Lipoprotein(a) and cardiovascular disease risk

Lipoprotein(a) (Lp[a]) is a modified atherogenic low-density lipoprotein particle containing apolipoprotein(a) (apo[a]). Although Lp(a) is considered to be a causal risk factor and independent genetic marker of cardiovascular disease (CVD), there is little consensus between the different national guidelines on how to use the information provided to estimate this risk accurately.

The Heart UK Consensus Statement on Lipoprotein(a) (Cegla J, Neely RDG, France M et al.; HEART UK Medical, Scientific and Research Committee. HEART UK consensus statement on Lipoprotein[a]: A call to action. Atherosclerosis 2019; 291: 62–70) makes several recommendations for Lp(a) measurement.  One such recommendation is the use of a method that does not suffer from apo(a) size-related bias, resulting in the over-estimation of Lp(a) in samples with large apo(a) molecules, and underestimation in samples with small apo(a) molecules. The size of the apo(a) protein is genetically determined and varies widely. As such, the levels of Lp(a) can vary up to 1000-fold between individuals.

The paper goes on to recommend that only assays based on the Denka method with calibrators traceable in nmol/L to WHO/IFCC reference material can be recommended for the accurate determination of Lp(a). Serum Lp(a) levels should be measured in individuals with a family history of premature atherosclerotic CVD, a first-degree relative with elevated Lp(a) levels, calcific aortic valve stenosis, or familial hypercholesterolemia.

Recent years have seen major scientific advances in the understanding of Lp(a) and its causal role in premature CVD. Elevated Lp(a) levels are associated robustly and specifically with an increased CVD risk.

Based on the above, a more widespread clinical use of Lp(a) should be considered to refine assessment of cardiovascular risk based on its accurate and reliable measurement. The Randox Lp(a) assay is available for use on a wide range of chemistry analysers.  Using the Denka Seiken methodology, the assay detects the complete Lp(a) molecule and uses a five-point calibrator to reflect the heterogeneity of apo(a) isoforms present in the general population.

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