The dependence of FMD% on baseline diameter: a problem solved by allometric scaling - no problem in this case.

We recently published an original research article in Clinical Science reporting that the age-associated impairment in brachial artery FMD (flow-mediated dilation), a non-invasive measure of conduit artery endothelial function, was exacerbated in MA/O (middle-aged and older) adults with IFG (impaired fasting plasma glucose) concentrations, but this was not observed in MA/O adults with IFG who perform regular aerobic exercise [1]. This paper was the latest report in an extensive series of studies performed by our laboratory over the last decade investigating the effects of aging on vascular endothelial function in humans, the modulatory influences involved and the underlying mechanisms [2]. Several of the articles in this series have reported results on brachial artery FMD among different groups of young and MA/O healthy adults, as was the case in the present study [1]. After the publication of our paper [1], Professor Atkinson in his Correspondence to the Journal has suggested that a statistical issue related to scaling the FMD values may have confounded the interpretation of our results. This suggestion was apparently based on the findings of two articles that are just now being published in final form [3,4], i.e. several months after the online publication of our article. Using only the group means reported in our paper [1], Professor Atkinson found a strong correlation between % FMD {calculated as [(peak− baseline diameter)/baseline diameter×100]} and baseline diameter (r= − 0.74), which he suggested may have led to an underestimation of % FMD in some groups, especially those with higher baseline diameters. He stated further that our analysis of covariance was not the correct approach for accounting for differences in baseline diameter. Rather, the correct approach would have been to use allometric scaling. We wish to reply to the comments of Professor Atkinson. To be able to accurately discern a possible confounding effect of baseline diameter on our results, individual subject data, not mean group values, should be used. When the individual data from our study are plotted, the relationship between % FMD and baseline diameter is weaker (r= − 0.43) than calculated by Professor Atkinson, with the latter explaining only 19 % of variation in % FMD (R2 = 0.188). Moreover, the group with the largest baseline diameter, i.e. the non-exercising MA/O adults with IFG,