HDL-C levels remained unchanged after therapy; however, the frequency of HDL-C levels below normal decreased. subsets, FMD significantly improved in the 21 lcSSc patients (from 2.1% to 5.6%, em P /em = 0.001). In the seven dcSSc patients, we observed a tendency of improvement in FMD (from 3% to 6%, em P /em = 0.25). Changes in PWV, ccIMT and ABI were not significant. Mean triglyceride (1.7 0.97 versus 1.3 0.46 mmol/l, em P /em = 0.0004), total cholesterol (5.3 1.6 mmol/l versus 4.2 1.3 mmol/l, em P /em = 0.0003), low density lipoprotein cholesterol (3.0 1.3 versus 2.2 1.0 mmol/l, em P /em = 0.005) and C-reactive protein levels (CRP) (5.1 5.2 versus 3.4 2.7, em P /em = 0.01) levels significantly decreased after rosuvastatin treatment. Mean C3, C4 and IC levels also decreased significantly as compared to pretreatment values. Conclusions Six-month rosuvastatin therapy improves endothelial function Dehydrodiisoeugenol and lowers CRP, C3, C4 and IC levels indicating possible favourable effects of this statin on the cardiovascular and immune system in SSc. strong class=”kwd-title” Keywords: rosuvastatin, systemic sclerosis, atherosclerosis, cardiovascular, endothelial function, flow-mediated vasodilation, arterial stiffness, pulse-wave velocity Introduction Systemic sclerosis (SSc) is a systemic autoimmune disease of uncertain etiology characterized by progressive fibrosis of the skin, the small blood vessels and various internal organs. Population-based and other cohort studies have emphasized that survival is decreased in patients with SSc [1-3]. Several reports including our previous studies, have found macrovascular abnormalities in SSc patients. These include endothelial dysfunction indicated by abnormally low flow-mediated dilation (FMD) of the brachial artery [4,5], increased carotid intima-media thickness (IMT) and increased arterial stiffness [6-8]. Statins may improve endothelial dysfunction, arterial stiffness and reduce levels of inflammatory markers in various conditions including chronic kidney disease, rheumatoid arthritis and dyslipidemia. In SSc, the vascular effects of atorvastatin, simvastatin and pravastatin have been investigated so far . Atorvastatin exerted beneficial effects on microvascular function, digital ulcers, and soluble markers of endothelial Dehydrodiisoeugenol function, as well as FMD [10,11]. Simvastatin and pravastatin reduced the Kit production of soluble endothelial activation markers [12,13]. It is not Dehydrodiisoeugenol fully clear which of the multiple mechanisms of statins may be involved in SSc-related vascular changes. Although a pronounced reduction of LDL-cholesterol is present in patients undergoing statin therapy, additional mechanisms have been suggested to improve endothelium-dependent vasodilation in case of HMG-coA reductase inhibitor therapy. A key point is promoting activity of the endothelial NO synthase. This can either be caused by a weakened interaction between the endothelial NO synthase (eNOS) and caveolin-1, or the association of e-NOS and hsp90, as well as by an upregulation of eNOS mRNA by inhibition of the Rho kinase pathway or a reduction in ICAM-1 and P-selectin levels, which also result in increased endothelial NO production . In this study, we wished to determine the effects of rosuvastatin, a potent reducer of total (TC) and LDL cholesterol (LDL-C) [15,16], on serum inflammatory markers and complement levels, on endothelial and macrovascular function, as well as on arterial stiffness in patients with SSc. In addition, we determined the possible effects of rosuvastatin on microvascular function by assessing cutaneous blood flow. The primary endpoint of the study was rosuvastatin effects on the vasculature (FMD, carotid artery intima media thickness (ccIMT), pulse wave velocity (PWV), ankle-brachial index (ABI)), while the secondary outcome included laboratory marker changes (lipids, C-reactive protein (CRP), immune complexes and complement). The assessment of acute phase reactants and complement has been included in scleroderma activity index . Methods Patients SSc patients undergoing follow-up visits at our institution were randomly screened for inclusion and exclusion criteria described below. Altogether 28 patients including 25 women and three men were eligible for the study. The diagnosis was established according to the 1980 American College of Rhematology criteria for SSc . The mean age of the patients was 60.4 11.0 years (range: 34 to 83 years) and the mean disease duration was 13.6 7.7 years (range 2 to 30 years). Among these patients, 21 (75%) had the limited (lcSSc) and seven (25%) had the diffuse cutaneous form of SSc (dcSSc). Clinical manifestations of SSc included Raynaud’s phenomenon (96%), distal skin manifestations including sclerosis and ulcers (68%), proximal skin involvement (25%), cardiac manifestations including conduction defects, atrial fibrillation, arrhythmias (25%), gastrointestinal manifestations, such as esophageal dysmotility, gastroesophageal reflux (54%), renal involvement (4%).