Gelsolin levels are decreased in ankylosing spondylitis patients undergoing anti-TNF-alpha therapy.

OBJECTIVES: To determine whether circulating gelsolin (GSN) levels in patients with ankylosing spondylitis (AS) undergoing TNF-α antagonist-infliximab-therapy are altered compared with controls and to establish whether disease activity, systemic inflammation and metabolic syndrome are potential determinants of circulating GSN levels in these patients. METHODS: We assessed GSN serum concentrations in a series of 30 non-diabetic AS patients without cardiovascular (CV) disease undergoing TNF-α antagonist-infliximab therapy and 48 matched controls. GSN levels were measured immediately before and after an infliximab infusion. Correlations of GSN serum levels with disease activity, systemic inflammation and metabolic syndrome were assessed. Potential changes in GSN concentration following an infusion of anti-TNF-α monoclonal antibody-infliximab were also analysed. RESULTS: Although at the time of the study AS patients undergoing anti-TNF-α therapy had adequate control of the disease (mean BASDAI 2.94), they showed lower GSN serum levels than healthy controls (mean±SD: 38660.42±23624.6 ng/ml versus 68975.43±31246.79 ng/ml; p<0.0001). When AS patients were stratified according to sex, we observed that GSN levels were significantly lower in men than in women (p=0.032). However, no differences in GSN levels according to the specific clinical features of the disease were seen. No association was found between GSN concentration and adipokines or biomarkers of endothelial cell activation. However, correlation between basal GSN levels and insulin resistance was observed. A single infliximab infusion did not lead to significant changes in GSN levels. CONCLUSIONS: GSN concentration is reduced in AS patients undergoing periodical anti-TNF-α therapy and low disease activity. Potential association with some metabolic syndrome features seems to exist.

Correlation between two biomarkers of atherosclerosis, osteopontin and angiopoietin-2, in non-diabetic ankylosing spondylitis patients undergoing TNF-α antagonist therapy.

OBJECTIVES: To determine whether circulating osteopontin (OPN) levels in patients with ankylosing spondylitis (AS) undergoing TNF-α antagonist-infliximab-therapy are increased compared with controls and to establish whether disease activity, systemic inflammation, metabolic syndrome, adipokines and biomarkers of atherosclerosis are potential determinants of circulating OPN levels in these patients. METHODS: We assessed OPN serum concentrations in a series of 30 non-diabetic AS patients without cardiovascular disease undergoing TNF-α antagonist-infliximab therapy and 48 matched controls. OPN levels were measured immediately before and after an infliximab infusion, at time 0 and at time 120 minutes respectively. Correlations of OPN serum levels with clinical features, disease activity, systemic inflammation, metabolic syndrome and several biomarkers of atherosclerosis were assessed. Potential changes in OPN concentration following an infusion of anti-TNF-α monoclonal antibody-infliximab were also analysed. RESULTS: At the time of the study AS patients undergoing anti-TNF-α therapy had low disease activity (mean BASDAI 2.94) and they showed similar OPN serum levels to healthy controls. No differences in OPN levels according to the specific clinical features of the disease were seen. Also, no correlation between OPN concentration and insulin resistance and adipokines was observed. However, a positive correlation between OPN and angiopoietin-2 (Angpt-2) serum levels was found (r=0.397; p=0.04). In addition, a single infliximab infusion led to a marginal statistically significant reduction in OPN levels (24112.19±14608.73 pg/ml at time 0 versus 21806.62±11390.83 pg/ml at time 120'; p=0.05). CONCLUSIONS: OPN and Angpt-2 serum levels are correlated in non-diabetic AS patients undergoing TNF-α antagonist therapy.

The 11q23.3 genomic region-rs964184-is associated with cardiovascular disease in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is an inflammatory disease associated with high risk of cardiovascular (CV) events. Recently, the rs964184 polymorphism has been associated with coronary artery disease in nonrheumatic Caucasian individuals. 2160 Spanish RA patients were genotyped for the rs964184 polymorphism. Sex, age at diagnosis and traditional CV risk factors (diabetes mellitus, dyslipidemia and smoking habit) were associated with increased risk of CV events. Interestingly, RA patients carrying the rs964184 GG genotype had significantly higher risk of CV events than those with CC genotype [hazard ratio (HR) = 2.91, 95% confidence interval (CI): 1.36-6.26, P = 0.006] after adjusting the results for sex, age at diagnosis and traditional CV risk factors. Our results indicate that rs964184 polymorphism is associated with CV disease in RA.

