Clinical risk factors cannot distinguish FH from elevated Lp(a), 378-patient lipid clinic study argues for universal genetic and Lp(a) testing (J Clin Lipidol 2026)

Original title: Moving beyond clinical risk factors for diagnosis: The necessity of systematic Lp(a) measurement and familial hypercholesterolemia genetic testing

J Clin Lipidol · 7 May 2026 · 6

Helm BM, Huerta V, Clary JM

Study of 378 lipid clinic patients receiving both Lp(a) screening and familial hypercholesterolaemia (FH) genetic testing, testing whether standard clinical risk factors (LDL-C, family history, personal history of premature ASCVD) can distinguish FH from elevated Lp(a). Genetic testing found FH in 22.5%, elevated Lp(a) in 35.7%, and both in 12.7% of patients. While higher LDL-C and younger age were associated with FH, personal or family history of premature ASCVD failed to differentiate FH, elevated Lp(a), or dual diagnoses, and predicted probabilities for each diagnosis overlapped considerably. The authors conclude clinical risk factors and scoring systems cannot substitute for systematic Lp(a) measurement and FH genetic testing in accurately diagnosing and managing these high-risk conditions.

Original abstract

Background: Elevated lipoprotein(a) [Lp(a)] and familial hypercholesterolemia (FH) are common, underdiagnosed monogenic dyslipidemias that significantly increase cardiovascular risk.

Objective: We investigated whether standard clinical risk factors-low-density lipoprotein cholesterol (LDL-C), family history, and personal history of premature atherosclerotic cardiovascular disease (pASCVD)-can accurately distinguish these conditions.

Methods: We analyzed 378 lipid clinic patients receiving Lp(a) screening and FH genetic testing with multinomial logistic regression.

Results: we found that while higher LDL-C and younger age were associated with FH, personal/family histories of pASCVD failed to differentiate between FH, elevated Lp(a), or dual diagnoses. Genetic testing for FH and Lp(a) measurement revealed that 22.5% had FH, 35.7% had elevated Lp(a), and 12.7% had both. Despite statistical associations, predicted probabilities for each diagnosis overlapped considerably, and clinical risk factors commonly used in FH clinical diagnostic criteria would insufficiently distinguish these genetic disorders.

Conclusions: Results demonstrate that clinical risk factors and scoring systems cannot reliably substitute diagnostic FH genetic testing and Lp(a) measurement-essential for accurate diagnosis and management for these high-risk disorders.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.