High levels of Vascular Cell Adhesion Molecule 1 associate with a “vasculopathic” phenotype in systemic sclerosis with higher mortality

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ID: 322835
2026
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Abstract
Abstract Objectives To determine disease-specific associations of serum vascular cell adhesion molecule-1 (VCAM-1) and associated mortality in systemic sclerosis (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 (IQR 36.4-56.7). Participants with upper quartile VCAM-1 (Q4) had increased mortality compared to others (HR 2.17, 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;1.68-5.65, p < 0.001), SSc-attributable myocardial disease (HR 2.85;1.51-5.38, p = 0.001) and all-cause cardiovascular disease (HR 2.50;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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Authors Matthew Parker, Mandana Nikpour, Dylan Hansen, Aimee Hanson, Joanne Sahhar, Matthew A Brown, Tamera J. Corte, Susanna Proudman, Tony Kenna, Australian Scleroderma Interest Group, Maryam Tabesh, Jennifer Ng, Kelly Hollis, Linda Bradbury, Lauren Host, Kim Griggs, Leah McWilliams, Jennifer Walker, Nava Ferdowsi, Gene-Siew Ngian, Emily Lin, Diane Apostolopoulos, Peter Youssef, Madana Nikpour, Stephanie Frade, T. Hibbert, Helen Cooley, Gabor Major, Gemma Strickland, Lindsey Bunce, Helen Marsden, Shereen Paramalingam, Alannah Quinlivan, Laura Ross, Peter Wong, Mathuja Bavanendrakumar, Amanda Saracino, Jessica Fairley, Kimti Kumar, Lucy Croyle, Mahin Moghaddami, Ross Penglase, Tamera Corte, Zoe Brown, Wendy Stevens
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Journal Lara D. Veeken
Year 2026
DOI
10.1093/rheumatology/keag391
URL
https://doi.org/10.1093/rheumatology/keag391
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