Population genomic screening leads to improved lipid management in patients with familial hypercholesterolemia

BackgroundThe Helix Research NetworkTM program is a large population genomics initiative that screens an all-comers population of patients for CDC Tier 1 genetic conditions, including familial hypercholesterolemia (FH). We evaluated changes in clinical management and LDL cholesterol (LDL-C) levels among patients we identified to have FH. MethodsParticipants across eight U.S. health systems provided samples that underwent clinical-grade exome sequencing. Individuals with a positive screening result for a Tier 1 condition were offered no-cost genetic counseling through their health system. Using medication and laboratory testing records, we evaluated changes in patients lipid-lowering therapies and LDL-C levels. ResultsAmong 211,263 adults enrolled between 2017-2024, 1,020 ([~]1/207) had a pathogenic FH variant in LDLR (72%), APOB (27%), or PCSK9 (1%). Of the 453 with retrospective and prospective electronic health record (EHR) data available (mean of 13.6 and 2.3 years, respectively), 85% lacked a prior clinical FH diagnosis. Overall, 33% received new/modified lipid-lowering therapy within the first year, but this proportion was higher in those with a newly documented FH diagnosis code (55% vs 18% for those without documentation, p<0.001). Patients with new/modified therapies had a mean LDL-C reduction of 59 mg/dL, compared to 18 mg/dL in patients with no therapeutic change (difference=41 mg/dL, p<0.001). ConclusionsIdentification of patients with FH likely led to improvements in clinical management and LDL-C levels. EHR documentation of the diagnosis code was associated with greater likelihood of therapeutic modifications which, in turn, were associated with larger LDL-C reductions. Findings underscore the powerful potential of population genomic screening for promoting optimal lipid management in individuals with FH.