Does correction of low-density lipoprotein cholesterol for lipoprotein(a) change the clinical classification of familial hypercholesterolemia? A retrospective study in patients referred to a lipid clinic

Introduction: Lipoprotein(a) [Lp(a)] contributes to measured low-density lipoprotein cholesterol (LDL-C), potentially affecting the classification of familial hypercholesterolemia (FH). This study evaluated how correcting LDL-C for the estimated cholesterol contribution of Lp(a) affects the clinical classification of FH using the Dutch Lipid Clinic Network (DLCN) criteria. Materials and Methods: This retrospective observational study included 339 patients evaluated for suspected FH at a tertiary lipid clinic. Corrected LDL-C was calculated by subtracting the estimated cholesterol content of Lp(a) (30% of Lp(a) mass) from pretreatment LDL-C. DLCN scores, recalculated from source data, and all four DLCN categories were determined before and after correction. Changes across categories were tested with the Bowker test of symmetry, and changes at the DLCN ≥6 and ≥3 thresholds with the McNemar test. Results: LDL-C correction reduced mean LDL-C from 5.02 ± 2.01 to 4.75 ± 2.01 mmol/L (p < 0.001). In total, 33 patients (9.7%; 95% CI 7.0-13.4%) moved to a lower DLCN category, and none moved upward (Bowker test, p < 0.001). The proportion with probable or definite FH (DLCN ≥6) decreased from 22.4% to 18.3%, and that with DLCN ≥3 from 54.3% to 49.0% (both p < 0.001). Conclusion: Correcting LDL-C for the estimated cholesterol contribution of Lp(a) modestly but significantly changed the clinical DLCN classification of patients with suspected FH, shifting approximately one in ten patients into a lower diagnostic category. Without a genetic reference standard, these findings reflect changes in clinical classification, not improved diagnostic accuracy.