Selenium, selenoprotein P and autoantibodies to selenium transport proteins in Swedish heart failure patients - a pilot study in preparation for a randomized supplementation trial
Authors: Molvin J , Jujic A , Smith J G , Forsgard N , Thunstrom E , Ljungman C , Karlstrom P , Christersson C , James S , Svensson M K , Palmcrantz-Graf E , Hage C , Schomburg L , Dahlstrom U , Magnusson M 
Published: October 2024

Abstract

Background
Severe selenium (Se) deficiency, as in Keshan disease, is associated with a fatal form of heart failure (HF), preventable and reversible with Se supplementation. Recent studies have identified Se deficiency as highly prevalent, up to 70%, among patients with HF, and associated with a poorer prognosis. Observational data suggest that Se concentrations &lt;100 μg/L in HF patients and selenoprotein P (SELENOP) concentrations &lt;4.1 mg/L are associated with increased mortality and hospital readmissions. Further, in recent studies, natural autoantibodies (aAb) towards SELENOP have been detected with the potential to disrupt transportation mechanisms. While the evidence does not yet support Se supplementation for HF patients in clinical practice, it does justify the initiation of large, well-designed randomized controlled trials (RCTs).

Purpose
To assess and confirm the previously reported high prevalence of Se deficiency, measured by both Se and SELENOP concentrations in HF patients and exploring the prevalence of aAb to SELENOP. This will provide a rationale for further, adequately powered and designed, studies of Se supplementation in HF patients.

Methods
A total of 527 blood samples were obtained from a nationwide Swedish HF biobank, sourced from various hospitals. In those samples; serum Se concentrations in 455 samples using mass spectrometry, SELENOP concentrations in 520 samples using an immunoassay, and prevalence of aAb to SELENOP in 513 samples using an immunoluminometric assay were analyzed. In addition, SELENOP concentrations in 320 HF patients from a Swedish single-center study were analysed.

Results
The study population had a mean age of 70.3 (±11.8) years (30.5% women). Prevalence of Se deficiency was higher than previously reported. In the national HF registry, the median Se concentration was 75 µg/L and Se concentrations below 100 μg/L were found in 426 (93%) samples. SELENOP concentrations had a median of 3.5 mg/L, corresponding to ~80 μg/L Se, with 80.5% of subjects below SELENOP-concentration of 4.3 mg/L (corresponding to ~100 μg/L Se). In the confirmatory single-center study, the SELENOP median concentration was 3.1 mg/L, corresponding to Se concentrations of ~70 µg/L and SELENOP -concentrations below 4.3 mg/L (corresponding to approximately 100 μg/L Se) were observed in 89.4% of the study population. Further, aAb to SELENOP were prevalent in 9.7% of the population, compared to approximately 1% in healthy subjects.

Conclusion
This pilot study demonstrates a high prevalence of suboptimal Selenium status in Swedish HF patients which further underscores the need for suitably designed intervention studies to address the efficacy and safety of Se supplementation which can possibly constitute an inexpensive, safe and readily available treatment option for HF patients.