Time to Make a Change: Assessing LDL-C Accurately in the Era of Modern Pharmacotherapeutics and Precision Medicine
Purpose of Review
The Friedewald equation for estimation of low-density lipoprotein cholesterol (LDL-C) was published in 1972 as an alternative to direct assessment by preparative ultracentrifugation. In this equation, very low-density lipoprotein is estimated by dividing triglycerides by a fixed factor (5 in mg/dL or 2.2 in mmol/L) and subtracting this term from non-high-density lipoprotein cholesterol (non-HDL-C). This method was derived in fasting samples from a small cohort of patients with primarily genetic dyslipidemias followed at the NIH. The method served well as the global standard for LDL-C estimation for decades, but is not well suited to modern clinical practice because it tends to underestimate LDL-C at low LDL-C and high triglyceride levels. The concern is that underestimation could lead to undertreatment in high-risk patients.
Derived from big data and now validated around the world, a novel LDL-C equation created at Johns Hopkins replaces the fixed factor seen in the classic equation with a patient-specific variable based on triglyceride and non-HDL-C levels.
Given its superior accuracy in fasting and non-fasting populations alike, the novel equation is now the preferred method for LDL-C estimation and is being incorporated by leading clinical laboratories.
KeywordsCardiovascular prevention Dyslipidemia Lipid metabolism Friedewald equation Novel low-density lipoprotein equation Precision medicine
Low-density lipoprotein cholesterol
Very low-density lipoprotein cholesterol
Intermediate-density lipoprotein cholesterol
High-density lipoprotein cholesterol
Non-high-density lipoprotein cholesterol
Proprotein convertase subtilisin/kexin type 9
National Cholesterol Education Program
10-year atherosclerotic cardiovascular disease
American College of Cardiology
Cholesterol Treatment Trialists
Improved Reduction of Outcomes: Vytorin Efficacy International Trial
Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk
Compliance with Ethical Standards
Conflict of Interest
SSM and SRJ have patent applications pending on the novel equation for LDL-C estimation. In addition, SSM reports personal fees for serving on scientific advisory boards for Amgen, Sanofi/Regeneron, Quest Diagnostics, and Akcea Therapeutics, as well as grants/research support from the PJ Schafer Cardiovascular Research Fund, the David and June Trone Family Foundation, American Heart Association, Aetna Foundation, Maryland Innovation Initiative, Nokia, Google, Apple, and iHealth.
Authors VP, RQ, ME, RV, and VS have no conflicts of interest to disclose.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: •• Of major importance
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