Rheumatology Advance Access originally published online on May 22, 2009
Rheumatology 2009 48(7):834-839; doi:10.1093/rheumatology/kep082
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Non-invasive assessment of coronary flow reserve and ADMA levels: a case–control study of early rheumatoid arthritis patients
1Department of Health Technologies, Cardiology Unit, IRCCS Orthopedic Galeazzi Institute, University of Milan, 2Rheumatology Unit, L. Sacco University Hospital, Milan, 3Department of Health Technologies, CIRFF/Centre of Pharmacoeconomics, Federico II University of Naples, Naples, 4Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Milan and 5Division of Rheumatology, University of Padua, Padua, Italy.
Correspondence to: Maurizio Turiel, Department of Health Technologies, Cardiology Unit, IRCCS Orthopedic Galeazzi Institute, University of Milan, Via R. Galeazzi 4, 20161 Milano, Italy. E-mail: maurizio.turiel{at}unimi.it
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Abstract |
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Objective. Plasma concentration of asymmetric dimethylarginine (ADMA), a major endogenous inhibitor of nitric oxide synthase, is considered a novel risk factor for endothelial dysfunction associated with enhanced atherosclerosis. Coronary microcirculation abnormalities have been demonstrated in patients with early rheumatoid arthritis (ERA) without any signs or symptoms of coronary artery disease (CAD). The aim of the study was to compare the ERA and control groups with ADMA, intima-media thickness (IMT) and coronary flow reserve (CFR) levels. It assessed whether ERA patients have more cardiovascular risk (endothelial dysfunction and coronary microvascular abnormalities), and evaluated whether any difference in IMT/CFR between ERA and controls can be explained by any difference in ADMA levels between the groups.
Methods. The study involved 25 ERA patients (female/male 21/4; mean age 52.04 ± 14.05 years; disease duration 
12 months) and 25 healthy volunteers with no history or current signs of CAD or other traditional risk factors. Dipyridamole trans-thoracic stress echocardiography was preformed to evaluate CFR, and carotid ultrasound to measure the IMT of the common carotid arteries. Blood samples were obtained in order to assess ADMA levels before the patients had received any biological or non-biological DMARDs, or steroid therapy.
Results. CFR was significantly reduced in the ERA patients (2.5 ± 0.5 vs 3.5 ± 0.8; P <0.01). In particular, 6/25 (24%) had a CFR of <2 consistent with potentially dangerous coronary flow impairment. Common carotid IMT was significantly greater in the ERA patients, although still within the normal range (0.68 ± 0.1 vs 0.56 ± 0.11 mm; P <0.01). There was a significant correlation between CFR and plasma ADMA levels in the ERA population (r = –0.53; P <0.01). IMT was negatively associated with CFR (P <0.05).
Conclusions. Plasma ADMA levels were significantly higher in the ERA patients. A statistically significant negative effect of ADMA levels on CFR value was observed. The effect of ADMA levels on IMT is not significant.
KEY WORDS: Asymmetric dimethylarginine, Rheumatoid arthritis, Coronary artery disease, Coronary flow reserve, Trans-thoracic echocardiography
*Vito De Gennaro Colonna and Piercarlo Sarzi-Puttini equally contributed to this work.
Submitted 5 May 2008;
revised version accepted 17 March 2009.
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