Free oxygen radicals in whole blood correlate strongly with high-sensitivity C-reactive protein Matthey T. Harris, MD, Warren W. Davis, MD, Ngoc-Anh Le, PhD,* Barry Eggleston, PhD, Garth E. Austin, MD, PhD, Mohamad Moussa, MD, W. Virgil Brown, MD Emory University School of Medicine (Drs. Harris, Le, Brown), 1670 Clairmont Road, Mail Code 151, Decatur, GA 30033, USA; Atlanta VA Medical Center, Atlanta, GA, USA (Drs. Davis, Austin, Moussa); Rho Incorporated, Chapel Hill, NC, USA (Dr. Eggleston) BACKGROUND: Increased concentrations of reactive oxygen molecules are believed to be a driving force in inflammation. Although evident in tissue culture and animal models, it has been difficult to link reactive oxygen species (ROS) and inflammatory markers in humans. In patients recruited to represent a broad spectrum of risk factors, we investigated the relationship between the plasma concentration of oxygen radicals and high-sensitivity C-reactive protein (hs-CRP), utilizing a new chemistry with an easily oxidized chromophore. METHODS: ROS and hs-CRP were measured in blood from 59 fasting subjects selected to have variable risk predicted by classical risk factors. ROS were determined using the free oxygen radical monitor, which is an indirect colorimetric assay for the concentration of hydroperoxides in whole blood. RESULTS: Using log transformation, the correlation between ROS and hs-CRP was r = 0.505 (P  0.0001). This relationship between ROS and hs-CRP was comparable (r = 0.527, P = 0.001) in the subgroup not currently on statin therapy (n = 39). ROS were not correlated with Framingham risk, r =-0.027 (P = 0.84). CONCLUSION: ROS directly measured in human blood correlates strongly with hs-CRP. © 2007 National Lipid Association. All rights reserved. KEYWORDS: Cardiovascular disease; Free oxygen radicals; hs-C-reactive protein; Risk factors Atherosclerosis is linked to an underlying inflammatory process and a state of high oxidative stress. 1–3 Many markers of inflammation have been studied, including soluble adhesion molecules, such as intercellular adhesion molecule-1 and vas- cular cell adhesion molecule-1, inflammatory cytokines inter- leukin (IL)-6, IL-1, tumor necrosis factor- (TNF-), and C-reactive protein (CRP) as indicators of active arteriosclero- sis. 4 To date, high-sensitivity CRP (hs-CRP) has been the most extensively studied and standardized measurement of inflam- mation. It has been well documented to correlate with both prevalence and incidence of arteriosclerotic vascular disease. 5 hs-CRP is made by the liver in response to inflammatory cytokines, such as IL-6, and is therefore an indirect measure of inflammation. 6 IL-6 is believed to be a product of inflamma- tion in the arterial wall, responsive to generation of reactive oxygen species (ROS). ROS (hydroxyl radical, superoxide radical, hydrogen peroxide, and singlet oxygen) are the prod- ucts of several enzyme systems activated during development of arteriosclerosis (e.g., nicotinamide adenine dinucleotide phos- phate [NADPH] oxidase, myeloperoxidase, 5-lipoxygenase). 7–9 In vitro, ROS appears to promote a proinflammatory state through production of cytokines 10 and subsequent stimulation of pro-oxidant enzyme activities. 7,11 The causal * Corresponding author. E-mail address: ale@emory.edu Submitted October 10, 2007. Accepted for publication October 12, 2007. 1933-2874/$ -see front matter © 2007 National Lipid Association. All rights reserved. doi:10.1016/j.jacl.2007.10.008 Journal of Clinical Lipidology (2007) 1, 593–598