{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:45:16Z","timestamp":1790433916692,"version":"4.1.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute on Minority Health"},{"name":"Health Disparities of the National Institutes of Health","award":["2U54MD007597"],"award-info":[{"award-number":["2U54MD007597"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>When LDL cholesterol (LDL-C) estimation equations are benchmarked against \u201cdirect\u201d LDL-C (LDLdirect) values from electronic health records (EHRs), the implicit assumption is that reported direct values derive from chemical assays rather than from calculations. This assumption has not been systematically tested.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed 19 470 same-day lipid panels from the All of Us Research Program (50+ health provider organizations). We defined the effective divisor, Deff = TG\/(TC \u2212 HDL-C \u2212 LDLdirect), where TG is triglycerides and TC is total cholesterol, and tested for evidence that reported \u201cdirect\u201d values were Friedewald-calculated (Deff \u2248 5.0), with validation on the National Health and Nutrition Examination Survey (NHANES) and the Medical Information Mart for Intensive Care IV (MIMIC-IV).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 19 470 panels (from All of Us), 7.6% (1482) were algebraically confirmed Friedewald-substituted (|LDLFW \u2212 LDLdirect| \u2264 0.02 mg\/dL [0.0005 mmol\/L], where LDLFW is the Friedewald-calculated LDL-C) and 31.1% met a broader criterion (\u2264 0.5 mg\/dL [0.013 mmol\/L]). The Deff distribution showed a 27.6-fold spike at 5.0 (z = 68 vs empirical background; z = 263 vs shuffled-LDL null). Contamination deflated observed Friedewald mean absolute error (MAE) by 30.7% (11.85 vs 17.10 mg\/dL [0.306 vs 0.442 mmol\/L]; true MAE 44.3% higher). Near treatment thresholds, contamination masked 12 percentage points of misclassification among near-threshold cases at 70 mg\/dL [1.81 mmol\/L] (26% apparent vs 38% true). Within-patient discordance confirmed substitution (39.6-fold gap, P &amp;lt; 10\u207b\u2075). NHANES validation showed 28.3-fold enrichment. In MIMIC-IV, the spike was absent in measured panels (0.8\u00d7) but present in calculated panels (z = 210).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A minimum of 7.6% of \u201cdirect\u201d LDL-C values in this national multi-site EHR cohort are algebraically confirmed Friedewald-substituted (up to 31.1% under a broader criterion), deflating observed equation error and attenuating the apparent advantage of improved methods. Deff decontamination should be a standard preprocessing step for EHR-based equation benchmarking.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jalm\/jfag098","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T13:24:47Z","timestamp":1784035487000},"source":"Crossref","is-referenced-by-count":2,"title":["Detecting Friedewald-Substituted \u201cDirect\u201d LDL Cholesterol in a National Multi-Site Electronic Health Record Cohort: Prevalence and Benchmarking Impact"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4471-8420","authenticated-orcid":false,"given":"Ronald","family":"Doku","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Howard University College of Medicine , Washington, DC ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nana Yaw A","family":"Osafo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Howard University College of Medicine , Washington, DC ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Kwagyan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Howard University College of Medicine , Washington, DC ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William M","family":"Southerland","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Howard University College of Medicine , Washington, DC ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"2026071409244272300_jfag098-B1","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1093\/clinchem\/18.6.499","article-title":"Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge","volume":"18","author":"Friedewald","year":"1972","journal-title":"Clin Chem"},{"key":"2026071409244272300_jfag098-B2","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1001\/jamacardio.2020.0013","article-title":"A new equation for calculation of LDL-C in patients with normolipidemia and\/or hypertriglyceridemia","volume":"5","author":"Sampson","year":"2020","journal-title":"JAMA Cardiol"},{"key":"2026071409244272300_jfag098-B3","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1001\/jama.2013.280532","article-title":"Comparison of a novel method vs the Friedewald equation for estimating LDL-C levels from the standard lipid profile","volume":"310","author":"Martin","year":"2013","journal-title":"JAMA"},{"key":"2026071409244272300_jfag098-B4","doi-asserted-by":"crossref","first-page":"36","DOI":"10.5334\/gh.1214","article-title":"Accuracy of 23 equations for estimating LDL cholesterol in 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Cardiol"},{"key":"2026071409244272300_jfag098-B14","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1093\/clinchem\/hvad190","article-title":"The Sampson-NIH equation is the preferred calculation method for LDL-C","volume":"70","author":"Sampson","year":"2024","journal-title":"Clin Chem"},{"key":"2026071409244272300_jfag098-B15","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1093\/clinchem\/hvaf073","article-title":"A modified Sampson\u2013NIH equation with improved accuracy for estimating low levels of low-density lipoprotein-cholesterol","volume":"71","author":"Sampson","year":"2025","journal-title":"Clin Chem"},{"key":"2026071409244272300_jfag098-B16","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1093\/clinchem\/hvad199","article-title":"Extensive evidence supports the Martin-Hopkins equation as the LDL-C calculation of choice","volume":"70","author":"Grant","year":"2024","journal-title":"Clin 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