Impact of disease duration on proteomic bioprofile and prognosis in rheumatoid arthritis patients.

Cardiovascular disease worsens the prognosis of rheumatoid arthritis (RA) and vice-versa. Inflammation may be a common pathway for both conditions. It is expected that a longer RA duration leads to a greater inflammatory cumulative exposure burden; however, studies on the association between RA disease duration and outcomes are scarce. Our aim is to compare the characteristics, biomarker expression and outcomes according to the duration of RA. Prospective cohort study including 399 RA patients, with detailed clinical, echocardiographic, and proteomic phenotyping that were compared across tertiles of RA disease duration. Cox proportional models were used to study the association of disease duration with cardiovascular outcomes. RA duration tertiles were: tertile 1 with median of 3.2; tertile 2 with median of 8.8; and tertile 3 with median of 21.8 years. Compared to tertile 1, patients in tertile 3 were older, had more erosive disease, more frequent echocardiographic alterations, lower haemoglobin and walked a shorter distance on the 6MWT. Natriuretic peptides, cathepsin L1, galectin 9, matrix metalloproteinase-12, adrenomedullin and tumour necrosis factor receptor 11A were higher in patients with longer disease duration. Compared to patients in tertile 1, those in tertile 3 had higher risk of a subsequent cardiovascular hospitalisation or cardiovascular death (HR 2.71, 95%CI 1.06-6.92, p=0.04). RA patients with longer disease duration had more organ damage and worse outcomes than those with shorter disease duration. Biomarker expression suggested that patients with longer RA duration had activation of pathways related to inflammation, extracellular matrix organisation, fibrosis and congestion.