Abstract 1138: The Oxidized Disulphide Cystine Predicts Adverse Long Term Cardiovascular Outcomes
Introduction: Plasma levels of major amnio-thiol compounds provide a means of quantifying systemic oxidative stress. High levels of the oxidized disulphide cystine have been associated with endothelial dysfunction and risk factor burden in cross sectional studies. We hypothesized that plasma cystine levels would be predictive of adverse long term cardiovascular outcomes in subjects with suspected coronary artery disease.
Methods: We studied 970 patients undergoing coronary angiography, aged 64±11 years, 68.8 % male, and measured cystine levels using HPLC. Patients were followed for “major events” defined as death, MI, hospitalized unstable angina, heart failure or stroke and “all events” which included revascularization, for a mean period of 2.4±1 years. ROC analysis identified the optimal threshold for cystine levels to predict major events as 108uM (sensitivity 40%, specificity 70%).
Results: Patients with high cystine levels (mean 132±21uM) had worse prognosis compared to those with lower levels (mean 87±14uM); the mean time to first event was 3.2 yrs for those with low cystine versus 2.8 yrs for those with high cystine (Kaplan Meier, log rank p=0.003, Figure⇓). Multivariate Cox regression analysis including age, gender, BMI, history of MI, CAD (stenosis >50%), risk factors and cystine group, demonstrated that along with MI, CAD and treated hyperlipidemia, a high cystine level was an independent predictor of both major events (HR 1.59 (1.16 –2.19), p=0.004) and all events (HR 1.43 (1.07–1.93), p=0.017).
Conclusions: Increased oxidative stress measured as plasma cystine levels is predictive of adverse CV outcomes in patients with and without CAD.