Comparative accuracy of LDL-cholesterol estimation: a meta-analysis of the Friedewald and Martin-Hopkins equation

Introduction: Low-density lipoprotein cholesterol (LDL-C) is a cornerstone biomarker for cardiovascular risk. The Friedewald formula has long been the standard for estimating LDL-C, however, it has limitations, particularly in patients with hypertriglyceridemia or low LDL-C levels. Several alternative equations, including the Martin–Hopkins (M/H) and Sampson formulas, have been developed to improve accuracy. Among them, M/H has gained recognition for its performance in specifi c populations, but it represents only one of several refi ned methods used across professional communities. This study aimed to perform a meta-analysis comparing the accuracy and precision of the Friedewald and M/H formulas in diverse populations, acknowledging that other approaches also exist. Methods: A systematic review of articles published between 2018 and 2024 was conducted using PubMed, Embase, Scopus (Elsevier), and Web of Science-eligible studies directly compared both formulas against direct LDL-C measurement in adult populations. A random-effects model was used to pool mean absolute errors (MAEs), root mean square errors (RMSEs), correlation coeffi cients, and p-values. Heterogeneity was assessed using the I² statistic. Results: Eight novel studies, involving a total of 192,094 participants, were included. The M/H formula showed signifi cantly lower MAE (3.6 mg/dL vs. 8.4 mg/dL, p < 0.001), lower RMSE (5.1 mg/dL vs. 9.8 mg/dL, p < 0.001), and a stronger correlation with direct LDL-C (r = 0.92 vs. r = 0.84) compared to the Friedewald formula. The superiority of the M/H formula was especially evident in patients with triglycerides >200 mg/dL or LDL-C <70 mg/dL. Conclusion: The M/H formula provides more accurate and precise LDL-C estimation than Friedewald, particularly in clinically vulnerable groups. However, it should be considered one of several improved approaches, alongside other equations such as Sampson, which may perform better in certain populations. M/H can be recommended as a strong option, but is not the sole alternative for routine lipid profi ling.