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

**Authors:** Justin K. Lui, Fatima El-Adili, Matthew Cozzolino, Morgan Winburn, Marcin A. Trojanowski, Deepa M. Gopal, Michael P. LaValley, Elizabeth S. Klings, Andreea M. Bujor

PMC · DOI: 10.1371/journal.pone.0328734 · PLOS One · 2025-07-31

## TL;DR

This study explores how combining three blood markers helps identify early heart issues in patients with systemic sclerosis, improving risk assessment.

## Contribution

The study introduces a multi-biomarker approach to better detect and assess heart disease risk in systemic sclerosis patients.

## Key findings

- Cluster 3 patients had elevated levels of all three biomarkers and reduced heart strain.
- Cluster 3 had a significantly higher risk of mortality compared to Cluster 1.
- Combining biomarkers improves risk stratification and detection of cardiac disease.

## Abstract

We sought to investigate the relationship between serum biomarkers of cardiac dysfunction, longitudinal strain on echocardiography, and all-cause mortality in patients with systemic sclerosis.

This was an observational study using a biorepository of serum samples of patients with systemic sclerosis who underwent echocardiography. We investigated 3 biomarkers: periostin, galectin-3, and N-terminal prohormone brain natriuretic peptide and applied a K-means clustering resulting in 3 patient clusters. We subsequently measured left ventricular and right ventricular free wall longitudinal strain in each cluster. We then determined the association between each cluster and time to all-cause mortality compared to N-terminal prohormone brain natriuretic peptide, alone.

The 125 patients with systemic sclerosis included in the study were divided into 3 clusters based on biomarker levels (Cluster 1: N = 75; Cluster 2: N = 39; Cluster 3: N = 11). Compared to Cluster 1, Cluster 2 had only elevated periostin levels whereas Cluster 3 had elevated levels of all 3 serum biomarkers and was characterized by reduced left ventricular and right ventricular free wall longitudinal strain, regionally and globally. When adjusted for age, sex, systemic sclerosis disease duration, and forced vital capacity, patients in Cluster 3 had a HR of 14.42 (95% CI: 4.82, 43.18) for all-cause mortality compared to those in Cluster 1.

In conclusion, combining N-terminal prohormone brain natriuretic peptide, periostin, and galectin-3 as serum biomarkers enhances risk stratification and sensitivity in detection of cardiac disease in patients with systemic sclerosis. However, before implementation in routine care, further prospective studies must refine biomarker sensitivity, specificity, and accuracy together with optimizing detection strategies and establishing clinical protocols for integration.

## Linked entities

- **Proteins:** postn (periostin, osteoblast specific factor), LGALS3 (galectin 3)
- **Diseases:** systemic sclerosis (MONDO:0005100), cardiac disease (MONDO:0005267)

## Full-text entities

- **Genes:** POSTN (periostin) [NCBI Gene 10631] {aka OSF-2, OSF2, PDLPOSTN, PN}, LGALS3 (galectin 3) [NCBI Gene 3958] {aka CBP35, GAL3, GALBP, GALIG, L31, LGALS2}
- **Diseases:** Diffuse SSc (MESH:D045743), cardiac strain (MESH:D013180), cardiovascular diseases (MESH:D002318), cerebrovascular disease (MESH:D002561), multiorgan connective tissue disease (MESH:D003240), depressed myocardial deformation (MESH:D003866), SSc renal involvement (MESH:C565423), ILD (MESH:D017563), structural abnormalities (MESH:C566527), lung disease (MESH:D008171), pulmonary edema (MESH:D011654), and aortic (MESH:D001018), Abnormal LV function (MESH:D018487), deaths (MESH:D003643), autoimmune conditions (MESH:D001327), PH (MESH:D006976), myocardial infarction (MESH:D009203), LA dilation (MESH:C565277), renal insufficiency (MESH:D051437), in myocardial deformation (MESH:D009140), mitral, (MESH:D008946), congestive heart failure (MESH:D006333), Abnormal right ventricular function (MESH:D018497), cardiac fibrosis (MESH:D005355), chronic kidney disease (MESH:D051436), Raynaud's (MESH:D011928), COPD (MESH:D029424), SSc (MESH:D012595), cardiopulmonary disease (MESH:D006323), cardiac abnormalities (MESH:D018376), abnormal (MESH:D000014), myocardial fibrotic (MESH:D009202), PAH (MESH:D000081029), impaired renal function (MESH:D007674), sudden cardiac death (MESH:D016757), skin disease (MESH:D012871), cardiac remodeling (MESH:D020257), Valvular disease (MESH:D006349), cardiac complications (MESH:D006331), function (MESH:D003291)
- **Chemicals:** Antinuclear (-), carbon (MESH:D002244)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12312888/full.md

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12312888/full.md

## References

46 references — full list in the complete paper: https://tomesphere.com/paper/PMC12312888/full.md

---
Source: https://tomesphere.com/paper/PMC12312888