirsten B.; Kayikcioglu, Meral; Khovidhunkit, Weerapan; Lalic, Katarina; Latkovskis, Gustavs; Laufs, Ulrich; Liberopoulos, Evangelos; Lima-Martinez, Marcos M.; Lin, Jie; Maher, Vincent; Marais, A. David; März, Winfried; Mirrakhimov, Erkin; Miserez, André R.; Mitchenko, Olena; Nawawi, Hapizah; Nordestgaard, Børge G.; Panayiotou, Andrie G.; Paragh, György; Petrulioniene, Zaneta; Pojskic, Belma; Postadzhiyan, Arman; Raslova, Katarina; Reda, Ashraf; Reiner, Željko; Sadiq, Fouzia; Sadoh, Wilson Ehidiamen; Schunkert, Heribert; Shek, Aleksandr B.; Stoll, Mario; Stroes, Erik; Su, Ta-Chen; Subramaniam, Tavintharan; Susekov, Andrey V.; Tilney, Myra; Tomlinson, Brian; Truong, Thanh Huong; Tselepis, Alexandros D.; Tybjærg-Hansen, Anne; Vázquez Cárdenas, Alejandra; Viigimaa, Margus; Wang, Luya; Yamashita, Shizuya; Kastelein, John J.P.; Bruckert, Eric; Vohnout, Branislav; Schreier, Laura; Pang, Jing; Ebenbichler, Christoph; Dieplinger, Hans; Innerhofer, Reinhold; Winhofer-Stöckl, Yvonne; Greber-Platzer, Susanne; Krychtiuk, Konstantin; Speidl, Walter; Toplak, Hermann; Widhalm, Kurt; Stulnig, Thomas; Huber, Kurt; Höllerl, Florian; Rega-Kaun, Gersina; Kleemann, Lucas; Mäser, Martin; Scholl-Bürgi, Sabine; Säly, Christoph; Mayer, Florian J.; Sablon, Gaelle; Tarantino, Eric; Nzeyimana, Charlotte; Pojskic, Lamija; Sisic, Ibrahim; Nalbantic, Azra D.; Jannes, Cinthia E.; Pereira, Alexandre C.; Krieger, Jose E.; Petrov, Ivo; Goudev, Assen; Nikolov, Fedya; Tisheva, Snejana; Yotov, Yoto; Tzvetkov, Ivajlo; Baass, Alexis; Bergeron, Jean; Bernard, Sophie; Brisson, Diane; Brunham, Liam R.; Cermakova, Lubomira; Couture, Patrick; Francis, Gordon A.; Gaudet, Daniel; Hegele, Robert A.; Khoury, Etienne; Mancini, G.B. John; McCrindle, Brian W.; Paquette, Martine; Ruel, Isabelle; Cuevas, Ada; Asenjo, Sylvia; Wang, Xumin; Meng, Kang; Song, Xiantao; Yong, Qiang; Jiang, Tao; Liu, Ziyou; Duan, Yanyu; Hong, Jing; Ye, Pucong; Chen, Yan; Qi, Jianguang; Liu, Zesen; Li, Yuntao; Zhang, Chaoyi; Peng, Jie; Yang, Ya; Yu, Wei; Wang, Qian; Yuan, Hui; Cheng, Shitong; Jiang, Long; Chong, Mei; Jiao, Jian; Wu, Yue; Wen, Wenhui; Xu, Liyuan; Zhang, Ruiying; Qu, Yichen; He, Jianxun; Fan, Xuesong; Wang, Zhenjia; Chow, Elaine; Pećin, Ivan; Perica, Dražen; Symeonides, Phivos; Vrablik, Michal; Ceska, Richard; Soska, Vladimir; Tichy, Lukas; Adamkova, Vera; Franekova, Jana; Cifkova, Renata; Kraml, Pavel; Vonaskova, Katerina; Cepova, Jana; Dusejovska, Magdalena; Pavlickova, Lenka; Blaha, Vladimir; Rosolova, Hana; Nussbaumerova, Barbora; Cibulka, Roman; Vaverkova, Helena; Cibickova, Lubica; Krejsova, Zdenka; Rehouskova, Katerina; Malina, Pavel; Budikova, Milena; Palanova, Vaclava; Solcova, Lucie; Lubasova, Alena; Podzimkova, Helena; Bujdak, Juraj; Vesely, Jiri; Jordanova, Marta; Salek, Tomas; Urbanek, Robin; Zemek, Stanislav; Lacko, Jan; Halamkova, Hana; Machacova, Sona; Mala, Sarka; Cubova, Eva; Valoskova, Katerina; Burda, Lukas; Bendary, Ahmed; Daoud, Ihab; Emil, Sameh; Elbahry, Atef; Rafla, Samir; Sanad, Osama; Kazamel, Ghada; Ashraf, Mohamed; Sobhy, Mohamed; El-Hadidy, Amro; Shafy, Mohamed A.; Kamal, Saif; Bendary, Mohamed; Talviste, Grete; Angoulvant, Denis; Boccara, Franck; Cariou, Bertrand; Carreau, Valérie; Carrie, Alain; Charrieres, Sybil; Cottin, Yves; Di-Fillipo, Mathilde; Ducluzeau, Pierre H.; Dulong, Sonia; Durlach, Vincent; Farnier, Michel; Ferrari, Emile; Ferrieres, Dorota; Ferrieres, Jean; Gallo, Antonio; hankard, Regis; Inamo, Jocelyne; Lemale, Julie; Moulin, Philippe; Paillard, François; Peretti, Noel; Perrin, Agnès; Pradignac, Alain; Rabes, Jean P.; Rigalleau, Vincent; Sultan, Ariane; Schiele, François; Tounian, Patrick; Valero, René; Verges, Bruno; Yelnik, Cécile; Ziegler, Olivier; Haack, Ira A.; Schmidt, Nina; Dressel, Alexander; Klein, Isabel; Christmann, Jutta; Sonntag, Antonia; Stumpp, Christine; Boger, Diana; Biedermann, Dana; Usme, Monica M.N.; Beil, F. Ulrich; Klose, Gerald; König, Christel; Gouni-Berthold, Ioanna; Otte, Britta; Böll, Gereon; Kirschbaum, Anja; Merke, Jürgen; Scholl, Johannes; Segiet, Thomas; Gebauer, Marco; Predica, Florentina; Mayer, Manfred; Leistikow, Frank; Füllgraf-Horst, Sabine; Müller, Cornelius; Schüler, Melanie; Wiener, Judith; Hein, Konrad; Baumgartner, Peter; Kopf, Stefan; Busch, Reinhold; Schömig, Michael; Matthias, Stephan; Allendorf-Ostwald, Nicole; Fink, Bruno; Böhm, Dieter; Jäkel, Alexander; Koschker, Ann-Cathrin; Schweizer, Rüdiger; Vogt, Anja; Parhofer, Klaus; König, Wolfgang; Reinhard, Wibke; Bäßler, Andrea; Stadelmann, Alexander; Schrader, Volker; Katzmann, Julius; Tarr, Adrienne; Steinhagen-Thiessen, Elisabeth; Kassner, Ursula; Paulsen, Gerret; Homberger, Jürgen; Zemmrich, Claudia; Seeger, Wolfgang; Biolik, Kathrin; Deiss, Dorothee; Richter, Corinna; Pantchechnikova, Elina; Dorn, Elena; Schatz, Ulrike; Julius, Ulrich; Spens, Antje; Wiesner, Tobias; Scholl, Michael; Rizos, Christos V.; Sakkas, Nikolaos; Elisaf, Moses; Skoumas, Ioannis; Tziomalos, Konstantinos; Rallidis, Loukianos; Kotsis, Vasileios; Doumas, Michalis; Athyros, Vasileios; Skalidis, Emmanouil; Kolovou, Genovefa; Garoufi, Anastasia; Bilianou, Eleni; Koutagiar, Iosif; Agapakis, Dimitrios; Kiouri, Estela; Antza, Christina; Katsiki, Niki; Zacharis, Evangelos; Attilakos, Achilleas; Sfikas, George; Koumaras, Charalambos; Anagnostis, Panagiotis; Anastasiou, Georgia; Liamis, George; Koutsogianni, Amalia-Despoina; Karányi, Zsolt; Harangi, Mariann; Bajnok, László; Audikovszky, Mária; Márk, László; Benczúr, Béla; Reiber, István; Nagy, Gergely; Nagy, András; Reddy, Lakshmi L.; Shah, Swarup A.V.; Ponde, Chandrashekhar K.; Dalal, Jamshed J.; Sawhney, Jitendra P.S.; Verma, Ishwar C.; Altaey, Mays; Al-Jumaily, Khalid; Rasul, Dilshad; Abdalsahib, Ali F.; Jabbar, Amer A.; Al-ageedi, Mohanad; Agar, Ruth; Cohen, Hofit; Ellis, Avishay; Gavishv, Dov; Harats, Dror; Henkin, Yaacov; Knobler, Hila; Leavit, Leah; Leitersdorf, Eran; Rubinstein, Ardon; Schurr, Daniel; Shpitzen, Shoshi; Szalat, Auryan; Casula, Manuela; Zampoleri, Veronica; Gazzotti, Marta; Olmastroni, Elena; Sarzani, Riccardo; Ferri, Claudio; Repetti, Elena; Sabbà, Carlo; Bossi, Antonio