We are pleased to make some further comments in order to clarify the implications and conclusions of our study. We agree with Vacca et al that the relationship between SSc and atherosclerosis is controversial and that there is no consensus among studies in the literature concerning the role of the initial condition known as endothelial dysfunction ([1-3]). To put it bluntly, opposite positions have been published even by the same research group ([4, 5]).

First, it is necessary to clarify the difference between the subclinical manifestations of atherosclerosis (as in our study) and outright vascular damage ([6]). This was clearly pointed out in our study, and in our conclusions we suggested that there may be a relationship between subclinical atherosclerosis and SSc as well as other rheumatic diseases (above all pathognomic rheumatoid arthritis) ([7]), although we did say that further studies will be necessary to establish whether this is true.

As far as ADMA is concerned, we concentrated on other tests and therefore it is not surprising that we did not find any correlation between plasma ADMA levels and CFR. However, it is known that ADMA is an independent marker of cardiovascular risk ([8, 9]) that is strictly related to endothelial dysfunction (the primum movens of atherosclerosis).

It is clear that angiography is the gold standard for determining coronary atherosclerosis, but it has the drawback of being invasive, and noninvasive techniques should be preferred ([10, 11]). Additionally, angiography is many times more expensive than dynamic evaluation. Among these, we believe that a dynamic evaluation such as CFR assessment is better than the coronary tomography cited by Vacca et al in the letter to the editor ([5]). The critical but interesting analysis in the letter to the editor lacked these significant considerations.


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    Veale DJ, Collidge TA, Belch JJ.Increased prevalence of symptomatic macrovascular disease in systemic sclerosis.Ann Rheum Dis1995;54:8535.
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    Montisci R, Vacca A, Garau P, Colonna P, Ruscazio M, Passiu G, et al.Detection of early impairment of coronary flow reserve in patients with systemic sclerosis.Ann Rheum Dis2003;69:8903.
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    De Gennaro Colonna V, Bianchi M, Pascale V, Ferrario P, Morelli F, Pascale W, et al.Asymmetric dimethylarginine (ADMA): an endogenous inhibitor of nitric oxide synthase and a novel cardiovascular risk molecule.Med Sci Monit2009;15:RA91101.
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