Sabatel-Pérez, FernandoSánchez-Prieto, JoaquínBecerra-Muñoz, Víctor ManuelAlonso-Briales, Juan HoracioMata, PedroRodríguez-Padial, Luis2024-02-192024-02-192021-02-13http://hdl.handle.net/10668/4254http://hdl.handle.net/20.500.12105/18254The majority of familial hypercholesterolemia index cases (FH-IC) remain underdiagnosed and undertreated because there are no well-defined strategies for the universal detection of FH. The aim of this study was to evaluate the diagnostic yield of an active screening for FH-IC based on centralized analytical data. From 2016 to 2019, a clinical screening of FH was performed on 469 subjects with severe hypercholesterolemia (low-density lipoprotein cholesterol ≥220 mg/dL), applying the Dutch Lipid Clinic Network (DLCN) criteria. All patients with a DLCN ≥ 6 were genetically tested, as were 10 patients with a DLCN of 3-5 points to compare the diagnostic yield between the two groups. FH was genetically confirmed in 57 of the 84 patients with DLCN ≥ 6, with a genetic diagnosis rate of 67.9% and an overall prevalence of 12.2% (95% confidence interval: 9.3% to 15.5%). Before inclusion in the study, only 36.8% (n = 21) of the patients with the FH mutation had been clinically diagnosed with FH; after genetic screening, FH detection increased 2.3-fold (p < 0.001). The sequential, active screening strategy for FH-IC increases the diagnostic yield for FH with a rational use of the available resources, which may facilitate the implementation of FH universal and family-based cascade screening strategies.engVoRhttp://creativecommons.org/licenses/by/4.0/Familial hypercholesterolemiaGenetic screeningAtherosclerosis preventionEarly detectionHiperlipoproteinemia tipo IIPruebas genéticasAterosclerosisPrevención primariaDiagnóstico precozHumansPrevalenceConfidence IntervalsHypercholesterolemiaHyperlipoproteinemia Type IIMutationGenetic TestingLipoproteins, LDLLipidsCholesterolAttribution 4.0 International3366849410.3390/jcm100407492077-0383Journal of Clinical Medicineopen access