Firstly, we demonstrated that RA is associated with increased aortic stiffness compared with healthy controls, and that aortic stiffness correlates with current, but not historical measures of inflammation. We also established that patients with RA have reduced endothelial function compared with matched control subjects and that endothelial function is independently associated with inflammatory markers.

Having shown that inflammation is a key mediator in aortic stiffening and endothelial dysfunction, we investigated the effect of anti-inflammatory treatments. We demonstrated that anti-TNF-α therapy reduces aortic stiffness and improves endothelial function to a level comparable with healthy individuals. Also, we showed that endothelial function and aortic stiffness can be improved with cholesterol reduction therapies, simvastatin and ezetimibe.

The mechanism by which inflammation leads to aortic stiffening remains unclear. One possible explanation is endothelial dysfunction. We tested this hypothesis by determining whether an improvement of endothelial function with tetrahydrobiopterin (BH₄), leads also to a reduction of aortic stiffness. We showed that BH₄ improves endothelial function, but had no effect on aortic PWV in patients with active RA. This suggests that endothelial dysfunction is not the driving force behind aortic stiffening in RA and that these conditions may just exist in parallel, both influences by inflammation.

The future work will involve exploring other possible mechanisms, which could explain the inflammation-induced aortic stiffening, such as changes in the composition of extracellular matrix and inflammatory cell infiltrations within the aortic wall.