Carlo; Borghi, Claudio; Muntoni, Sandro; Cipollone, Francesco; Purrello, Francesco; Pujia, Arturo; Passaro, Angelina; Marcucci, Rossella; Pecchioli, Valerio; Pisciotta, Livia; Mandraffino, Giuseppe; Pellegatta, Fabio; Mombelli, Giuliana; Branchi, Adriana; Fiorenza, Anna Maria; Pederiva, Cristina; Werba, Josè Pablo; Parati, Gianfranco; Carubbi, Francesca; Iughetti, Lorenzo; Iannuzzi, Arcangelo; Iannuzzo, Gabriella; Calabrò, Paolo; Averna, Maurizio; Biasucci, Giacomo; Zambon, Sabina; Roscini, Anna Rita; Trenti, Chiara; Arca, Marcello; Federici, Massimo; Del Ben, Maria; Bartuli, Andrea; Giaccari, Andrea; Pipolo, Antonio; Citroni, Nadia; Guardamagna, Ornella; Bonomo, Katia; Benso, Andrea; Biolo, Gianni; Maroni, Lorenzo; Lupi, Alessandro; Bonanni, Luca; Zenti, Maria Grazia; Matsuki, Kota; Hori, Mika; Ogura, Masatsune; Masuda, Daisaku; Kobayashi, Takuya; Nagahama, Kumiko; Al-Jarallah, Mohammed; Radovic, Mirjana; Lunegova, Olga; Bektasheva, Erkayim; Khodzhiboboev, Elyor; Erglis, Andrejs; Gilis, Dainus; Nesterovics, Georgijs; Saripo, Vita; Meiere, Ruta; Upena-RozeMicena, Arta; Terauda, Elizabete; Jambart, Selim; Khoury, Petra E.; Elbitar, Sandy; Ayoub, Carine; Ghaleb, Youmna; Aliosaitiene, Urte; Kutkiene, Sandra; Kasim, Noor A.M.; Nor, Noor S.M.; Ramli, Anis S.; Razak, Suraya A.; Al-Khateeb, Alyaa; Kadir, Siti H.S.A.; Muid, Suhaila A.; Rahman, Thuhairah A.; Kasim, Sazzli S.; Radzi, Ahmad B.M.; Ibrahim, Khairul S.; Razali, Salmi; Ismail, Zaliha; Ghani, Rohana A.; Hafidz, Muhammad I.A.; Chua, Ang L.; Rosli, Marshima M.; Annamalai, Muthukkaruppan; Teh, Lay K.; Razali, Rafezah; Chua, Yung A.; Rosman, Azhari; Sanusi, Abdul R.; Murad, Nor A.A.; Jamal, A. Rahman A.; Nazli, Sukma A.; Razman, Aimi Z.; Rosman, Norhidayah; Rahmat, Radzi; Hamzan, Nur S.; Azzopardi, C.; Mehta, Roopa; Martagon, Alexandro J.; Ramirez, Gabriela A.G.; Villa, Neftali E.A.; Vazquez, Arsenio V.; Elias-Lopez, Daniel; Retana, Gustavo G.; Rodriguez, Betsabel; Macías, Jose J.C.; Zazueta, Alejandro R.; Alvarado, Rocio M.; Portano, Julieta D.M.; Lopez, Humberto A.; Sauque-Reyna, Leobardo; Herrera, Laura G.G.; Mendia, Luis E.S.; Aguilar, Humberto Garcia; Cooremans, Elizabeth R.; Aparicio, Berenice P.; Zubieta, Victoria M.; Gonzalez, Perla A.C.; Ferreira-Hermosillo, Aldo; Portilla, Nacu C.; Dominguez, Guadalupe J.; Garcia, Alinna Y.R.; Cazares, Hector E.A.; Gonzalez, Jesus R.; Valencia, Carla V.M.; Padilla, Francisco G.; Prado, Ramon M.; De los Rios Ibarra, Manuel O.; Villicaña, Ruy D.A.; Rivera, Karina J.A.; Carrera, Ricardo A.; Alvarez, Jose A.; Martinez, Jose C.A.; de los Reyes Barrera Bustillo, Manuel; Vargas, Gonzalo C.; Chacon, Roberto C.; Andrade, Mario H.F.; Ortega, Ashanty F.; Alcala, Hector G.; de Leon, Laura E.G.; Guzman, Berenice G.; Garcia, Jose