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Comparing a novel equation for calculating low-density lipoprotein cholesterol with the Friedewald equation: A VOYAGER analysis

Journal article
Authors M. K. Palmer
P. J. Barter
P. Lundman
S. J. Nicholls
P. P. Toth
Björn W. Karlson
Published in Clinical Biochemistry
Volume 64
Pages 24-29
ISSN 0009-9120
Publication year 2019
Published at Institute of Medicine, Department of Molecular and Clinical Medicine
Pages 24-29
Language en
Links dx.doi.org/10.1016/j.clinbiochem.20...
Keywords Friedewald, Low-density lipoprotein cholesterol, Non-high-density lipoprotein cholesterol, Very-low-, guidelines, management
Subject categories Clinical Laboratory Medicine

Abstract

Treating elevated low-density lipoprotein cholesterol (LDL-C) to risk-stratified target levels is recommended in several guidelines. Thus, accurate estimation of LDL-C is required. LDL-C is typically calculated using the Friedewald equation: (total cholesterol) - (non-high-density lipoprotein cholesterol [non-HDL-C]) - (triglycerides [TGs]/5). As the equation uses a fixed value equal to 5 as a divisor for TGs, it does not account for inter-individual variability, often resulting in underestimation of risk and potentially undertreatment. It is specifically inapplicable in patients with fasting triglycerides >= 400 mg/dL. A novel method of LDL-C calculation was derived and validated by Martin et al.: (non-HDL-C) - (triglycerides/adjustable factor). This equation uses an adjustable factor, the median TG:very-low-density lipoprotein cholesterol ratio in strata defined by levels of TG and non-HDLC, as divisor for TGs, and the adjustable factor ranging from 3 to 12 has been shown to provide more accurate estimates of LDL-C compared with the Friedewald equation using a direct assay as the gold standard. We used 70,209 baseline and on-treatment lipid values from the VOYAGER meta-analysis database to determine the difference in calculated LDL-C values using the Friedewald and novel equations. In patients with TGs < 400 mg/dL, LDL-C values calculated using the novel equation were plotted against those calculated using the Friedewald equation. The novel equation generally resulted in LDL-C values greater than the Friedewald calculation, with differences increasing with decreasing LDL-C levels; 23% of individuals who reached a LDL-C target of 70 mg/dL with the Friedewald equation did not achieve this target when the novel equation was used to calculate LDL-C; these figures were 8% and 2% for < 100 mg/dL and < 130 mg/dL targets, respectively. In patients with triglycerides >= 400 mg/dL, in whom the Friedewald equation is not valid, lipid values calculated using the novel equation were compared with those obtained by beta-quantification. Values calculated with the novel equation did not appear to be closely related with those calculated by beta-quantification in these patients. In conclusion, the novel equation provides a higher estimation of exact LDL-C values than the Friedewald equation, particularly in patients with low LDL-C levels, which may result in undertreatment of some patients whose LDL-C was calculated using the Friedewald method. However, neither may be suitable for patients with TG >= 400 mg/dL.

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