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Rheumatology Advance Access originally published online on January 23, 2007
Rheumatology 2007 46(5):759-762; doi:10.1093/rheumatology/kel426
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© The Author 2007. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Endothelial dysfunction precedes atherosclerosis in systemic sclerosis—relevance for prevention of vascular complications

G. Szucs*, O. Tímár1,*, Z. Szekanecz1, H. Dér1, G. Kerekes1, S. Szamosi, Y. Shoenfeld2, G. Szegedi3 and P. Soltész1

Division of Rheumatology, and 1Cardiovascular Unit, Third Department of Medicine, University of Debrecen Medical and Health Science Center, Debrecen, Hungary, 2Department of Medicine B and Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel and 3Research Center for Autoimmune Diseases, Hungarian Academy of Sciences, Debrecen, Hungary.

Correspondence to: Z. Szekanecz, 3rd Department of Internal Medicine, Rheumatology Division, University of Debrecen, Medical and Health Science Center, Hungary, Móricz Zs krt. 22., H-4004 Debrecen, Hungary.E-mail: szekanecz{at}iiibel.dote.hu


   Abstract

Objectives. The pathogenesis of systemic sclerosis (SSc) includes vasculopathy with endothelial dysfunction. The aim of this study was to investigate endothelium-dependent, flow-mediated dilatation (FMD), as well as endothelium-independent, nitroglycerin-mediated dilatation (NMD) of the brachial artery and to assess common carotid intimal-medial thickness (ccIMT) in SSc patients compared with healthy controls.

Methods. FMD and NMD of the brachial artery were determined using high-resolution ultrasound imaging and the values were expressed as percentage change from baseline in 29 SSc patients and 29 healthy controls. The two groups were very similar regarding sex, age and traditional cardiovascular risk factors. In addition, common carotid arteries were assessed by duplex colour ultrasound, ccIMT determined using high resolution ultrasound and expressed in mm thickness in the same patients and controls. Correlations between FMD, NMD, ccIMT, age and the SSc subtype (diffuse or limited form) were analysed.

Results. In the 29 SSc patients (mean age: 51.8 yrs), the FMD was significantly lower (4.82 ± 3.76%) in comparison with the controls (8.86 ± 3.56%) (P < 0.001). No difference was found in NMD between patients (19.13 ± 17.68%) and controls (13.13 ± 10.40%) (P > 0.1). There was a tendency of increased ccIMT in SSc patients (0.67 ± 0.26 mm) compared with healthy subjects (0.57 ± 0.09), but this difference was not significant (P = 0.067). A significant, positive correlation between ccIMT and age in SSc (r = 0.470, P = 0.013) was detected, as well as in healthy controls (r = 0.61, P = 0.003), but no correlation was found between FMD and age. In addition, ccIMT, but not FMD and NMD, displayed significant correlation with disease duration (r = 0.472, P = 0.011). NMD displayed significant inverse correlation with the age in SSc patients (r = –0.492, P = 0.012), but not in controls. We did not find any correlation between FMD, NMD, ccIMT and SSc subtype.

Conclusions. There is an impairment of endothelium-dependent vasodilatation indicated by low FMD in SSc. At the same time, the endothelium-independent dilatation assessed by NMD is still preserved giving an opportunity of nitroglycerine therapy. Carotid atherosclerosis indicated by ccIMT may occur at higher ages and after longer disease duration. Thus, the assessment of FMD in the pre-atherosclerotic stage may have a beneficial diagnostic, prognostic and therapeutic relevance.

KEY WORDS: Systemic sclerosis, Endothelial dysfunction, Atherosclerosis, Flow-mediated vasodilatation, Nitrate-mediated vasodilatation, Intima-media thickness


*Contributed equally to this work.

Submitted 20 April 2006; revised version accepted 30 November 2006.
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