The National Cholesterol Education Program maintains guidelines to assess the accuracy of methods for measuring cholesterol levels in patients. A recent study published in the journal Clinical Chemistry found that seven leading commercial methods produce results of mixed accuracy when compared to well-established techniques.
In 2008, there were several different commercial homogeneous direct measurement methods for HDL-cholesterol and LDL-cholesterol determination that were distributed worldwide under various trade names. These methods use a wide variety of surfactants, ionic polymers, and other components that either selectively prevent or enable measurements of cholesterol in specific classes of lipoproteins among the full range of lipoprotein particles present in serum. Despite their advantages, there has been concern whether direct lipoprotein cholesterol methods generate equivalent values as older more skill-demanding methods and to the established reference measurement procedures for HDL-C and LDL-C used as the basis for clinical guidelines.
A research team led by W. Greg Miller of Virginia Commonwealth University evaluated seven commercially available direct measurement reagents for quantifying HDL-C and LDL-C. The team examined 175 patients in all-37 with no known disease and 138 with known cardiovascular disease and other conditions such as dyslipidemia-and compared the results to those obtained by reference measurement procedures. They evaluated trueness, accuracy for individual samples, imprecision, and specificity for HDL and LDL lipoproteins, thus providing a comprehensive assessment of the analytical performance of the current direct lipoprotein methods.
“In the non-diseased individuals, six of eight HDL-C and five of eight LDL-C direct methods met the National Cholesterol Education Program [guidelines],” said research team member Elizabeth T. Leary, PhD, Chief Scientific Officer at Pacific Biomarkers, Inc. “However, all the methods failed to meet the NCEP’s goals for diseased individuals, because of compromised specificity toward abnormal proteins.”
Dr. Leary continued, “Homogeneous methods suffer from non-specificity in unusual samples, i.e., lipoproteins which are structurally or compositionally altered as in certain diseases (e.g. diabetes), unusual phenotypes or after certain drug treatments. Each homogeneous method is based on a different separation principle and some homogeneous methods may be better than others. As observed in the study, all methods are more variable in diseased samples. The fact is that no method can be ‘correct’ all of the time including the ‘reference methods’. It all depends on the definition of truth. The bottom line is that one needs to know the assays, use them appropriately and interpret the data accordingly.”