Author + information
- Received November 15, 2012
- Revision received January 14, 2013
- Accepted January 14, 2013
- Published online August 20, 2013.
- Seth S. Martin, MD⁎,⁎ (, )
- Michael J. Blaha, MD⁎,
- Mohamed B. Elshazly, MD⁎,
- Eliot A. Brinton, MD†,
- Peter P. Toth, MD, PhD‡,§,
- John W. McEvoy, MB BCh⁎,
- Parag H. Joshi, MD⁎,
- Krishnaji R. Kulkarni, PhD∥,
- Patrick D. Mize, PhD∥,
- Peter O. Kwiterovich, MD⁎,
- Andrew P. DeFilippis, MD⁎,¶,
- Roger S. Blumenthal, MD⁎ and
- Steven R. Jones, MD⁎
Reprint requests and correspondence:
Dr. Seth S. Martin, Division of Cardiology, Johns Hopkins Hospital, 600 North Wolfe Street, Carnegie 565-G, Baltimore, Maryland 21287
Objectives The aim of this study was to compare Friedewald-estimated and directly measured low-density lipoprotein cholesterol (LDL-C) values.
Background LDL-C is routinely estimated by the Friedewald equation to guide treatment; however, compatibility with direct measurement has received relatively little scrutiny, especially at levels <70 mg/dl now targeted in high-risk patients.
Methods We examined 1,340,614 U.S. adults who underwent lipid profiling by vertical spin density gradient ultracentrifugation (Atherotech, Birmingham, Alabama) from 2009 to 2011. Following standard practice, Friedewald LDL-C was not estimated if triglyceride levels were ≥400 mg/dl (n = 30,174), yielding 1,310,440 total patients and 191,333 patients with Friedewald LDL-C <70 mg/dl.
Results Patients were 59 ± 15 years of age and 52% were women. Lipid distributions closely matched those in the National Health and Nutrition Examination Survey. A greater difference in the Friedewald-estimated versus directly measured LDL-C occurred at lower LDL-C and higher triglyceride levels. If the Friedewald-estimated LDL-C was <70 mg/dl, the median directly measured LDL-C was 9.0 mg/dl higher (5th to 95th percentiles, 1.8 to 15.4 mg/dl) when triglyceride levels were 150 to 199 mg/dl and 18.4 mg/dl higher (5th to 95th percentiles, 6.6 to 36.0 mg/dl) when triglyceride levels were 200 to 399 mg/dl. Of patients with a Friedewald-estimated LDL-C <70 mg/dl, 23% had a directly measured LDL-C ≥70 mg/dl (39% if triglyceride levels were concurrently 150 to 199 mg/dl; 59% if triglyceride levels were concurrently 200 to 399 mg/dl).
Conclusions The Friedewald equation tends to underestimate LDL-C most when accuracy is most crucial. Especially if triglyceride levels are ≥150 mg/dl, Friedewald estimation commonly classifies LDL-C as <70 mg/dl despite directly measured levels ≥70 mg/dl, and therefore additional evaluation is warranted in high-risk patients.
Atherotech provided the investigators with de-identified data generated from commercial lipid analyses. This was an investigator-initiated study and Atherotech did not provide payments for the research or writing of the manuscript. Atherotech did not participate in the analysis of the data or influence the conclusions. Dr. Brinton is on the medical advisory board for Atherotech, Inc.; has received compensation for consultancy and lecturers from Abbott Laboratories, AstraZeneca, Merck & Co., Bristol-Myers Squibb, Daiichi Sankyo Inc., Kaneka Pharma America, Takeda Pharmaceuticals, Kowa Pharmaceuticals, GlaxoSmithKline, Boehringer Ingelheim, LipoScience Inc., Amarin Pharmaceuticals, Health Diagnostics Laboratory, Roche/Genentech, Essentialis, Arisaph; and has received research grants from Abbott Laboratories, Merck & Co., Amarin Pharmaceuticals, Health Diagnostics Laboratory, and Roche/Genentech. Dr. Toth is on the medical advisory board for Atherotech, Inc.; has received compensation for consultancy and lecturers from Abbott Laboratories, Aegerion, Amgen, Amylin, AstraZeneca, GlaxoSmithKline, Kowa, and Merck & Co. Dr. Kulkarni is the Atherotech Diagnostics Lab Research Director; and receives royalty from the University of Alabama in Birmingham. Dr. Mize was an employee of Atherotech Diagnostics Lab during this study. Dr. Kwiterovich received compensation for consultancy from Merck & Co; and research grants from Pfizer. Dr. DeFilippis is a compensated study adjudicator for Radiometer. Dr. Jones is on the medical advisory board for Atherotech, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received November 15, 2012.
- Revision received January 14, 2013.
- Accepted January 14, 2013.
- American College of Cardiology Foundation