Rheumatoid Arthritis: Delfino L

Sitia S, Atzeni F, Sarzi-Puttini P, Di Bello V, Tomasoni L, Delfino L, Antonini-Canterin F, Di Salvo G, De Gennaro Colonna V, La Carrubba S, Carerj S, Turiel M. · IRCCS Orthopedic Galeazzi Institute, University of Milan, Department of Health Technologies, Cardiology Unit, Milan, Italy. · Autoimmun Rev. · Pubmed #18817899 No free full text.

Abstract: Autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary antiphospholipid syndrome (APS), systemic sclerosis and systemic vasculitis, affect a large number of people in whom one of the leading causes of morbidity and mortality is cardiovascular disease. Cardiovascular disease is associated with the development of accelerated atherosclerosis. It seems to occur at a younger age than in the general population, is often asymptomatic and, in addition to traditional risk factors, also involves specific risk factors as chronic inflammation, the duration and activity of the autoimmune disease, and immunosuppressive therapy. The early phases of cardiovascular involvement in patients with autoimmune diseases may be clinically silent, with only a microcirculation disorder present. There are various means of detecting morphological cardiac damage: coronary angiography remains the gold standard for diagnosing coronary stenosis, but new, non invasive and more reliable methods have been introduced into clinical practice in order to detect subclinical microcirculation abnormalities.

Turiel M, Atzeni F, Tomasoni L, de Portu S, Delfino L, Bodini BD, Longhi M, Sitia S, Bianchi M, Ferrario P, Doria A, De Gennaro Colonna V, Sarzi-Puttini P. · Department of Health Technologies, Cardiology Unit, IRCCS Orthopedic Galeazzi Institute, University of Milan, Milano, Italy. · Rheumatology (Oxford). · Pubmed #19465588 No free full text.

Abstract: 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 <or=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.

Gattorno M, Piccini A, Lasigliè D, Tassi S, Brisca G, Carta S, Delfino L, Ferlito F, Pelagatti MA, Caroli F, Buoncompagni A, Viola S, Loy A, Sironi M, Vecchi A, Ravelli A, Martini A, Rubartelli A. · G. Gaslini Institute, Genoa, Italy. · Arthritis Rheum. · Pubmed #18438814 links to  free full text

Abstract: OBJECTIVE: To assess the clinical response to interleukin-1 (IL-1) blockade and in vitro IL-1beta and IL-18 secretion in patients with systemic-onset juvenile idiopathic arthritis (JIA). METHODS: Twenty-two patients with systemic-onset JIA were treated with the IL-1 receptor antagonist (IL-1Ra) anakinra. Monocytes from 18 patients and 20 healthy donors were activated by different Toll-like receptor ligands. Intracellular and secreted IL-1beta and IL-18 were analyzed by Western blotting and enzyme-linked immunosorbent assay. RESULTS: Ten patients with systemic-onset JIA exhibited a dramatic response to anakinra and were classified as complete responders. Eleven patients had an incomplete response or no response, and 1 patient could not be classified in terms of response. Compared with patients who had an incomplete response or no response, complete responders had a lower number of active joints (P = 0.02) and an increased absolute neutrophil count (P = 0.02). In vitro IL-1beta and IL-18 secretion in response to various stimuli was not increased and was independent of treatment efficacy. Likewise, secretion of IL-1Ra by monocytes from patients with systemic-onset JIA was not impaired. An overall low level of IL-1beta secretion upon exposure to exogenous ATP was observed, unrelated to treatment responsiveness or disease activity. CONCLUSION: Two subsets of systemic-onset JIA can be identified according to patient response to IL-1 blockade. The 2 subsets appear to be characterized by some distinct clinical features. In vitro secretion of IL-1beta and IL-18 by monocytes from patients with systemic-onset JIA is not increased and is independent of both treatment outcome and disease activity.

Magagnin V, Caiani EG, Delfino L, Champlon C, Cerutti S, Turiel M. · Biomedical Engineering Dept., Polytechnic of Milan, Italy. · Conf Proc IEEE Eng Med Biol Soc. · Pubmed #17946419 No free full text.

Abstract: Coronary flow velocity reserve (CFVR) is conventionally obtained by manual tracings of Doppler profiles, as ratio of stress vs baseline diastolic peak velocity. When <1.9, this parameter evidences reduced coronary flow and possible microcirculatory disease. Our goals were: 1) to develop a novel technique for semi-automated detection of Doppler flow velocity profile, allowing the automated computation of CFVR and other parameters; 2) to validate this technique in comparison with conventional measurements obtained by manual tracing; 3) to test for differences between normal (N) subjects and patients with rheumatoid arthritis (RA). Linear correlation and Bland-Altman analyses showed that the proposed method was highly accurate and repeatable compared to the manual measurements. Comparison between N and RA groups evidenced significant differences in some of the automated parameters.

Atzeni F, Sarzi-Puttini P, De Blasio G, Delfino L, Tomasoni L, Turiel M. · Rheumatology Unit, L. Sacco Hospital, University of Milan, Milan, Italy. · Ann N Y Acad Sci. · Pubmed #17894002 No free full text.

Abstract: Cardiovascular involvement in rheumatoid arthritis (RA) is common, although the true prevalence of cardiac abnormalities is difficult to measure, as much disease remains clinically silent. The pathogenesis of cardiac lesions in RA is related to the primary disorder of microcirculation with diffuse arteriolar and capillary lesions. Previous studies demonstrated that coronary flow reserve (CFR) is impaired in patients with connective tissue diseases (CTD). This review focuses on transthoracic Doppler echocardiography as a noninvasive method used to assess CFR in RA patients. CFR is early reduced in RA patients without clinical evidence of heart disease as a result of impaired microcirculation. CFR seems a useful technique able to follow-up and to assess effects of new drugs on RA patients.