Lp(a): When and how to measure it

Abstract

Lipoprotein(a) has long been regarded as a risk factor for cardiovascular disease; however, its routine use in clinical practice has been hampered by difficulties inherent in the measurement of this complex lipoprotein. The major challenges relate to its size heterogeneity and related issues including (1) use of appropriate calibrators (2) standardization of calibration protocols (3) traceability and (4) reporting units. In the UK, results from the current EQA schemes for lipoprotein(a) suggest that there is considerable work required to standardize lipoprotein(a) measurement. This is becoming increasingly pertinent with the increasing recognition of lipoprotein(a) as an independent risk factor for cardiovascular disease in international guidelines and the emergence of novel antisense therapies to effectively reduce lipoprotein(a). This article raises awareness of the importance of measurement of lipoprotein(a) for the assessment of cardiovascular disease risk and gives guidance to clinical laboratories regarding choice of appropriate assays.

Keywords: Lp(a); lipoprotein(a); measurement of Lp(a); measurement of lipoprotein(a).

Figure 1.

(a) Lp(a) is an LDL-like particle containing apoB (grey ribbon) bound to apo(a) (black and white circles). The black circles represent the Kringle IV-2 domain, with variable number of repeats apo(a). Lp(a) plasma concentrations are inversely proportional to the number of Kringle IV type 2 repeats on apo(a).

Figure 2.

Schematic of the Denka calibration. Calibrators are prepared in separate pools with different levels of Lp(a), and therefore the isoform composition better matches the test sample leading to improved isoform insensitivity.