Comparability of methods for LDL subfraction determination: A systematic review

Atherosclerosis. 2009 Aug;205(2):342-8. doi: 10.1016/j.atherosclerosis.2008.12.011. Epub 2008 Dec 14.


Identifying and aggressively treating individuals at elevated risk of developing cardiovascular disease (CVD) is critical to optimizing health outcomes. The CVD risk factors defined by the National Cholesterol Education Program do not fully predict individuals at high risk of developing CVD. Validation of potential methodologies against a reference method is essential to the adoption of a potential new risk factor to improve risk prediction. Low-density lipoprotein (LDL) subfraction has been advanced as a potential additional CVD risk factor. Currently, there is no reference method for determining LDL subfractions or standardizing the different methods used to measure LDL subfractions. We conducted a systematic review to identify reports comparing two or more methods of measuring LDL subfractions. Nine articles were identified that separated and quantified LDL subfractions by at least two methods. Comparative data were available for nuclear magnetic resonance vs. gel electrophoresis (GE), LipoPrint vs. other GE methods, ultracentrifugation vs. GE, and high performance gel filtration chromatography vs. GE. We found a wide range of agreement (from 7 to 94% concordance for classifying LDL patterns) among methods for LDL subfraction determinations. Different criteria and definitions were used among the articles to classify individuals with respect to CVD risk. No study used CVD or other clinical outcomes as an outcome measure. In summary, the currently available literature does not provide adequate data about comparability in terms of test performance to choose one or another method to serve as a standard nor are data on comparability in terms of predicting CVD outcomes.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review
  • Systematic Review

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / diagnosis
  • Chemistry, Clinical / instrumentation
  • Chemistry, Clinical / methods*
  • Cholesterol, LDL / analysis*
  • Chromatography, Gel / methods
  • Chromatography, High Pressure Liquid
  • Electrophoresis / methods
  • Female
  • Humans
  • Magnetic Resonance Spectroscopy / methods
  • Male
  • Middle Aged
  • Models, Statistical
  • Reproducibility of Results
  • Risk Factors


  • Cholesterol, LDL