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Background: Cardiovascular (CV) disease represents one of the leading causes of morbidity and mortality in rheumatoid arthritis (RA). Enhanced atherosclerosis and impaired endothelial function develop early after the onset of the disease and generally remain clinically silent for long-term. Assessing preclinical atherosclerosis before structural abnormalities occur both in large arteries and in the coronary bed should be the main challenge for both cardiologists and rheumatologists who want try to change the clinical outcomes of RA patients. Our goal was to assess the most sensitive and feasible diagnostic tools able to detect preclinical atherosclerotic damage in RA patients without overt CV disease.Methods: 120 adult patients with RA who fulfilled the ACR classification criteria [M 20 (16.6%), F 100 (83.4%)], mean age 61± 13 years) without clinical evidence of CV disease and 80 healthy controls matched for age and sex were recruited.All patients underwent a dypiridamole stress echo with evaluation of coronary flow reserve (CFR) in the left descending coronary artery.Results: 72/120 patients (60%) had CFR<2.5. All patients had normal ejection fraction and left ventricular dimensions, wall thickness and wall motion. Performing a stepwise regression, the predictive variables of decreased CFR were the isovolumetric relaxation time (P<0.0001), deceleration time (P<0.0001), E/A ratio (P<0.0001), E wave (P<0.0001), A wave (P<0.0001) and left ventricular mass (P<0.0001).Conclusions: In our study RA patients without clinical evidence of CV diseases showed an early impairment of coronary microcirculation and endothelial dysfunction. This suggests that reduced CFR is an early marker of enhanced atherosclerosis in a preclinical stage and it is associated with endothelial dysfunction. Moreover, isovolumetric relaxation time, deceleration time, E/A ratio, E and A wave, ejection fraction and left ventricular mass resulted predictors of coronary microvascular integrity.