Reagent | Lipoprotein(a) Assay
Traceable to the WHO/IFCC Reference Material
Benefits of the Randox Lp(a) Assay
WHO/IFCC reference material
The Randox Lp(a) assay is calibrated in nmol/l and traceable to the WHO/IFCC reference material (IFCC SRM 2B) and provides an acceptable bias compared with the Northwest Lipid Metabolism Diabetes Research Laboratory (NLMDRKL) gold standard method.
Dedicated five-point calibrator available
Five-point calibrator with accuracy-based assigned target values (in nmol/l) is available, accurately reflecting the heterogeneity of the apo(a) isoforms. Dedicated Lp(a) control is available offering a complete testing package.
A correlation coefficient of r=0.995 was displayed when the Randox method was compared against other commercially available methods.
The Randox Lp(a) assay displayed a within run precision of <2.54%.
The Randox Lp(a) assay is available in a liquid ready-to-use format for convenience and ease-of-use.
Applications are available detailing instrument-specific settings for the convenient use of the Randox Lp(a) assay on a wide range of clinical chemistry analysers.
Instrument Specific Applications (ISA’s) are available for a wide range of biochemistry analysers. Contact us to enquire about your specific analyser.
The biggest challenge that exists surrounding Lp(a) measurement is the heterogeneity of the apo(a) isoforms, resulting in the underestimation or overestimation of Lp(a) concentrations. In immunoassays, the variable numbers of repeated KIV-2 units in Lp(a) act as multiple epitopes. This is where standardisation across calibrators is vital. Unless the calibrants do have the same range of isoforms as test samples, those with higher numbers of the KIV-2 repeat, will represent with an overestimation in Lp(a) concentrations and those with smaller numbers of the KIV-2 repeat, will represent with an underestimation. The smaller isoforms are strongly associated with higher Lp(a) concentrations. Lack of standardisation of the calibrant would result in an underestimation of Lp(a) associated CVD risk. It is important to note that an Lp(a) immunoassay employing isoform insensitive antibodies does not exist 1.
The gold standard Lp(a) method is the Northwest Lipid Metabolism and Diabetes Research Laboratory (NLMDRKL) method which employs an isoform insensitive antibody and is meticulously calibrated with well characterised material; however, this test is not commercially available 1.
Lp(a) assays that are standardised to the WHO/IFCC reference material, transferring values from mg/dl to nmol/l are more uniformed. The Denka Seiken Lp(a) assay is the most reliable commercially available Lp(a) assay, because 1:
1. The isoform size variations are reduced as a range of calibrators from separate pools of serum were used which covered a range of Lp(a) concentrations.
2. The isoform size and concentrations are inversely correlated better matching calibrants with test samples.
3. Methods based on the Denka Lp(a) assay, calibrated in nmol/l and traceable to WHO/IFCC reference material gave acceptable bias compared with the NLMDRL gold standard method.
Lp(a) measurement could be of value in those with a family history of premature CVD (<60 years), especially when a causative mutation for familial hypercholesterolemia (FH) hasn’t been identified. In patients with heterozygous FH (HeFH), Lp(a) levels are higher compared to their non-affected siblings. Lp(a) has been identified as a strong risk factor of coronary heart disease (CHD) in patients with HeFH, independent of age, sex, smoking status, and LDL-C levels 1.
Understanding a FH patients Lp(a) levels can aid the physician in identifying the patient’s risk of a cardiovascular event and in the evaluation of treatment methods. However, Lp(a) is not a predictor of CHD in HeFH patients on currently available cholesterol-lowering treatment but may be when lower LDL-C levels are achieved. On this basis, it is recommended that Lp(a) levels are measured in all genetic dyslipidaemias 1.
Lp(a) has been identified as a potent risk factor for calcific aortic valve stenosis. Understanding a patients Lp(a) levels could aid in informing the selection of the interval for valve surveillance as patients with elevated Lp(a) levels are likely to require earlier intervention 1.
Lp(a) measurements aids in the re-classifying of those deemed at an intermediate CVD risk. Patients who over 10 years have >15% risk of a CV event should be receiving treatment, such as statin therapy irrespective of Lp(a) levels. The uptake of statin therapy in the UK as a primary prevention method for those deemed at an intermediate risk of CVD is poor 1. In the ‘Statin initiations and QRISK2 scoring in UK general practice: a THIN database study’ concluded that most patients deemed at a high risk of CVD were not initiated on statin therapy 2. Only 14% of patients with a 10-year CVD risk (10 – 19.9% risk) were initiated on statin therapy with one in six statin initiations were to low-risk patients 1, 2.
Lp(a) is believed to remain relatively stable over a lifespan as Lp(a) is predominantly genetically determined. Lp(a) testing is believed to more cost effective in comparison to genetic testing at this time. A single Lp(a) test is believed to be enough to improve the accuracy of cardiovascular risk assessment, however, qualification levels that are close to the action thresholds should be considered on a case-by-case basis. Repeat testing can be initiated if a secondary cause is suspected or therapeutic measures to lower Lp(a) levels have been instigated 1. The once-only recommendation for Lp(a) testing is consistent with the recently published European Guidelines 3, however HEART UK 1, recommend that Lp(a) are measured in specific cohorts as opposed to all adults. Currently, Lp(a) screening is not currently advocated by the HEART UK consensus panel. The European guideline aims to identify those at a very high risk (Lp(a) levels >430nmol/l), however, HEART UK argues that the risk conferred by Lp(a) occurs at a much lower threshold. Consequently, the HEART UK approach is to measure Lp(a) in specific populations and manage Lp(a) associated risk in those with levels >90nmol/l 1.
The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), through its Working Group on Lp(a) and together with research institutions and several diagnostic companies recommends that laboratories use assays which do not suffer from apo(a) size-related bias. The IFCC SRM 2B was accepted by the WHO Expert Committee on Biological Standardisation as the First WHO/IFCC International Reference Reagent for Lp(a) to ensure conformity by diagnostic companies to the European Union’s Directive on In vitro Diagnostic Medical Devices for the metrological traceability of calibrator materials 4.
Lp(a) has been identified to play a role in COVID-19. Those with either baseline elevated Lp(a) or those whose Lp(a) levels increased following infection from COVID-19, or both, may be at a significantly increased risk of developing thromboses. Elevate Lp(a) levels may cause acute destabilisation of pre-existing but quiescent, atherosclerotic plaques, which could induce an acute myocardial infarction and stroke 5.
Lipid EQA Scheme
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 Finnikin S, Ryan R, Marshall T. Statin initiations and QRISK2 scoring in UK general practice: a THIN database study. British Journal of General Practice 2017; 67(665): 881-887. https://bjgp.org/content/67/665/e881.long (accessed 3 December 2019).
 Mach F, Baigent C, Catapano AL, Koskinas KC, Casula m. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. European Heart Journal 2019; (): 1-78. https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehz455/5556353 (accessed 3 December 2019).
 Dati F, Tate JR, Marcovina SM, Steinmetz A, et al. First WHO/IFCC International Reference Reagent for Lipoprotein(a) for Immunoassay–Lp(a) SRM 2B. Clinical Chemistry and Laboratory Medicine 2004; 42(6): 670-676.
 Moriarty PM, Gorby LK, Stroes ES, Kastelein JP, Davidson M, et al. Lipoprotein(a) and Its Potential Association with Thrombosis and Inflammation in COVID-19: a Testable Hypothesis. Current Atherosclerosis Reports 2020; 22(48): 1-8.