Validating the NIH LDL-C equation in a specialized lipid cohort: Does it add up?

Victoria Higgins; Lawrence A Leiter; Sarah R Delaney; Daniel R Beriault

doi:10.1016/j.clinbiochem.2021.10.003

Validating the NIH LDL-C equation in a specialized lipid cohort: Does it add up?

Clin Biochem. 2022 Jan:99:60-68. doi: 10.1016/j.clinbiochem.2021.10.003. Epub 2021 Oct 14.

Authors

Victoria Higgins¹, Lawrence A Leiter², Sarah R Delaney³, Daniel R Beriault⁴

Affiliations

¹ DynaLIFE Medical Labs, Edmonton, AB, Canada; Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada.
² Departments of Medicine and Nutritional Sciences, University of Toronto, Toronto, ON, Canada; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.
³ Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Laboratory Medicine, St. Michael's Hospital, Toronto, ON, Canada. Electronic address: Sarah.delaney@unityhealth.to.
⁴ Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada; Department of Laboratory Medicine, St. Michael's Hospital, Toronto, ON, Canada. Electronic address: Daniel.beriault@unityhealth.to.

PMID: 34656564
DOI: 10.1016/j.clinbiochem.2021.10.003

Abstract

Background: Guideline recommendations for the management of lipids in patients at risk for cardiovascular disease is largely based on low-density lipoprotein cholesterol (LDL-C) concentration. LDL-C is commonly calculated by the Friedewald equation, which has many limitations. The National Institutes of Health (NIH) equation better estimates LDL-C, particularly in patients with hypertriglyceridemia and/or low LDL-C. We validated the NIH LDL-C equation at the first Canadian clinical laboratory to implement this equation.

Methods: A total of 3161 lipid ultracentrifugation results from a specialized lipid cohort of 2836 patients were included. LDL-C was calculated using the NIH and Friedewald equations and compared to LDL-C measured by ultracentrifugation. We determined the accuracy of these equations at treatment thresholds and developed NIH equation restriction criteria to ensure only accurate results are reported.

Results: Ultracentrifugation LDL-C more strongly correlated with NIH-calculated LDL-C (r² = 0.889) than Friedewald-calculated LDL-C (r² = 0.807) and resulted in fewer non-sensical negative LDL-C values. The correlation for NIH-calculated LDL-C improved to r² = 0.975 after applying our restriction criteria. The NIH equation showed equivalent or superior concordance with ultracentrifugation at treatment thresholds. The LDL-C mean absolute difference increased with increasing TG and decreasing LDL-C concentrations, although the NIH equation was more robust under both conditions.

Conclusions: We validated the NIH equation against ultracentrifugation in a cohort with a wide lipid concentration range, which supported its superiority over the Friedewald equation. We recommend clinical implementing the NIH equation for all patients except those with type III hyperlipoproteinemia or TG > 9.04 mmol/L, with an LDL-C lower reporting limit of <0.50 mmol/L.

Keywords: LDL-C; Lipid; Lipoprotein; Low-density lipoprotein cholesterol; Ultracentrifugation.

Publication types

Validation Study

MeSH terms

Adolescent
Adult
Aged
Aged, 80 and over
Cholesterol, LDL / blood*
Female
Humans
Hyperlipoproteinemia Type III / blood*
Hypertriglyceridemia / blood*
Male
Middle Aged
National Institutes of Health (U.S.)
Ultracentrifugation
United States

Substances

Cholesterol, LDL