Reactive hyperemia as a test of endothelial or microvascular function?

e would like to compliment Binggeli et al. (1) on their hallenging study investigating the improvement in the cutaneous ascular response to reactive hyperemia following statin therapy in ypercholesterolemic patients. We recently published similar findngs regarding the reactive hyperemia test in young, healthy ontrol subjects. Unfortunately, we were not aware of each other’s ork at the time of publication (2). The two main goals of our tudy were: to characterize the reactive hyperemic response in the utaneous circulation to varying periods of occlusion (between 3 nd 15 min), and to examine the role of nitric oxide (NO) in the eactive hyperemic response in the skin. In addition, we attempted o improve and standardize the analysis of reactive hyperemia with he goal of decreasing the variability in the measured response to ossibly improve the clinical utility of this test. Similar to the ndings of Binggeli et al. (1), we (2) found that the vascular esponse to reactive hyperemia was extremely variable, even in the oung healthy population. Despite our improvement in the analsis technique, we still observed within-subject coefficients of ariation ranging from 6% to 11% and, more importantly, etween-subject coefficients of variation ranging from 19% to 74% 2). Furthermore, we also found, using microdialysis and laseroppler flowmetry, that NO does not contribute to either the peak r total (area under the curve) reactive hyperemic response (2). In ur opinion, these findings significantly limit the clinical utility of sing the reactive hyperemic response in the skin as a test of ndothelial function in a given individual. However, it is recogized that periodic evaluation of the reactive hyperemic response cross a treatment period within an individual may provide some mportant information regarding improvement in microvascular unction. We agree with Dr. Celermajer in his accompanying Editorial omment (3) in pointing out that there is a need for a noninvasive ethod to assess endothelial function in humans and that testing f microvasculature function may not correlate with endothelial unction. In this context, we published a study that investigated the ocal hyperemic response to heating a small area of skin (4). In this tudy, we found that there are at least two separate mechanisms in he “thermal hyperemia” response: 1) an initial peak that is axon eflex-mediated, and 2) a sustained plateau phase that is dependent n NO (4). Evaluation of the thermal hyperemia response as described in ur study, therefore, may be a better tool to independently assess oth endothelial and microvascular function than reactive hypermia. Using this technique, we were able to demonstrate diminshed thermal hyperemia responses in healthy older subjects ( 65 ears old) in comparison to younger subjects (5). Thus, using our tandardized local heating protocol may prove valuable in providng a noninvasive and reliable test of endothelial function, alhough, clearly, more work needs to be done to explore this ossibility. We would like to encourage other investigators to test he efficacy of the thermal hyperemia test of endothelial function as iscussed in our study in various patient populations and across reatments. n hristopher T. Minson, PhD epartment of Exercise and Movement Science 22 C Esslinger Hall 240 University of Oregon ugene, Oregon 97403-1240 -mail: [email protected]