Formula-dependent LDL-C threshold classification and reporting uncertainty in the UK Biobank.

Authors

Bohao Xue, Teng Ma, Cheng Shen, Xin Pan, Yichen Ling, Liangyu Chu, Wenting Yan, Ningjian Wang, Jin Li, Dachun Xu

Published in

Clinical chemistry and laboratory medicine. Sep 11, 2026. Epub Sep 11, 2026.

Abstract

Calculated low-density lipoprotein cholesterol (LDL-C) is widely reported, but formula-dependent estimation differences may alter classification near decision thresholds. We assessed formula-dependent LDL-C classification relative to direct LDL-C in UK Biobank and examined cardiovascular outcomes descriptively.
We analyzed 397,490 participants after quality-control exclusions and exclusion of those with missing direct LDL-C or triglycerides ≥4.52 mmol/L (≥400 mg/dL). Friedewald, Sampson-NIH, and Martin-Hopkins estimates were compared with the UK Biobank direct LDL-C comparator at a 2.60 mmol/L (100 mg/dL) method-comparison threshold. Analyses assessed threshold discordance, triglyceride strata, apolipoprotein B (apoB)/non-high-density lipoprotein cholesterol (non-HDL-C) phenotypes, threshold-window sensitivity analyses, and narrower atherosclerotic cardiovascular disease (ASCVD) endpoints.
Total threshold discordance was 5.96 % for Friedewald, 3.91 % for Sampson-NIH, and 3.23 % for Martin-Hopkins. Discordance increased with triglycerides. At 2.26-4.51 mmol/L (200-399 mg/dL), Friedewald had the largest negative calculated-minus-comparator difference and discordant low frequency (median difference -0.379 mmol/L; 12.9 %), whereas Martin-Hopkins had smaller differences (median -0.119 mmol/L; 4.3 %). Broad cardiovascular composite and narrower ASCVD endpoint models did not support binary threshold discordance as a stable adverse prognostic marker. Discordant low participants had higher triglycerides, body mass index (BMI), diabetes prevalence, and cholesterol-lowering medication use, but lower apoB and non-HDL-C.
LDL-C formula selection affected classification, especially in triglyceride-rich samples near 2.60 mmol/L (100 mg/dL). Calculated LDL-C may warrant interpretation as an estimate with formula-related uncertainty near decision thresholds; non-HDL-C and, where available, apoB may provide complementary information.

PMID:
42721054
Bibliographic data and abstract were imported from PubMed on 11 Sep 2026.

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