Calculated low-density lipoprotein cholesterol remains a viable and important test for screening and targeting therapy

Abstract

Background: Most clinical laboratories use calculated (C) low-density lipoprotein cholesterol (LDL-C) for measurement. Some studies have questioned the linearity of CLDL-C in the clinically useful low range. Moreover, it is generally believed that calculation leads to poor precision such that variation in CLDL-C is greater than the 4% guideline since the calculation is dependent on three primary variables. Actually, the degree of variability of a calculated value will be small if the variability of each primary value is small as compared to its contribution to the calculated value. When LDL-C is low, high-density lipoprotein cholesterol (HDL-C), that has poorer precision, becomes more important in defining the precision of CLDL-C. New homogeneous (direct) HDL-C (dHDL) methods show better precision than the older heterogeneous methods. We hypothesized that a direct homogeneous HDL-C method would substantially improve the low range precision of LDL-C as compared to older heterogeneous HDL-C methods.

Methods: We compared CLDL-C to a standardized electrophoretic method that shows very high precision. We also compared the precision of CLDL-C calculated using a homogeneous dHDL and a heterogeneous indirect method.

Results: We found good linearity for CLDL-C down to 500 mg/L (x0.002586). The main source of CLDL-C variation was HDL-C. Precision was within guidelines when the dHDL method was used. Using our automated methods for lipoprotein lipids, assuming our reference method is accurate, the formula that calculated CLDL-C (mg/dL) using triglyceride (mg/dL) (x0.001129) x0.2 suggested by some gave more accurate results than the formula using triglyceride (mg/dL) x0.16 suggested by others.

Conclusions: Given the potential for CLDL-C to meet the precision guidelines, until direct LDL-C methods can be refined, CLDL-C should continue to be the primary test used for assessing LDL-C clinically. Standardized testing for CLDL-C for manufacturers should be available so that the formula used for each instrument can provide well-defined accuracy.