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Background: The most commonly used method for low-density lipoprotein cholesterol (LDL-C) estimation is the Friedewald equation, which has notable limitations. However, more accurate methods have been proposed. This study investigates the advantages and limitations of these methods and identifies the contexts in which each equation is the most or least applicable. Methods: A cohort of 222 individuals underwent a standard lipid profile assessment, including directly measuring their LDL-C (dLDL-C). LDL-C was also estimated using the Friedewald, Martin–Hopkins, and Sampson equations. The differences (%Delta) between the estimated and measured LDL-C were analyzed in relation to dLDL-C, high-density lipoprotein cholesterol (HDL-C), and triglyceride levels. Results: The %Delta was significantly lower (p < 0.0001) for the Martin–Hopkins (−8.8 ± 9.8) and Sampson (−9.5 ± 9.2) equations compared to Friedewald (−12.2 ± 9.2). All equations increasingly underestimated LDL-C as the dLDL-C levels decreased. The %Delta of the Martin–Hopkins equation showed significant positive correlations with dLDL-C (≤130 mg/dL) and triglycerides and a significant negative correlation with HDL-C. In a subgroup of 30 individuals with extreme %Delta values, patterns of gross underestimation were observed, particularly when low LDL-C, low triglycerides, and high HDL-C coincided. Conclusions: The Martin–Hopkins equation is a superior method for LDL-C estimation and a valuable tool in precision medicine. However, clinicians and laboratory professionals must be aware of its limitations and recognize patterns that could lead to significant LDL-C underestimation. We propose an algorithm for clinical laboratories to provide personalized LDL-C assessments.
Mănescu et al. (Fri,) studied this question.