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Updated: Aug 5, 2026
Imaging Features of Systemic Sclerosis-Associated Interstitial Lung Disease
Published on: June 16, 2020
High levels of vascular cell adhesion molecule-1 associate with a 'vasculopathic' phenotype in systemic sclerosis
Matthew J S Parker1,2,3, Mandana Nikpour2,4, Dylan Hansen5
1Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
Insights
High serum vascular cell adhesion molecule-1 (VCAM-1) levels in systemic sclerosis (SSc) patients are linked to increased mortality, primarily due to vascular disease. This suggests VCAM-1 plays an independent role in SSc pathophysiology.
Area of Science:
- Rheumatology
- Immunology
- Cardiovascular Research
Background:
- Systemic sclerosis (SSc) is a complex autoimmune disease characterized by vascular dysfunction and fibrosis.
- Vascular cell adhesion molecule-1 (VCAM-1) is implicated in inflammatory and vascular processes.
- Understanding biomarkers associated with SSc mortality is crucial for patient management.
Purpose of the Study:
- To investigate the association between serum VCAM-1 levels and cause-specific mortality in patients with SSc.
- To explore the relationship between VCAM-1 levels and specific organ manifestations in SSc.
Main Methods:
- Serum VCAM-1 was measured in 388 SSc participants from the Australian Scleroderma Cohort Study.
- Data were linked with the National Death Index for mortality analysis.
- Participants were stratified into VCAM-1 quartiles, and associations with clinical characteristics and mortality were examined.
Main Results:
- Higher VCAM-1 levels (upper quartile) were significantly associated with increased all-cause mortality (HR 2.17).
- Increased mortality in the highest VCAM-1 quartile was linked to pulmonary arterial hypertension (PAH), SSc-attributable myocardial disease, and digital ulcers.
- No significant differences in established mortality risk factors were observed across VCAM-1 quartiles, except for vascular manifestations.
Conclusions:
- Elevated serum VCAM-1 levels in SSc are associated with increased mortality, driven by vascular complications.
- VCAM-1 may play an independent role in the pathophysiology of systemic sclerosis, beyond established risk factors.
- VCAM-1 could serve as a potential biomarker for vascular disease burden and mortality risk in SSc.
Objectives:
To determine disease-specific associations of serum vascular cell adhesion molecule-1 (VCAM-1) and associated mortality in SSc.
Methods:
Participants were identified from the Australian Scleroderma Cohort Study. Data were linked with the National Death Index for cause-specific mortality. VCAM-1 was measured using a magnetic Luminex assay. Participant characteristics and information on organ specific manifestations were extracted until February 2024. Participants were stratified into VCAM-1 quartiles.
Results:
Of 388 participants, 87.1% were female and 76.8% had limited cutaneous disease. Median age at diagnosis was 45.7 years (interquartile range 36.4-56.7). Participants with upper quartile VCAM-1 (quartile 4; Q4) had increased mortality compared with others [hazard ratio (HR) 2.17, 95% CI 1.54-3.04; P < 0.001]. Despite the significant increased mortality in Q4, there were no statistically significant differences in sex, age, disease duration, disease subtype, autoantibody profile or forced vital capacity across the VCAM-1 quartiles. Q4 were more likely to have pulmonary arterial hypertension (PAH; P = 0.028), SSc-attributable myocardial disease (P = 0.009) and digital ulcers (P = 0.003). In cause-specific mortality analysis, Q4 were more likely to have PAH (HR 3.08, 95% CI 1.68-5.65; P < 0.001), SSc-attributable myocardial disease (HR 2.85, 95% CI 1.51-5.38; P = 0.001) and all-cause cardiovascular disease (HR 2.50, 95% CI 1.60-3.89; P < 0.001) listed as a cause or contributor to death. Q4 VCAM-1 level was not associated with interstitial lung disease presence, severity or cause-specific mortality.
Conclusion:
The increased mortality in participants with SSc and Q4 VCAM-1 levels is attributable to increased frequency of vascular disease manifestations. Q4 participants do not have a disproportionate frequency of other established risk factors for increased mortality, suggesting an independent role for VCAM-1 in disease pathophysiology.
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