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-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.