{"doi":"10.1093/clinchem/hvaf099","title":"Modern Low-Density Lipoprotein Cholesterol Formulas Outperform Direct Methods in Patients with Hypertriglyceridemia and Low Levels of Low-Density Lipoprotein Cholesterol","abstract":"BACKGROUND: Direct measurement of low-density lipoprotein cholesterol (LDL-C) is widely used and recommended by professional society guidelines despite its potential limitations in patients with hypertriglyceridemia and low LDL-C. This study evaluated the performance of 3 direct LDL-C (LDL-CD) assays, 2 modern LDL-C calculation methods [LDL-C Martin (LDL-CM), LDL-C modified Sampson (LDL-CS)] and the conventional Friedewald (LDL-CF) method against the reference method, beta-quantification (LDL-CBQ). METHODS: A total of 181 remnant sera from patients with standard lipid panel orders or from patients with LDL-CBQ orders with triglycerides (TG) ≥ 400 mg/dL (4.5 mmol/L), or with TG ≥ 150 mg/dL (1.69 mmol/L) and LDL-C < 70 mg/dL (1.8 mmol/L) were included. LDL-CD and lipid panel data were gathered from Abbott Alinity, Roche Cobas, and Siemens Atellica platforms. RESULTS: LDL-CD among the 3 platforms showed a median CV of 11.2%. In patients with TG <400 mg/dL, LDL-CM and LDL-CS demonstrated less bias and less misclassification at the clinical decision LDL-C levels than LDL-CF or LDL-CD. In the 400 to 800 mg/dL (9.0 mmol/L) TG group, LDL-CS was superior to LDL-CD or LDL-CM in accuracy. When TG is ≥ 800 mg/dL, LDL-CD (Roche) showed substantial bias from LDL-CBQ while LDL-CS (Roche) showed smaller but significant bias. CONCLUSIONS: In summary, LDL-CD or LDL-CF showed little advantage over the 2 modern LDL-C calculation methods. LDL-CS showed the best overall correlation with LDL-CBQ and therefore is recommended to replace LDL-CF and potentially LDL-CD when making clinical decisions in patients with low LDL-C and hypertriglyceridemia.","journal":"Clinical Chemistry","year":2025,"id":511622,"datarank":0.41588830833596724,"base_score":2.772588722239781,"endowment":2.772588722239781,"self_citation_contribution":0.41588830833596724,"citation_network_contribution":0.0,"self_endowment_contribution":0.41588830833596724,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9642,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1369685,"name":"Xin Yi","orcid":"0000-0002-6824-0743","position":1,"is_corresponding":false},{"id":597519,"name":"Steven W. Cotten","orcid":"0000-0003-1431-9883","position":2,"is_corresponding":false},{"id":1370393,"name":"J. Nederby Nielsen","orcid":null,"position":3,"is_corresponding":false},{"id":459040,"name":"Leslie J. Donato","orcid":"0000-0003-0126-7623","position":4,"is_corresponding":false},{"id":1369686,"name":"Patricia M Jones","orcid":"0000-0002-7132-7209","position":5,"is_corresponding":false},{"id":475971,"name":"Alagar R Muthukumar","orcid":null,"position":6,"is_corresponding":false},{"id":1239341,"name":"Rafael Zubirán","orcid":"0000-0003-4274-3585","position":7,"is_corresponding":false},{"id":311171,"name":"Alan T. Remaley","orcid":"0000-0003-2473-5549","position":8,"is_corresponding":false},{"id":626155,"name":"Jing Cao","orcid":"0000-0002-3163-8897","position":9,"is_corresponding":false},{"id":850106,"name":"Jeffrey W. Meeusen","orcid":"0000-0002-0784-034X","position":0,"is_corresponding":true}],"reference_count":29,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:47:55.918021Z","pmid":"40899684","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}