Biomarkers of endothelial dysfunction are elevated in patients with rheumatoid arthritis with oketsu (blood stasis)

Oketsu is one of the important pathological concepts in Kampo medicine, primarily denoting blood stasis/stagnant syndrome. Previously, we reported a correlation between oketsu and the disease activity of rheumatoid arthritis (RA). Shortening of life span due to cardiovascular disease (CVD) in RA patients has been reported. It is considered that endothelial dysfunction, a preclinical stage of arteriosclerosis, is affected by inflammation and is closely related to the CVD complication in RA patients. In this study, we examined the relationship between oketsu and plasma biomarkers that indicate endothelial dysfunction. The subjects were 50 RA patients who had been receiving constant treatment over the preceding 3 months, and they were divided into oketsu group (n=25) and non-oketsu group (n=25) by oketsu score. Disease activity of RA, neutrophil elastase as inflammation marker, and coagulation factors were measured and compared. Endothelial dysfunction was assessed by plasma biomarkers such as soluble thrombomodulin (sTM), von Willebrand factor (vWF), tissue-plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular adhesion molecule-1 (sVCAM-1). Patient characteristics and disease activity were not significantly different between the two groups, except for the grade of bone deformity. Among biomarkers of endothelial dysfunction, t-PA, sICAM-1 and sVCAM-1 were significantly elevated in RA patients with oketsu. In conclusion, the elevation of biomarkers indicating endothelial dysfunction is assumed to accelerate the progression of arteriosclerosis in RA patients with oketsu.