Discordance of low-density lipoprotein (LDL) cholesterol with alternative LDL-related measures and future coronary events

Circulation. 2014 Feb 4;129(5):553-61. doi: 10.1161/CIRCULATIONAHA.113.005873. Epub 2013 Dec 17.


Background: Low-density lipoprotein cholesterol (LDL-C) is the traditional measure of risk attributable to LDL. Non-high-density lipoprotein cholesterol (NHDL-C), apolipoprotein B (apoB), and LDL particle number (LDL-P) are alternative measures of LDL-related risk. However, the clinical utility of these measures may only become apparent among individuals for whom levels are inconsistent (discordant) with LDL-C.

Methods and results: LDL-C was measured directly, NHDL-C was calculated, apoB was measured with immunoassay, and LDL-P was measured with nuclear magnetic resonance spectroscopy among 27 533 healthy women (median follow-up 17.2 years; 1070 incident coronary events). Participants were grouped by median LDL-C (121 mg/dL) and each of NHDL-C, apoB, and LDL-P. Discordance was defined as LDL-C greater than or equal to the median and the alternative measure less than the median, or vice versa. Despite high LDL-C correlations with NHDL-C, apoB, and LDL-P (r=0.910, 0.785, and 0.692; all P<0.0001), prevalence of LDL-C discordance as defined by median cut points was 11.6%, 18.9%, and 24.3% for NHDL-C, apoB, and LDL-P, respectively. Among women with LDL-C less than the median, coronary risk was underestimated for women with discordant (greater than or equal to the median) NHDL-C (age-adjusted hazard ratio, 2.92; 95% confidence interval, 2.33-3.67), apoB (2.48, 2.01-3.07), or LDL-P (2.32, 1.88-2.85) compared with women with concordant levels. Conversely, among women with LDL-C greater than or equal to the median, risk was overestimated for women with discordant (less than the median) NHDL-C (0.40, 0.29-0.57), apoB (0.34, 0.26-0.46), or LDL-P (0.42, 0.33-0.53). After multivariable adjustment for potentially mediating factors, including HDL cholesterol and triglycerides, coronary risk remained underestimated or overestimated by ≈20% to 50% for women with discordant levels.

Conclusions: For women with discordant LDL-related measures, coronary risk may be underestimated or overestimated when LDL-C alone is used.

Clinical trial registration url: http://www.clinicaltrials.gov. Unique identifier: NCT00000479.

Keywords: lipids; lipoproteins; primary prevention.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Cohort Studies
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / diagnosis*
  • Coronary Artery Disease / epidemiology
  • Female
  • Follow-Up Studies
  • Humans
  • Lipoproteins, LDL / blood*
  • Magnetic Resonance Spectroscopy / methods
  • Middle Aged
  • Prospective Studies
  • Risk Factors
  • Surveys and Questionnaires


  • Lipoproteins, LDL

Associated data

  • ClinicalTrials.gov/NCT00000479