Improving clinicians understanding of lipoprotein sub-fractions through new technology.

  • Peter Wilding
  • Published 2008 in Clinical chemistry and laboratory medicine

Abstract

The ability of clinical laboratories to provide rapid, and automated low cost, results for the lipoprotein sub-fractions HDL and LDL (high and low density lipoproteins) (1), coupled with numerous articles advocating their use (2), has greatly increased the use of these tests by clinicians. However, for many years it has been known that HDL and LDL have sub-fractions discernible by techniques such as ultra-centrifugation that might be better predictors of disease or have value as prognostic indicators. Various authors have also shown distinct differences in the levels of certain sub-fractions relative to stages of coronary artery disease. In spite of these findings, there has been almost no use made by most physicians, other than those specializing in diagnosis and treatment of hyper-lipidemic states, of the concentrations of sub-fractions of HDL or LDL. The paper in this issue by Mueller and colleagues (3) presents a method for the convenient measurement of the HDL sub-fraction HDL2b, and the authors suggest that use of such a method would significantly improve the assessment of patients with myocardial infarction. In proposing the deployment of the convenient method described, the paper raises again the question of how to justify the introduction of new technology for a test that is rarely, if ever, requested in routine clinical laboratories and whether the laboratory should play a leading role in the education of clinicians to use a test once a convenient method has been developed. The HDL sub-fraction in question, namely HDL2b, has recently been shown to be a key factor in the rate of cholesteryl ester transfer (CET) which rises significantly as coronary heart disease progresses (4). In this instance, increases in CET are associated with low levels of HDL2b. This would indicate that testing for HDL2b would have clinical value. However, it has also been shown that low levels of HDL2b occur in patients with end-stage renal disease (5). Thus, the use of this test as a diagnostic or prognostic aid needs further evaluation. Another issue that influences the introduction of a new test in the laboratory is the need for expertise to perform the analyses. If the new test simply involves the use of new reagents, or minor modification to existing instrumentation, introduction is invariably simple. Where it involves the use of a technology not commonly found in the clinical laboratory, the introduction is more problematic even if the demands on technical competence are minimal. The technology proposed by Mueller and colleagues for the determination of HDL2b concentrations is an automated system for capillary electrophoresis (CE) that has been successfully used in research laboratories for over 10 years but few, if any routine clinical laboratories employ this technology. However, generalized lack of experience alone should not prevent the introduction of CE into routine use if it is to prove a useful tool in clarifying the status of patients with coronary artery disease. The particular technology described in the paper by Mueller et al. for the measurement of HDL2b involves the use of an automated system that has been well described and reported for operating accuracy and precision, particularly for identification and quantitation of DNA fragments (6). Moreover, it meets many of the criteria for convenience and result presentation desirable in the clinical laboratory. The careful comparison with the generally accepted reference technology, namely density gradient ultra-centrifugation, provides a reasonable indicator of the accuracy of measurement of HDL2b by CE. However, the evidence available in the literature does suggest that automated CE is the more precise method. Thus it follows that use of good, convenient and economic technology should provide improved understanding of the possible role of HDL2b measurement in assessing coronary heart disease. A cautionary approach to the development of widespread application of CE for HDL2b measurement is still advocated until the issues of nomenclature, reference materials and more extensive studies with well categorized clinical material have been addressed. These issues highlight the dilemma faced by any clinical laboratorian when faced with demands to introduce new tests for routine clinical use when the clinicians understanding of the significance is poor, when the nomenclature and characterization of the analyte is imperfect, or when the availability of reference materials to provide quality measurement is less than desirable. In addition, the determination of appropriate reference values must precede routine use of the test to facilitate meaningful interpretation. The solution to such problems lies in successful clinical studies that are designed to address all these issues and provide incontrovertible evidence that the introduction of a new test brings improved clinical care. In the 1980s clinical chemists provided convenient methods for HbA1c, but its introduction was delayed until major studies clearly illustrated the test’s value in assessing compliance in diabetic patients. Today, there is much improved technology

DOI: 10.1515/CCLM.2008.120

Cite this paper

@article{Wilding2008ImprovingCU, title={Improving clinicians understanding of lipoprotein sub-fractions through new technology.}, author={Peter Wilding}, journal={Clinical chemistry and laboratory medicine}, year={2008}, volume={46 4}, pages={427-8} }