Original contribution| Volume 1, ISSUE 6, P593-598, December 2007

Free oxygen radicals in whole blood correlate strongly with high-sensitivity C-reactive protein

Published:October 22, 2007DOI:


      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.


      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.


      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).


      ROS directly measured in human blood correlates strongly with hs-CRP.


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        • Libby P.
        Inflammation in atherosclerosis.
        Nature. 2002; 420: 868-874
        • Tracy R.P.
        Inflammation in cardiovascular disease.
        Circulation. 1998; 97: 2000-2002
        • Ross R.
        Atherosclerosis: an inflammatory disease.
        N Engl J Med. 1999; 340: 115-126
        • Pearson T.A.
        • Mensah G.A.
        • Alexander R.W.
        • et al.
        Markers of inflammation and cardiovascular disease.
        Circulation. 2003; 107: 499-511
        • Ridker P.M.
        Clinical application of C-reactive protein for cardiovascular disease and detection and prevention.
        Circulation. 2003; 107: 363-369
        • Rattazzi M.
        • Puato M.
        • Faggin E.
        • et al.
        C-reactive protein and interleukin-6 in vascular disease: culprits or passive bystanders?.
        J Hypertens. 2003; 21: 1787-1803
        • Griendling K.K.
        • Fitzgerald G.A.
        Oxidative stress and cardiovascular injury.
        Circulation. 2003; 108: 1912-1916
        • Taniyama Y.
        • Griendling K.K.
        Reactive oxygen species in the vasculature, molecular and cellular mechanisms.
        Hypertension. 2003; 42: 1075-1081
        • Griendling K.K.
        • Fitzgerald G.A.
        Oxidative stress and cardiovascular injury.
        Circulation. 2003; 108: 2034-2040
        • Wang Z.
        • Castresana M.R.
        • Newman W.H.
        Reactive oxygen and NF-κB in VEGF-induced migration of human vascular smooth muscle cells.
        Biochem Biophys Res Commun. 2001; 285: 669-674
        • Volk T.
        • Hensel M.
        • Schuster H.
        • et al.
        Secretion of MCP-1 and IL-6 by cytokine stimulated production of reactive oxygen species in endothelial cells.
        Mol Cell Biol. 2000; 206: 105-112
        • Alberti A.
        • Bolognini L.
        • Macciantelli D.
        • et al.
        The radical cation of N,N,-diethyl-para-phenylendiamine: a possible indicator of oxidative stress in biological samples.
        Res Chem Intermed. 2000; 26: 253-267
        • Wilson P.W.F.
        • D’Agostino R.B.
        • Levy D.
        • et al.
        Prediction of coronary heart disease using risk factor categories.
        Circulation. 1998; 97: 1837-1847
        • Herrington D.
        • Kesler K.
        • Reiber J.
        • et al.
        Arterial compliance adds to conventional risk factors for prediction of angiographic coronary artery disease.
        Am Heart J. 2003; 146: 662-667
        • Wang T.D.
        • Chen W.J.
        • Lin J.W.
        • et al.
        Efficacy of fenofibrate and simvastatin on endothelial function and inflammatory markers in patients with combined hyperlipidemia: relations with baseline lipid profiles.
        Atherosclerosis. 2003; 170: 315-323
        • Beswick R.A.
        • Dorrance A.M.
        • Leite R.
        • et al.
        NADH/NADPH oxidase and enhanced superoxide production in the mineralocorticoid hypertensive rat.
        Hypertension. 2001; 38: 1107-1111
        • Rajagopalan S.
        • Kurz S.
        • Munzel T.
        • et al.
        Angiotensin II mediated hypertension in the rat increases vascular superoxide production via membrane NADP/NADPH oxidase activation: contribution to alterations of vasomotor tone.
        J Clin Invest. 1996; 97: 1916-1923
        • Warnholtz A.
        • Nickenig G.
        • Schulz E.
        • et al.
        Increased NADH-oxidase-mediated superoxide production in the early stages of atherosclerosis.
        Circulation. 1999; 99: 2027-2033
        • Sato K.
        • Komaru T.
        • Shioiri H.
        • et al.
        Hypercholesterolemia impairs transduction of vasodilator signals derived from ischemic myocardium.
        Arterioscler Thromb Vasc Biol. 2004; 24: 2034-2039
        • Hink U.
        • Li H.
        • Mollnau H.
        • et al.
        Mechanisms underlying endothelial dysfunction in diabetes mellitus.
        Circ Res. 2001; 88: e14-e22
        • Kim Y.K.
        • Lee M.S.
        • Son S.M.
        • et al.
        Vascular NADH oxidase is involved in impaired endothelium-dependent vasodilation in OLETF rats, a model of type 2 diabetes.
        Diabetes. 2002; 51: 522-527
        • Tomasz J.G.
        • Mussa S.
        • Gastaldi D.
        • et al.
        Mechanisms of increased vascular superoxide production in human diabetes mellitus.
        Circulation. 2002; 105: 1656-1662
        • Folsom A.R.
        • Aleksic N.
        • Catellier D.
        • et al.
        C-reactive protein and incident coronary heart disease in the Atherosclerosis Risk in Communities (ARIC) study.
        Am Heart J. 2002; 144: 233-238
        • Ridker P.M.
        • Cushman M.
        • Stampfer M.J.
        • et al.
        Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men.
        N Engl J Med. 1997; 336: 973-979
        • Ridker P.M.
        • Buring J.E.
        • Cook N.R.
        • et al.
        C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: an 8-year follow-up of 15,218 initially healthy American women.
        Circulation. 2003; 107: 391-397
        • Ridker P.M.
        • Rifai N.
        • Rose L.
        • et al.
        Comparison of C-reactive protein and LDL cholesterol levels in the prediction of first cardiovascular events.
        N Engl J Med. 2002; 347: 1557-1565
        • Koenig W.
        • Sund M.
        • Frolich M.
        • et al.
        C-reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984–1992.
        Circulation. 1999; 99: 237-242
        • Tracy R.P.
        • Lemaitre R.N.
        • Psaty B.M.
        • et al.
        Relationship of C-reactive protein to risk of cardiovascular disease in elderly.
        Arterioscler Thromb Vasc Biol. 1997; 17: 1121-1127
      1. Belcaro G, Carratelli M, Cesarone M, et al. Oxygen free radicals: a method, a product, an application. Int J Angiol. In press.

      2. Iamelle L, Vernocchi A, Amboni P, et al. Normal values of free radicals in newborns and comparison with adults (abstract). Ospedali Riuniti di Bergamo. Clin Pathol Clin Chem Lab (Largo Barozzi). 1:24100.

        • Abramson J.L.
        • Hooper W.C.
        • Jones D.P.
        • et al.
        Association between novel oxidative stress markers and C-reactive protein among adults without clinical coronary disease.
        Atherosclerosis. 2005; 178: 115-121