Selenium Deficiency Linked to Anemia in Heart Failure Patients

Amra Jujić, PhD

Credit: Lund University

Findings from a recent study are providing clinicians with an overview of the association between selenoprotein P concentrations and the subsequent risk of anemia in patients with heart failure.

A functional biomarker of selenium status and transport, selenoprotein P deficiency was associated with reduced hemoglobin levels, greater transferrin receptor 1 levels, and an overall increased prevalence of anemia, suggesting selenium deficiency may contribute to poorer iron status and the development of anemia in this patient population.¹

“Understanding these mechanisms may contribute to the development of targeted interventions to improve iron and selenium status and mitigate anemia in various clinical conditions, including heart failure,” wrote Amra Jujić, PhD, of the department of cardiology at Lund University in Sweden, and colleagues.¹

A common comorbidity of heart failure, anemia is associated with poor clinical status and worsened outcomes in this patient population. Estimates of the incidence of anemia in hospitalized heart failure patients range from 10%-50%, and little is known about whether anemia functions as a mediator or simply a marker of heart failure severity. A more comprehensive understanding of the mechanisms underlying the association between anemia and heart failure, as well as other potential influencing factors, is essential for helping these patients achieve better outcomes.^2,3

To assess the relationship between selenoprotein P concentrations and anemia, hemoglobin levels, and iron status in heart failure patients, a team of investigators conducted the HeARt and brain failure inVESTigation study (HARVEST-Malmö) in a cohort of 324 consecutive patients who were hospitalized between March 2014 and June 2018. For inclusion, patients were required to have been admitted to the department of internal medicine or cardiology for the treatment of newly diagnosed or worsened chronic heart failure.¹

Investigators analyzed selenoprotein P in 320 participants, of whom 310 had complete data available to assess the relationship between continuous selenoprotein P concentrations and hemoglobin, anemia, and iron status. For the purpose of analysis, investigators used transferrin receptor 1 levels to determine iron deficiency and defined anemia as hemoglobin < 115 g/L for women and <130 g/L for men.¹

Among the cohort, 30% of participants were female, the mean age was 75.0 (Standard deviation [SD], 11.6) years, and anemia was observed in 133 (42.9%) patients. Investigators noted those with anemia were older, more often male, with lower hemoglobin, greater high-sensitivity C-reactive protein, worse renal function, reduced selenoprotein P levels, and increased expression of transferrin receptor 1.¹

Greater selenoprotein P concentrations were associated with increased hemoglobin concentrations (B = 3.23; P = .002) and lower transferrin receptor 1 concentrations (B = −0.20; P < .001). Conversely, selenoprotein P deficiency was associated with lower hemoglobin concentrations (B = −7.64: P = .001), greater transferrin receptor 1 concentrations (B = 0.31; P = .003), and higher odds of anemia (Odds ratio [OR], 2.17; 95% Confidence interval [CI], 1.23 to 3.82; P = .008).¹

Further analysis revealed selenoprotein P was positively correlated with hemoglobin (Spearman's rho, 0.235; P >.001), and negatively correlated with transferrin receptor 1 (Spearman's rho, −0.265; P <.001) and high-sensitivity C-reactive protein (Spearman's rho, −0.246; P >.001). Further, transferrin receptor 1 was negatively correlated with hemoglobin (Spearman's rho, −0.229; P <.001).¹

In order to account for potential malnutrition factors impacting the concentrations of selenium and iron, investigators incorporated albumin into their analyses. Even after this adjustment, the lowest quartile of selenoprotein P concentrations remained associated with anemia (OR, 1.96; 95% CI, 1.10 to 3.51; P = .024).¹

Further limitations not immediately addressed in the study include its single-center and cross-sectional design, lack of data on dietary intake, and homogeneous patient population consisting predominantly of individuals of Swedish descent. Still, the study’s many strengths help reinforce its findings and lay the foundation for future research about the exact mechanisms by which selenoprotein P influences iron metabolism and the development of anemia.¹

“The results suggest that selenium deficiency, as indicated by lower [selenoprotein P] concentrations, may contribute to the development of anaemia and poorer iron status in [heart failure] patients. Further research is warranted to elucidate the underlying mechanisms,” investigators concluded.¹

References:

1. Jujić A, Molvin J, Isholth HH, et al. Association between low selenoprotein P concentrations and anaemia in hospitalized heart failure patients. ESC Heart Failure. https://doi.org/10.1002/ehf2.14651
2. Anand IS, Gupta P. Anemia and Iron Deficiency in Heart Failure. Circulation. https://doi.org/10.1161/CIRCULATIONAHA.118.030099
3. Silver MA, Anker SD. Anemia and Heart Failure: Guidance for Clinicians and Trialists. July 6, 2021. Accessed January 24, 2024. https://www.acc.org/Latest-in-Cardiology/Articles/2021/07/06/12/18/Anemia-and-Heart-Failure