Association of multiple inflammatory markers with carotid intimal medial thickness and stenosis (from the Framingham Heart Study)

Am J Cardiol. 2007 Jun 1;99(11):1598-602. doi: 10.1016/j.amjcard.2007.01.036. Epub 2007 Apr 18.


Inflammatory markers, particularly C-reactive protein (CRP), predict incident cardiovascular disease and are associated with the presence of subclinical atherosclerosis. The relations between multiple inflammatory markers and direct measures of atherosclerosis are less well established. Participants in the Offspring Cohort of the Framingham Heart Study (n = 2,885, 53% women, mean age 59 years) received routine assessments of common carotid artery intima-media thickness (CCA-IMT), internal carotid artery intima-media thickness (ICA-IMT), and the presence or absence of > or =25% carotid stenosis by ultrasonography. Circulating inflammatory markers assessed from an examination 4 years later included CRP, interleukin-6 (IL-6), intercellular adhesion molecule-1, monocyte chemoattractant protein-1, P-selectin, and CD40 ligand. Assessed as a group, inflammatory markers were significantly associated with ICA-IMT (p = 0.01), marginally with carotid stenosis (p = 0.08), but not with CCA-IMT. Individually, with an increase from the 25th to 75th percentile in IL-6, there were significant increases in ICA-IMT and carotid stenosis (for ICA-IMT, estimated fold increase 1.04, 95% confidence interval 1.03 to 1.06, p = 0.0004; for carotid stenosis, odds ratio 1.25, 95% confidence interval 1.06 to 1.47, p = 0.007) after adjustment for age, gender, and established risk factors for atherosclerosis. There was a similar significant multivariate-adjusted association of CRP with ICA-IMT but not with carotid stenosis. Smoking appeared to modify the associations of ICA-IMT with CRP (p = 0.009) and with IL-6 (p = 0.006); the association was more pronounced in current (vs former or never) smokers. In conclusion, there were modest associations of inflammatory markers, particularly IL-6, with carotid atherosclerosis. This association appears more pronounced in current smokers than in former smokers and nonsmokers.

Publication types

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

MeSH terms

  • Aged
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • CD40 Ligand / blood
  • Carotid Artery, Common / diagnostic imaging
  • Carotid Artery, Common / metabolism*
  • Carotid Artery, Common / pathology*
  • Carotid Stenosis / blood*
  • Carotid Stenosis / diagnostic imaging
  • Carotid Stenosis / epidemiology
  • Chemokine CCL2 / blood
  • Confounding Factors, Epidemiologic
  • Female
  • Humans
  • Inflammation Mediators / blood*
  • Intercellular Adhesion Molecule-1 / blood
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • P-Selectin / blood
  • Predictive Value of Tests
  • Tunica Intima / diagnostic imaging
  • Tunica Intima / metabolism
  • Tunica Intima / pathology*
  • Tunica Media / diagnostic imaging
  • Tunica Media / metabolism
  • Tunica Media / pathology*
  • Ultrasonography


  • Biomarkers
  • CCL2 protein, human
  • Chemokine CCL2
  • Inflammation Mediators
  • Interleukin-6
  • P-Selectin
  • Intercellular Adhesion Molecule-1
  • CD40 Ligand
  • C-Reactive Protein