Response to Letter Regarding Article, “Anti–Tumor Necrosis Factor-α Therapy Reduces Aortic Inflammation and Stiffness in Patients With Rheumatoid Arthritis”
Authors: Kaisa M. Mäki-Petäjä, Maysoon Elkhawad, Joseph Cheriyan, Francis R. Joshi, Andrew J.K. Östör, Frances C. Hall, James H.F. Rudd, Ian B. Wilkinson
Journal: Circulation (2013)

We thank the authors for their interest in our study. 1They raise several relevant points, which we address below.We agree that further work is needed to ascertain the origin of 18F-fluoro-deoxyglucose (FDG) uptake in patients with rheumatoid arthritis.Although we cannot be certain, we feel that subclinical vasculitis is the most likely explanation for our findings for several reasons.First, we compared aortic FDG uptake in rheumatoid arthritis subjects with an atherosclerotic population with stable cardiovascular disease, matched for age.We were careful to exclude those rheumatoid arthritis subjects with established cardiovascular disease or diabetes mellitus.Even so, we found that the aortic FDG uptake in the rheumatoid arthritis subjects was significantly higher than in the control group.Second, we agree that the image displayed in our article has a patchy distribution of FDG uptake, suggesting atherosclerosis.However, this was not the case for all the subjects; indeed, we found that rheumatoid arthritis patients had higher proportion of active slices compared with our control subjects.Using a target to background ratio threshold of >1.6, our results showed that, on average, 90% of arterial slices were hot in the rheumatoid arthritis group compared with only 71% in the cardiovascular disease group.Third, unpublished data showed that our rheumatoid arthritis group had significantly lower median aortic calcium scores than the cardiovascular controls: 90 Houndsfield units (interquartile range, 1-230 Houndsfield units) versus 650 Houndsfield units (interquartile range, 238-2626 Houndsfield units; P<0.05), even less than would be expected compared with previous studies of this type. 2Given that the ages of the 2 groups were similar, this implies a low level of atherosclerosis in the rheumatoid arthritis group and supports our assertion that at least part of the FDG signal arises from a vasculitic aorta.Finally, we believe that subclinical vasculitis would also better explain the aortic stiffening seen in patients with rheumatoid arthritis, 3 especially reversible stiffening, because atherosclerosis per se does not seem to be related to aortic stiffening.Tezuka et al 4 also suggest that vasculitis is normally associated with higher FDG uptake values than we reported in our study.We agree.Indeed, we cited a cutoff standardized uptake value value of 2.7 that had been proposed for the diagnosis of Takayasu arteritis, 5 although others have found lower thresholds useful for the diagnosis of primary large-vessel vasculitis or its recurrence.Finally, we agree that methodological issues relating to imaging itself can account for differences in measured FDG uptake values.It should be noted, however, that both our subject and control groups underwent identical imaging protocols tailored for vascular imaging. 6e suggest that what we observed in our study was a low level of subclinical vascular inflammation, which, over decades, is capable of explaining the excessive cardiovascular death seen in the rheumatoid population.