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Current dyslipidemia management in patients with atherosclerotic cardiovascular disease (ASCVD) is based on traditional serum lipids. Yet, there is some indication from basic research that serum apolipoproteins A-I, (a), B, C-I, C-II, C-III, and E may give better pathophysiological insight into the root causes of dyslipidemia. To facilitate the future adoption of clinical serum apolipoprotein (apo) profiling for precision medicine, strategies for accurate testing should be developed in advance. Recent discoveries in basic science and translational medicine set the stage for the IFCC Working Group on Apolipoproteins by Mass Spectrometry. Main drivers were the convergence of unmet clinical needs in cardiovascular disease (CVD) patients with enabling technology and metrology. First, the residual cardiovascular risk after accounting for established risk factors demonstrates that the current lipid panel is too limited to capture the full complexity of lipid metabolism in patients. Second, there is a need for accurate test results in highly polymorphic and atherogenic apolipoproteins such as apo(a). Third, sufficient robustness of mass spectrometry technology allows reproducible protein quantification at the molecular level. Fourth, several calibration hierarchies in the revised ISO 17511:2020 guideline facilitate metrological traceability of test results, the highest achievable standard being traceability to SI. This article outlines the conceptual approach aimed at achieving a novel, multiplexed Reference Measurement System (RMS) for seven apolipoproteins based on isotope dilution mass spectrometry and peptide-based calibration. This RMS should enable standardization of existing and emerging apolipoprotein assays to SI, within allowable limits of measurement uncertainty, through a sustainable network of Reference Laboratories., (© American Association for Clinical Chemistry 2020.)

The role of lipids, lipoproteins and lipoprotein(a) [Lp(a)] in coronary artery disease (CAD) is known but the role of major apolipoproteins (apos) other than apo A-I and apo B remains unclear. In this study, using immunoturbidimetry we have estimated serum levels of total cholesterol, HDL-C, LDL-C, triglyceride, LDL-apoB and all major apos; A-I, A-II, B, C-II, C-III and E, in 751 healthy Indian subjects (470 men and 281 women, age 25-65 years), determined their percentiles, and established reference intervals. The effects of age, smoking and alcohol on all these analytes were also evaluated. This is the first study to provide reference intervals for all apos, in both sexes from a general population. The percentiles and the reference intervals have clinical relevance and will be useful in assessing the risk of CAD in patients with hyperlipidemia and other diseases.