Applying an LDL-C Threshold-based Approach to Identify Individuals with Familial Hypercholesterolemia

Background: Familial hypercholesterolemia (FH) remains underdiagnosed and undertreated. The optimal electronic health record (EHR) screening strategy for FH is unclear.

Objective: To evaluate an LDL-C threshold-based approach of identifying patients with FH from the EHR to determine the optimal LDL-C range for FH consideration.

Methods: Individuals from UT Southwestern Medical Center with an LDL-C level ≥190mg/dL at any time were enrolled in an FH registry. These 5,786 patients were divided into four categories of LDL-C (190- 219, 220 - 249, 250 - 299, and ≥ 300mg/dL) with 100 individuals randomly selected for manual chart review in each category. Chart review included 1) the presence of secondary causes of dyslipidemia, 2) diagnosis of possible/definite FH by modified Simon Broome criteria, and 3) probable/definite FH by modified Dutch Lipid Clinic Network (DLCN) criteria.

Results: Of the 400 individuals with an LDL-C level ≥190mg/dL (mean age 52 years ± 14), the presence of secondary causes increased across each LDL-C category (p < 0.001) with the greatest prevalence in those ≥ 300mg/dL (52%). The prevalence of possible/probable or definite FH also varied by LDL-C category, with the highest prevalence of FH by Simon Broome criteria in the 220 - 249mg/dL category (52%) and by DLCN criteria in the 250 - 299mg/dL category (46%).

Conclusions: Among those with LDL-C ≥ 190mg/dL, the prevalence of secondary causes increased markedly with higher LDL-C, while the diagnosis of FH has a parabolic relationship. Patients with intermediate LDL-C (220 - 299mg/dL) may be the optimal group to prioritize for FH screening.