doi:10.1016/j.rec.2020.06.003engLamiquiz-Moneo, ItziarCiveira, FernandoMateo-Gallego, RocíoLaclaustra, MartínMoreno-Franco, BelénTejedor, María TeresaPalacios, LourdesMartín, CésarCenarro, AnaDiagnostic yield of sequencing familial hypercholesterolemia genes in individuals with primary hypercholesterolemiaART-2021-131159Introduction and objectives: Our objective was to approximate the prevalence of mutations in candidate genes for familial hypercholesterolemia (FH) in a middle-aged Spanish population and to establish the predictive value of criteria for clinical suspicion in the detection of causative mutations. Methods: Unrelated individuals aged = 18 years from the Aragon Workers’ Health Study (AWHS) with high low-density lipoprotein cholesterol (LDL-C) and clinical suspicion of FH (participants with LDL-C concentrations above the 95th percentile, participants with premature cardiovascular disease and/or participants with high LDL-C [130 mg/dL] under statin therapy), assuming that any participant with FH exhibits at leats 1 trait, were selected and the LDLR, APOB, PCSK9, APOE, STAP1 and LDLRAP1 genes were sequenced by next generation sequencing technology. Results: Of 5400 individuals from the AWHS, 4514 had complete data on lipid levels and lipid-lowering drugs, 255 participants (5.65%) met the criteria for suspicion of FH, 24 of them (9.41%) were diagnosed with hyperlipoproteinemia(a), and 16 (6.27% of those sequenced) were found to carry causative mutations in candidate genes: 12 participants carried 11 different pathogenic LDLR alleles and 4 participants carried 1 pathogenic mutation in PCSK9. LDL-C concentrations > 220 mg/dL and LDL-C > 130 mg/dL despite statin therapy showed the strongest association with the presence of mutations (P = .011). Conclusions: Our results show that the prevalence of FH in Spain is 1:282 and suggest that the combination of high untreated LDL-C and high levels of LDL-C despite statin therapy are the best predictors of a positive FH genetic test.2021http://zaguan.unizar.es/record/14818510.1016/j.rec.2020.06.003http://zaguan.unizar.es/record/148185oai:zaguan.unizar.es:148185info:eu-repo/grantAgreement/ES/DGA/B14-7Rinfo:eu-repo/grantAgreement/ES/MINECO-ISCIII/CIBERCVinfo:eu-repo/grantAgreement/ES/MINECO/PI15-01983info:eu-repo/grantAgreement/ES/MINECO/PI18-01777Revista Española de Cardiología (English Edition) 74, 8 (2021), 664-673by-nc-ndhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccess