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

Abstract

Clinically diagnosed 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 management and prognosis of FH. The aim was to identify the clinical characteristics associated with the request for a GT in suspected heFH. 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 in those conducted/not conducted a genetic study and within the former, those who had/did not have a GT+. 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 LDLc and lower BMI and triglycerides, associated higher odds of being conducted a genetic study. These patients had higher baseline LDLc (252mg/dL vs. 211mg/dL among clinically diagnosed patients) and experienced larger reductions over the follow-up (157.7mg/dL, vs. 113.5mg/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/PCSK9-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. 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.