Published Online
on November 29, 2004

A more recent version of this article appeared on December 7, 2004

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Submitted on March 29, 2004
Revised on July 10, 2004
Accepted on September 7, 2004

Brachial Artery Vasodilator Function and Systemic Inflammation in the Framingham Offspring Study

Joseph A. Vita MD^*, John F. Keaney Jr MD, Martin G. Larson ScD, Michelle J. Keyes MA, Joseph M. Massaro PhD, Izabella Lipinska PhD, Birgitta T. Lehman RDCS, Shuxia Fan RN, Ewa Osypiuk MD, Peter W.F. Wilson MD, Ramachandran S. Vasan MD, Gary F. Mitchell MD, and Emelia J. Benjamin MD, ScM

From the Evans Memorial Department of Medicine (J.A.V., J.F.K., R.S.V., E.J.B.), Whitaker Cardiovascular Institute (J.A.V., J.F.K., I.L.), and Department of Preventive Medicine (M.G.L., R.S.V., E.J.B.), Boston University School of Medicine, Boston, Mass; Cardiovascular Engineering, Inc (G.F.M.), Holliston, Mass; and the NHLBI’s Framingham Study (M.G.L., M.J.K., J.M.M., B.T.L., S.F., E.O., P.W.F.W., R.S.V., E.J.B.), Framingham, Mass.

^* To whom correspondence should be addressed. E-mail: jvita{at}bu.edu.

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.

Methods and 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.

Key words: endothelium • inflammation • atherosclerosis • risk factors • cardiovascular diseases

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