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A multi-biomarker approach to risk stratification and detection of early cardiac disease in systemic sclerosis

Justin K Lui1, Fatima El-Adili2,3, Matthew Cozzolino4

  • 1Pulmonary Center, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, United States of America.

Plos One
|July 31, 2025
PubMed

Insights

Elevated cardiac biomarkers in systemic sclerosis patients predict mortality. A combination of N-terminal prohormone brain natriuretic peptide, periostin, and galectin-3 identifies high-risk individuals with reduced cardiac strain.

Area of Science:

  • Cardiology
  • Rheumatology
  • Biomarker Research

Background:

  • Systemic sclerosis (SSc) is associated with significant cardiac morbidity and mortality.
  • Early detection of cardiac dysfunction in SSc is crucial for risk stratification and management.
  • Current diagnostic methods may not fully capture the spectrum of cardiac involvement in SSc.

Purpose of the Study:

  • To investigate the relationship between serum biomarkers of cardiac dysfunction, echocardiographic longitudinal strain, and all-cause mortality in SSc patients.
  • To identify distinct patient clusters based on biomarker profiles and assess their association with mortality.
  • To evaluate the added value of combining multiple biomarkers for cardiac risk assessment in SSc.

Main Methods:

  • Observational study utilizing a biorepository of serum samples from SSc patients who underwent echocardiography.
  • Investigated three serum biomarkers: periostin, galectin-3, and N-terminal prohormone brain natriuretic peptide (NT-proBNP).
  • Applied K-means clustering to stratify patients into three groups based on biomarker levels and assessed cardiac strain and mortality outcomes.

Main Results:

  • 125 SSc patients were divided into three clusters based on biomarker levels.
  • Cluster 3, with elevated levels of all three biomarkers, exhibited reduced left and right ventricular longitudinal strain.
  • Cluster 3 patients had a significantly higher hazard ratio (14.42) for all-cause mortality compared to Cluster 1, even after adjustment for clinical factors.

Conclusions:

  • Combining NT-proBNP, periostin, and galectin-3 enhances risk stratification and sensitivity for detecting cardiac disease in SSc.
  • This multi-biomarker approach identifies patients with significant cardiac dysfunction and increased mortality risk.
  • Further prospective studies are needed to validate these findings and establish clinical protocols for routine implementation.
Abstract

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