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.


CONCLUSIONS
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.
Tikiz
Canan
C
Department of Physical Medicine and Rehabilitation, University of Celal Bayar, Faculty of Medicine, Manisa, Turkey. canan.tikiz@bayar.edu.tr
Utuk
Ozan
O
Pirildar
Timur
T
Bayturan
Ozgur
O
Bayindir
Petek
P
Taneli
Fatma
F
Tikiz
Hakan
H
Tuzun
Cigdem
C
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D000077583:Quinapril; D019821:Simvastatin / Q000008:administration & dosage*; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; D044005:Tetrahydroisoquinolines; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D002097:C-Reactive Protein; D019821:Simvastatin; D000077583:Quinapril