Posters 26 - 29 May, 2019 03. Lipids - 03.09 Managing familial hypercholesterolemia EAS19-0705. MOLECULAR ASPECTS OF HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA IN IBERO-AMERICAN COUNTRIES A.C. Alves 1, 2 , R. Alonso 3 , A. Cuevas 3 , A. Medeiros Margarida 1, 2 , A. Pereira C 4 , C. Jannes E 4 , E. J. Krieger 4 , R. Arroyo 5 , L. Schreier 6 , P. Corral 7 , V. Ba~ nares G 8 , M. Araujo 9 , S. Asenjo 10 , M. Stoll 11 , N. Dell'Oca 11 , X. Reyes 11 , A. Ressia 11 , R. Campo 12 , A. Merchan 13 , M. Maga~ na-Torres Teresa 14 , A. Vasques-Cardenas N 15 , P. Mata 5 , R. Santos 16 , M. Bourbon 1, 2 . 1 Instituto Nacional de Saúde Doutor Ricardo Jorge- Lisboa- Portugal, Departamento de Promoç~ ao da Saúde e Prevenç~ ao de Doenças N~ ao Transmissíveis- Unidade de I&D- Grupo de Investigaç~ ao Cardiovascular, Lisboa, Portugal; 2 Faculdade de Ci^ encias - Universidade de Lisboa, BioISId Biosystems & Integrative Sciences Institute, Lisboa, Portugal; 3 Clinica Las Condes, Departamento de Nutricion, Santiago, Chile; 4 University of S~ ao Paulo Medical School Hospital, Laboratory of Genetics and Molecular Cardiology- Heart Institute InCor, S~ ao Paulo, Brazil; 5 Fundacion Hipercolesterolemia Familiar, Fundacion Hipercolesterolemia Familiar, Madrid, Spain; 6 Facultad de Farmacia y Bioquimica- Universidad de Buenos Aires, Departamento de Bioquimica Clinica- Laboratorio de Lipidos y Aterosclerosis-, Buenos Aires, Argentina; 7 Facultad de Medicina- Universidad FASTA, Departamento Investigacion, Buenos Aires, Argentina; 8 Administracion Nacional de Laboratorios e Institutos de Salud "Dr Carlos Malbran’’, Centro Nacional de Genetica Medica, Buenos Aires, Argentina; 9 Facultad de Medicina - Universidad FASTA, Departamento Investigacion, Buenos Aires, Argentina; 10 Universidad Concepci on, Facultad Medicina, Chacabuco S/n concepci on, Chile; 11 Comision Honoraria de Salud Cardiovascular, Programa GENYCO- Laboratorio de Genetica Molecular, Montevideo, Uruguay; 12 Fundaci on Cardiovascular de Colombia, Cardiologia, Bogota, Colombia; 13 Fundacion Clinica SHAIO, Cardiologia, Bogota, Colombia; 14 Instituto Mexicano del Seguro Socia, Centro de Investigacion Biomedica del Occidente, Guadalajara, Mexico; 15 Universidad Autonoma de Guadalajara, Facultad de Medicina Zapopan, Guadalajara, Mexico; 16 University of Sao Paulo Medical School Hospital, Lipid Clinic Heart Institute InCor, S~ ao Paulo, Brazil Background and Aims: Homozygous Familial Hypercholesterolemia (HoFH) is a rare disorder, affecting 1 in 300,000 to 1,000,000 people in the general population. It is estimated that there are 600 to 1,800 HoFH in the Ibero-America, most of them not diagnosed and/or not treated adequately. The objective of this work is to describe molecular characteristics of HoFH diagnosis in Argentina, Brazil, Chile, Colombia, Mexico, Portugal, Spain, and Uruguay. Methods: Descriptive analysis of country data related to homozygous patients (clinical molecular). Patients with bi allelic mutations in LDLR; APOB; PCSK9 and LDLRAP1 were included. Results: The study population consists of 134 clinically defined HoFH in- dividuals 80 adults and 54 children/teenagers. Genetic characterization was available for all except 5 subjects. The great majority (88%) consists of true HoFH with mutations in LDLR gene. Only 1 true homozygote for APOB mutation was found and only 1 homozygote for PCSK9 (compound het- erozygote). Five patients with autosomal recessive hypercholesterolemia were also found, all true homozygotes. From the list of 47 variants found in homozygous patients, 13 are classified as variants of unknown significance but 7 were found in severe true HoFH patients; these variants are therefor likely to be pathogenic. Conclusions: A large number of Homozygous FH patients, especially children/teenagers, are reported here although this only represent 1/5 of the at least 600 homozygous expected in Iberoamerica. It is necessary to continue the efforts to identify clinically and genetically these patients in order to improve their prognosis. Posters 26 - 29 May, 2019 03. Lipids - 03.09 Managing familial hypercholesterolemia EAS19-0713. HIGHER EXPRESSION OF GENES RELATED TO T- AND B-CELL PATHWAYS IN PBMCS FROM CHILDREN WITH VERSUS WITHOUT FAMILIAL HYPERCHOLESTEROLEMIA: A CROSS-SECTIONAL STUDY I. Narverud 1, 2 , J.J. Christensen 1, 2 , S.S. Bakke 3 , S.M. Ulven 2 , A. Rundblad 2 , P. Aukrust 4,5, 6, 7 , T. Espevik 3 , M.P. Bogsrud 1, 8 , K. Retterstøl 2, 9 , T. Ueland 4, 6, 7 , B. Halvorsen 4, 6, 7 , K.B. Holven 1, 2 . 