A New Equation for Calculation of Low-Density Lipoprotein Cholesterol in Patients With Normolipidemia and/or Hypertriglyceridemia | Cardiology | JAMA Cardiology | JAMA Network
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Original Investigation
February 26, 2020

A New Equation for Calculation of Low-Density Lipoprotein Cholesterol in Patients With Normolipidemia and/or Hypertriglyceridemia

Author Affiliations
  • 1Clinical Center, Department of Laboratory Medicine, National Institutes of Health, Bethesda, Maryland
  • 2Prism Health Dx Inc, Austin, Texas
  • 3Pacific Biomarker, Seattle, Washington
  • 4Department of Science and Technology, Laboratory Corporation of America Holdings, Burlington, North Carolina
  • 5NMR Diagnostics, Laboratory Corporation of America Holdings, Burlington, North Carolina
  • 6Cardiovascular Laboratory Medicine, Mayo Clinic, Rochester, Minnesota
  • 7Division of Clinical Core Laboratory Services, Mayo Clinic, Rochester, Minnesota
  • 8Lipoprotein Metabolism Laboratory, Translational Vascular Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland
JAMA Cardiol. 2020;5(5):540-548. doi:10.1001/jamacardio.2020.0013
Key Points

Question  Is it possible to provide a more accurate estimate of low-density lipoprotein cholesterol in patients with hypertriglyceridemia and/or a low level of low-density lipoprotein cholesterol?

Findings  In this decision analytical model, a new low-density lipoprotein cholesterol equation was derived that can be used to more accurately estimate the low-density lipoprotein cholesterol level in patients with plasma triglyceride levels up to 800 mg/dL and is at least equivalent or more accurate than other equations for patients with normolipidemia and a low level of low-density lipoprotein cholesterol.

Meaning  The new low-density lipoprotein cholesterol equation can be readily implemented by clinical laboratories without incurring any additional costs compared with a standard lipid panel and may improve the use of calculated low-density lipoprotein cholesterol in cardiovascular disease risk management.


Importance  Low-density lipoprotein cholesterol (LDL-C), a key cardiovascular disease marker, is often estimated by the Friedewald or Martin equation, but calculating LDL-C is less accurate in patients with a low LDL-C level or hypertriglyceridemia (triglyceride [TG] levels ≥400 mg/dL).

Objective  To design a more accurate LDL-C equation for patients with a low LDL-C level and/or hypertriglyceridemia.

Design, Setting, and Participants  Data on LDL-C levels and other lipid measures from 8656 patients seen at the National Institutes of Health Clinical Center between January 1, 1976, and June 2, 1999, were analyzed by the β-quantification reference method (18 715 LDL-C test results) and were randomly divided into equally sized training and validation data sets. Using TG and non–high-density lipoprotein cholesterol as independent variables, multiple least squares regression was used to develop an equation for very low-density lipoprotein cholesterol, which was then used in a second equation for LDL-C. Equations were tested against the internal validation data set and multiple external data sets of either β-quantification LDL-C results (n = 28 891) or direct LDL-C test results (n = 252 888). Statistical analysis was performed from August 7, 2018, to July 18, 2019.

Main Outcomes and Measures  Concordance between calculated and measured LDL-C levels by β-quantification, as assessed by various measures of test accuracy (correlation coefficient [R2], root mean square error [RMSE], mean absolute difference [MAD]), and percentage of patients misclassified at LDL-C treatment thresholds of 70, 100, and 190 mg/dL.

Results  Compared with β-quantification, the new equation was more accurate than other LDL-C equations (slope, 0.964; RMSE = 15.2 mg/dL; R2 = 0.9648; vs Friedewald equation: slope, 1.056; RMSE = 32 mg/dL; R2 = 0.8808; vs Martin equation: slope, 0.945; RMSE = 25.7 mg/dL; R2 = 0.9022), particularly for patients with hypertriglyceridemia (MAD = 24.9 mg/dL; vs Friedewald equation: MAD = 56.4 mg/dL; vs Martin equation: MAD = 44.8 mg/dL). The new equation calculates the LDL-C level in patients with TG levels up to 800 mg/dL as accurately as the Friedewald equation does for TG levels less than 400 mg/dL and was associated with 35% fewer misclassifications when patients with hypertriglyceridemia (TG levels, 400-800 mg/dL) were categorized into different LDL-C treatment groups.

Conclusions and Relevance  The new equation can be readily implemented by clinical laboratories with no additional costs compared with the standard lipid panel. It will allow for more accurate calculation of LDL-C level in patients with low LDL-C levels and/or hypertriglyceridemia (TG levels, ≤800 mg/dL) and thus should improve the use of LDL-C level in cardiovascular disease risk management.