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.