1 Norwegian National Advisory Unit on Familial Hypercholesterolemia-, Department of Endocrinology- Morbid Obesity and Preventive Medicine- Oslo University Hospital, Oslo, Norway; 2 Department of Nutrition-, Institute of Basic Medical Sciences- University of Oslo, Oslo, Norway; 3 Center of Molecular Inflammation Research-, Department of Clinical Research and Molecular Medicine- Norwegian University of Science and Technology, Trondheim, Norway; 4 Research Institute for Internal Medicine-, Oslo University Hospital, Oslo, Norway; 5 Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Oslo, Norway; 6 K.G. Jebsen Inflammatory Research Center, Institute of Clinical medicine- University of Oslo, Oslo, Norway; 7 Institute of Clinical Medicine-, University of Oslo, Oslo, Norway; 8 Unit for Cardiac and Cardiovascular Genetics-, Oslo University Hospital, Oslo, Norway; 9 Lipid Clinic, Department of Endocrinology- Morbid Obesity and Preventive Medicine- Oslo University Hospital, Oslo, Norway Background and Aims: Subjects with familial hypercholesterolemia (FH) display high total and low-density lipoprotein (LDL)-cholesterol leading to accelerated atherosclerosis and premature coronary heart disease (CHD). Previously, we have shown higher intima-media thickness and systemic inflammation in FH versus control children. The aim was to perform an immune gene expression analysis in children with and without FH to explore the immunological pathways involved in early atherosclerosis. Methods: Expression analysis of immunological genes in peripheral blood mononuclear cells (PBMCs) from non-statin treated children with (n¼30) and without (n¼21) FH was performed with nCounter GX Human Immunology Kit v2 on the nCounter ® analysis system (Nanostring Technologies). Genes were thereafter categorized into pathways based on their function. Results: Of 594 targets, 93 genes were differentially expressed between children with and without FH (FDR < 5%). In FH versus control children, the main pathways related to these genes were (higher expressed genes/genes changed): apoptosis (3/7); B-cells (5/6); T-cells (18/19); TNF super family (6/8); antigen presentation (1/7); cell growth, proliferation and differen- tiation (5/7); interleukins (5/9); toll like receptors (2/5). Adjusting for LDL- cholesterol mostly attenuated or neutralized the significant differences. Conclusions: Children with FH had higher expression level of genes related to B-cell and T-cell pathways in PBMCs compared with control children, indicating a role of these cells in early atherosclerosis. Also, LDL- cholesterol seems to be the main driver of these immunological genes in these FH children. Posters 26 - 29 May, 2019 03. Lipids - 03.09 Managing familial hypercholesterolemia EAS19-0718. TREATMENT WITH PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 INHIBITORS (PCSK9-I) IN CLINICAL ROUTINE e NEW DATA REGARDING FAMILIAL HYPERCHOLESTEROLAEMIA (FH) GENOTYPE SAFETY AND EFFICACY F. Schumann , T. Hollstein, E. Steinhagen-Thiessen, U. Kassner. Charit e Universit€ atsmedizin Berlin, Stoffwechselcentrum Lipidclinic, Berlin, Germany Background and Aims: The aim of this study is to provide new safety and effectivity data of PCSK9-I with focus on the FH genotype in a “real-world” cohort. Methods: We recruited 134 patients receiving PCSK9-I who had been genetically tested for FH. Our patients had a high or very high cardiovas- cular risk unable to reach low-density lipoprotein cholesterol (LDL-C) goal under maximal conventional lipid-lowering therapy. They were treated with either Alirocumab (75/ 150 mg) or Evolocumab (140mg). Blood was Abstracts / Atherosclerosis 287 (2019) e123ee288 e215