Identification of the PTPN22 functional variant R620W as susceptibility genetic factor for giant cell arteritis.

OBJECTIVE: To analyse the role of the PTPN22 and CSK genes, previously associated with autoimmunity, in the predisposition and clinical phenotypes of giant cell arteritis (GCA). METHODS: Our study population was composed of 911 patients diagnosed with biopsy-proven GCA and 8136 unaffected controls from a Spanish discovery cohort and three additional independent replication cohorts from Germany, Norway and the UK. Two functional PTPN22 polymorphisms (rs2476601/R620W and rs33996649/R263Q) and two variants of the CSK gene (rs1378942 and rs34933034) were genotyped using predesigned TaqMan assays. RESULTS: The analysis of the discovery cohort provided evidence of association of PTPN22 rs2476601/R620W with GCA (PFDR=1.06E-04, OR=1.62, CI 95% 1.29 to 2.04). The association did not appear to follow a specific GCA subphenotype. No statistically significant differences between allele frequencies for the other PTPN22 and CSK genetic variants were evident either in the case/control or in stratified case analysis. To confirm the detected PTPN22 association, three replication cohorts were genotyped, and a consistent association between the PTPN22 rs2476601/R620W variant and GCA was evident in the overall meta-analysis (PMH=2.00E-06, OR=1.51, CI 95% 1.28 to 1.79). CONCLUSIONS: Our results suggest that the PTPN22 polymorphism rs2476601/R620W plays an important role in the genetic risk to GCA.

A case-control study suggests that the CCR6 locus is not involved in the susceptibility to giant cell arteritis.

OBJECTIVES: Polymorphisms of the CC chemokine receptor 6 (CCR6) gene have been recently reported to be associated with a number of autoimmune diseases. We aimed to investigate the possible influence of CCR6 rs3093024 gene variant in the susceptibility to and clinical expression of GCA. METHODS: The CCR6 polymorphism rs3093024 was genotyped in a total of 463 Spanish patients diagnosed with biopsy-proven GCA and 920 healthy controls using a TaqMan® allelic discrimination assay. PLINK software was used for the statistical analyses. RESULTS: No significant association between this CCR6 variant and GCA was observed (p=0.42, OR=0.94, CI95% 0.79-1.10). Similarly, when patients were stratified according to the specific clinical features of GCA such as polymyalgia rheumatica, visual ischaemic manifestations or irreversible occlusive disease, no statistical significant difference was detected either between the case subgroups and the control set or between GCA patients with and without the specific features of the disease. CONCLUSIONS: Our results suggest that the CCR6 rs3093024 polymorphism may not play a relevant role in the GCA pathophysiology.

Single-nucleotide polymorphisms at the 9p21.3 genomic region not associated with the risk of cardiovascular disease in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic polygenic inflammatory disease associated with accelerated atherosclerosis and high risk of cardiovascular disease (CVD). In this study, we evaluated the potential association of 9p21.3 single-nucleotide polymorphisms (SNPs) - previously linked to coronary artery disease - and CVD risk in 2001 Spanish RA patients genotyped for 9p21.3 SNPs using TaqMan™ assays. Carotid intima media thickness (cIMT) and presence of carotid plaques were also analyzed. Cox regression model did not disclose significant differences between patients who experienced CVD and those who did not. Neither association was found between cIMT or carotid plaques and SNPs allele distribution. In conclusion, results do not support a role of rs10116277 or rs1537375 SNPs in CVD risk in Spanish RA patients.

No evidence of association between functional polymorphisms located within IL6R and IL6ST genes and Henoch-Schönlein purpura.

Henoch-Schönlein purpura (HSP) is the most common type of primary small-sized blood vessel vasculitis in children and an uncommon condition in adults. Interleukin (IL)-6 is a proinflammatory cytokine whose effect is controlled by the IL-6 receptor (IL-6R). IL-6 transducer (IL-6ST/gp130) is the signal-transducing subunit of the IL-6R. Two hundred and eighty five Spanish HSP patients and 877 sex and ethnically matched controls were genotyped for the IL6R rs2228145 and IL6ST/gp130 rs2228044 functional polymorphisms. No significant differences in the genotype and allele frequencies between HSP patients and controls were observed. Moreover, there were no differences between HSP patients according to the age at disease onset, presence of nephritis or gastrointestinal manifestations. Our results do not confirm association of IL6R rs2228145 and IL6ST/gp130 rs2228044 polymorphisms with HSP.

Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with cardiovascular disease in patients with rheumatoid arthritis.

OBJECTIVE: The methionine sulfoxide reductase A (MSRA) gene is related to oxidative stress that has been involved in the susceptibility to rheumatoid arthritis (RA) in genome-wide pathway analysis and replication studies. The aim of the present study was to determine whether the MSRA gene is implicated in susceptibility to cardiovascular (CV) disease in RA patients. METHODS: A total of 1302 patients fulfilling the 1987 American College of Rheumatism classification criteria for RA were genotyped for the MSRA rs10903323 (G/A) polymorphism. Two hundred and thirty-three (17.9%) patients experienced CV events. Human leucocyte antigen (HLA)-DRB1 genotyping was performed using molecular-based methods. Multiple logistic regression models were constructed with adjustments for gender, age at RA diagnosis, follow-up, rheumatoid shared epitope, and traditional CV risk as potential confounders. RESULTS: There were no statistically significant differences in the allele or genotype frequencies for the MSRA rs10903323 polymorphism between RA patients who experienced CV events and those who did not. However, an adjusted logistic regression model disclosed that the minor allele G yielded a marginally significant increased risk of CV events in this series of patients with RA [p = 0.05, odds ratio (OR) 1.68, 95% confidence interval (CI) 1.00-2.85]. When the logistic regression model was adjusted for anti-cyclic citrullinated peptide (anti-CCP) antibody status instead of for shared epitope, an increased risk of having ischaemic heart disease was found in patients carrying the minor allele G (p = 0.04, OR 2.00, 95% CI 1.03-3.88). CONCLUSION: The MSRA rs10903323 gene polymorphism may be implicated in the increased risk to develop CV events, in particular ischaemic heart disease, observed in RA patients.

Late-onset systemic lupus erythematosus in Northwestern Spain: differences with early-onset systemic lupus erythematosus and literature review.

To further investigate into the epidaemiology of systemic lupus erythematosus (SLE) in Southern Europe, we have assessed the incidence, clinical spectrum and survival of patients diagnosed with late-onset SLE (age ≥ 50 years) according to the 1982 American College of Rheumatology (ACR) classification criteria at the single hospital for a well-defined population of Lugo, Northwestern (NW) Spain. Between January 1987 and December 2006, 51 (39.3%) of the 150 patients diagnosed as having SLE fulfilled definitions for late-onset SLE. The predominance of women among late-onset SLE (4:1) was reduced when compared with that observed in early-onset SLE (7:1). However, the incidence of late-onset SLE was significantly higher in women (4.2 [95% confidence interval (CI): 3.1-5.6] per 100,000 population) than in men (1.3 [95% CI: 0.6-2.2] per 100,000 population) (p < 0.001). As observed in early-onset SLE, the most frequent clinical manifestation in patients with late-onset SLE was arthritis (71.2%). Renal disease was less common in late-onset SLE (13.5%) than in early-onset SLE (26.4%); p = 0.07). In contrast, secondary Sjögren syndrome was more commonly found in the older age-group (27.1% versus 12.1%; p = 0.03). A non-significantly increased incidence of serositis was also observed in late-onset SLE patients (33.9% versus 22.0%; p = 0.13). Hypocomplementaemia (72.9% versus 91.2%) and positive results for anti-DNA and anti-Sm (49.2% and 6.8% versus 68.1% and 23.1, respectively) were significantly less common in late-onset SLE patients than in early-onset SLE. The probability of survival was reduced in late-onset SLE (p < 0.001). With respect to this, the 10-year and 15-year survival probability were 74.9 % and 63.3% in the late-onset SLE group and 96.3% and 91.0% in patients with early-onset SLE, respectively. In conclusion, our results confirm that in NW Spain SLE is not uncommon in individuals 50 years and older. In keeping with earlier studies, late-onset SLE patients from NW Spain have some clinical and laboratory differences with respect to those individuals with early-onset SLE. Our data support the claim of a reduced probability of survival in the older age-group of SLE patients.