J.G.; Cuellar, Juan C.G.; Cruz, Jose R.G.; Garcia, Anell Hernandez; Almada, Jesus R.H.; Herrera, Ursulo J.; Sobrevilla, Fabiola L.; Rodriguez, Eduardo M.; Sibaja, Cristina M.; Rodriguez, Alma B.M.; Oyervides, Jose C.M.; Vazquez, Daniel I.P.; Rodriguez, Eduardo A.R.; Osorio, Ma L.R.; Saucedo, Juan R.; Tamayo, Margarita T.; Talavera, Luis A.V.; Arroyo, Luis E.V.; Carrillo, Eloy A.Z.; Isara, Alphonsus; Obaseki, Darlington E.; Al-Waili, Khalid; Al-Zadjali, Fahad; Al-Zakwani, Ibrahim; Al-Kindi, Mohammed; Al-Mukhaini, Suad; Al-Barwani, Hamida; Rana, Asim; Shah, Lahore S.U.; Starostecka, Ewa; Konopka, Agnieszka; Lewek, Joanna; Bartłomiejczyk, Marcin; Gąsior, Mariusz; Dyrbuś, Krzysztof; Jóźwiak, Jacek; Gruchała, Marcin; Pajkowski, Marcin; Romanowska-Kocejko, Marzena; Żarczyńska-Buchowiecka, Marta; Chmara, Magdalena; Wasąg, Bartosz; Parczewska, Aleksandra; Gilis-Malinowska, Natasza; Borowiec-Wolna, Justyna; Stróżyk, Aneta; Woś, Marlena; Michalska-Grzonkowska, Aleksandra; Medeiros, Ana M.; Alves, Ana C.; Silva, Francisco; Lobarinhas, Goreti; Palma, Isabel; de Moura, Jose P.; Rico, Miguel T.; Rato, Quitéria; Pais, Patrícia; Correia, Susana; Moldovan, Oana; Virtuoso, Maria J.; Salgado, Jose M.; Colaço, Ines; Dumitrescu, Andreea; Lengher, Calin; Mosteoru, Svetlana; Meshkov, Alexey; Ershova, Alexandra; Rozkova, Tatiana; Korneva, Victoria; Yu, Kuznetsova T.; Zafiraki, Vitaliy; Voevoda, Mikhail; Gurevich, Victor; Duplyakov, Dmitry; Ragino, Yulia; Safarova, Maya; Shaposhnik, Igor; Alkaf, Fahmi; Khudari, Alia; Rwaili, Nawal; Al-Allaf, Faisal; Alghamdi, Mohammad; Batais, Mohammed A.; Almigbal, Turky H.; Kinsara, Abdulhalim; AlQudaimi, Ashraf H.A.; Awan, Zuhier; Elamin, Omer A.; Altaradi, Hani; Rajkovic, Natasa; Popovic, Ljiljana; Singh, Sandra; Stosic, Ljubica; Rasulic, Iva; Lalic, Nebojsa M.; Lam, Carolyn; Le, Tan J.; Siang, Eric L.T.; Dissanayake, Sanjaya; I-Shing, Justin T.; Shyong, Tai E.; Jin, Terrance C.S.; Balinth, Karin; Buganova, Ingrid; Fabryova, Lubomira; Kadurova, Michaela; Klabnik, Alexander; Kozárová, Miriam; Sirotiakova, Jana; Battelino, Tadej; Kovac, Jernej; Mlinaric, Matej; Sustar, Ursa; Podkrajsek, Katarina T.; Fras, Zlatko; Jug, Borut; Cevc, Matija; Pilcher, Gillian J.; Blom, D.J.; Wolmarans, K.H.; Brice, B.C.; Muñiz-Grijalvo, Ovidio; Díaz-Díaz, Jose L.; de Isla, Leopoldo P.; Fuentes, Francisco; Badimon, Lina; Martin, François; Lux, Angela; Chang, Nien-Tzu; Ganokroj, Poranee; Akbulut, Mehmet; Alici, Gökhan; Bayram, Fahri; Can, Levent H.; Celik, Ahmet; Ceyhan, Ceyhun; Coskun, Fatma Y.; Demir, Mesut; Demircan, Sabri; Dogan, Volkan; Durakoglugil, Emre; Dural, Ibrahim E.; Gedikli, Omer; Hacioglu, Aysa; Ildizli, Muge; Kilic, Salih; Kirilmaz, Bahadir; Kutlu, Merih; Oguz, Aytekin; Ozdogan, Oner; Onrat, Ersel; Ozer, Savas; Sabuncu, Tevfik; Sahin, Tayfun; Sivri, Fatih; Sonmez, Alper; Temizhan, Ahmet; Topcu, Selim; Tuncez, Abdullah; Vural, Mirac; Yenercag, Mustafa; Yesilbursa, Dilek; Yigit, Zerrin; Yildirim, Aytul