Inflammation and microvascular and macrovascular endothelial dysfunction in rheumatoid arthritis: effect of treatment.

OBJECTIVE: To determine whether abnormalities in microvascular and macrovascular function in rheumatoid arthritis (RA) are associated with plasma markers [von Willebrand factor (VWF)] of endothelial dysfunction and inflammation [C-reactive protein (CRP)] and whether the abnormalities would be altered by treatment. Endothelial dysfunction and inflammation in RA may contribute to adverse cardiovascular events. Although endothelial dysfunction in RA has been demonstrated by altered plasma markers, the relationships with macrovascular and microvascular function are relatively unexplored.

METHODS: We recruited 66 patients with chronic RA, 48 community controls (CC), and 25 patients with diabetes and hypertension as a disease control group (DC). Subjects had venous blood sampled for plasma markers, and underwent laser Doppler perfusion imaging of forearm skin (to assess microvascular circulation) following acetylcholine and sodium nitroprusside iontophoresis, to assess endothelium-dependent and endothelium-independent responses, respectively. Brachial artery flow-mediated dilatation assessed endothelial dysfunction in a macrovascular bed. A subgroup of 29 patients with RA were assessed pretherapy and after 2-4 weeks of antirheumatic therapy.

RESULTS: As expected, patients with RA had higher CRP, erythrocyte sedimentation rate (ESR), and VWF. Endothelium-independent vasoreactivity was abnormal in RA, and this correlated negatively with CRP. All aspects of microvascular function were abnormal in the DC compared to the CC. Macrovascular function was preserved in RA but was abnormal in the DC group. Four weeks of antiinflammatory therapy reduced CRP and ESR but had no effect on any vascular function index in the patients with RA.

CONCLUSION: Patients with RA have abnormal endothelium-independent microvascular function that correlates with inflammation but is not altered by short-term antiinflammatory therapy.