Influence of MHCIITA rs3087456 and rs4774 polymorphisms in the susceptibility to cardiovascular disease of patients with rheumatoid arthritis.

OBJECTIVES: MHCIITA is a major regulator of MHC expression that has been reported to be involved in the susceptibility to rheumatoid arthritis (RA) and myocardial infarction. In this study we investigated the potential association of two MHCIITA gene polymorphisms with cardiovascular (CV) risk in patients with RA. METHODS: 1302 patients fulfilling the 1987 ACR classification criteria for RA were genotyped for the MHCIITA rs3087456 and rs4774 gene polymorphisms to determine the influence of MHCIITA variants in the development of CV events. The potential influence of these polymorphisms in the development of subclinical atherosclerosis was also analysed in a subgroup of patients with no history of CV events by the assessment of two surrogate markers of atherosclerosis; brachial and carotid ultrasonography to determine endothelial function and carotid artery intima-media thickness, respectively. RESULTS: No statistically significant differences in the allele or genotype frequencies for each individual MHCIITA gene polymorphism between RA patients who experienced CV events, or not, were found. This was also the case when each polymorphism was assessed according to results obtained from surrogate markers of atherosclerosis. Also, in assessing the combined influence of both MHCIITA gene polymorphisms in the risk of CV disease after adjustment for gender, age at time of disease diagnosis, follow-up time, traditional CV risk factors, and shared epitope status, patients with CV events only showed a marginally decreased frequency of the MHCIITA rs3087456-rs4774 G-G allele combination (p=0.08; odds ratio: 0.63 [95% confidence interval: 0.37-1.05]). CONCLUSIONS: Our data do not support an influence of MHCIITA rs3087456 and rs4774 polymorphisms in the increased risk of CV events of patients with RA.

Lack of association of IL6R rs2228145 and IL6ST/gp130 rs2228044 gene polymorphisms with cardiovascular disease in patients with rheumatoid arthritis.

Interleukin-6 (IL-6) is a key mediator of inflammation in rheumatoid arthritis (RA) and its actions may be controlled by the IL-6 receptor (IL-6R). IL-6 transducer (IL-6ST/ gp130) is the signal transducing subunit of the IL-6R. We assessed the influence of the IL6R and the IL6ST/gp130 genes in the risk of cardiovascular (CV) disease in RA. For this purpose, 1250 Spanish patients with RA were genotyped for the IL6R rs2228145 and IL6ST/gp130 rs2228044 functional gene polymorphisms. Patients were stratified according to the presence or absence of CV events. Also, a subgroup of patients without CV events was assessed for the presence of subclinical atherosclerosis using two surrogate markers of atherosclerosis (flow-mediated endothelium-dependent vasodilatation and carotid intima-media thickness). No significant differences in the genotype and allele frequencies for both gene polymorphisms between patients with and without CV events were observed. It was also the case when values of surrogate markers of atherosclerosis were compared according to IL6R and IL6ST genotype frequencies. In conclusion, our results do not confirm an association of IL6R rs2228145 and IL6ST/gp130 rs2228044 polymorphisms with CV disease in RA.

Lack of association of NAMPT rs9770242 and rs59744560 polymorphisms with disease susceptibility and cardiovascular risk in patients with rheumatoid arthritis.

OBJECTIVES: Visfatin is an adipokine encoded by the NAMPT (PBEF1) gene. In this study we assessed the potential association of two NAMPT gene polymorphisms with disease susceptibility and cardiovascular (CV) risk in patients with rheumatoid arthritis (RA). METHODS: A total of 1,395 patients fulfilling the 1987 ACR classification criteria for RA and 1,230 matched controls, were genotyped for the NAMPT rs9770242 and rs59744560 gene polymorphisms, located within the proximal promoter, using predesigned TaqMan single nucleotide polymorphism genotyping assay. Also, HLA-DRB1 genotyping was performed using molecular based methods. In a second step, 1,196 patients in whom full information was available were assessed to determine the influence of NAMPT rs9770242 and rs59744560 polymorphisms in the development of CV events. Also, the potential influence of these polymorphisms in the development of subclinical atherosclerosis was assessed in a subgroup of patients with no history of CV events by brachial artery reactivity to determine flow-mediated endothelium-dependent and endothelium-independent vasodilatation (n=125) and by B-mode ultrasonography to determine the carotid artery intima-media thickness (n=105). RESULTS: No statistically significant differences in the allele or genotype frequencies for the NAMPT gene polymorphisms between RA patients and controls were found. A modest non significant lower frequency of the minor allele G of rs9770242 polymorphism was observed among patients with CV disease (20.62%) compared to those without CV disease (22.83%) (p=0.39). Also, a slight nonsignificant lower frequency of the minor allele T of rs59744560 polymorphism in patients with CV events (9.81%) compared with those RA patients who did not experience CV disease (13.07%) (p=0.11) was observed. Likewise, no significant association between the NAMPT polymorphisms with surrogate markers of subclinical atherosclerosis was found in patients with RA. CONCLUSIONS: NAMPT rs9770242 and rs59744560 polymorphisms are not markers of disease susceptibility and CV disease in RA.

