Underestimation of low density lipoprotein-cholesterol with the friedewald equation versus a direct homogenous low density lipoprotein-cholesterol assay

Background: Low-density lipoprotein cholesterol (LDL-C) concentrations are the primary therapeutic target in patients with atherosclerotic cardiovascular disease (ASCVD). However, at low LDL-C concentrations, there is a significant underestimation using the Friedewald equation compared with ultracentrifugation. Methods: In this pilot study, we compared LDL-C concentrations obtained using the Friedewald equation (LDL-F) vs those concentrations from a direct LDL-C (LDL-D) assay in 152 consecutive specimens from patients with triglyceride levels between 200-399 mg/dL and LDL-F <100 mg/dL. Also, we compared LDL-F and LDL-D results to the novel formula (LDL-N). Results: The LDL-F value was significantly lower than that of LDL-D when LDL concentrations were 70-99 mg/dL (P <.001, 14% negative bias), and this decrease was accentuated in specimens with LDL <70 mg/dL, (P <.001, 27% negative bias). When compared with the LDL-N value, LDL-F and LDL-D values showed a 17% and 2% negative bias for specimens with LDL-C values of 70-99 mg/dL and 36% and 1% negative bias, respectively, at LDL-C <70 mg/dL (P <.001 for comparisons of LDL-F and LDL-N values). Conclusions: To provide accurate LDL-C levels in patients at high risk for ASCVD, if beta quantification by ultracentrifugation is unavailable and if LDL-C is <100 mg/dL and triglycerides are 200-399 mg/dL, laboratories should revert to direct LDL-C measurements or use the novel formula. Although LDL-N is more cost-effective, LDL-D can be run on most platforms, does not require a specimen from a fasting individual, is standardized, and has the advantage of being validated in large trials such as the Heart Protection Study.