Performance of LDL-C only compared to the Dutch Lipid Clinic Network Score for screening of familial hypercholesterolaemia: the Austrian experience and literature review.
Level 4 - case-series / case-control
Retrospective multicenter diagnostic cohort study and chart review
PubMed 39535057 · doi:10.1093/eurjpc/zwae331
What was done
A retrospective multicenter diagnostic cohort study and literature review evaluated 469 patients undergoing routine molecular genotyping for familial hypercholesterolaemia (FH) mutations (LDLR, APOB, PCSK9, LDLRAP, APOE) over 4 years at two Austrian specialist lipid clinics. The diagnostic performance of the Dutch Lipid Clinic Network Score (DLCNS) was compared against original chart documentation and against an off-treatment LDL-C threshold exceeding 190 mg/dL, using genetic diagnosis as the reference standard.
What was found
A disease-causing genetic variant was detected in 21.3% of the 469 patients tested. A median of 3 out of 8 DLCNS criteria (excluding genetic and LDL-C components) were missing in routine clinical records. DLCNS was recorded in only 48% of charts and had significant discrepancies compared to retrospective recalculation (P < 0.001). Overall diagnostic performance of DLCNS did not exceed off-treatment LDL-C alone (Δ = 0.006; P = 0.660). Comparing an off-treatment LDL-C cut-off of >190 mg/dL against DLCNS ≥ 6 yielded higher sensitivity (84.9% vs. 53.8%) but lower specificity (39.0% vs. 84.1%).
Why it matters
In routine practice, clinical scores like DLCNS frequently suffer from missing data and inconsistent calculation. A simple off-treatment LDL-C cut-off (>190 mg/dL) provides a practical, high-sensitivity screening threshold to identify index cases needing genetic testing.
Limits
The study is retrospective and conducted in tertiary specialist lipid clinics, introducing selection and referral bias that may not reflect primary care. The lower specificity of LDL-C alone (39.0%) increases false-positive screening rates and subsequent genetic testing costs. Methodology and study counts for the literature review were not detailed in the abstract.
Cited by
- supports The clinical phenotypic criteria for familial hypercholesterolemia includes an untreated LDL cholesterol level greater than 190 mg/dL.