B.; Yildirir, Aylin; Yilmaz, Mehmet B.; Atallah, Bassam; Traina, Mahmoud; Sabbour, Hani; Hay, Dana A.; Luqman, Neama; Elfatih, Abubaker; Abdulrasheed, Arshad; Kwok, See; Oca, Nicolas D.; Reyes, Ximena; Alieva, Rano B.; Kurbanov, Ravshanbek D.; Hoshimov, Shavkat U.; Nizamov, Ulugbek I.; Ziyaeva, Adolat V.; Abdullaeva, Guzal J.; Do, Doan L.; Nguyen, Mai N.T.; Kim, Ngoc T.; Le, Thanh T.; Le, Hong A.; Tokgozoglu, Lale; Catapano, Alberico L.; Ray, Kausik K.Vallejo-Vaz, Antonio J.; Stevens, Christophe A. T.; Lyons, Alexander R. M.; Dharmayat, Kanika I.; Freiberger, Tomas; Hovingh, G. Kees; Mata, Pedro; Raal, Frederick J.; Santos, Raul D.; Soran, Handrean; Watts, Gerald F.; Abifadel, Marianne; Aguilar-Salinas, Carlos A.; Alhabib, Khalid F.; Alkhnifsawi, Mutaz; Almahmeed, Wael; Alnouri, Fahad; Alonso, Rodrigo; Al-Rasadi, Khalid; Al-Sarraf, Ahmad; Al-Sayed, Nasreen; Araujo, Francisco; Ashavaid, Tester F.; Banach, Maciej; Béliard, Sophie; Benn, Marianne; Binder, Christoph J.; Bogsrud, Martin P.; Bourbon, Mafalda; Chlebus, Krzysztof; Corral, Pablo; Davletov, Kairat; Descamps, Olivier S.; Durst, Ronen; Ezhov, Marat; Gaita, Dan; Genest, Jacques; Groselj, Urh; Harada-Shiba, Mariko; Holven, Kirsten B.; Kayikcioglu, Meral; Khovidhunkit, Weerapan; Lalic, Katarina; Latkovskis, Gustavs; Laufs, Ulrich; Liberopoulos, Evangelos; Lima-Martinez, Marcos M.; Lin, Jie; Maher, Vincent; Marais, A. David; März, Winfried; Mirrakhimov, Erkin; Miserez, André R.; Mitchenko, Olena; Nawawi, Hapizah; Nordestgaard, Børge G.; Panayiotou, Andrie G.; Paragh, György; Petrulioniene, Zaneta; Pojskic, Belma; Postadzhiyan, Arman; Raslova, Katarina; Reda, Ashraf; Reiner, Željko; Sadiq, Fouzia; Sadoh, Wilson Ehidiamen; Schunkert, Heribert; Shek, Aleksandr B.; Stoll, Mario; Stroes, Erik; Su, Ta-Chen; Subramaniam, Tavintharan; Susekov, Andrey V.; Tilney, Myra; Tomlinson, Brian; Truong, Thanh Huong; Tselepis, Alexandros D.; Tybjærg-Hansen, Anne; Vázquez Cárdenas, Alejandra; Viigimaa, Margus; Wang, Luya; Yamashita, Shizuya; Kastelein, John J. P.; Bruckert, Eric; Vohnout, Branislav; Schreier, Laura; Pang, Jing; Ebenbichler, Christoph; Dieplinger, Hans; Innerhofer, Reinhold; Winhofer-Stöckl, Yvonne; Greber-Platzer, Susanne; Krychtiuk, Konstantin; Speidl, Walter; Toplak, Hermann; Widhalm, Kurt; Stulnig, Thomas; Huber, Kurt; Höllerl, Florian; Rega-Kaun, Gersina; Kleemann, Lucas; Mäser, Martin; Scholl-Bürgi, Sabine; Säly, Christoph; Mayer, Florian J.; Sablon, Gaelle; Tarantino, Eric; Nzeyimana, Charlotte; Pojskic, Lamija; Sisic, Ibrahim; Nalbantic, Azra D.; Jannes, Cinthia E.; Pereira, Alexandre C.; Krieger, Jose E.; Petrov, Ivo; Goudev, Assen; Nikolov, Fedya; Tisheva, Snejana; Yotov, Yoto; Tzvetkov, Ivajlo; Baass, Alexis; Bergeron, Jean; Bernard, Sophie; Brisson, Diane; Brunham, Liam R.; Cermakova, Lubomira; Couture, Patrick; Francis, Gordon A.; Gaudet, Daniel; Hegele, Robert A.; Khoury, Etienne; Mancini, G. B. John; Mccrindle, Brian