Lipoprotein-Associated Phospholipase A2 Tests Help Diagnose Heart Disease

The measurement of low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (non-HDL-C) is currently the mainstay when assessing the risk of atherosclerosis leading to cardiovascular disease.

A need exists for other biomarkers of risk because not everyone with cardiovascular disease (CVD) has elevated LDL-C or non-HDL-C, and even if these markers are elevated and treatment is aggressive, there can still be residual risk that they fail to explain.

A senior scientist of laboratory medicine at the Mayo Clinic (Rochester, MN, USA) has examined an important component of atherothrombogenesis, which is inflammation, and elevated circulating biomarkers of inflammation can be used to identify individuals at higher risk of CVD. One of those markers is Lipoprotein-Associated Phospholipase A2 (Lp-PLA2), an enzyme expressed by the macrophages inside atherosclerotic plaques that circulate bound to lipoproteins. Unlike some biomarkers of inflammation, Lp-PLA2 is not an acute phase reactant, which makes it more specific for the vascular inflammation associated with CVD.

The US Food and Drug Administration (FDA, Silver Springs, MD, USA) has approved two assays for Lp-PLA2 that carry the trademark name PLAC test (diaDexus, South San Francisco, CA, USA). One measures the concentration of the protein and the other measures the enzymatic activity of the protein. The concentration assay is an enzyme-linked immunosorbent assay (ELISA) method, while the activity assay is a spectrophotometric assay run on automated chemistry analyzers.

While the two assays measure the same protein, the correlation coefficients between them, somewhat surprisingly, range from 0.3 to 0.6. Laboratorians and clinicians should also be aware of several other differences between the assays. The first is evident from their respective approved patient populations: the concentration assay is cleared for coronary heart disease and stroke while the activity assay is cleared only for coronary heart disease. Last and perhaps most important, results from the ELISA test can be dramatically inaccurate as a result of pre-analytical specimen handling conditions.

Leslie J. Donato, PhD, DABCC, co-director of cardiovascular laboratory medicine and co-director of the hospital clinical laboratory and point-of-care at the Mayo Clinic and the author of the review, noted that the activity assay does not display any pre-analytical effect such as storage. The only analytical vulnerability of the activity assay that is a small but progressive decrease in activity which results over the life of each lot. The laboratory director can easily monitor for this loss in signal using laboratory quality control metrics. Given the pre-analytical variability that exists with the concentration assay, her group has chosen to use the activity assay when measuring Lp-PLA2. The study was published in the July 2016 edition of the journal Clinical Laboratory News.

Related Links:
Mayo Clinic
US Food and Drug Administration
diaDexus