title: High plasma thiocyanate levels are associated with enhanced myeloperoxidase-induced thiol oxidation and long-term survival in subjects following a first myocardial infarction.
abstract: 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 μM 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.
authors: The Heart Research Institute , Newtown, Sydney , Australia.
authors: P E
authors: PE
authors: Nedoboy
authors: P E
authors: PE
authors: Morgan
authors: T J
authors: TJ
authors: Mocatta
authors: A M
authors: AM
authors: Richards
authors: C C
authors: CC
authors: Winterbourn
authors: M J
authors: MJ
authors: Davies
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000401:mortality; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000097:blood*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012907:Smoking; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D013861:Thiocyanates / Q000097:blood*
chemical_list: D013438:Sulfhydryl Compounds; D013861:Thiocyanates; D009195:Peroxidase; C031760:thiocyanate
keywords: cardiovascular disease; myeloperoxidase; myocardial infarction; protein oxidation; smoking; thiocyanate; thiol oxidation