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Identifying a target group for selenium supplementation in high-risk cardiac surgery: a secondary analysis of the
Quirin Notz1, Daren K Heyland2,3, Zheng-Yii Lee4,5
1Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Würzburg, Oberdürrbacher Str. 6, 97080, Würzburg, Germany. notz_q@ukw.de.
Background:
Recent data from the randomized SUSTAIN CSX trial could not confirm clinical benefits from perioperative selenium treatment in high-risk cardiac surgery patients. Underlying reasons may involve inadequate biosynthesis of glutathione peroxidase (GPx3), which is a key mediator of selenium's antioxidant effects. This secondary analysis aimed to identify patients with an increase in GPx3 activity following selenium treatment. We hypothesize that these responders might benefit from perioperative selenium treatment.
Methods:
Patients were selected based on the availability of selenium biomarker information. Four subgroups were defined according to the patient's baseline status, including those with normal kidney function, reduced kidney function, selenium deficiency, and submaximal GPx3 activity.
Results:
Two hundred and forty-four patients were included in this analysis. Overall, higher serum concentrations of selenium, selenoprotein P (SELENOP) and GPx3 were correlated with less organ injury. GPx3 activity at baseline was predictive of 6-month survival (AUC 0.73; p = 0.03). While selenium treatment elevated serum selenium and SELENOP concentrations but not GPx3 activity in the full patient cohort, subgroup analyses revealed that GPx3 activity increased in patients with reduced kidney function, selenium deficiency and low to moderate GPx3 activity. Clinical outcomes did not vary between selenium treatment and placebo in any of these subgroups, though the study was not powered to conclusively detect differences in outcomes.
Conclusions:
The identification of GPx3 responders encourages further refined investigations into the treatment effects of selenium in high-risk cardiac surgery patients.
Insights
Perioperative selenium treatment did not show overall clinical benefits in high-risk cardiac surgery patients. However, some patients with specific conditions, like reduced kidney function, showed increased glutathione peroxidase (GPx3) activity, suggesting potential benefits in targeted groups.
Area of Science:
- Biochemistry
- Cardiology
- Nutritional Science
Background:
- Previous trials showed no clear benefit of perioperative selenium in high-risk cardiac surgery.
- Inadequate glutathione peroxidase 3 (GPx3) biosynthesis may limit selenium's effectiveness.
- This study investigates selenium's impact on GPx3 activity and identifies potential responders.
Purpose of the Study:
- To identify patients who respond to selenium treatment with increased GPx3 activity.
- To explore if these responders benefit from perioperative selenium in cardiac surgery.
Main Methods:
- Secondary analysis of 244 patients from the SUSTAIN CSX trial.
- Patients categorized by kidney function, selenium status, and baseline GPx3 activity.
- Serum selenium, SELENOP, and GPx3 activity measured.
Main Results:
- Higher selenium, SELENOP, and GPx3 correlated with less organ injury.
- Baseline GPx3 predicted 6-month survival.
- Selenium increased selenium and SELENOP but not GPx3 in the overall cohort.
- GPx3 activity increased in subgroups with reduced kidney function, selenium deficiency, and low-to-moderate GPx3.
- No significant clinical outcome differences observed between selenium and placebo groups.
Conclusions:
- Identifying GPx3 responders is crucial for future research.
- Further investigation into selenium's effects in specific patient subgroups is warranted.
