Lipoprotein(a), commonly referred to as Lp(a), is one of the most atherogenic lipoproteins in the circulation. Its significance as a cardiovascular risk marker is well-recognized, even for optimally treated patients with healthy cholesterol levels. Lp(a) particles are similar to low-density lipoprotein (LDL) particles, except that they carry an additional protein called apolipoprotein(a), or apo(a), which is variable in size and confers additional atherothrombotic properties.
To date, the most readily available biomarker for Lp(a) status has been Lp(a) mass. However, few clinicians understand what this metric actually measures or how it is determined. Most assume that Lp(a) mass represents the collective weight of all of the apo(a) molecules per deciliter of plasma.
But as the researchers discuss in the article, Lp(a) mass refers not to apo(a) mass or to any one chemical component of the particle, but to its entire mass: lipids, proteins, and carbohydrates combined. Lp(a) mass measurements are therefore affected by differences in the mass of the apo(a) protein, which can vary substantially, as well as those of the particle’s lipidome and proteome.
Until very recently, there have been no commercially available assays that are completely insensitive to the variability in Lp(a) mass, precluding the accurate determination of Lp(a) particle concentration. Since lipoprotein “particle number” (molar concentration) has been found to be superior to component-based metrics (i.e., LDL particle vs. cholesterol concentrations) for cardiovascular disease risk prediction, the development and implementation of a mass-insensitive Lp(a) assay that can determine Lp(a) particle concentrations is a high priority.
“With the increasing recognition of the importance of Lp(a) as a risk marker for cardiovascular disease, understanding the basics of the metric, and using consistent and accurate units of measurement, will become essential,” says William Harris, Ph.D., Senior Scientist at HDL, Inc. and senior author of the article. “A fuller understanding of what the concentration units mean will help improve study-to-study comparisons and thereby advance our understanding of the pathobiology of this lipoprotein particle. Ultimately, assays that reliably report Lp(a) particle concentrations are likely to be, as is the case for LDL, the preferred approach to assessing Lp(a) status.”
The paper, “Lipoprotein(a) Mass – A Massively Misunderstood Metric,” is currently in press at the Journal of Clinical Lipidology
. The commentary was prepared by lead author Joseph P. McConnell, Ph.D. and colleagues Philip A. Guadagno, MS; Thomas D. Dayspring, MD; Daniel M. Hoefner, Ph.D.; Dawn L. Thiselton, Ph.D.; G. Russell Warnick, MS; and William S. Harris, Ph.D.
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