Significance of various parameters derived from biological variability for lipid and lipoprotein analyses

Analytical, within-subject, and between-subject components of variability have been determined for total cholesterol, LDL-cholesterol, HDL-cholesterol, and its HDL2 and HDL3 subfractions, triglycerides, apolipoproteins A-I and B, and lipoprotein(a) in serum specimens from a cohort of 10 healthy subjects over a 1-month period. From these data, we have calculated the desirable analytical imprecisions, the indices of individuality, the critical differences for significant change detection, and the number of specimens required to estimate the homeostatic set-point of an individual. Practically, the analytical goal for imprecision was not achieved for HDL2 subfraction, lipoprotein(a), and direct LDL-cholesterol determination (obtained vs. theoretical analytical CV, 8.2% vs. 5.9%, 7.4% vs. 3.8%, and 3.2% vs. 2.6%, respectively). All analytes had marked individuality, showing that the use of population-based reference values is inadequate for their interpretation. The applicable differences required for two results to be significantly different (p < or = 0.05) are total cholesterol: 10%; triglycerides: 49%; LDL-cholesterol: 16%; HDL-cholesterol: 14%; HDL2-cholesterol: 40%; HDL3-cholesterol: 16%; apolipoprotein A-I: 11%; apolipoprotein B: 12%; and lipoprotein(a): 29%. Furthermore, it should be clear that population screening for the assessment of risk of coronary artery disease by means of some of the assays studied would result in a significant number of patients requiring analysis of multiple specimens.