Abstract 15810: Applying an LDL-C Threshold Based Approach to Identify Individuals With Familial Hypercholesterolemia

Background: Familial hypercholesterolemia (FH) is an inherited disorder associated with increased LDL-C and premature coronary heart disease, which remains significantly underdiagnosed. Screening those with very high LDL-C may help identify those with FH, but the optimal means of applying this approach is unclear. Methods: Individuals from UT Southwestern Medical Center, a large, tertiary academic center, with an LDL-C level ≥ 190 mg/dL at any time were enrolled in an FH registry. These 5,786 patients were divided into four categories of LDL-C: 190.0 - 219.9, 220.0 - 249.9, 250.0 - 299.9, and ≥ 300.0 mg/dL. One hundred individuals were randomly selected from each category for manual chart review to determine 1) the presence of secondary causes of dyslipidemia (obstructive liver disease, nephrotic syndrome, hypothyroidism, specific medication use, other secondary cause) and 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 ≥ 190 mg/dL (mean age 52 years ± 14) in this cohort, the presence of secondary causes increased across each LDL-C category ( p < 0.001) (Figure) with the greatest prevalence in those ≥ 300.0 mg/dL (52%). The prevalence of FH also varied by LDL-C category, with the highest prevalence of FH by Simon Broome criteria in the 220.0 - 249.9 mg/dL category (52%) and by DLCN criteria in the 250.0 - 299.9 mg/dL category (46%). Conclusions: Amongst those with LDL-C ≥ 190 mg/dL, the prevalence of secondary causes increases with higher LDL-C, while the diagnosis of FH has a parabolic relationship. Patients with intermediate LDL-C (220 - 299 mg/dL) may be the optimal group to prioritize for FH screening using an LDL-C based approach.