Clinical Research
Metabolic Syndrome
Ezetimibe and Simvastatin Reduce Inflammation, Disease Activity, and Aortic Stiffness and Improve Endothelial Function in Rheumatoid Arthritis

https://doi.org/10.1016/j.jacc.2007.04.076Get rights and content
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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.

Abbreviations and Acronyms

AIx
augmentation index
CRP
C-reactive protein
DAS
Disease Activity Score
ESR
erythrocyte sedimentation rate
FMD
flow-mediated dilatation
GTN
glyceryl trinitrate
oxLDL
oxidized low-density lipoprotein
PWV
pulse wave velocity
RA
rheumatoid arthritis

Cited by (0)

The laboratory in which this work was carried out is sponsored by the British Heart Foundation.

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.