Best practice for LDL-cholesterol: when and how to calculate

Abstract

The lipid profile is important in the risk assessment for cardiovascular disease. The lipid profile includes total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides (TGs) and low-density lipoprotein (LDL)-cholesterol (LDL-C). LDL-C has traditionally been calculated using the Friedewald equation (invalid with TGs greater than 4.5 mmol/L and is based on the assumption that the ratio of TG to cholesterol in very- low-density lipoprotein (VLDL) is 5 when measured in mg /dL). LDL-C can be quantified with a reference method, beta-quantification involving ultracentrifugation and this is unsuitable for routine use. Direct measurement of LDL-C was expected to provide a solution with high TGs. However, this has some challenges because of a lack of standardisation between the reagents and assays from different manufacturers as well as the additional costs. Furthermore, mild hypertriglyceridaemia also distorts direct LDL-C measurements. With the limitations of the Friedewald equation, alternatives have been derived. Newer equations include the Sampson-National Institutes of Health (NIH) equation 2 and the Martin-Hopkins equation. The Sampson-NIH2 equation was derived using beta-quantification in a population with high TG and multiple least squares regression to calculate VLDL-C, using TGs and non-HDL-C as independent variables. These data were used in a second equation to calculate LDL-C. The Sampson-NIH2 equation can be used with TGs up to 9 mmol/L. The Martin-Hopkins equation uses a 180 cell stratification of TG/non-HDL-C to determine the TG:VLDL-C ratio and can be used with TGs up to 4.5 mmol/L. Recently, an extended Martin-Hopkins equation has become available for TGs up to 9.04 mmol/L.This article discusses the best practice approach to calculating LDL-C based on the available evidence.