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 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 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. do not meet the criteria for allometric scaling [common slope of logarithmically transformed baseline and peak diameter = 0.998 (95 % confidence interval, 0.95-1.04)]. As a result, allometric scaling of FMD does not alter our primary findings and conclusions Readers should be aware that, since the technique of brachial artery FMD was first introduced two decades ago, more than 2000 articles have been published using the conventional presentation of FMD as % and/or mm . During this period, several normalization and scaling adjustments have been suggested to improve the accuracy, sensitivity and potential physiological/clinical significance of the data. Certainly, the standard expressions of FMD as % and mm have their limitations, at least in theory. At this time, however, the only values of brachial artery FMD shown to be predictive of future cardiovascular events are these conventional expressions In the future, allometric scaling or other normalization approaches for expressing FMD may prove superior to the conventional approaches of % and mm FMD used since the inception of the technique. Such procedures may be particularly effective when large differences in baseline diameter, shear or other factors exist between groups. However, caution should be exercised before these proposed scaling/normalizing techniques are adopted until they are properly validated in large data sets from www.clinsci.org 5

Regular aerobic exercise protects against impaired fasting plasma glucose-associated vascular endothelial dysfunction with aging

Abstract In the present study, we tested the hypothesis that age-associated vascular endothelial dysfunction is exacerbated by IFG (impaired fasting plasma glucose) and that regular aerobic exercise prevents this effect. Data were analysed from a cohort of 131 non-smoking men and women without overt clinical disease. Compared with young adult controls (age = 24 + − 1 years, n = 29; values are means + − S.E.M.), brachial artery FMD (flow-mediated dilation), a measure of conduit artery EDD (endothelium-dependent dilation), was 33 % lower [7.93 + − 0.33 against 5.27 + − 0.37 % (% change), P < 0.05] in MA/O (middle-aged/older) adults with NFG (normal fasting plasma glucose) ( 99 mg/dl, 62 + − 1 years, n = 35). In MA/O adults with IFG (100-125 mg/dl, 64 + − 1 years, n = 28), FMD was 30 % lower (3.37 + − 0.35 % ) than in their peers with NFG and 58 % lower than young controls (P < 0.05). Brachial artery FMD was greater (6.38 + − 0.35 % ) in MA/O adults with NFG who regularly performed aerobic exercise (>45 min/day for 5 days/week, 62 + − 1 years, n = 23) compared with their non-exercising peers and only slightly less than young controls (P < 0.05). Most importantly, FMD was completely preserved in MA/O adults with IFG who regularly performed aerobic exercise (6.99 + − 0.69 % , 65 + − 1 years, n = 16). In the pooled sample, fasting plasma glucose was inversely related to FMD (r = − 0.42, P < 0.01) and was the strongest independent predictor of FMD (R 2 = 0.32). Group differences in FMD were not affected by other subject characteristics or brachial artery properties, including brachial artery dilation to sublingual NTG (nitroglycerine, i.e. endothelium-independent dilation). IFG exacerbates age-associated vascular endothelial dysfunction and this adverse effect is completely prevented in MA/O adults who regularly perform aerobic exercise