The role of plasma aminothiols in the prediction of coronary microvascular dysfunction and plaque vulnerability

Background: Although oxidative stress is considered a key pathogenic step in mediating vascular dysfunction and atherosclerosis development, their association has not been evaluated in human coronary circulation in vivo. Accordingly, we hypothesized that higher oxidative stress would be associated with abnormal coronary epicardial structure and microvascular function. Methods: We measured coronary flow velocity reserve (CFVR) and hyperemic microvascular resistance (HMR) as indices of microvascular function, and epicardial plaque volume and necrotic core using intravascular ultrasound (IVUS) in 47 patients undergoing cardiac catheterization. Plasma glutathione, cystine and their ratio served as measures of oxidative stress while high-sensitivity C-reactive protein (hs-CRP) served as a measure of inflammation. Results: Lower glutathione, a measure of increased oxidative stress was associated with impaired microvascular function [CFVR (r = 0.39, p = 0.01) and HMR (r = -0.43, p = 0.004)], greater plaque burden (r = -0.32, p = 0.03) and necrotic core (r = -0.39, p = 0.008). Similarly, higher cystine/glutathione ratio was associated with impaired microvascular function [CFVR (r = -0.29, p = 0.04)] and greater necrotic core (r = 0.37, p = 0.01). In comparison, higher hs-CRP was associated only with greater necrotic core (r = 0.45, p = 0.003). After multivariate adjustment for age, gender, hypertension, diabetes, acute coronary syndrome presentation, body mass index, tobacco abuse, statin use and hs-CRP, glutathione remained an independent predictor of CFVR, HMR and necrotic core (p < 0.05). Conclusions: Lower plasma glutathione level a measure of increased oxidative stress, was an independent predictor of impaired coronary microvascular function and plaque necrotic core. (C) 2011 Elsevier Ireland Ltd. All rights reserved.