Author + information
- Received February 6, 2007
- Revision received April 20, 2007
- Accepted April 22, 2007
- Published online August 28, 2007.
- Kaisa M. Mäki-Petäjä, BSc⁎,1,⁎ (, )
- Anthony D. Booth, MD, MRCP2,⁎,
- Frances C. Hall, DPhil, FRCP†,3,
- Sharon M.L. Wallace, BA, RN⁎,
- John Brown, DM, FRCP‡,
- Carmel M. McEniery, PhD⁎ and
- Ian B. Wilkinson, DM, FRCP2,⁎
- ↵⁎Reprint requests and correspondence:
Kaisa Mäki-Petäjä, Clinical Pharmacology Unit, University of Cambridge, Addenbrooke’s Hospital, BOX 110, Cambridge CB2 0QQ, United Kingdom.
Objectives The aim of this study was to investigate the effect of simvastatin and ezetimibe on inflammation, disease activity, endothelial dysfunction, and arterial stiffness in a cohort of rheumatoid arthritis (RA) patients.
Background Rheumatoid arthritis is a chronic inflammatory condition associated with increased cardiovascular risk. Statins reduce inflammation and disease activity in RA patients, but whether this is due to pleiotropism or cholesterol lowering per se is unclear.
Methods Twenty patients received 20 mg simvastatin or 10 mg ezetimibe each for 6 weeks in a randomized double-blind crossover study. Disease activity, blood pressure, aortic pulse wave velocity (PWV), brachial artery flow-mediated dilation (FMD), and serum inflammatory markers were measured before and after each treatment.
Results Both ezetimibe and simvastatin significantly reduced total cholesterol (−0.62 ± 0.55 mmol/l and −1.28 ± 0.49 mmol/l, respectively; p < 0.001), low-density lipoprotein cholesterol (−0.55 ± 0.55 mmol/l and −1.28 ± 0.49 mmol/l; p < 0.0001), and C-reactive protein (−5.35 ± 9.25 mg/l and −5.05 ± 6.30 mg/l; p < 0.001). Concomitantly, Disease Activity Score (−0.55 ± 1.01 and −0.67 ± 0.91; p = 0.002), aortic PWV (−0.69 ± 1.15 m/s and −0.71 ± 0.71 m/s; p = 0.001), and FMD (1.37 ± 1.17% and 2.51 ± 2.13%; p = 0.001) were significantly improved by both drugs.
Conclusions This study demonstrates that both ezetimibe and simvastatin reduce disease activity and inflammatory markers to a similar extent in patients with RA. Therapy is also associated with a concomitant reduction in aortic PWV and improvement in endothelial function. This suggests that cholesterol lowering per se has anti-inflammatory effects and improves vascular function in RA.
↵1 Kaisa Mäki-Petäjä’s doctoral studies are funded by GlaxoSmithKline.
↵2 Drs. Booth and Wilkinson are supported by grants from the British Heart Foundation.
↵3 Dr. Hall is supported by the British Medical Association’s Doris Hillier Prize and has received an unrestricted grant from Pfizer for the development of a cardiovascular risk reduction website.
The laboratory in which this work was carried out is sponsored by the British Heart Foundation.
- Received February 6, 2007.
- Revision received April 20, 2007.
- Accepted April 22, 2007.
- American College of Cardiology Foundation