High levels of VCAM-1 independently predict mortality in systemic sclerosis.

Abstract

Introduction/Aim: Systemic sclerosis (SSc) is a systemic autoimmune disease with significant morbidity and mortality. Risk factors for mortality in SSc include increased age, male gender and pulmonary fibrosis as determined by CT scan or pulmonary function. Serum biomarkers have the potential to further refine prognosis. We evaluate the prognostic utility of 28 serum biomarkers in a large national cohort of people with SSc. Method(s): Participants were identified from the Australian Scleroderma Cohort Study and included if sufficient sera and clinical data was available as baseline prior to study commencement (2017). 28 biomarkers were analysed at a single laboratory following manufacturer protocols. Biomarker values were dichotomised with thresholds calculated to maximise discrimination for mortality. Associations between biomarkers and survival were evaluated using univariable and step-wise multivariable Cox regression analysis for pre-specified clinical variables. Result(s): 407 participants with SSc were included (259 SSc-ILD and 179 SSc-controls without ILD); 70 (17.2%) had pulmonary hypertension at baseline. Mean age at biomarker collection of 58.8 years (50.5-66.4), 80 (19.7%) male, disease duration 8.29 years (3.38-16.98), mean follow up 6.31 years (3.11-9.22). Mean FVC% was 92.4% and mean DLco% was 63.6%. On univariable analysis, 16 biomarkers were associated with all-cause mortality. On multivariable analysis, 5 biomarkers (VCAM-1, Endothelin-1, E-selectin, Matrix Metalloproteinase-3 and Surfactant protein-D) remained independently associated with mortality, with VCAM-1 having the strongest association with mortality (HR 3.33; 2.21-5.01; p < 0.001). VCAM-1 remained predictive of mortality following adjustment for DLCO%, pulmonary hypertension, age, gender and ILD (HR 2.76, 1.76-4.35, p < 0.01). The association between VCAM-1 and mortality remained true for participants with ILD (HR 4.04, 2.37-6.90), early SSc (HR 6.57; 2.67-16.19), diffuse (HR 3.72; 1.81-7.63) and limited disease (HR 3.68; 2.23-6.05). Conclusion(s): Serum biomarkers including VCAM-1 are useful in predicting mortality in patients with SSc, with and without ILD, and in early, diffuse and limited disease.