Abstract

Rheumatic heart disease (RHD) remains a persistent public health challenge, particularly prevalent in developing and underdeveloped regions despite concerted global eradication efforts. The progressive stage of RHD, marked by valvular calcification, necessitates the imperative need to identify prognostic biomarkers. Fetuin-A, well-known for its role as a negative inhibitor of ectopic calcification, is investigated in our study as a potential biomarker for cardiac valve calcification in RHD patients. Individuals with confirmed presence of RHD via echocardiography, who exhibited moderate to severe cardiac valve involvement, were enrolled alongside age and sex-matched healthy controls. Enzyme Linked Immunosorbent Assay was performed to analyse serum concentration of fetuin-A in healthy controls and RHD patients. Cytokine profiling was carried out using Cytometric Bead Array. Sixty confirmed RHD patients along with age and sex-matched case-control were evaluated for their serum fetuin-A and serum cytokines levels. Our findings reveal significantly reduced serum fetuin-A levels in RHD patients (1.96 ± 0.608 ng/ml) compared to healthy controls (2.85 ± 0.55 ng/ml) (p < 0.0001). Cytokine profiling shows nearly two-fold elevations in interleukin (IL)-17A, tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), IL-6, IL-10, IL-4 and IL-2 levels among RHD patients versus healthy controls, with IL-6 showing the maximum elevation in serum concentration. Pearson's correlation coefficient (r) values indicate a strong negative correlation between fetuin-A levels in RHD patients and various inflammatory cytokines, including IL-17A (-0.9754), IFN-γ (-0.8142), TNF-α (-0.8281), IL-10 (-0.9183), IL-6 (-0.8479), IL-4 (-0.9182) and IL-2 (-0.9430) (p < 0.05, statistically significant). This study suggests that fetuin-A can be explored as a plausible biomarker for cardiac valve calcification and has an inverse correlation with inflammatory cytokines involved in RHD.

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