Pos0432 characterization of the cardiovascular disease proteomic profile in spondyloarthritis patients: potential biomarkers for persistent inflammation

Background patients with Spondyloarthritis (SpA) have an increased risk of cardiovascular disease. Taking into account the strong relationship between inflammation and CVD, there is an urgent need to identify different molecular drivers of CVD signs and their association with inflammation. Objectives to investigate the alteration of CVD-related proteins in the plasma of SpA patients, their association with clinical features, and to evaluate their potential role as biomarkers for the identification of persistent inflammation. Methods a cross-sectional study including 120 patients with SpA and 30 age-sex-matched healthy donors (HDs) was carried out. Clinical and laboratory parameters and CVD risk factors were recorded. To measure the presence of persistent inflammation, levels of c-reactive protein (CRP) were collected retrospectively for 5 years previous to the study, a patient was considered to have persistent inflammation with increased CRP in at least 50% of the measures during the previous 5 years. Levels of 92 proteins with a recognized role in CVD were analyzed in the plasma using proximity extension assay (PEA) technology (Olink Target 96 CVD III panel, Cobiomic Biosciences). Results SpA patients showed higher rates of CVD comorbidities compared to HDs. Plasma levels of TNF-R1, RARRES-2, CHI3L1, PGLYRP-1, CTSD, UPAR, IL2RA, TIMP-4, CTSB, GDF-15, MMP-9, and PDGF-A were significantly increased in SpA compared to HDs. Specifically, these proteins are also related to biological processes such as neutrophil degranulation, immune response, cell activation, atherosclerosis, apoptosis, and inflammatory response. Besides, a significant alteration of these CVD-related proteins in SpA was also associated with the presence of arterial hypertension, insulin resistance, obesity, hyperuricemia, and high levels of acute phase reactants. 36% of SpA patients displayed persistence of inflammation. Interestingly, SpA patients with persistent inflammation showed higher levels of ankylosing spondylitis disease activity (ASDAS) score, CRP, glucose, complement component 3, and lower levels of HDL-cholesterol and apolipoprotein A compared to SpA patients with non-persistent inflammation, suggesting the relationship of inflammation with metabolic alterations. In addition, 8 out of 12 CVD-related proteins altered in SpA patients were specifically changed in patients with persistent inflammation: MMP-9, RARRES-2, PGLYRP-1, UPAR, TNF-R1, PDGF-A, IL-2RA and GDF-15, highlighting levels of MMP-9 protein as a potential biomarker for persistent inflammation in SpA (AUC=0.796 p>0.0001). Conclusion 1) SpA patients show an altered CVD proteome profile which is strongly associated with CVD risk factors and clinical inflammatory markers, 2) SpA patients with persistent inflammation display a deeper alteration in their plasma CVD protein pattern suggesting the link between subclinical CVD risk and the chronic inflammation, and 3) this study identifies novel potential biomarkers to distinguish SpA patients with persistent inflammation. Funded by ISCIII (PI20/00079, PMP21/00119, and RICOR-RD21/0002/0033) co-financed by ERDF. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared.