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

Background and aims: Familial hypercholesterolemia (FH) is an inherited disorder characterized by high levels of blood cholesterol from birth and premature coronary heart disease. Thus, the identification of FH patients is crucial to prevent or delay the onset of cardiovascular events, and the availability of a tool helping with the diagnosis in the setting of general medicine is essential to improve FH patient identification.Methods: This study evaluated the performance of the Dutch Lipid Clinic Network (DLCN) score in FH patients enrolled in the LIPIGEN study, an Italian integrated network aimed at improving the identification of patients with genetic dyslipidaemias, including FH.Results: The DLCN score was applied on a sample of 1377 adults (mean age 42.9 +/- 14.2 years) with genetic diagnosis of FH, resulting in 28.5% of the sample classified as probable FH and 37.9% as classified definite FH. Among these subjects, 43.4% had at least one missing data out of 8, and about 10.0% had 4 missing data or more. When analyzed based on the type of missing data, a higher percentage of subjects with at least 1 missing data in the clinical history or physical examination was classified as possible FH (DLCN score 3-5). We also found that using real or estimated pre-treatment LDL-C levels may significantly modify the DLCN score.Conclusions: Although the DLCN score is a useful tool for physicians in the diagnosis of FH, it may be limited by the complexity to retrieve all the essential information, suggesting a crucial role of the clinical judgement in the identification of FH subjects

Twelve Variants Polygenic Score for Low-Density Lipoprotein Cholesterol Distribution in a Large Cohort of Patients With Clinically Diagnosed Familial Hypercholesterolemia With or Without Causative Mutations

: Background A significant proportion of individuals clinically diagnosed with familial hypercholesterolemia (FH), but without any disease-causing mutation, are likely to have polygenic hypercholesterolemia. We evaluated the distribution of a polygenic risk score, consisting of 12 low-density lipoprotein cholesterol (LDL-C)-raising variants (polygenic LDL-C risk score), in subjects with a clinical diagnosis of FH. Methods and Results Within the Lipid Transport Disorders Italian Genetic Network (LIPIGEN) study, 875 patients who were FH-mutation positive (women, 54.75%; mean age, 42.47±15.00 years) and 644 patients who were FH-mutation negative (women, 54.21%; mean age, 49.73±13.54 years) were evaluated. Patients who were FH-mutation negative had lower mean levels of pretreatment LDL-C than patients who were FH-mutation positive (217.14±55.49 versus 270.52±68.59 mg/dL, P<0.0001). The mean value (±SD) of the polygenic LDL-C risk score was 1.00 (±0.18) in patients who were FH-mutation negative and 0.94 (±0.20) in patients who were FH-mutation positive (P<0.0001). In the receiver operating characteristic analysis, the area under the curve for recognizing subjects characterized by polygenic hypercholesterolemia was 0.59 (95% CI, 0.56-0.62), with sensitivity and specificity being 78% and 36%, respectively, at 0.905 as a cutoff value. Higher mean polygenic LDL-C risk score levels were observed among patients who were FH-mutation negative having pretreatment LDL-C levels in the range of 150 to 350 mg/dL (150-249 mg/dL: 1.01 versus 0.91, P<0.0001; 250-349 mg/dL: 1.02 versus 0.95, P=0.0001). A positive correlation between polygenic LDL-C risk score and pretreatment LDL-C levels was observed among patients with FH independently of the presence of causative mutations. Conclusions This analysis confirms the role of polymorphisms in modulating LDL-C levels, even in patients with genetically confirmed FH. More data are needed to support the use of the polygenic score in routine clinical practice

Spectrum of mutations in Italian patients with familial hypercholesterolemia: New results from the LIPIGEN study

Background Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by elevated plasma levels of LDL-cholesterol that confers an increased risk of premature atherosclerotic cardiovascular disease. Early identification and treatment of FH patients can improve prognosis and reduce the burden of cardiovascular mortality. Aim of this study was to perform the mutational analysis of FH patients identified through a collaboration of 20 Lipid Clinics in Italy (LIPIGEN Study). Methods We recruited 1592 individuals with a clinical diagnosis of definite or probable FH according to the Dutch Lipid Clinic Network criteria. We performed a parallel sequencing of the major candidate genes for monogenic hypercholesterolemia (LDLR, APOB, PCSK9, APOE, LDLRAP1, STAP1). Results A total of 213 variants were detected in 1076 subjects. About 90% of them had a pathogenic or likely pathogenic variants. More than 94% of patients carried pathogenic variants in LDLR gene, 27 of which were novel. Pathogenic variants in APOB and PCSK9 were exceedingly rare. We found 4 true homozygotes and 5 putative compound heterozygotes for pathogenic variants in LDLR gene, as well as 5 double heterozygotes for LDLR/APOB pathogenic variants. Two patients were homozygous for pathogenic variants in LDLRAP1 gene resulting in autosomal recessive hypercholesterolemia. One patient was found to be heterozygous for the ApoE variant p.(Leu167del), known to confer an FH phenotype. Conclusions This study shows the molecular characteristics of the FH patients identified in Italy over the last two years. Full phenotypic characterization of these patients and cascade screening of family members is now in progress

