title: Friedewald-estimated versus directly measured low-density lipoprotein cholesterol and treatment implications.
abstract: OBJECTIVE
  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.
authors.affiliation: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland 21287, USA. smart100@jhmi.edu
authors.forename: Seth S
authors.initials: SS
authors.lastname: Martin
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Blaha
authors.forename: Mohamed B
authors.initials: MB
authors.lastname: Elshazly
authors.forename: Eliot A
authors.initials: EA
authors.lastname: Brinton
authors.forename: Peter P
authors.initials: PP
authors.lastname: Toth
authors.forename: John W
authors.initials: JW
authors.lastname: McEvoy
authors.forename: Parag H
authors.initials: PH
authors.lastname: Joshi
authors.forename: Krishnaji R
authors.initials: KR
authors.lastname: Kulkarni
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Mize
authors.forename: Peter O
authors.initials: PO
authors.lastname: Kwiterovich
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Defilippis
authors.forename: Roger S
authors.initials: RS
authors.lastname: Blumenthal
authors.forename: Steven R
authors.initials: SR
authors.lastname: Jones
mesh_terms: D000328:Adult; D000368:Aged; D001055:Apolipoproteins B / Q000097:blood; D001774:Blood Chemical Analysis / Q000379:methods; D002499:Centrifugation, Density Gradient; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D018570:Risk Assessment; D014280:Triglycerides / Q000097:blood
chemical_list: D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides
keywords: Friedewald equation; HDL-C; LDL-C; NHANES; National Health and Nutrition Examination Survey; VAP; VLDL-C; Vertical Auto Profile; high-density lipoprotein cholesterol; low-density lipoprotein cholesterol; very low density lipoprotein cholesterol