Performance of four homogeneous direct methods for LDL-cholesterol.

BACKGROUND Homogeneous LDL-cholesterol methods from Genzyme, Reference Diagnostics, Roche, and Sigma were evaluated for precision, accuracy, and specificity for LDL in the presence of abnormal lipoproteins. METHODS Each homogeneous method was performed by a Roche/Hitachi 911 according to the vendors' instructions, and the results were compared with the beta-quantification reference method. We measured precision over 20 days using quality-control and frozen serum specimens. Sera from 100 study participants, including 60 with hyperlipidemias, were assayed by each method. Accuracy was evaluated from regression and total error analysis. Specificity was evaluated from the bias (as a percentage) vs concentration of triglycerides. RESULTS The total CV was <2% for all methods. Regression slope and intercept (with 95% confidence intervals) were as follows: Genzyme, 0.955 (0.92 to 0.99) and 30.3 (-12 to 73) mg/L; Reference Diagnostics, 0.975 (0.93 to 1.02) and -8 (-63 to 47) mg/L; Roche, 1.067 (1.02 to 1.11) and -101 (-161 to -42) mg/L; and Sigma, 0.964 (0.91 to 1.02) and 164 (89 to 239) mg/L. The percentages of individual results with >12% bias were as follows: Genzyme, 8.0%; Reference Diagnostics, 11.0%; Roche, 10.0%; and Sigma, 30.0%. Total error calculated from mean systematic bias and all-sources random bias was as follows: Genzyme, 12.6%; Reference Diagnostics, 16.5%; Roche, 41.6%; and Sigma, 38.3%. Slopes of bias (as a percentage) vs triglycerides were P <0.001 for all methods except the Roche method, which was P = 0.094. CONCLUSIONS The evaluated methods show nonspecificity toward abnormal lipoproteins, thus compromising their ability to satisfy the National Cholesterol Education Program goal for a total error of <12%. These homogeneous LDL-cholesterol results do not improve on the performance of LDL-cholesterol calculated by the Friedewald equation at triglyceride concentrations <4000 mg/L.