Effects of Angiotensin-converting enzyme inhibition and statin treatment on inflammatory markers and endothelial functions in patients with longterm rheumatoid arthritis

OBJECTIVE: To investigate the effects of angiotensin-converting enzyme (ACE) inhibitors and statins (hydroxy-methyl-glutaryl-CoA reductase inhibitors) on inflammatory markers and endothelial functions in patients with rheumatoid arthritis (RA). METHODS: A total of 45 patients with longterm RA were randomized into 3 groups to receive 8 weeks of treatment with placebo (n = 15), simvastatin (20 mg/day, n = 15), or quinapril (10 mg/day, n = 15) as an adjunct to existing antirheumatic drug treatment. Factors with a role in the development of endothelial dysfunction, such as C-reactive protein (CRP), fibrinogen, nitric oxide (NO), and serum cytokine concentrations including interleukin 1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) were measured at baseline and in the posttreatment period. Brachial artery vasodilator responses were assessed by high resolution ultrasound to evaluate endothelial functions. RESULTS: Simvastatin treatment significantly decreased serum CRP and TNF-a [from 14 +/- 6 to 7 +/- 3 mg/l (p = 0.025) and 30 +/- 5 to 16 +/- 4 pg/ml (p = 0.012), respectively], while quinapril had no significant changes in these 2 measures. IL-1beta and IL-6 showed insignificant changes in patients in the 2 drug groups. Endothelium-dependent vasodilatation was improved significantly in the simvastatin group [from 5.3 +/- 1.1% to 8.9 +/- 1.4% (p = 0.025)], while there was no difference in endothelium-independent vasodilatation [9.0 +/- 1.8% to 11.2 +/- 2.5% (p = 0.17)]. The quinapril group showed no significant changes in both types of vasodilation although there was a tendency to an increase in endothelium-dependent vasodilatation [from 6.1 +/- 0.8% to 7.8 +/- 0.7% (p = 0.06)]. Treatment with the 2 drugs had no significant effects on resting arterial diameter. CONCLUSION: We show that simvastatin 20 mg daily improves endothelial function in patients with RA. Its beneficial effect may be attributed to lowering CRP and TNF-alpha concentrations. ACE inhibition with daily 10 mg quinapril was found to have no significant effects on inflammatory markers and endothelial vasodilator response.