A Tale of Two Approaches Measuring and Calculating Low-Density Lipoprotein Cholesterol

Objectives To summarize and assess the literature on the performances of methods beyond the Friedewald formula (FF) used in routine practice to determine low-density lipoprotein cholesterol (LDL-C). Methods A literature review was performed by searching the PubMed database. Many peer-reviewed articles were assessed. Results The examined methods included direct homogeneous LDL-C assays, the FF, mathematical equations derived from the FF, the Martin-Hopkins equation (MHE), and the Sampson equation. Direct homogeneous assays perform inconsistently across manufacturers and disease status, whereas most FF-derived methods exhibit variable levels of performance across populations. The MHE consistently outperforms the FF but cannot be applied in the setting of severe hypertriglyceridemia. The Sampson equation shows promise against both the FF and MHE, especially in severe hypertriglyceridemia, but data are still limited on its validation in various settings, including disease and therapeutic states. Conclusions There is still no consensus on a universal best method to estimate LDL-C in routine practice. Further studies are needed to assess the performance of the Sampson equation.