{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:53:30Z","timestamp":1790178810736,"version":"4.1.0"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T00:00:00Z","timestamp":1751500800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2022R1A5A8019303"],"award-info":[{"award-number":["2022R1A5A8019303"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>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\u2009mg\/dL. Recent studies have demonstrated the superior accuracy of the Martin\u2013Hopkins 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.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Objectives and methods<\/jats:title>\n<jats:p>This study evaluated the performance of the Martin\u2013Hopkins 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-C<jats:sub>F<\/jats:sub>), the original Martin\u2013Hopkins method (LDL-C<jats:sub>M-N<\/jats:sub>), and two alternative models that applied TG\/VLDL-C ratios derived from our data\u2014one using median values (LDL-C<jats:sub>KM-N<\/jats:sub>) and the other using optimal values tailored to each stratum (LDL-C<jats:sub>KO-N<\/jats:sub>).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>The Martin\u2013Hopkins method showed significantly higher concordance than the Friedewald formula for TG levels\u2009&lt;\u2009400\u2009mg\/dL (79.6% for LDL-C<jats:sub>F<\/jats:sub> vs. 83.2% for LDL-C<jats:sub>M-180<\/jats:sub>, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Concordance improved by less than 2% for TG levels\u2009&lt;\u2009150\u2009mg\/dL (83.3% vs. 84.9%), but by approximately 10% for TG levels of 150\u2013399\u2009mg\/dL (68.8% vs. 78.0%). The largest discrepancy was observed in classifying LDL-C levels\u2009&lt;\u200970\u2009mg\/dL among individuals with TG levels of 150\u2013399\u2009mg\/dL (47.5% for LDL-C<jats:sub>F<\/jats:sub> vs. 90.3% for LDL-C<jats:sub>M-180<\/jats:sub>). However, the overall concordance differed only modestly between the 10-cell and 180-cell Martin\u2013Hopkins equations (82.8% for LDL-C<jats:sub>M-10<\/jats:sub> vs. 83.2% for LDL-C<jats:sub>M-180<\/jats:sub>, 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-C<jats:sub>KO-N<\/jats:sub> estimates outperforming their LDL-C<jats:sub>KM-N<\/jats:sub> counterparts. However, this improvement was not statistically significant in LDL-C estimates derived from TG-only stratification.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Applying optimal TG\/VLDL-C ratios within the Martin\u2013Hopkins method improves accuracy compared to median ratios, particularly when stratifications incorporate both TG and non\u2013high-density lipoprotein cholesterol (non\u2013HDL-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\u2013HDL-C stratifications.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0327169","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T17:34:23Z","timestamp":1751564063000},"page":"e0327169","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Refining the Martin\u2013Hopkins method for estimating low-density lipoprotein cholesterol levels: Median versus optimal TG\/VLDL-C ratio"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3752-1112","authenticated-orcid":true,"given":"Jongseok","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyelim","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hwajung","family":"Cha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Seok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In Cheol","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,7,3]]},"reference":[{"key":"pone.0327169.ref001","author":"World Health Organization","year":"2021"},{"issue":"19","key":"pone.0327169.ref002","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1001\/jama.2013.282775","article-title":"What\u2019s new with measuring cholesterol?","volume":"310","author":"JM Gaziano","year":"2013","journal-title":"JAMA"},{"issue":"19","key":"pone.0327169.ref003","doi-asserted-by":"crossref","first-page":"2486","DOI":"10.1001\/jama.285.19.2486","article-title":"Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III)","volume":"285","author":"Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.","year":"2001","journal-title":"JAMA"},{"issue":"10","key":"pone.0327169.ref004","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1194\/jlr.R500010-JLR200","article-title":"Thematic review series: the pathogenesis of atherosclerosis: an interpretive history of the cholesterol controversy, part III: mechanistically defining the role of hyperlipidemia","volume":"46","author":"D Steinberg","year":"2005","journal-title":"J Lipid Res"},{"key":"pone.0327169.ref005","unstructured":"National Health Insurance Service. 2015 National Health Screening Statistical Yearbook; 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