Flow-mediated dilation (FMD) is used as a surrogate marker for endothelial function, a subclinical indicator of coronary artery disease (CAD) and for that reason; FMD is commonly used to compare endothelial function across groups differing in age and number and/or type of CAD risk factors. The traditional calculation of FMD involves arterial diameter prior to cuff inflation and then peak arterial diameter following cuff release. Generally, arterial response during cuff inflation is not taken into consideration. The aims of the present study were to determine 1) if there were differences in brachial artery response, more specifically vasoconstriction, during cuff inflation in a diverse population of subjects, 2) if variability existed, the resulting impact on the calculation of traditional FMD, and 3) if arterial stiffness was a physiological determinant in this process. A total of 84 subjects, varying in age (18-62 years) and CAD risk factor profiles were studied. Low flow-mediated constriction (L-FMC), during cuff inflation, traditional FMD, and modified FMD, which accounts for L-FMC, were calculated to investigate brachial artery response during all three stages of the FMD measurement. Subjects ≥ 50 years old had lower FMD response compared with those ≤ 35 years old but only the modified FMD was statistically significant. The same effect was seen when comparing healthy subjects to those with multiple risk factors for CAD; there was an attenuated FMD response that only reached statistical significance with modified FMD. L-FMC was modestly but significantly associated with FMD. L-FMC was weakly but positively correlated with brachial pulse wave velocity (PWV). Our results indicate that modified FMD, which takes into consideration brachial response to cuff inflation, may be a more sensitive indicator of endothelial dysfunction and that arterial stiffening may be a physiological determinant in this process. / text