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

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.

How should low-density lipoprotein cholesterol be calculated in 2022?

PURPOSE OF REVIEW: The reference method for low-density lipoprotein-cholesterol (LDL-C) quantitation is ß-quantification, a technically demanding method that is not convenient for routine use. Indirect calculation methods to estimate LDL-C, including the Friedewald equation, have been used since 1972. This calculation has several recognized limitations, especially inaccurate results for triglycerides (TG) >4.5 mmol/l (>400 mg/dl). In view of this, several other equations were developed across the world in different datasets.The purpose of this review was to analyze the best method to calculate LDL-C in clinical practice by reviewing studies that compared equations with measured LDL-C. RECENT FINDINGS: We identified 45 studies that compared these formulae. The Martin/Hopkins equation uses an adjustable factor for TG:very low-density lipoprotein-cholesterol ratios, validated in a large dataset and demonstrated to provide more accurate LDL-C calculation, especially when LDL <1.81 mmol/l (<70 mg/dl) and with elevated TG. However, it is not in widespread international use because of the need for further validation and the use of the adjustable factor. The Sampson equation was developed for patients with TG up to 9 mmol/l (800 mg/dl) and was based on ß-quantification and performs well on high TG, postprandial and low LDL-C samples similar to direct LDL-C. SUMMARY: The choice of equation should take into the level of triglycerides. Further validation of different equations is required in different populations.