Association of vitamin D deficiency with inflammatory cytokines and disease severity in chronic heart failure

Abstract

Introduction and aim. Vitamin D deficiency has been associated with impaired cardiovascular dysfunction and adverse outcomes in chronic heart failure (CHF); yet the connection between inflammatory and cardiac biomarkers in different disease severities remains incompletely understood. Therefore, this study aimed to investigate the role of vitamin D and related biochemical parameters in the etiopathophysiology and severity of chronic heart failure. Material and methods. A total of 219 people diagnosed with chronic heart failure, aged 30 and 89 years, were enrolled and stratified according to the functional class (I–II, n=123; III–IV, n=96). An age and sex-matched control group of 51 apparently healthy individuals was included. Serum levels of vitamin D, natriuretic peptide (BNP), N-terminal pro–brain natriuretic peptide (NT-proBNP), interleukin-6 (IL-6), interleukin-18 (IL-18) and tumor necrosis factor-alpha (TNF-α), galectin-3 and fibroblast growth factor-23 (FGF-23) were quantified using validated immunoassays. Comparisons between groups were performed using nonparametric statistical tests. Associations between variables were evaluated using Spearman’s correlation analysis. The diagnostic utility of the selected biomarkers for different levels of severity of CHF was evaluated using receiver operating characteristic (ROC) curve analysis. Results. Vitamin D deficiency was associated with CHF severity. Across increasing NYHA functional classes, serum levels of IL-6, IL-18, TNF-α, BNP, NT-proBNP, galectin-3, and FGF-23 differed significantly (p<0.001). Vitamin D concentrations were positively associated with left ventricular ejection fraction and inversely related to BNP, NT-proBNP, IL-6, IL-18, TNF-α, galectin-3, and FGF-23. ROC analysis indicated that IL-6 (AUC 0.799, sensitivity 75%, specificity 78%) and galectin-3 (AUC 0.791, sensitivity 72%, specificity 80%) were the most discriminative biomarkers in patients with CHF with vitamin D deficiency, supporting their clinical utility for risk stratification and disease monitoring. Conclusion. This study provides novel evidence by integrating inflammatory cytokines, galectin-3, FGF-23, and natriuretic peptides in patients with vitamin D-deficient CHF, identifying IL-6 and galectin-3 as the most discriminative biomarkers of disease severity in this clinical setting.