Population Genomic Screening and Improved Lipid Management in Patients With Familial Hypercholesterolemia

作者：Matthew E. Levy, Kelly M. Schiabor Barrett, Megan Betts, David Kann, Alexandre Bolze, Basil Khuder, Natalie Telis, Lisa M. McEwen, Amy C. Sturm, Chad Haldeman‐Englert, Jeremy Cauwels, Douglas Stoller, C. Anwar A. Chahal, Christopher N. Chapman, Ashley Waring, Douglas A. Olson, Joseph J. Grzymski, Nicole Washington, William Lee, Elizabeth T. Cirulli, Catherine Hajek · 发表于：Circulation Genomic and Precision Medicine · 年份：2025 · DOI：10.1161/circgen.125.005206 · 被引用次数：1 · 研究领域：Lipoproteins and Cardiovascular Health、Genetic Associations and Epidemiology、Lipid metabolism and disorders

BACKGROUND: The Helix Research Network program is a large population genomics initiative that screens an all-comers population of patients for Centers for Disease Control and Prevention Tier 1 genetic conditions, including familial hypercholesterolemia (FH). We evaluated changes in clinical management and low-density lipoprotein cholesterol (LDL-C) levels among patients we identified to have FH. METHODS: Participants across 9 US 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. RESULTS: Among 228 602 adults enrolled between 2017 to 2025, 1155 (≈1/198) had a pathogenic FH variant in LDLR (74%), APOB (25%), or PCSK9 (1%). Of the 622 with retrospective and prospective electronic health record data available (mean of 11.8 and 2.1 years, respectively), 84% 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 (57% versus 17% for those without documentation; P <0.001). Patients with new/modified therapies had a mean LDL-C reduction of 52 mg/dL, compared with 20 mg/dL in patients with no therapeutic change (difference=32 mg/dL; P <0.001). CONCLU...