Monitoring of low density lipoprotein cholesterol (LDL-C) levels is a key element of anti-atherogenic therapy in patients with atherosclerotic cardiovascular diseases, especially those at high and very high risk. The target LDL-C levels (< 1.8 mmol/L for high risk and < 1.4 mmol/L for very high risk) are important indicators for quality of medical care. Traditionally, the Friedewald formula has been used to estimate LDL-C, but its accuracy is limited when triglyceride (TG) levels exceed 4.5 mmol/L. This article reviews current approaches to optimization of the LDL-C calculation formulas, their applicability in clinical practice, and regional variations. The Friedewald formula, proposed in 1972, has long been the primary method for LDL-C estimation. However, its limitations, particularly at high TG levels, have led to the development of alternative formulas, such as the Martin method and the Sampson formula. The Martin method, based on the analysis of over 1.35 million lipid profiles, suggests the use of correction factors depending on TG levels. The Sampson formula, which accounts for complex metabolic processes, demonstrates high accuracy, especially at TG levels < 4.5 mmol/L. There are regional variations in lipid levels associated with climatic, cultural, and genetic factors. For example, in South Korea, a formula tailored to the local population has been proposed, showing higher accuracy compared to the Friedewald formula. In the Russian Federation, a formula based on the analysis of 750,000 lipid profiles has been developed, demonstrating high accuracy across a wide range of TG levels (0.1–30 mmol/L). These studies highlight the need to adapt calculation methods to local populations. In clinical practice, the choice of LDL-C calculation method depends on the study objectives and clinical characteristics of the disease. The American Heart Association (AHA) recommends the Martin method, while the National Institute of Health (NIH) favors the Sampson formula. In Russia, the Friedewald formula is still used, although its accuracy is questioned. In multicenter studies of lipid-lowering drugs, newer formulas are preferred, such as the NIH formula, which has shown high accuracy at low LDL-C levels. The need for accurate LDL-C determination to assess the cardiovascular risk and monitor the treatment efficacy drives the development of new calculation methods. The Friedewald formula, despite its widespread use, is less accurate than modern methods, especially at high TG levels. Optimization of the formulas to account for regional population characteristics seems an important step toward improvement of the quality of diagnosis and treatment of atherosclerotic diseases. © 2025 Elsevier B.V., All rights reserved.