Biologic Therapy Improves Lipid-rich Necrotic Core With Concomitant Reduction In S100A8/A9 In Psoriasis: Results From A Prospective, Observational Study

Introduction: S100A8/A9 is an alarmin protein complex secreted by activated neutrophils in response to inflammation and associated with atherosclerosis and cardiovascular disease. Psoriasis is a chronic inflammatory disease linked with increased levels of S100A8/A9, elevated atherosclerotic risk, and premature cardiovascular disease. Lipid-rich necrotic core (LRNC) is a high-risk coronary plaque feature predictive of future cardiovascular events with increased prevalence in psoriasis. Whether S100A8/A9 associates with LRNC is understudied. We aimed to characterize the relationship between S100A8/A9 and LRNC pre- and post-initiation of biologic therapy in psoriasis over 1 year. Methods: Participants were part of an ongoing cohort study of 320 consecutive patients, of whom 125 had comprehensive measurement of S100 proteins by enzyme-linked immunosorbent assay and quantifiable coronary computed tomography angiography scans. LRNC was measured using Elucid Bioimaging software. Results: S100A8/A9 positively associated with neutrophils (R=0.19, P =0.03) and inflammatory markers GlycA (R=0.30, P =0.001) and hs-CRP (R=0.24, P =0.005). Only S100A8/A9 associated with LRNC area (β=0.19, P =0.03) beyond adjustment for cardiovascular risk factors, statin use, biologic therapy, and neutrophils (β=0.22, P =0.02) ( Figure 1A ). Over 1 year, biologic therapy reduced S100A8/A9 levels by 79% (-197 (-320-21.4) vs -42.3 (-167.2-50.5); P =0.04) ( Figure 1B ) and decreased LRNC area by 0.6 mm 2 (0.04 (-0.48-0.77) vs -0.56 (-1.8-0.13); P =0.02) ( Figure 1C ). Conclusion: Of the S100 family, the S100A8/A9 heterodimer uniquely associated with LRNC in fully adjusted models. Further, biologic therapy over 1 year reduced LRNC area concomitantly with S100A8/A9 in psoriasis. These findings underscore the impact of the S100 family in high-risk coronary plaque development and support the need for mechanistic studies to better elucidate these findings.