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The aim of our study was to assess the atherosclerotic burden in patients with the first symptoms of coronary artery disease (CAD). The study population consisted of 100 consecutive patients (new-onset severe angina or myocardial infarction) and 70 age and sex matched asymptomatic volunteers. Functional and morphologic atherosclerotic markers were sought in carotid, brachial and femoral arteries of all individuals by means of high-resolution ultrasonography, whereas coronary arteriography was performed in the CAD patients only. A total of 347 coronary lesions [230 (66%) obstructive] were discovered in the CAD patients as well as 105 peripheral plaques [26 (25%) obstructive]. The mean percentage diameter stenosis of the culprit coronary lesion was 83.8 ± 15.8%, the mean vessel score 1.7 (range 0–3), the mean stenosis score 19.8 (range 1.5–89.0), and the mean extent score 49.1% (range 10–65%). Endothelium-dependent vasodilation, as assessed by the brachial flow-mediated response (FMR), was reduced by 50% in the CAD patients (P < 0.001 vs. controls). Furthermore, endothelium-independent vasodilation was significantly impaired in all investigated peripheral arteries of the CAD patients (P < 0.05–0.001 vs. controls). Intima-media thickness (IMT) was increased in the carotid arteries of the CAD patients by 43%, in brachial arteries by 20% and in femoral arteries by 57% (P < 0.01–0.001 vs. controls). Decreased FMR or increased carotid IMT was found to be independent risk factors for the CAD, and they correlated with the coronary vessel and extent scores. In conclusion, the atherosclerotic process was quite advanced in coronary as well as peripheral arteries of our patients with the first clinical presentation of CAD.