The relationship between plasma levels of oxidized and reduced thiols and early atherosclerosis in healthy adults.

ABSTRACT

OBJECTIVES: The study investigated the relationship between biomarkers of oxidative stress and early atherosclerosis. BACKGROUND: Oxidative stress is an important etiologic factor in the pathogenesis of vascular disease. We hypothesized that oxidative stress would predict early atherosclerosis in a relatively healthy population. METHODS: One hundred fourteen healthy non-smokers, without known clinical atherosclerosis, had carotid intima-media thickness (IMT) measured using ultrasound. Oxidative stress was estimated by measuring plasma levels of 1) glutathione (GSH), an important intracellular antioxidant thiol, its oxidized disulfide form (GSSG), and their redox state (E(h) GSH/GSSG), and 2) cysteine (Cys), an important extracellular antioxidant thiol, its oxidized disulfide form cystine (CySS), and their redox state (E(h)Cys/CySS). RESULTS: The univariate predictors of IMT were age, body mass index, low-density lipoprotein cholesterol, triglycerides, high-density lipoprotein cholesterol, high-sensitivity C-reactive protein (hs-CRP), and Framingham risk score. Intima-media thickness was also higher in males and hypertensive subjects. Among the oxidative stress markers, GSH (r = -0.39, p < 0.0001), CySS (r = 0.18, p = 0.049), and E(h) GSH/GSSG (r = 0.34, p < 0.0002) correlated with IMT. After adjusting for traditional risk factors and hs-CRP, only E(h) GSH/GSSG remained an independent predictor of IMT. E(h) GSH/GSSG predicted IMT in a manner that was both independent of and additive to Framingham risk score. CONCLUSIONS: Glutathione redox state (E(h) GSH/GSSG), an in vivo measure of intracellular oxidative stress, is an independent predictor for the presence of early atherosclerosis in an otherwise healthy population. This finding supports a role for oxidative stress in the pathogenesis of premature atherosclerosis, and its measurement may help in the early identification of asymptomatic subjects at risk of atherosclerotic disease.