International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Standardization Project for the Measurement of Lipoprotein(a). Phase 2: Selection and Properties of a Proposed Secondary Reference Material for Lipoprotein(a).

Abstract

A secondary reference material for lipoprotein(a) is required to standardize the measurement of lipopro-tein(a) in clinical laboratories worldwide. Towards this aim, the International Federation of Clinical Chemistry Working Group for the Standardization of Lipopro-tein(a) Assays has initiated a standardization project involving a total of 33 diagnostic company and clinical chemistry laboratories from 12 countries. In Phase 1, the analytical performance of 40 lipoprotein(a) assay systems was evaluated by testing sera and manufactured lipoprotein(a) calibrator materials for precision, linear-ity, and parallelism. Twenty test systems were nonopti-mized according to the results for a pooled serum, which tested nonlinear in 16 systems and imprecise in 4. Acceptable analytical properties and harmonization of lipoprotein(a) values were shown by some commercial calibrators, suggesting their possible use as reference materials. This study highlights the problems that currently occur for lipoprotein(a) measurement in existing assay systems. Following up on Kåre Berg's discovery of lipoprotein(a) [Lp(a)] 9 (1), numerous clinical studies have indicated the usefulness of Lp(a) as a risk marker for atherosclerotic diseases (2-5). The further identification of close structural similarities between apolipoprotein(a) [apo(a)] and plasminogen highlighted the importance of Lp(a) in both atherosclerosis and thrombogenesis (6). One consequence of these findings has been the considerable increase in the number of commercial immunochemical methods and calibrator materials for the measurement of Lp(a). However , the diverse composition and immunochemical properties of antibodies and calibrators used to measure Lp(a) has led to a wide range of values, which are not comparable between different methods or laboratories. The inadequate standardization of Lp(a) assays has been clearly shown in a number of surveys (7-10), and the large between-method discrepancies in Lp(a) values have been attributed mainly to the use of different standard materials, which vary in isoform composition. A lack of assay precision and optimization has also contributed to poor performance by laboratories using commercially

Lipoprotein (a) measurements for clinical application

“…In an attempt to standardize the measurement of Lp(a), the major aim of the International Federation of Clinical Chemistry (IFCC) working group on Lp(a), was to select and characterize a secondary reference material to be used by manufacturers of commercially available methods to assign an accuracy-based Lp(a) target value to their assay calibrators ( 22 ). Among the different preparations evaluated, a proposed reference material (PRM) was selected to be further characterized.…”

Association between different growth curve definitions of overweight and obesity and cardiometabolic risk in children

“…All analyses were done at the Department of Clinical Biochemistry at Sainte-Justine using the standardized guidelines of the International Federation of Clinical Chemistry. 17,18 We calculated the level of low-density lipoprotein (LDL) cholesterol using the Friedewald equation. 19 We measured insulin levels using the ultrasensitive insulin kit on the Access immunoassay system.…”

The role of lipoprotein[a] in atherosclerosis

“…This important problem was addressed in an open forum at an International Conference on Lp[a] in 1992 [3] and more recently by an international working group organized to develop reference methods, reagents, and standards for measuring Lp[a] [4]. This working group has done much to raise world-wide awareness of the problems associated with Lp[a] quantitation and the need to solve the problems so that results from different studies can be directly compared.…”

“…An important step toward eliminating the possibility of assay dependence on kringle content is the conversion to a system that reports Lp[a] in terms of molar rather than weight concentrations. During the past year, several new studies have addressed different aspects of Lp[a] quantitation [4][5][6][7].…”