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Background: The association between autoimmune diseases and atherosclerosis is well described in many connective tissue diseases and lead to increased cardiovascular (CV) morbidity and mortality. Systemic sclerosis (SSc) is characterized by multi-system organ inflammation, endothelial wall damage and vasculopathy, all of which can increase the risk for atherosclerosis and CV disease (CVD). The increase in carotid intima-media thickness (cIMT) in SSc patients (pts) was demonstrated to be a useful marker of systemic subclinical atherosclerosis. At the same time, early coronary dysfunction can be studied by coronary flow reserve (CFR) assessed with trans-thoracic echocardiography (TTE). Finally, asymmetric dimethylarginine (ADMA), the major endogenous inhibitor of nitric oxide synthase, has been well recognized as a new marker of endothelial dysfunction.Aim of the study was to find out an early CV involvement in SSc pts.Methods: 18 pts with SSc (2 male, 16 female, aged 52±15 years) without signs or symptoms of CVD and 18 controls matched for age and sex. All of them underwent a dypiridamole echocardiographic stress test with CFR evaluation, cIMT measurement and plasma ADMA levels determination.Results: Despite normal standard echocardiographic examinations, SSc pts showed lower CFR (2.81±0.48 vs 3.19±0.20; P<0.02) and increased plasma ADMA levels (0.83±0.08 vs 0.60±0.02; P<0.01) compared to controls in absence of stastical differences of cIMT (0.70±0.09 vs 0.69±0.08; NS). We found a significant negative correlation between CFR and ADMA (r= -0.39; P 0.0002). No other correlations were detected.Conclusions: In our study, SSc pts without clinical evidence of CVD showed a subclinical impairment of coronary microcirculation in association with endothelial dysfunction, while cIMT was still in normal range. This suggest that CFR and ADMA could be considered preclinical markers of CVD in SSc, able to detect an earlier stage of atherosclerosis before anatomic change in cIMT.