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

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.