Refining the Martin-Hopkins method for estimating low-density lipoprotein cholesterol levels: Median versus optimal...

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.