Clinical implications of discordance between low-density lipoprotein cholesterol and particle number

J Clin Lipidol. Mar-Apr 2011;5(2):105-13. doi: 10.1016/j.jacl.2011.02.001.

Abstract

Background: The amount of cholesterol per low-density lipoprotein (LDL) particle is variable and related in part to particle size, with smaller particles carrying less cholesterol. This variability causes concentrations of LDL cholesterol (LDL-C) and LDL particles (LDL-P) to be discordant in many individuals.

Methods: LDL-P measured by nuclear magnetic resonance spectroscopy, calculated LDL-C, and carotid intima-media thickness (IMT) were assessed at baseline in the Multi-Ethnic Study of Atherosclerosis, a community-based cohort of 6814 persons free of clinical cardiovascular disease (CVD) at entry and followed for CVD events (n = 319 during 5.5-year follow-up). Discordance, defined as values of LDL-P and LDL-C differing by ≥ 12 percentile units to give equal-sized concordant and discordant subgroups, was related to CVD events and to carotid IMT in models predicting outcomes for a 1 SD difference in LDL-C or LDL-P, adjusted for age, gender, and race.

Results: LDL-C and LDL-P were associated with incident CVD overall: hazard ratios (HR 1.20, 95% CI [CI] 1.08-1.34; and 1.32, 95% CI 1.19-1.47, respectively, but for those with discordant levels, only LDL-P was associated with incident CVD (HR 1.45, 95% CI 1.19-1.78; LDL-C HR 1.07, 95% CI 0.88-1.30). IMT also tracked with LDL-P rather than LDL-C, ie, adjusted mean IMT of 958, 932, and 917 microm in the LDL-P > LDL-C discordant, concordant, and LDL-P < LDL-C discordant subgroups, respectively, with the difference persisting after adjustment for LDL-C (P = .002) but not LDL-P (P = .60).

Conclusions: For individuals with discordant LDL-C and LDL-P levels, the LDL-attributable atherosclerotic risk is better indicated by LDL-P.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Atherosclerosis / metabolism*
  • Atherosclerosis / pathology
  • Carotid Arteries / pathology
  • Cholesterol, LDL / chemistry
  • Cholesterol, LDL / metabolism*
  • Female
  • Humans
  • Lipoproteins, LDL / chemistry
  • Lipoproteins, LDL / metabolism*
  • Male
  • Middle Aged
  • Tunica Intima / metabolism
  • Tunica Intima / pathology

Substances

  • Cholesterol, LDL
  • Lipoproteins, LDL