The Potential of Cardiac Biomarkers in Differentiating Disease Subtypes in Patients with Systemic Sclerosis: Focus on GDF15, MR-pro ANP, and suPAR

Systemic sclerosis, a connective tissue disease of unknown etiology and unpredictable outcomes, is characterized by the fibrosis of the skin and internal organs, vasculopathy, and immune system dysregulation. The disease is classified into two main subtypes, which differ in clinical presentation, complications, and prognosis. While several biomarkers have been proposed to distinguish between these subtypes, none have achieved high sensitivity and specificity. The search for dependable markers that can differentiate between the two primary subtypes of systemic sclerosis continues. To address this gap, our study evaluated the utility of novel cardiac biomarkers, including growth differentiation factor 15 (GDF15), galectin-3, mid-regional pro-atrial natriuretic peptide (MR-proANP), glutathione S-transferase π, mid-regional adrenomedullin, and soluble urokinase plasminogen activator receptor (suPAR), in a cohort of 79 patients with both lcSSc and dSSc subtypes. The results demonstrated a significant elevation of GDF15 (medians: 2.07 vs. 1.10 ng/L; <i>p</i> < 0.001) and MR-proANP (92.55 vs. 65.60 pmol/L; <i>p</i> < 0.05) levels in SSc patients compared to healthy controls. Moreover, GDF15 (1.65 vs. 2.34 ng/mL; <i>p</i> < 0.05), MR-proANP (80.87 vs. 109.27 pmol/L; <i>p</i> < 0.05), and suPAR (1.83 vs. 2.44 ng/mL; <i>p</i> < 0.05) levels were notably higher in patients with dSSc compared to those with lcSSc. In the ROC analysis, only GDF-15, MR-proANP, and suPAR proved to have a statistically significant area under the curve (AUC). Patients with the GDF-15 ≥ 2182 ng/mL, MR-prANP ≥ 85.808 pmol/L, and suPAR ≥ 2.315 ng/mL have more than six-, eight-, and seven-times-higher odds for dcSSc, respectively. These findings highlight the potential of GDF15, suPAR, and MR-proANP as biomarkers for differentiating between the two main subtypes of systemic sclerosis.