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Effects of Angiotensin-Converting Enzyme Inhibition and Statin Treatment on Inflammatory Markers and Endothelial Functions in Patients with Longterm Rheumatoid Arthritis

CANAN TIKIZ, OZAN UTUK, TIMUR PIRILDAR, OZGUR BAYTURAN, PETEK BAYINDIR, FATMA TANELI, HAKAN TIKIZ, and CIGDEM TUZUN

ABSTRACT.

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 1ß (IL-1ß), IL-6, and tumor necrosis factor-a (TNF-a) 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-1ß 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-a concentrations. ACE inhibition with daily 10 mg quinapril was found to have no significant effects on inflammatory markers and endothelial vasodilator response. (J Rheumatol 2005;32:2095-101)

Key Indexing Terms:

RHEUMATOID ARTHRITIS
ENDOTHELIAL FUNCTION
INFLAMMATORY MARKERS
STATIN
ANGIOTENSIN-CONVERTING ENZYME INHIBITOR


From the Department of Physical Medicine and Rehabilitation, Department of Cardiology, Department of Internal Medicine, Division of Rheumatology, Department of Radiology, and Department of Clinical Biochemistry, University of Celal Bayar, Faculty of Medicine, Manisa, Turkey.

C. Tikiz, MD, Assistant Professor; Ç. Tüzün, MD, Professor, Department of Physical Medicine and Rehabilitation; O. Ütük, MD, Assistant Professor; Ö. Bayturan, MD, Assistant Professor; H. Tikiz, MD, Associate Professor, Department of Cardiology; T. Pirildar, MD, Assistant Professor, Division of Rheumatology; P. Bayindir, MD, Assistant Professor, Department of Radiology; F. Taneli, MD, Department of Clinical Biochemistry.

Address reprint requests to Dr. C. Tikiz, 1748 sokak, 26/4, 35530 Karsiyaka, Izmir, Turkey. E-mail; canan.tikiz@bayar.edu.tr

Accepted for publication June 14, 2005.




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