Journal Article

Refining the Martin–Hopkins method for estimating low-density lipoprotein cholesterol levels: Median versus optimal TG/VLDL-C ratio

Jeong, In Cheol, Lee, Jongseok, Lee, Hyelim, Cha, Hwajung, Seok, Jun

2025

Overview

Low-density lipoprotein cholesterol (LDL-C), a major modifiable risk factor for cardiovascular diseases, is typically calculated using the Friedewald formula when triglyceride (TG) levels are below 400 mg/dL. Recent studies have demonstrated the superior accuracy of the Martin-Hopkins method across diverse populations. While this method estimates very-low-density lipoprotein cholesterol (VLDL-C) using strata-specific median TG/VLDL-C ratios, its reliance on median statistics raises questions about whether these ratios are truly optimal. This study evaluated the performance of the Martin-Hopkins method compared to the Friedewald formula, focusing on its potential for improvement by applying optimal TG/VLDL-C ratios. Using data from 18,322 individuals in the Korea National Health and Nutrition Examination Survey (KNHANES), we derived strata-specific optimal TG/VLDL-C ratios designed to maximize concordance with directly measured LDL-C values, based on LDL-C categories defined by clinical guidelines. We compared the performance of four LDL-C estimation models: the Friedewald formula (LDL-CF), the original Martin-Hopkins method (LDL-CM-N), and two alternative models that applied TG/VLDL-C ratios derived from our data-one using median values (LDL-CKM-N) and the other using optimal values tailored to each stratum (LDL-CKO-N). The Martin-Hopkins method showed significantly higher concordance than the Friedewald formula for TG levels < 400 mg/dL (79.6% for LDL-CF vs. 83.2% for LDL-CM-180, p < 0.001). Concordance improved by less than 2% for TG levels < 150 mg/dL (83.3% vs. 84.9%), but by approximately 10% for TG levels of 150-399 mg/dL (68.8% vs. 78.0%). The largest discrepancy was observed in classifying LDL-C levels < 70 mg/dL among individuals with TG levels of 150-399 mg/dL (47.5% for LDL-CF vs. 90.3% for LDL-CM-180). However, the overall concordance differed only modestly between the 10-cell and 180-cell Martin-Hopkins equations (82.8% for LDL-CM-10 vs. 83.2% for LDL-CM-180, a difference of 0.4%), indicating only a marginal benefit despite the substantial increase in the number of strata. Using optimal TG/VLDL-C ratios increased overall concordance compared to median ratios within the same stratification, with LDL-CKO-N estimates outperforming their LDL-CKM-N counterparts. However, this improvement was not statistically significant in LDL-C estimates derived from TG-only stratification. Applying optimal TG/VLDL-C ratios within the Martin-Hopkins method improves accuracy compared to median ratios, particularly when stratifications incorporate both TG and non-high-density lipoprotein cholesterol (non-HDL-C) levels. This enhancement can be achieved without increasing the number of strata, offering a practical pathway to refine LDL-C estimation while avoiding excessive stratification. Our findings suggest that while median statistics may be sufficient for TG-only stratifications, they do not fully capture optimal TG/VLDL-C ratios for combined TG and non-HDL-C stratifications.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Accuracy / Adult / Aged / Biology and Life Sciences / Cardiovascular diseases / Cholesterol / Cholesterol, LDL / Cholesterol, LDL - blood / Cholesterol, VLDL - blood / Classification / Datasets / Density / Engineering and Technology / Estimates / Estimation / Female / Health aspects / High density lipoprotein / Humans / Lipoproteins / Lipoproteins (very low density) / Low density lipoprotein / Male / Measurement / Measurement techniques / Medicine and Health Sciences / Middle Aged / Nutrition Surveys / People and Places / Performance evaluation / Ratios / Republic of Korea / Research and Analysis Methods / Risk factors / Statistical analysis / Statistics / Triglycerides / Triglycerides - blood