LDL particle subclasses, LDL particle size, and carotid atherosclerosis in the Multi-Ethnic Study of Atherosclerosis (MESA)

Samia Mora, Moyses Szklo, James D. Otvos, Philip Greenland, Bruce M. Psaty, David C. Goff, Daniel H. O'Leary, Mohammed F. Saad, Michael Y Tsai, A. Richey Sharrett

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297 Scopus citations


Background: Previous studies showing that smaller low-density lipoprotein (LDL) size is associated with greater atherosclerotic risk did not adequately control for small and large LDL particle correlation. Methods and results: We studied the association of lipoproteins measured by proton nuclear magnetic resonance spectroscopy with carotid intima-media thickness (IMT) in apparently healthy individuals (N = 5538, 38% White, 28% African American, 22% Hispanic, 12% Chinese). Small and large LDL particle concentrations (LDL-p) were inversely correlated (r = -0.63, P < 0.0001). Controlling for risk factors but not for LDL subclass correlation, LDL size and small LDL-p separately were associated with IMT (-20.9 and 31.7 μm change in IMT per 1-S.D., respectively, both P < 0.001), but large LDL-p was not (4.9 μm, P = 0.27). When LDL subclasses were included in the same model, large and small LDL-p were both associated with IMT (36.6 and 52.2 μm higher IMT per 1-S.D., respectively, both P < 0.001; 17.7 and 11.6 μm per 100 nmol/L, respectively). LDL size was not significant after accounting for LDL subclasses and risk factors (P = 0.10). Conclusion: Both LDL subclasses were significantly associated with subclinical atherosclerosis, with small LDL confounding the association of large LDL with atherosclerosis. Future studies of LDL size should account for the strong inverse correlation of LDL subclasses.

Original languageEnglish (US)
Pages (from-to)211-217
Number of pages7
Issue number1
StatePublished - May 2007

Bibliographical note

Funding Information:
This research was supported by contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95169 from the National Heart, Lung, and Blood Institute. The authors thank the other investigators, staff, and participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org .


  • Carotid arteries
  • Lipids
  • Lipoproteins
  • Magnetic resonance spectroscopy
  • Subclinical atherosclerosis


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