Testing
Formula-based Lp(a)-C estimates overstate cholesterol content and understate true LDL-C, direct-assay study of 278 patients (J Clin Lipidol 2026)
Original title: Direct Lp(a)-C measurement reveals formula-based overestimation of Lp(a)-C and underestimation of corrected LDL-C: Implications for LDL-C target interpretation
Comparison of directly measured Lp(a) cholesterol (Lp(a)-C, immunocapture assay) with two widely used formula-based estimates (Rosenson-Marcovina and Dahlen) in an elevated-Lp(a) cohort (n=278, mean Lp(a) 250.8 nmol/L) and a community cohort (n=94). Direct Lp(a)-C averaged 14.9±6.0 mg/dL versus 19.3±8.3 mg/dL (Rosenson-Marcovina) and 35.4±14.8 mg/dL (Dahlen), all p<.001; corrected LDL-C was correspondingly higher by direct measurement (62.6±30.9 mg/dL) than by either formula (58.2±33.0 and 42.5±34.7 mg/dL). Formula-based correction produced a negative corrected LDL-C in up to 6.1% of participants, with discordance greatest in those with smaller apo(a) isoforms. The authors conclude fixed-assumption formulas systematically overestimate Lp(a)-C and understate LDL-derived cholesterol, which could distort LDL-C goal attainment in the era of ultralow LDL-C targets.
Original abstract
Background: Measured low-density lipoprotein cholesterol (LDL-C) includes cholesterol carried by lipoprotein(a) [Lp(a)-C]. Formula-based approaches are used to estimate Lp(a)-C and derive LDL-C corrected for Lp(a)-C (LDL-Ccorr) but rely on fixed compositional assumptions that may not reflect Lp(a) heterogeneity.
Objective: To compare direct measurement of Lp(a)-C with formula-based approaches for estimating Lp(a)-C and corrected LDL-C across a wide range of Lp(a) concentrations.
Methods: We compared directly measured Lp(a)-C using an immunocapture-based assay (Direct Lp(a)-C) with 2 commonly used formula-based approaches (Rosenson-Marcovina [RM] and Dahlén [D]) in 2 independent cohorts spanning a broad range of Lp(a) concentrations: an elevated Lp(a) cohort (n = 278) in stable subjects and a community-based cohort (n = 94). LDL-Ccorr was calculated by subtracting Lp(a)-C from measured LDL-C using a direct assay. Apolipoprotein(a) [apo(a)] isoform size was determined in the community cohort.
Results: In the elevated Lp(a) cohort (mean Lp(a) 250.8 nmol/L), Direct Lp(a)-C was 14.9 ± 6.0 mg/dL vs 19.3 ± 8.3 mg/dL and 35.4 ± 14.8 mg/dL using RM and D methods (P < .001). Corresponding LDL-Ccorr values were 62.6 ± 30.9 mg/dL (direct), 58.2 ± 33.0 mg/dL, and 42.5 ± 34.7 mg/dL (P < .001). Formula-based correction produced negative LDL-Ccorr values in up to 6.1% of participants. Across increasing Lp(a) strata, apolipoprotein B and measured LDL-C were stable, whereas formula-derived LDL-Ccorr declined significantly. Discordance increased with higher Lp(a)-C and was greatest among individuals with smaller apo(a) isoforms.
Conclusion: Fixed-assumption formula-based correction overestimates Lp(a)-C and underestimates LDL-derived cholesterol, particularly at elevated Lp(a) levels and across apo(a) isoform sizes. In the era of ultralow LDL-C targets, this systematic bias may influence LDL goal attainment. Direct measurement of Lp(a)-C provides an assay-based approach to assess LDL-derived cholesterol in elevated Lp(a).
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.