Use of a reference material proposed by the international federation of clinical chemistry and laboratory medicine to evaluate analytical methods forthe determination of plasma lipoprotein(a)

Background: As part of the NIH/National Heart, Lung and Blood Institute Con tract for the Standardization of Lipoprotein(a) [Lp(a)] Measurements, a stu dy was performed in collaboration with the IFCC Working Group for the Stand ardization of Lp(a) Assays. The aims of the study, performed with the parti cipation of 16 manufacturers and 6 research laboratories, were to evaluate the IFCC proposed reference material (PRM) for its ability to transfer an a ccuracy-based value to the immunoassay calibrators and to assess concordanc e in results among different methods. Methods: Two different purified Lp(a) preparations with protein mass concen trations determined by amino acid analysis were used to calibrate the refer ence method. A Lp(a) value of 107 nmol/L was assigned to PRM. After uniform ity of calibration was demonstrated in the 22 evaluated systems, Lp(a) was measured on 30 fresh-frozen sera covering a wide range of Lp(a) values and apolipoprotein(a) [apo(a)] sizes. Results: The among-laboratory CVs for these samples (6-31%) were, in genera l, higher than those obtained for PRM (2.8%) and the quality-control sample s (14%, 12%, and 9%, respectively), reflecting the broad range of apo(a) si zes in the 30 samples and the sensitivity of most methods to apo(a) size he terogeneity. Thus, although all of the assays were uniformly calibrated thr ough the use of PRM, no uniformity in results was achieved for the isoform- sensitive methods. Conclusions: Linear regression analyses indicated that to various degrees, apo(a) size heterogeneity affects the outcome of the immunochemical methods used to measure Lp(a). We have also shown that the inaccuracy of Lp(a) val ues determined by methods sensitive to apo(a) size significantly affects th e assessment of individual risk status for coronary artery disease. (C) 200 0 American Association for Clinical Chemistry.