Amor-Salamanca, AlmudenaCastillo, SergioGonzalez-Vioque, EmilianoDominguez, FernandoQuintana, LucíaLluís-Ganella, CarlaEscudier, Juan ManuelVirues-Ortega, JavierLara-Pezzi, EnriqueAlonso-Pulpon, LuisGarcia-Pavia, Pablo2019-07-292019-07-292017-10-03J Am Coll Cardiol. 2017; 70(14):1732-17400735-1097http://hdl.handle.net/20.500.12105/7983BACKGROUND: Genetic screening programs in unselected individuals with increased levels of low-density lipoprotein cholesterol (LDL-C) have shown modest results in identifying individuals with familial hypercholesterolemia (FH). OBJECTIVES: This study assessed the prevalence of genetically confirmed FH in patients with acute coronary syndrome (ACS) and compared the diagnostic performance of FH clinical criteria versus FH genetic testing. METHODS: Genetic study of 7 genes (LDLR, APOB, PCSK9, APOE, STAP1, LDLRAP1, and LIPA) associated with FH and 12 common alleles associated with polygenic hypercholesterolemia was performed in 103 patients with ACS, age ≤65 years, and LDL-C levels ≥160 mg/dl. Dutch Lipid Clinic (DLC) and Simon Broome (SB) FH clinical criteria were also applied. RESULTS: The prevalence of genetically confirmed FH was 8.7% (95% confidence interval [CI]: 4.3% to 16.4%; n = 9); 29% (95% CI: 18.5% to 42.1%; n = 18) of patients without FH variants had a score highly suggestive of polygenic hypercholesterolemia. The prevalence of probable to definite FH according to DLC criteria was 27.2% (95% CI: 19.1% to 37.0%; n = 28), whereas SB criteria identified 27.2% of patients (95% CI: 19.1% to 37.0%; n = 28) with possible to definite FH. DLC and SB algorithms failed to diagnose 4 (44%) and 3 (33%) patients with genetically confirmed FH, respectively. Cascade genetic testing in first-degree relatives identified 6 additional individuals with FH. CONCLUSIONS: The prevalence of genetically confirmed FH in patients with ACS age ≤65 years and with LDL-C levels ≥160 mg/dl is high (approximately 9%). FH clinical algorithms do not accurately classify patients with FH. Genetic testing should be advocated in young patients with ACS and high LDL-C levels to allow prompt identification of patients with FH and relatives at risk.engAMhttp://creativecommons.org/licenses/by-nc-nd/4.0/Dutch Lipid ClinicSimon Broome criteriaCholesterolGeneticsLow-density lipoprotein cholesterolAdaptor Proteins, Signal TransducingApolipoprotein B-100Apolipoproteins ECholesterol, LDLComorbidityFemaleGenetic TestingHumansHypolipidemic AgentsMaleMiddle AgedMultifactorial InheritancePatient SelectionPrevalencePrognosisProprotein Convertase 9Receptors, LDLReproducibility of ResultsRisk AssessmentRisk FactorsSpainSterol EsteraseAcute Coronary SyndromeHyperlipoproteinemia Type IIAttribution-NonCommercial-NoDerivatives 4.0 Internacional2895833070141732-174010.1016/j.jacc.2017.08.0091558-3597Journal of the American College of Cardiologyopen access