Lack of association between LEP rs2167270 (19 G>A) polymorphism and disease susceptibility and cardiovascular disease in patients with rheumatoid arthritis.

OBJECTIVES: To assess the potential association between LEP rs2167270 (19 G>A) gene polymorphism and disease susceptibility and cardiovascular disease (CV) in patients with rheumatoid arthritis (RA). METHODS: 773 patients fulfilling the 1987 American College of Rheumatology classification criteria for RA, seen at the rheumatology outpatient clinics of Hospital Xeral-Calde, Lugo, and Hospital San Carlos, Madrid, Spain, and 957 matched controls, were studied. Patients were genotyped for the LEP rs2167270 (19G>A) polymorphism, located within the 5´UTR, using predesigned TaqMan single nucleotide polymorphism genotyping assay. Also, HLA-DRB1 genotyping was performed using molecular based methods. Subclinical atherosclerosis was assessed in a subgroup of patients with no history of CV events by brachial artery reactivity to determine flow-mediated endothelium-dependent and endothelium-independent vasodilatation (n=133) and by B-mode ultrasonography of the carotid artery intima-media thickness (n=113). RESULTS: No statistically significant differences in the genotype or allele frequencies of the LEP rs2167270 gene polymorphism between patients with RA and controls were seen. Likewise, LEP rs2167270 polymorphism did not influence the development of CV events. Also, no significant differences in LEP rs2167270 genotype or allele distribution were seen when results of surrogate markers of subclinical atherosclerosis were assessed. CONCLUSIONS: LEP rs2167270 polymorphism does not seem to be a genetic risk factor for disease susceptibility or clinically evident CV disease and subclinical atherosclerosis in patients with RA.

Vascular endothelial growth factor A and cardiovascular disease in rheumatoid arthritis patients.

To determine the contribution of the vascular endothelial growth factor A (VEGFA) rs2010963 (-634 G>C) and rs1570360 (-1154 G>A) polymorphisms to the risk of cardiovascular (CV) disease in a series of patients with rheumatoid arthritis (RA). Six hundred sixty-one patients fulfilling the 1987 American College of Rheumatology classification criteria for RA, seen at the rheumatology outpatient clinics of the Hospital Xeral-Calde, Lugo, and the Hospital San Carlos, Madrid, Spain, were studied. Patients were genotyped for the VEGFA rs2010963 (-634 G>C) and rs1570360 (-1154 G>A) polymorphisms using predesigned TaqMan single nucleotide polymorphism (SNP) genotyping assay (Applied Biosystems, Foster City, CA). Also, human leukocyte antigen (HLA) DRB1 genotyping was performed using molecular-based methods. Clinical histories of the patients were reviewed for the presence of CV events that were considered to be present if the patient had ischemic heart disease, heart failure, cerebrovascular accident, or peripheral arteriopathy. Also, a subgroup of patients without the history of CV events was assessed for the presence of subclinical atherosclerosis manifested by the presence of endothelial dysfunction by brachial artery reactivity (n = 126) and increased carotid artery intima-media thickness (n = 105) using high resolution Doppler ultrasonography. No significant association between the VEGFA rs2010963 and the rs1570360 polymorphisms (neither isolated nor joined as allelic combinations) with clinically evident CV disease was found in this series of patients with RA. It was also the case when we examined the contribution of these polymorphisms to the development of subclinical atherosclerosis. VEGFA polymorphisms do not seem to exert a significant influence on the risk of CV disease in patients with RA.

