Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Association of BMI, lipid-lowering medication, and age with prevalence of type 2 diabetes in adults with heterozygous familial hypercholesterolaemia: a worldwide cross-sectional study

Background: Statins are the cornerstone treatment for patients with heterozygous familial hypercholesterolaemia but research suggests it could increase the risk of type 2 diabetes in the general population. A low prevalence of type 2 diabetes was reported in some familial hypercholesterolaemia cohorts, raising the question of whether these patients are protected against type 2 diabetes. Obesity is a well known risk factor for the development of type 2 diabetes. We aimed to investigate the associations of known key determinants of type 2 diabetes with its prevalence in people with heterozygous familial hypercholesterolaemia. Methods: This worldwide cross-sectional study used individual-level data from the EAS FHSC registry and included adults older than 18 years with a clinical or genetic diagnosis of heterozygous familial hypercholesterolaemia who had data available on age, BMI, and diabetes status. Those with known or suspected homozygous familial hypercholesterolaemia and type 1 diabetes were excluded. The main outcome was prevalence of type 2 diabetes overall and by WHO region, and in relation to obesity (BMI ≥30·0 kg/m2) and lipid-lowering medication as predictors. The study population was divided into 12 risk categories based on age (tertiles), obesity, and receiving statins, and the risk of type 2 diabetes was investigated using logistic regression. Findings: Among 46 683 adults with individual-level data in the FHSC registry, 24 784 with heterozygous familial hypercholesterolaemia were included in the analysis from 44 countries. 19 818 (80%) had a genetically confirmed diagnosis of heterozygous familial hypercholesterolaemia. Type 2 diabetes prevalence in the total population was 5·7% (1415 of 24 784), with 4·1% (817 of 19 818) in the genetically diagnosed cohort. Higher prevalence of type 2 diabetes was observed in the Eastern Mediterranean (58 [29·9%] of 194), South-East Asia and Western Pacific (214 [12·0%] of 1785), and the Americas (166 [8·5%] of 1955) than in Europe (excluding the Netherlands; 527 [8·0%] of 6579). Advancing age, a higher BMI category (obesity and overweight), and use of lipid-lowering medication were associated with a higher risk of type 2 diabetes, independent of sex and LDL cholesterol. Among the 12 risk categories, the probability of developing type 2 diabetes was higher in people in the highest risk category (aged 55-98 years, with obesity, and receiving statins; OR 74·42 [95% CI 47·04-117·73]) than in those in the lowest risk category (aged 18-38 years, without obesity, and not receiving statins). Those who did not have obesity, even if they were in the upper age tertile and receiving statins, had lower risk of type 2 diabetes (OR 24·42 [15·57-38·31]). The corresponding results in the genetically diagnosed cohort were OR 65·04 (40·67-104·02) for those with obesity in the highest risk category and OR 20·07 (12·73-31·65) for those without obesity. Interpretation: Adults with heterozygous familial hypercholesterolaemia in most WHO regions have a higher type 2 diabetes prevalence than in Europe. Obesity markedly increases the risk of diabetes associated with age and use of statins in these patients. Our results suggest that heterozygous familial hypercholesterolaemia does not protect against type 2 diabetes, hence managing obesity is essential to reduce type 2 diabetes in this patient population. Funding: Pfizer, Amgen, MSD, Sanofi-Aventis, Daiichi-Sankyo, and Regeneron

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