In patients with rheumatoid arthritis (RA), cardiovascular disease(CVD)-related mortality is profoundly increased [1]. The risk of heartfailure in RA is almost twice that of the general population. Theincreasedriskcannotbeentirelyexplainedbytraditionalcardiovascularrisk factors. Instead, blood vessels may be damaged through inflamma-tion and immune-mediated processes [2–4].Asymmetricdimethylarginine(ADMA)isacardiovascularriskfactorandplaysaparticular,notyetfullyunderstoodroleinRA[5–7].ADMAisan endogenous inhibitor of nitric oxide (NO) synthesis, and this mech-anism may be one possible explanation for ADMA's involvement inCVD.However,inacohortof201RApatients,ADMAwasnotassociatedwith subendocardial viability ratio [8], a surrogate marker of coronarymicrovascular perfusion.Recently,homoarginine(hArg),anotherarginineanalogue,emergedas a novel cardiovascular risk factor [9–12], but the underlying mecha-nisms are still unresolved and much less understood than those ofADMA. As circulating hArg and ADMA may have opposing influenceson CVD, we proposed to use the plasma hArg-to-ADMA (hArg/ADMA)molar ratio to improve CVD risk prediction [13].Thus far, hArg has not been investigated in rheumatic diseasesincluding RA. In the present study, we newly determined hArg andADMA concentrations in plasma samples of 100 RA patients (88females, 12 males) collected in a previously reported study involvingcombined add-on supplementation for 12 weeks of omega-3 fattyacids, vitamins E and A, copper, and selenium or placebo (soy oil) [14].Written informed consent was provided by all subjects included in thestudy. The study protocol conformed to the ethical guidelines of the1975 Declaration of Helsinki as reflected in a priori approval by theFreiburg Ethics Committee International (Freiburg, Germany) and theEthics Committee of Charite-University of Medicine (Berlin, Germany).The results of the present study are shown in Figs. 1 and 2. Concentra-tions are reported as mean ± SEM.Plasma hArg concentrations in RA patients were comparable tothose measured by us and others in healthy subjects [13], and did notchange after 12 weeks in the placebo (2858 ± 152 vs. 2950 ±169 nmol/L) and in the verum (2952 ± 158 vs. 2854 ± 185 nmol/L)group. Plasma ADMA concentrations in RA patients were comparableto those in elderly subjects with CVD as measured by us and others[13], and did not change after 12 weeks in the placebo (561 ± 13 vs.566 ± 15 nmol/L) and in the verum (574 ± 21 vs. 576 ± 15 nmol/L)group. The plasma hArg/ADMA ratio was comparable to that measuredinhealthysubjects[13]anddidnotchangeafter12 weeksintheplace-bo (5.17 ± 0.29 vs. 5.32 ± 0.32) and in the verum (5.32 ± 0.33 vs.5.05 ± 0.34) group. At baseline, the plasma hArg/ADMA ratio did notdiffer betweenfemales and males(P = 0.56). There wasnocorrelationbetween the hArg and ADMA plasma concentrations in both groups atbaseline and after 12 weeks. Also, there was no correlation betweenthe hArg or ADMA plasma concentrations and C-reactive protein(CRP) in both groups at the beginning and after 12 weeks (data notshown). In subgroups of patients of both groups, add-on supplementa-tion with omega-3fatty acidsand antioxidants orplacebofor 12 weeksdidnotsignificantlychangethecreatinine-correctedexcretionofnitriteand nitrate, indicators of NO synthesis [20],orof15(S)-8-iso-PGF