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

The reference method for low-density lipoprotein-cholesterol (LDL-C) quantitation is β-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.

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 β-quantification and performs well on high TG, postprandial and low LDL-C samples similar to direct LDL-C.

The choice of equation should take into the level of triglycerides. Further validation of different equations is required in different populations.