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

Area of Science:

• Genomics
• Cardiovascular Medicine
• Genetic Screening

Background:

• The Helix Research Network program screens a large patient population for genetic conditions, including familial hypercholesterolemia (FH).
• FH is a significant risk factor for cardiovascular disease, necessitating effective management strategies.

Purpose of the Study:

• To evaluate changes in clinical management and low-density lipoprotein cholesterol (LDL-C) levels in patients identified with FH through population genomics screening.
• To assess the impact of FH diagnosis documentation on therapeutic modifications and LDL-C reduction.

Main Methods:

• Exome sequencing was performed on participants across 9 US health systems.
• Lipid-lowering therapies and LDL-C levels were evaluated using medication and laboratory testing records.
• Changes in clinical management were compared between patients with and without documented FH diagnosis codes.

Main Results:

• Among 228,602 adults, 1155 (≈1/198) had a pathogenic FH variant.
• 84% of identified FH patients lacked a prior clinical diagnosis.
• New or modified lipid-lowering therapy was received by 33% within the first year, with higher rates (57%) in those with a documented FH diagnosis code.
• Patients with new/modified therapies showed a mean LDL-C reduction of 52 mg/dL, compared to 20 mg/dL for those without changes.

Conclusions:

• Population genomic screening effectively identifies individuals with FH, leading to improved clinical management and LDL-C reduction.
• Documentation of FH diagnosis in electronic health records is associated with increased therapeutic modifications and greater LDL-C lowering.
• Genomic screening holds significant potential for optimizing lipid management in FH patients.