Flow-mediated vasodilatation of the brachial artery (FMD) is a marker which is related to endothelial nitric oxide bioavailability. Commercially available ultrasound machines equipped with online computer-assisted semi-automatic analysis software to measure FMD have recently become available in Japan. These devices enable more convenient examination, enhanced reproducibility of FMD measurement, and a shortened examination time. Using such devices, in the present multicenter prospective study we propose to: 1) establish standardized FMD values and determine the annual rates of FMD change in healthy subjects; 2) confirm the predictive value of FMD for future cardiovascular events in Japanese subjects; 3) evaluate the potential usefulness of a multimarker strategy, including measurements of FMD, pulse-wave velocity (PWV), ankle-brachial pressure index, biochemical markers, and proteomic biomarkers obtained by mass spectroscopic analysis to assess the prognosis of subjects with coronary artery disease; and 4) clarify the usefulness of FMD measurement to predict the rate of progression of carotid atherosclerosis, arterial stiffness and microalbuminuria in subjects with hypertension or diabetes mellitus. In total, we estimate that approximately 4000 Japanese subjects in 3 different study groups will eventually be enrolled in this prospective observational investigation. We anticipate that the present study will provide important evidence for the usefulness of FMD measurement in the risk stratification for cardiovascular disease.