B-300 Validation of the Lp(a) Ultra Assay on Beckman Coulter AU680: Overcoming Isoform Heterogeneity Challenges in Lipoprotein(a) Measurement

Abstract

Lipoprotein(a) [Lp(a)] is an established independent risk factor for atherosclerotic cardiovascular disease (ASCVD). Accurate quantification of Lp(a) is historically challenged by the size heterogeneity of apolipoprotein(a) isoforms, which range from 275 to 800 kDa. Traditional mass-based measurements (mg/dL) suffer from isoform-dependent bias, leading to potential misclassification of patient risk. Consequently, current consensus guidelines recommend reporting Lp(a) in molar units (nmol/L) using isoform-insensitive assays. This study evaluates the analytical performance of the Lp(a) Ultra assay (Sentinel CH. SpA), a latex-enhanced immunoassay calibrated in nmol/L, on the Beckman Coulter AU680 Clinical Chemistry Analyzer. Lp(a) Ultra is a latex immunoassay, where anti-Lp(a) antibodies adsorbed onto latex particles agglutinate in the presence of Lp(a). Limit of Detection (LoD) was determined using 4 samples (5 replicates over 3 days). Linearity was assessed using 13 concentration levels to cover the analytical measuring range. Method comparison was performed analyzing 110 serum samples on the Beckman Coulter AU680 versus the Roche LpA2 assay (Cobas c503). Total precision was established using five samples (human sera and controls), with 2 replicates for 2 runs over 34 days. The assay demonstrated robust performance characteristics. The Limit of Detection (LoD) was verified at 2.2 nmol/L. Linearity was confirmed across the measuring interval from 5.9 nmol/L (LLOQ) to 240 nmol/L (ULOQ), showing excellent polynomial regression fit within allowable limits. In the method comparison study, the Lp(a) Ultra assay on AU680 showed strong concordance with the Roche LpA2 method. Passing-Bablok regression analysis yielded a slope of 1.02, an intercept of -0.56 nmol/L, and a Pearson correlation coefficient (r) of 0.993. Linear regression analysis yielded a slope of 1.04, an intercept of –1.44 nmol/L, and a Pearson correlation coefficient (r) of 0.993. Total precision results show a maximum SD and CV of 1.65 nmol/L and 4.3% for samples at 33.5 nmol/L and 102.4 nmol/L, respectively. The Lp(a) Ultra assay demonstrates excellent analytical performance with robust sensitivity, linearity across the clinically relevant range, and strong correlation with an FDA-approved comparison method. Total precision meets stringent requirements. Critically, this assay provides isoform-independent quantification calibrated in molar units (nmol/L), addressing a long-standing challenge in Lp(a) measurement. Unlike mass-based measurements (mg/dL) susceptible to apolipoprotein(a) size polymorphism, molar reporting eliminates isoform-dependent bias and prevents patient risk misclassification. This approach aligns with international consensus guidelines recommending nmol/L as the preferred unit. By delivering standardized Lp(a) quantification on the Beckman Coulter AU680 platform, this assay supports accurate cardiovascular risk assessment and consistent result interpretation across laboratories.