Selenium-Binding Protein 1 Indicates Myocardial Stress and Risk for Adverse Outcome in Cardiac Surgery.

Selenium-binding protein 1 (SELENBP1) is an intracellular protein that has been detected in the circulation in response to myocardial infarction. Hypoxia and cardiac surgery affect selenoprotein expression and selenium (Se) status. For this reason, we decided to analyze circulating SELENBP1 concentrations in patients (n = 75) necessitating cardioplegia and a cardiopulmonary bypass (CPB) during the course of the cardiac surgery. Serum samples were collected at seven time-points spanning the full surgical process. SELENBP1 was quantified by a highly sensitive newly developed immunological assay. Serum concentrations of SELENBP1 increased markedly during the intervention and showed a positive association with the duration of ischemia (ρ = 0.6, p < 0.0001). Elevated serum SELENBP1 concentrations at 1 h after arrival at the intensive care unit (post-surgery) were predictive to identify patients at risk of adverse outcome (death, bradycardia or cerebral ischemia, "endpoint 1"; OR 29.9, CI 3.3-268.8, p = 0.00027). Circulating SELENBP1 during intervention (2 min after reperfusion or 15 min after weaning from the CPB) correlated positively with an established marker of myocardial infarction (CK-MB) measured after the intervention (each with ρ = 0.5, p < 0.0001). We concluded that serum concentrations of SELENBP1 were strongly associated with cardiac arrest and the duration of myocardial ischemia already early during surgery, thereby constituting a novel and promising quantitative marker for myocardial hypoxia, with a high potential to improve diagnostics and prediction in combination with the established clinical parameters.

Circulating levels of selenium-binding protein 1 (SELENBP1) are associated with risk for major adverse cardiac events and death.

OBJECTIVE: Selenium-binding protein 1 (SELENBP1) is an intracellular protein with variable expression in response to cellular stress. As the selenium (Se) status is affected by inflammation and hypoxia, we hypothesized that SELENBP1 contributes to disease-specific Se metabolism. To test this hypothesis, a quantitative assay was developed and used to monitor SELENBP1 in patients with acute coronary syndrome (ACS). MATERIALS AND METHODS: SELENBP1 was expressed, antibodies were generated and a luminometric immuno assay (LIA) was established and characterized. Serum samples were collected from controls (n = 37) and patients (n = 85) admitted to the Chest Pain Unit with suspected ACS. Blood samples were available from time of first medical contact in the ambulance, at admission to hospital, and after 2, 4, 6 and 12-36 h. RESULTS: Circulating SELENBP1 was close to limit of detection in healthy controls and elevated in patients with suspected ACS. SELENBP1 was unrelated to other biomarkers of myocardial damage such as troponin T or aspartate aminotransferase. Serum SELENBP1 enabled a categorization of patients on first medical contact as either high-risk or low-risk for major adverse cardiac events (MACE) or death, when using 0.8 nmol/l as threshold. The odds-ratios (OR) for MACE and death were OR = 11 (95% CI: 2-49, p = 0.0022) and OR = 12 (2-74, p = 0.014), respectively. CONCLUSIONS: Until now, SELENBP1 was mainly considered as an intracellular protein involved in Se metabolism and redox control. Our data indicate that SELENBP1 constitutes a circulating biomarker for cardiac events categorizing patients with suspected ACS at first medical contact into high-risk or low-risk for MACE and death, independent from and complimentary to current biomarkers.