Modern Low-Density Lipoprotein Cholesterol Formulas Outperform Direct Methods in Patients with Hypertriglyceridemia and Low Levels of Low-Density Lipoprotein Cholesterol

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-C_D) assays, 2 modern LDL-C calculation methods [LDL-C Martin (LDL-C_M), LDL-C modified Sampson (LDL-C_S)] and the conventional Friedewald (LDL-C_F) method against the reference method, beta-quantification (LDL-C_BQ). METHODS: A total of 181 remnant sera from patients with standard lipid panel orders or from patients with LDL-C_BQ 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-C_D and lipid panel data were gathered from Abbott Alinity, Roche Cobas, and Siemens Atellica platforms. RESULTS: LDL-C_D among the 3 platforms showed a median CV of 11.2%. In patients with TG <400 mg/dL, LDL-C_M and LDL-C_S demonstrated less bias and less misclassification at the clinical decision LDL-C levels than LDL-C_F or LDL-C_D. In the 400 to 800 mg/dL (9.0 mmol/L) TG group, LDL-C_S was superior to LDL-C_D or LDL-C_M in accuracy. When TG is ≥ 800 mg/dL, LDL-C_D (Roche) showed substantial bias from LDL-C_BQ while LDL-C_S (Roche) showed smaller but significant bias. CONCLUSIONS: In summary, LDL-C_D or LDL-C_F showed little advantage over the 2 modern LDL-C calculation methods. LDL-C_S showed the best overall correlation with LDL-C_BQ and therefore is recommended to replace LDL-C_F and potentially LDL-C_D when making clinical decisions in patients with low LDL-C and hypertriglyceridemia.