Impact of conducting a genetic study on the management of familial hypercholesterolemia

Background: Clinically diagnosed familial hypercholesterolemia (FH) may require a genetic test (GT) to confirm diagnosis. GT availability/accessibility is resource-dependent and usually restricted to specialized clinics. While GT has a diagnostic value, it has not yet defined its impact on long-term man-agement and prognosis of FH.Objective: The aim was to identify the clinical characteristics associated with the request for a GT in suspected heterozygous FH. Methods: Retrospective study including adult patients with clinically suspected to be FH. Positive GT (GT +) was defined as having a pathogenic/likely pathogenic variant. Patients were stratified based on whether they had a genetic study conducted, and among those with a genetic study, according to those who did or did not have a GT +. Results: From 4854 patients included, 3090 were performed a GT (GT +: 2113). Median follow-up: 6.2 years. A younger age, FH-related physical signs, premature coronary disease, higher low-density lipoprotein cholesterol (LDLc) and lower body mass index and triglycerides, associated higher odds of being conducted a genetic study. These patients had higher baseline LDLc (252 mg/dL vs. 211 mg/dL among clinically diagnosed patients) and experienced larger reductions over the follow-up (157.7 mg/dL vs. 113.5 mg/dL, respectively). A similar pattern was observed among patients with GT+ (vs. negative GT). LDLc target attainment was low but increased to 66-95% when a triple combination with statin/ezetimibe/proprotein convertase subtilisin kexin type 9-inhibitor was used. Cardiovascular events occurred in 3.2% and 3.1% of patients who conducted/not conducted a genetic study. Patients conducted a genetic analysis and those with GT+ tended to present the events earlier. Conclusions: Genetic study, vs. having a clinical-only diagnosis, impacts the management of FH. Cardiovascular prognosis was similar in both groups, perhaps as a result of the more intensive management of patients with a genetic study. (c) 2023 National Lipid Association. Published by Elsevier Inc. All rights reserved.