Iodine nutritional status and thyroid effects of exposure to ethylenebisdithiocarbamates

Italy is still characterized by a mild iodine deficiency and is among the most intensive users of chemical products for agriculture in Europe. The aim of this study was i) to evaluate thyroid effects of exposure to mancozeb, a fungicide widely used in agriculture, in a sample of Italian grapevine workers, and ii) to verify whether the iodine intake may modulate the risk of thyroid disruption due to the mancozeb metabolite ethylenthiourea (ETU)

[How to overcome barriers to implementation of prevention and management strategies of atherosclerotic cardiovascular disease through lipid-lowering therapy]

: Atherosclerotic cardiovascular diseases remain the main cause of mortality worldwide, due to a poor control of modifiable risk factors for atherosclerosis. High levels of low-density lipoprotein cholesterol represent the most relevant actor in the development of atherosclerotic cardiovascular diseases, as well as the main target of prevention strategies. Although lipid-lowering treatments were shown to be effective for cardiovascular prevention, several barriers (e.g. clinician reluctance to prescribe an intensive treatment, poor adherence of patients to therapy, high pharmacotherapy burden of high-risk patients and the fear for adverse events potentially associated with statins) still prevent therapy optimization. Such issues will be addressed in this review article, taking into account possible strategies for their solution, through an integrated approach including both management interventions and a larger use of the available pharmacologic options

Twelve Variants Polygenic Score for Low-Density Lipoprotein Cholesterol Distribution in a Large Cohort of Patients With Clinically Diagnosed Familial Hypercholesterolemia With or Without Causative Mutations

: Background A significant proportion of individuals clinically diagnosed with familial hypercholesterolemia (FH), but without any disease-causing mutation, are likely to have polygenic hypercholesterolemia. We evaluated the distribution of a polygenic risk score, consisting of 12 low-density lipoprotein cholesterol (LDL-C)-raising variants (polygenic LDL-C risk score), in subjects with a clinical diagnosis of FH. Methods and Results Within the Lipid Transport Disorders Italian Genetic Network (LIPIGEN) study, 875 patients who were FH-mutation positive (women, 54.75%; mean age, 42.47±15.00 years) and 644 patients who were FH-mutation negative (women, 54.21%; mean age, 49.73±13.54 years) were evaluated. Patients who were FH-mutation negative had lower mean levels of pretreatment LDL-C than patients who were FH-mutation positive (217.14±55.49 versus 270.52±68.59 mg/dL, P<0.0001). The mean value (±SD) of the polygenic LDL-C risk score was 1.00 (±0.18) in patients who were FH-mutation negative and 0.94 (±0.20) in patients who were FH-mutation positive (P<0.0001). In the receiver operating characteristic analysis, the area under the curve for recognizing subjects characterized by polygenic hypercholesterolemia was 0.59 (95% CI, 0.56-0.62), with sensitivity and specificity being 78% and 36%, respectively, at 0.905 as a cutoff value. Higher mean polygenic LDL-C risk score levels were observed among patients who were FH-mutation negative having pretreatment LDL-C levels in the range of 150 to 350 mg/dL (150-249 mg/dL: 1.01 versus 0.91, P<0.0001; 250-349 mg/dL: 1.02 versus 0.95, P=0.0001). A positive correlation between polygenic LDL-C risk score and pretreatment LDL-C levels was observed among patients with FH independently of the presence of causative mutations. Conclusions This analysis confirms the role of polymorphisms in modulating LDL-C levels, even in patients with genetically confirmed FH. More data are needed to support the use of the polygenic score in routine clinical practice

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

Background and aims: Familial hypercholesterolemia (FH) is an inherited disorder characterized by high levels of blood cholesterol from birth and premature coronary heart disease. Thus, the identification of FH patients is crucial to prevent or delay the onset of cardiovascular events, and the availability of a tool helping with the diagnosis in the setting of general medicine is essential to improve FH patient identification. Methods: This study evaluated the performance of the Dutch Lipid Clinic Network (DLCN) score in FH patients enrolled in the LIPIGEN study, an Italian integrated network aimed at improving the identification of patients with genetic dyslipidaemias, including FH. Results: The DLCN score was applied on a sample of 1377 adults (mean age 42.9 ± 14.2 years) with genetic diagnosis of FH, resulting in 28.5% of the sample classified as probable FH and 37.9% as classified definite FH. Among these subjects, 43.4% had at least one missing data out of 8, and about 10.0% had 4 missing data or more. When analyzed based on the type of missing data, a higher percentage of subjects with at least 1 missing data in the clinical history or physical examination was classified as possible FH (DLCN score 3–5). We also found that using real or estimated pre-treatment LDL-C levels may significantly modify the DLCN score. Conclusions: Although the DLCN score is a useful tool for physicians in the diagnosis of FH, it may be limited by the complexity to retrieve all the essential information, suggesting a crucial role of the clinical judgement in the identification of FH subjects

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&lt;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