Impact of Lipoprotein (a) on the Quantification of LDL-Cholesterol

BACKGROUND: Accurate LDL-C measurement is essential for cardiovascular risk management. The established methods to determine LDL-C also include Lp(a)-C and potentially distort the actual LDL-C value. The need for Lp(a)-adjusted LDL-C remains debated. Our study aimed to evaluate the impact of Lp(a) on the determination of LDL-C. METHODS: We included 3,923 datasets from two cohorts. LDL-C was determined by beta-quantification (LDL-CUC), the reference method recommended by the Lipid Research Clinics, and according to Friedewald (LDL-CFW), Martin/Hopkins (LDL-CMH), and Sampson (LDL-CSN). Correction of LDL-C was performed as follows: corrected LDL-C* = crude LDL-C - (Lp(a) x 0.23 + 1.00). Passing-Bablok regression and Spearman correlation were used for intermethod comparisons. RESULTS: Above 10 mg/dL Lp(a) had a significant effect on LDL-CUC. The effect increased with increasing concentrations of Lp(a) levels and, in relative terms, was most pronounced at lower LDL-C values. For Lp(a) > 58 mg/dL, the actual LDL-CUC was overestimated by ≥ 10%, which was considered clinically relevant. Similar overestimations were observed with the Friedewald, Martin/Hopkins, and Sampson formulas, with Friedewald showing the smallest deviation from LDL-C regardless of Lp(a)-correction. Artificial intelligence models showed that it was not possible to raise the suspicion of elevated Lp(a) from the conventional lipid profile. CONCLUSIONS: The influence of Lp(a) on the determination of LDL-C may lead to clinically significant overestimations of the actual LDL-C. Therefore, we recommend using Lp(a)-corrected LDL-C when 1) the Lp(a) concentration is high, 2) the LDL-C concentration is low, and 3) the LDL-C-lowering treatment is less effective than expected.