Enhanced identification of familial hypercholesterolemia using central laboratory algorithms

Area of Science:

• Cardiovascular Medicine
• Genetics
• Public Health

Background:

• Familial hypercholesterolemia (FH) is a common genetic disorder leading to high LDL cholesterol and early heart disease.
• Underdiagnosis and undertreatment of FH necessitate improved detection methods.

Purpose of the Study:

• To assess the effectiveness of using an LDL cholesterol cut-off (≥99.5th percentile) for identifying clinical and genetic FH.
• To investigate the underutilization of genetic testing and undertreatment in diagnosed FH patients.

Main Methods:

• Selected individuals with elevated LDL cholesterol from a large laboratory database.
• Phased approach: biochemical validation, clinical FH identification, and genetic determination.
• Utilized lipid profiles, questionnaires, and genetic testing for validation.

Main Results:

• Of 1103 subjects, 26% met clinical FH criteria, with 85% lacking genetic testing and 97% not meeting LDL targets.
• Genetic validation confirmed FH-causing variants in 13% of participants, rising to 19% in clinically diagnosed FH patients.
• A significant number of undiagnosed and undertreated FH cases were identified.

Conclusions:

• A targeted screening strategy using LDL cholesterol cut-offs in laboratory databases is feasible and clinically valuable.
• This approach can identify new FH patients and improve treatment in this high-risk population.
• Highlights the potential for improved FH case finding and management.