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Time to Make a Change: Assessing LDL-C Accurately in the Era of Modern Pharmacotherapeutics and Precision Medicine

  • Lipids (E. Michos, Section Editor)
  • Published:
Current Cardiovascular Risk Reports Aims and scope Submit manuscript

Abstract

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.

Recent Findings

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.

Summary

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.

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Abbreviations

LDL-C:

Low-density lipoprotein cholesterol

VLDL-C:

Very low-density lipoprotein cholesterol

IDL-C:

Intermediate-density lipoprotein cholesterol

HDL-C:

High-density lipoprotein cholesterol

Non-HDL-C:

Non-high-density lipoprotein cholesterol

PCSK9:

Proprotein convertase subtilisin/kexin type 9

TG:

Triglycerides

TC:

Total cholesterol

NCEP:

National Cholesterol Education Program

ASCVD:

10-year atherosclerotic cardiovascular disease

ACC:

American College of Cardiology

CTT:

Cholesterol Treatment Trialists

IMPROVE-IT:

Improved Reduction of Outcomes: Vytorin Efficacy International Trial

FOURIER:

Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk

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Papers of particular interest, published recently, have been highlighted as: •• Of major importance

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Authors and Affiliations

  1. Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins Hospital, 600 N. Wolfe Street, Baltimore, MD, 21287, USA

    Vincent A. Pallazola, Renato Quispe, Rachit Vakil, Vasanth Sathiyakumar, Steven R. Jones & Seth S. Martin

  2. Division of Cardiology, Department of Medicine, Weill Cornell Medical College-Qatar, Education City, Doha, Qatar

    Mohamed B. Elshazly

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  1. Vincent A. Pallazola
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Correspondence to Vincent A. Pallazola.

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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.

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Pallazola, V.A., Quispe, R., Elshazly, M.B. et al. Time to Make a Change: Assessing LDL-C Accurately in the Era of Modern Pharmacotherapeutics and Precision Medicine. Curr Cardiovasc Risk Rep 12, 26 (2018). https://doi.org/10.1007/s12170-018-0590-9

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