W.; Paquette, Martine; Ruel, Isabelle; Cuevas, Ada; Asenjo, Sylvia; Wang, Xumin; Meng, Kang; Song, Xiantao; Yong, Qiang; Jiang, Tao; Liu, Ziyou; Duan, Yanyu; Hong, Jing; Ye, Pucong; Chen, Yan; Qi, Jianguang; Liu, Zesen; Li, Yuntao; Zhang, Chaoyi; Peng, Jie; Yang, Ya; Yu, Wei; Wang, Qian; Yuan, Hui; Cheng, Shitong; Jiang, Long; Chong, Mei; Jiao, Jian; Wu, Yue; Wen, Wenhui; Xu, Liyuan; Zhang, Ruiying; Qu, Yichen; He, Jianxun; Fan, Xuesong; Wang, Zhenjia; Chow, Elaine; Pećin, Ivan; Perica, Dražen; Symeonides, Phivos; Vrablik, Michal; Ceska, Richard; Soska, Vladimir; Tichy, Lukas; Adamkova, Vera; Franekova, Jana; Cifkova, Renata; Kraml, Pavel; Vonaskova, Katerina; Cepova, Jana; Dusejovska, Magdalena; Pavlickova, Lenka; Blaha, Vladimir; Rosolova, Hana; Nussbaumerova, Barbora; Cibulka, Roman; Vaverkova, Helena; Cibickova, Lubica; Krejsova, Zdenka; Rehouskova, Katerina; Malina, Pavel; Budikova, Milena; Palanova, Vaclava; Solcova, Lucie; Lubasova, Alena; Podzimkova, Helena; Bujdak, Juraj; Vesely, Jiri; Jordanova, Marta; Salek, Tomas; Urbanek, Robin; Zemek, Stanislav; Lacko, Jan; Halamkova, Hana; Machacova, Sona; Mala, Sarka; Cubova, Eva; Valoskova, Katerina; Burda, Lukas; Bendary, Ahmed; Daoud, Ihab; Emil, Sameh; Elbahry, Atef; Rafla, Samir; Sanad, Osama; Kazamel, Ghada; Ashraf, Mohamed; Sobhy, Mohamed; El-Hadidy, Amro; Shafy, Mohamed A.; Kamal, Saif; Bendary, Mohamed; Talviste, Grete; Angoulvant, Denis; Boccara, Franck; Cariou, Bertrand; Carreau, Valérie; Carrie, Alain; Charrieres, Sybil; Cottin, Yves; Di-Fillipo, Mathilde; Ducluzeau, Pierre H.; Dulong, Sonia; Durlach, Vincent; Farnier, Michel; Ferrari, Emile; Ferrieres, Dorota; Ferrieres, Jean; Gallo, Antonio; Hankard, Regis; Inamo, Jocelyne; Lemale, Julie; Moulin, Philippe; Paillard, François; Peretti, Noel; Perrin, Agnès; Pradignac, Alain; Rabes, Jean P.; Rigalleau, Vincent; Sultan, Ariane; Schiele, François; Tounian, Patrick; Valero, René; Verges, Bruno; Yelnik, Cécile; Ziegler, Olivier; Haack, Ira A.; Schmidt, Nina; Dressel, Alexander; Klein, Isabel; Christmann, Jutta; Sonntag, Antonia; Stumpp, Christine; Boger, Diana; Biedermann, Dana; Usme, Monica M. N.; Beil, F. Ulrich; Klose, Gerald; König, Christel; Gouni-Berthold, Ioanna; Otte, Britta; Böll, Gereon; Kirschbaum, Anja; Merke, Jürgen; Scholl, Johannes; Segiet, Thomas; Gebauer, Marco; Predica, Florentina; Mayer, Manfred; Leistikow, Frank; Füllgraf-Horst, Sabine; Müller, Cornelius; Schüler, Melanie; Wiener, Judith; Hein, Konrad; Baumgartner, Peter; Kopf, Stefan; Busch, Reinhold; Schömig, Michael; Matthias, Stephan; Allendorf-Ostwald, Nicole; Fink, Bruno; Böhm, Dieter; Jäkel, Alexander; Koschker, Ann-Cathrin; Schweizer, Rüdiger; Vogt, Anja; Parhofer, Klaus; König, Wolfgang; Reinhard, Wibke; Bäßler, Andrea; Stadelmann, Alexander; Schrader, Volker; Katzmann, Julius; Tarr, Adrienne; Steinhagen-Thiessen, Elisabeth; Kassner, Ursula; Paulsen, Gerret; Homberger, Jürgen; Zemmrich, Claudia; Seeger, Wolfgang; Biolik, Kathrin; Deiss, Dorothee; Richter, Corinna; Pantchechnikova, Elina; Dorn, Elena; Schatz, Ulrike; Julius, Ulrich; Spens, Antje; Wiesner, Tobias; Scholl, Michael; Rizos, Christos V.; Sakkas, Nikolaos; Elisaf, Moses; Skoumas, Ioannis; Tziomalos, Konstantinos; Rallidis, Loukianos; Kotsis, Vasileios; Doumas, Michalis; Athyros, Vasileios; Skalidis, Emmanouil; Kolovou, Genovefa; Garoufi, Anastasi

Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer

International audienc

Search for intermediate mass black hole binaries in the first observing run of Advanced LIGO

International audienceDuring their first observational run, the two Advanced LIGO detectors attained an unprecedented sensitivity, resulting in the first direct detections of gravitational-wave signals produced by stellar-mass binary black hole systems. This paper reports on an all-sky search for gravitational waves (GWs) from merging intermediate mass black hole binaries (IMBHBs). The combined results from two independent search techniques were used in this study: the first employs a matched-filter algorithm that uses a bank of filters covering the GW signal parameter space, while the second is a generic search for GW transients (bursts). No GWs from IMBHBs were detected; therefore, we constrain the rate of several classes of IMBHB mergers. The most stringent limit is obtained for black holes of individual mass 100  M⊙, with spins aligned with the binary orbital angular momentum. For such systems, the merger rate is constrained to be less than 0.93  Gpc−3 yr−1 in comoving units at the 90% confidence level, an improvement of nearly 2 orders of magnitude over previous upper limits

First low-frequency Einstein@Home all-sky search for continuous gravitational waves in Advanced LIGO data

International audienceWe report results of a deep all-sky search for periodic gravitational waves from isolated neutron stars in data from the first Advanced LIGO observing run. This search investigates the low frequency range of Advanced LIGO data, between 20 and 100 Hz, much of which was not explored in initial LIGO. The search was made possible by the computing power provided by the volunteers of the Einstein@Home project. We find no significant signal candidate and set the most stringent upper limits to date on the amplitude of gravitational wave signals from the target population, corresponding to a sensitivity depth of 48.7  [1/Hz]. At the frequency of best strain sensitivity, near 100 Hz, we set 90% confidence upper limits of 1.8×10-25. At the low end of our frequency range, 20 Hz, we achieve upper limits of 3.9×10-24. At 55 Hz we can exclude sources with ellipticities greater than 10-5 within 100 pc of Earth with fiducial value of the principal moment of inertia of 1038  kg m2

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

International audienceSpinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signal-to-noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far