Renin–angiotensin system molecules are associated with subclinical atherosclerosis and disease activity in rheumatoid arthritis

Objectives: To compare serum levels of RAS components in women with RA versus healthy females and to investigate the association between these molecules and subclinical atherosclerosis. Methods: A cross-sectional study involving female RA patients without ischemic CVD. Disease activity was assessed using the DAS28 and the CDAI. IMT of the common carotid artery was evaluated by ultrasonography. Serum levels of Ang II, Ang-(1-7), ACE and ACE2 were determined by enzyme immunoassay. Results: Fifty women with RA, mean 48.2 (7.3) years, were compared to 30 healthy women, paired by age. RA patients had higher plasma levels of Ang II (p <.01), Ang-(1-7) (p <.01), and ACE (p <.01) than controls. The ratios of ACE to ACE2 were higher in RA patients, whereas Ang II/Ang-(1-7) ratios were lower in RA patients. The presence of hypertension and the treatment with ACE inhibitors did not significantly modify serum levels of Ang II, Ang-(1-7), ACE and ACE2 in patients with RA. Seven RA patients had altered IMT, and eight patients exhibited atherosclerotic plaque. There was a negative correlation between ACE2 levels and IMT (p =.041). IMT positively correlated with age (p =.022), disease duration (p =.012) and overall Framingham risk score (p =.008). Ang II concentrations positively correlated with DAS28 (p =.034) and CDAI (p =.040). Conclusion: Patients with RA had an activation of the RAS, suggesting an association with disease activity and cardiovascular risk.Rheumatological key messages Imbalance of both RAS axes may be associated with cardiovascular risk and disease activity in rheumatoid arthritis. Ultrasonography of the carotid arteries can identify early, subclinical atherosclerotic disease in rheumatoid arthritis patients. Angiotensin-converting enzyme inhibition or angiotensin 1 receptor blockade may be beneficial for rheumatoid arthritis patients.