Introduction Several systemic autoimmune diseases are associated with an increased prevalence of atherosclerosis which could not be explained by traditional risk factors alone. In systemic sclerosis (SSc), microvascular abnormalities are well recognized. Previous studies have suggested an increased prevalence of macrovascular disease as well. We compared patients with SSc to healthy controls for signs of early atherosclerosis by measuring intima-media thickness (IMT) of the common carotid artery in relation to traditional risk factors and markers of endothelial activation.

Atherosclerosis is considered to be a chronic inflammatory disorder. Several autoimmune rheumatic diseases are characterized by premature and accelerated atherosclerosis in which both classical and non-classical risk factors contribute to atherogenesis. SSc is characterized by vasculopathy, and microvascular involvement is common. Macrovascular involvement is considered rare, although increased prevalence of macrovascular disease has been reported as well. Here, we review the literature regarding coronary artery disease, cerebrovascular disease and peripheral arterial disease in SSc. An increased prevalence of distal peripheral artery disease in the digits has been found. The prevalence of coronary artery disease and cerebrovascular disease is not increased, although studies using intima-media thickness of the carotid artery as a marker of early atherosclerosis showed discrepant results. Besides traditional risk factors, as present in the general population, non-traditional risk factors are present in SSc as well, such as increased lipoprotein(a), oxidized LDL, inflammation, vasospasm and endothelial dysfunction. Moreover, markers of vascular damage in atherosclerosis, like antibodies to oxidized LDL, and increased levels of soluble vascular adhesion molecules, have been described in association with vascular damage in SSc. Nevertheless, generalized premature atherosclerosis has not been detected in SSc. Therefore, further research is necessary to assess the prevalence of clinically manifest or subclinical early atherosclerosis in SSc.

R aynaud's phenomenon (RP) is present in more than 95% of patients with systemic sclerosis (SSc). Its frequency and severity in combination with the presence of digital ulcers affect the quality of life of patients. 1 Although the aetiology of RP is multifactorial, endothelin-1 has been suggested to play a role in its pathogenesis. 2 Bosentan, an endothelin-1 receptor antagonist, has been shown to be effective in preventing the occurrence of new digital ulcers when compared with placebo. 3 Against this background, we hypothesized that bosentan can be a useful and effective strategy in SSc patients with RP. Therefore we assessed the effects of bosentan on RP on subjective and objective outcome parameters. Patients were allowed to continue their oral vasodilating therapy, but parenteral prostanoids had to be stopped one month before study entry.Fifteen patients (14 women, one man; mean age 52 years, range 34-70) were included. All had limited cutaneous SSc with a median disease duration of four years (range 2-8) and a median RP duration of 10 years (range 4-17). A pretreatment period of four weeks was followed by 16 weeks of bosentan treatment, and a four-week follow-up period. Bosentan was administered as 62.5 mg twice a day for 4 weeks, then 125 mg twice a day for 12 weeks. Patients had to keep a diary of RP attacks during the complete study period, and photoelectric plethysmography (PEP) during cooling and rewarming 4 was assessed at baseline, after eight and 16 weeks of treatment, and at the end of the follow-up period.Bosentan treatment resulted in a significant reduction in the daily duration, number and severity of RP attacks. The outdoor temperature was, however, significantly higher from week 12 until the end of the study. A significant improvement was already seen after eight weeks of treatment during which the outdoor temperature was stable (table 1).Despite the reported improvement in RP, blood flow determined by PEP during cooling and rewarming did not improve during treatment with bosentan (fig 1).In conclusion, treatment with bosentan resulted in an encouraging improvement in the frequency, duration and severity of RP attacks in patients with SSc, but we could not demonstrate an objective improvement in blood flow. The subjective improvement is in contrast with the results of the RAPIDS-1 study, a large randomized placebo-controlled trial in which bosentan was compared with placebo in the prevention of digital ulcers. 3 One might argue that our improvement was caused by seasonal temperature differences or a placebo effect, but no difference in outdoor temperature was seen until week 12. Also, our results show a higher percentage of improvement than the approximately 20-30% found in placebo-controlled trials of RP. 5-7 The absence of effect on blood flow, however, confirms the previously found negative results, but an objective improvement in blood flow was not always found in positive RP trials. 8 Another explanation for the lack of improvement in PEP Table 1 Outcome data of the Raynaud's phenomenon ...