Lp(a) measurements for clinical application: why the assays disagree (Marcovina and Albers, J Lipid Res 2016)

The high degree of size heterogeneity of apo(a), the distinct protein component of lipoprotein (a) [Lp(a)], renders the development and selection of specific antibodies directed to apo(a) more difficult and poses significant challenges to the development of immunoassays to measure its concentration in plasma or serum samples. Apo(a) is extremely variable in size not only between but also within individuals because of the presence of two different, genetically determined apo(a) isoform sizes. Therefore, the antigenic determinants per particle available to interact with the antibodies will vary in the samples and the calibrators, thus contributing to apo(a) size-dependent inaccuracy of different methods. The lack of rigorous validation of the immunoassays and common means of expressing Lp(a) concentrations hinder the harmonization of results obtained by different studies and contribute to the lack of common cut points for identification of individuals at risk for coronary artery disease or for interventions aimed at reducing Lp(a) levels. The aim of our review is to present and critically evaluate the issues surrounding the measurements of Lp(a), their impact on the clinical interpretation of the data, and the obstacles we need to overcome to achieve the standardization of Lp(a) measurements.