Increased arterial stiffness and indication of endothelial dysfunction in long-standing rheumatoid arthritis

Objective: Atherosclerotic progression is accelerated in rheumatoid arthritis (RA). We evaluated arterial stiffness and endothelial dysfunction in RA patients and controls by pulse wave analysis (PWA). Methods: Thirty RA patients with long-standing disease and 30 age- and sex-matched controls were examined using applanation tonometry of the radial artery before and after vasodilation by terbutaline (endothelium dependent) and nitroglycerin (endothelium independent). The aortic augmentation index (AIx) and time to reflected wave (transit time, Tr) were measured. Using the peripheral pulse curve, the stiffness index (SI) and the reflectance index (RI) were calculated. Tr and SI predominantly reflect large artery stiffness, whereas Aix and RI also reflect small vessel resistance. The PWA measurements were assessed in relation to adhesion molecules [soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intracellular adhesion molecule-1 (sICAM-1)], selectins (E, L and P), and inflammation [erythrocyte sedimentation rate (ESR), haptoglobin, interleukin (IL)-6, IL-1 receptor antagonist (IL-1-Ra), IL-2-soluble receptor (IL-2sR), and tumour necrosis factor receptors-I and -II (TNFR-I and TNFR-II)]. Results: RA patients had shorter Tr (p < 0.05) and higher SI (p < 0.001) than controls, indicating impaired large vessel compliance. After terbutaline, Tr remained shorter (p < 0.05), while SI (p < 0.01) and AIx (p < 0.01) were higher. The post-terbutaline changes in AIx and RI (Delta AIx, Delta RI), suggested to be the best PWA measurements of endothelial function, were smaller in RA patients (p=0.06). In RA, L-selectin and sVCAM-1 correlated with Delta RI and L-selectin also with Delta AIx. Both RI and Delta AIx correlated at baseline with a retrospective inflammatory activity score. Conclusion: Arterial stiffness was increased in RA patients. Endothelial dysfunction was implicated and correlated with levels of soluble adhesion molecules. Small vessel resistance correlated with the long-standing inflammatory load in RA.