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

Abstract

To determine disease-specific associations of serum vascular cell adhesion molecule-1 (VCAM-1) and associated mortality in systemic sclerosis (SSc). 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. 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. 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.