Circulating interleukin 17A and other inflammatory proteins may predict cardiovascular disease in early rheumatoid arthritis

Objective The objective of this study was to investigate the impact of 92 inflammatory proteins on the risk of cardiovascular disease (CVD) in patients with early RA. Methods This study included consecutive patients with early RA recruited 1995-2002. Stored plasma samples were analyzed for 92 inflammatory proteins. CVD diagnoses were retrieved from national in-patient and cause-of-death registries. Statistical analyses were pre-designated as hypothesis-driven or exploratory. For the latter, proteins were selected based on principal component analysis (i.e., factor loading >0.5 within main components). Potential predictors of CVD and coronary artery disease (CAD) were assessed using Cox regression. Results Data on baseline levels of proteins and CVD were available for 163 patients. As hypothesized, levels of IL-17A were associated with CVD [hazard ratio 1.35; 95% confidence interval 1.02-1.78, adjusted for age, sex, hypertension, diabetes, smoking and ESR], while not significantly with CAD. Osteoprotegerin (OPG) levels were significantly associated with both outcomes but only in crude models. No associations were observed for IL-6, TNF-α, monocyte chemotactic protein (MCP)-1 or IL-8. In the exploratory analyses, particularly MCP-3 had significant associations with both outcomes in crude models. Conclusion Circulating IL-17A at RA diagnosis predicted future CVD, although we cannot exclude that this finding is due to multiple testing. The association was independent of traditional CVD risk factors, and of ESR at the time of diagnosis. Furthermore, OPG may be a predictor of CVD. We also identified some novel potential biomarkers for CVD in RA.