Lack of association between ADIPOQ rs266729 and ADIPOQ rs1501299 polymorphisms and cardiovascular disease in rheumatoid arthritis patients.

To assess the potential association between ADIPOQ rs266729 and rs1501299 gene polymorphisms, either isolated or in combination, and cardiovascular disease in patients with rheumatoid arthritis (RA), 674 patients seen at the rheumatology outpatient clinics of Hospital Xeral-Calde, Lugo, and Hospital San Carlos, Madrid, Spain, were analyzed. Genotyping was performed using predesigned TaqMan assays (Applied Biosystems, Foster City, CA). Carotid intima-media thickness, flow-mediated endothelium-dependent and endothelium-independent post-nitroglycerin vasodilatation, which are used as surrogate markers of subclinical atherosclerosis, were measured in a subsample. No significant differences in the genotype, allele or allele combination frequencies of both polymorphisms were found between RA patients with or without cardiovascular events or subclinical atherosclerosis. Therefore, ADIPOQ rs266729 and rs1501299 polymorphisms do not seem to be associated with cardiovascular disease in RA.

Lack of association of PTPN22, STAT4 and TRAF1/C5 gene polymorphisms with cardiovascular risk in rheumatoid arthritis.

OBJECTIVES: To determine whether the PTPN22, STAT4 and TRAF1/C5 gene polymorphisms may be implicated in the development of cardiovascular (CV) events and subclinical atherosclerosis manifested by the presence of endothelial dysfunction or increased carotid intima-media thickness (IMT) in a series of Spanish patients with rheumatoid arthritis (RA). METHODS: Six hundred and twelve patients fulfilling the 1987 American College of Rheumatology classification criteria for RA, seen at the rheumatology outpatient clinics of Hospital Xeral-Calde, Lugo, and Hospital San Carlos, Madrid, were studied. Patients were genotyped using predesigned TaqMan single nucleotide polymorphism genotyping assays. Moreover, between March and December 2007, a subgroup of unselected RA patients with no history of CV events was studied for the presence of subclinical atherosclerosis by the assessment of the endothelial function (n=126) and the carotid artery IMT (n=110) by ultrasonography studies. RESULTS: No significant differences in the allele or genotype frequencies for the PTPN22, STAT4 and TRAF1/C5 gene polymorphisms between RA patients with or without CV events were found. It was also the case when we analysed the potential influence of the genotypes in the presence of endothelial dysfunction or increased carotid artery IMT of patients with RA. CONCLUSIONS: Our results do not show that the PTPN22, STAT4 and TRAF1/C5 gene polymorphisms may confer a direct risk of CV disease in patients with RA.

Visfatin is not associated with inflammation or metabolic syndrome in patients with severe rheumatoid arthritis undergoing anti-TNF-alpha therapy.

BACKGROUND AND OBJECTIVE: Visfatin is an insulin-mimetic adipokine. In non-rheumatoid arthritis (RA) patients circulating levels of visfatin are correlated with the amount of visceral fat. Recent studies have disclosed an implication of visfatin in inflammation. Chronic systemic inflammation is of major importance in the development of atherosclerosis in RA. In the present study we investigated whether inflammation, obesity or metabolic syndrome are potential determinants of circulating visfatin concentrations in a group of RA patients on periodical treatment with the TNF-alpha blocker infliximab due to severe disease. We also assessed whether the infusion of infliximab may alter circulating visfatin concentrations in patients with severe RA. METHODS: We investigated 33 non-diabetic patients with RA on periodical treatment with infliximab. Serum visfatin levels were determined immediately prior to and after infliximab infusion. RESULTS: There was no correlation between body mass index of RA patients and baseline serum level of visfatin. Also, no significant correlations between baseline visfatin levels and the age at the time of the study or at the onset of the disease, disease duration, ESR and CRP levels, DAS28, lipids, insulin sensitivity, resistin or the cumulative prednisone dose at the time of the study were found. Visfatin levels did not change upon infliximab infusion. CONCLUSIONS: In RA patients on TNF-alpha blocker treatment, circulating visfatin levels are unrelated to disease activity, adiposity or metabolic syndrome. The beneficial effect of anti-TNF-alpha therapy on cardiovascular mortality in RA does not seem to be mediated by changes in serum levels of visfatin.