High plasma thiocyanate levels are associated with enhanced myeloperoxidase-induced thiol oxidation and long-term survival in subjects following a first myocardial infarction

摘要

Elevated levels of myeloperoxidase (MPO) are associated with poor cardiovascular outcomes. MPO uses H2O2 to generate oxidants including HOCl and HOSCN, from chloride and thiocyanate (SCN-) ions, respectively. SCN- is the preferred substrate. Elevation of this anion decreases HOCl generation and increases HOSCN formation, a thiol-specific oxidant. Such changes are of potential relevance to people with elevated SCN- levels, such as smokers. In this retrospective study, we examined whether elevated plasma MPO and SCN- levels increased thiol oxidation as a result of increased HOSCN formation, and impacted on long-term survival in 176 subjects (74 non-smokers, 46 smokers, and 56 previous smokers) hospitalized after a first myocardial infarction. Plasma thiols were not significantly altered in smokers compared to non-smokers or past smokers. However, significant positive correlations were detected between SCN- levels and MPO-induced thiol loss in the total population (r = 0.19, P = 0.020) and smokers alone (r = 0.58, P < 0.0001). Twelve-year all-cause mortality data indicate that above median MPO is significantly associated with higher mortality, but below-median MPO and above-median SCN- results in increased survival, compared to below-median SCN-. Cox proportional hazard analysis showed a significant decrease in mortality for each 1 mu M increase in SCN- (0.991; P = 0.040). Subject age was, as expected, a strong predictor of subject survival. Overall these data suggest that subjects with below-median MPO and above-median SCN- have better long-term survival, and that elevated plasma levels of SCN- might be protective in at least some populations.