Article Text

Method of LDL Cholesterol Measurement Influences Classification of LDL Cholesterol Treatment Goals
  1. Mayank Agrawal, MD, MPH*,
  2. Horace J. Spencer, MS,
  3. Fred H. Faas, MD*
  1. From the Departments of *Internal Medicine and †Biostatistics, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, AR.
  1. Received May 30, 2010, and in revised form September 4, 2010.
  2. Accepted for publication September 5, 2010.
  3. Reprints: Mayank Agrawal, MD, MPH, University of Arkansas for Medical Sciences, 4301 W Markham St, 7D/20 (Old Hospital), Little Rock, AR 72205. E-mail: magrawal{at}
  4. Supported by the Central Arkansas Veterans Healthcare System and, in part, by award number 1UL1RR029884 from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Clinical Research Study


Background Low-density lipoprotein cholesterol (LDL-C) has been clearly associated with the risk of developing coronary heart disease. The best and most convenient method for determining LDL-C has come under increased scrutiny in recent years. We present comparisons of the Friedewald calculated LDL-C (C-LDL-C) and direct LDL-C (D-LDL-C) using 3 different homogenous assays. This highlights differences between the 2 methods of LDL-C measurement and how this affects the classification of samples into different LDL-C treatment goals as determined by the National Cholesterol Education Program Adult Treatment Panel III guidelines thus potentially affecting treatment strategies.

Methods Lipid profiles of a total of 2208 clinic patients were retrieved from the Central Arkansas VA Healthcare System clinical laboratory database. Samples studied were of 1-week period during the 3 periods studied: 2000 (period 1), 2002 (period 2), and 2005 (period 3). Different homogenous assays for D-LDL-C measurement were used for each of the 3 periods.

Results There is a fundamental disagreement between D-LDL-C and C-LDL-C, although Pearson correlation coefficients are 0.93, 0.97, and 0.98 for periods 1, 2, and 3, respectively. Using the model for period 1, when C-LDL-C is 70 mg/dL, the predicted D-LDL-C is 95 mg/dL (36% higher). The differences between C-LDL-C and predicted D-LDL-C progressively decrease at higher LDL-C cut points. In the assay used in period 3, there are 290 samples with D-LDL-C values between 100 and 130 mg/dL. Of these, only 182 samples show agreement with C-LDL-C values, whereas 90 samples with a D-LDL-C in the 100- to 130-mg/dL range are in the 70- to 100-mg/dL range using the C-LDL-C assay. Although the κ statistics suggests the LDL-C measures have relatively high levels of agreement, the significant generalized McNemar tests (P < 0.01) provide additional evidence of disagreement between C-LDL-C and D-LDL-C during all the 3 periods.

Conclusions Our results highlight D-LDL-C measurements using 3 different assays during 3 different periods. In all assays, there is a substantial lack of agreement between D-LDL-C and C-LDL-C, which, in most cases, resulted in higher D-LDL-C values than C-LDL-C. This leads to clinically significant misclassification of patient's LDL-C to a different LDL-C treatment goal, which would potentially result in more drug usage, thus exposing patients to more potential adverse effects and at a much greater cost with little evidence of benefit.

Key Words
  • direct LDL
  • calculated LDL
  • cholesterol

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