Elevated Lipoprotein(a) Level Influences Familial Hypercholesterolemia Diagnosis

Area of Science:

• Lipid metabolism disorders
• Cardiovascular genetics
• Diagnostic accuracy in inherited diseases

Background:

• Familial hypercholesterolemia (FH) and elevated lipoprotein(a) [Lp(a)] are common inherited lipid disorders.
• Accurate diagnosis of heterozygous FH is crucial for timely intervention.
• The Dutch Lipid Clinic Network (DLCN) criteria are widely used for FH diagnosis.

Purpose of the Study:

• To evaluate the impact of high Lp(a) levels on the accuracy of DLCN criteria for diagnosing heterozygous FH.
• To determine if adjusting LDL-C for Lp(a)-cholesterol improves FH diagnosis.
• To identify Lp(a) thresholds associated with diagnostic reclassification.

Main Methods:

• Utilized data from the Russian FH Registry, including 206 individuals with LDL-C >4.9 mmol/L not on lipid-lowering medication.
• Calculated LDL-C corrected for Lp(a)-cholesterol (LDL-C − 0.3 × Lp(a)).
• Applied DLCN criteria before and after LDL-C adjustment.

Main Results:

• 17% of potential FH cases (34/206) were reclassified to less severe FH, and 6% (13/206) to "unlike" FH after LDL-C adjustment.
• An Lp(a) level ≥40 mg/dL was associated with FH re-diagnosis (AUC=0.7, sensitivity 63%, specificity 78%).
• Reclassification rates were significantly higher in patients with Lp(a) ≥40 mg/dL (34% reclassified diagnosis) compared to those with Lp(a) <40 mg/dL (11% reclassified diagnosis).

Conclusions:

• High Lp(a) levels can lead to misclassification of FH diagnosis using standard DLCN criteria.
• Adjusting LDL-C for Lp(a)-cholesterol is recommended for FH patients with Lp(a) levels ≥40 mg/dL.
• This adjustment improves the accuracy of FH diagnosis according to DLCN criteria.