title: Brachial artery vasodilator function and systemic inflammation in the Framingham Offspring Study.
abstract: BACKGROUND
  In experimental studies, traditional risk factors and proinflammatory processes alter the regulatory functions of the vascular endothelium to promote atherosclerosis. These alterations include expression of leukocyte adhesion molecules and decreased bioavailability of endothelium-derived nitric oxide, an important regulator of vascular homeostasis and tone. The precise relations among risk factors, inflammation, and nitric oxide bioavailability remain uncertain.
  
  
  RESULTS
  To test the hypothesis that inflammation impairs endothelial function in humans, we measured brachial artery flow-mediated dilation, reactive hyperemia, and serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), soluble intracellular adhesion molecule-1 (sICAM-1), and monocyte chemotactic protein-1 (MCP-1) in 2701 participants from the Framingham Study (mean age 61 years, 53% women). There were modest unadjusted inverse correlations between flow-mediated dilation and CRP, IL-6, and sICAM-1 (P<0.001 for all) that were rendered nonsignificant after accounting for traditional coronary risk factors. For reactive hyperemia, we observed inverse correlations with markers of inflammation in unadjusted models that were attenuated 57% to 74% after accounting for risk factors. However, partial correlations of CRP, IL-6, and sICAM-1 with reactive hyperemia remained significant.
  
  
  CONCLUSIONS
  Our observations are consistent with the hypothesis that risk factors induce a state of inflammation that impairs vascular function. For flow-mediated dilation, we found no evidence that inflammation has additional effects beyond those attributable to traditional risk factors. The incremental contribution of CRP, IL-6, and sICAM-1 to reactive hyperemia above and beyond known risk factors suggests that systemic inflammation may contribute to impaired vasomotor function in forearm microvessels.
authors.affiliation: Evans Memorial Department of Medicine, Boston University School of Medicine, Boston, Mass, USA. jvita@bu.edu
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Vita
authors.forename: John F
authors.initials: JF
authors.lastname: Keaney
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Keyes
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Massaro
authors.forename: Izabella
authors.initials: I
authors.lastname: Lipinska
authors.forename: Birgitta T
authors.initials: BT
authors.lastname: Lehman
authors.forename: Shuxia
authors.initials: S
authors.lastname: Fan
authors.forename: Ewa
authors.initials: E
authors.lastname: Osypiuk
authors.forename: Peter W F
authors.initials: PW
authors.lastname: Wilson
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.forename: Gary F
authors.initials: GF
authors.lastname: Mitchell
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
mesh_terms: D015415:Biomarkers / Q000097:blood; D001916:Brachial Artery / Q000378:metabolism / Q000503:physiopathology*; D002097:C-Reactive Protein / Q000032:analysis; D018932:Chemokine CCL2 / Q000097:blood; D002986:Clinical Trials as Topic; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006940:Hyperemia / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D014664:Vasodilation
chemical_list: D015415:Biomarkers; D018932:Chemokine CCL2; D015850:Interleukin-6; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein