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(Hypertension. 2008;52:80.)
© 2008 American Heart Association, Inc.

Original Articles

Endothelial Function and Aminothiol Biomarkers of Oxidative Stress in Healthy Adults

Salman Ashfaq; Jerome L. Abramson; Dean P. Jones; Steven D. Rhodes; William S. Weintraub; W. Craig Hooper; Viola Vaccarino; R. Wayne Alexander; David G. Harrison; Arshed A. Quyyumi

From the Division of Cardiology (S.A.), University of Kansas School of Medicine, Wichita; the Division of Cardiology (J.L.A., S.D.R., V.V., R.W.A., D.G.H., A.A.Q.) and Department of Biochemistry (D.P.J.), Emory University School of Medicine, Atlanta, Ga; Christiana Health System (W.S.W.), Newark, Del; and the Centers for Disease Control and Prevention (W.C.H.), Atlanta, Ga.

Correspondence to Arshed A. Quyyumi, Emory University School of Medicine, 1364 Clifton Rd NE, Ste D403C, Atlanta GA 30322. E-mail aquyyum{at}emory.edu

Endothelial dysfunction is known to precede the development of atherosclerosis and results primarily from increased oxidative degradation of NO. We hypothesized that assessment of oxidative stress in the bloodstream will reliably predict endothelial function in healthy adults. A total of 124 healthy nonsmokers had endothelial function assessed using ultrasound measurement of brachial artery flow-mediated vasodilation. Plasma oxidative stress was estimated by measuring the levels of the reduced and oxidized forms of thiols, including glutathione (reduced glutathione and oxidized glutathione) and cysteine (cysteine and cystine), respectively, and the mixed disulfide. Among the traditional risk factors, there were significant and independent correlations between flow-mediated vasodilation and high-density lipoprotein level, body mass index, gender, and the Framingham risk score. Among the thiol markers, plasma cystine (r=–0.23; P=0.009) and the mixed disulfide (r=–0.23; P=0.01) levels correlated with endothelium-dependent but not endothelium-independent vasodilation, even after adjusting for the Framingham risk score and high-sensitivity C-reactive protein level. A higher level of oxidized metabolites was associated with worse endothelial function. In conclusion, the oxidative stress markers, cystine, and the mixed disulfide are independent predictors of endothelial function. These markers, in combination with the Framingham risk score, may help in the early identification of asymptomatic subjects with endothelial dysfunction who are at potentially increased risk for future atherosclerotic disease progression.

Key Words: risk factors • endothelial function • flow mediated vasodilation • antioxidants • oxidative stress

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