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Background Chest pain in aortic stenosis (AS) has been attributed to the loss of coronary flow reserve however; this has not been directly quantified to date. Purpose To determine whether there is a decrease in coronary flow as a cause of chest pain or dyspnea in patients with severe AS Methods Patients with AS and normal left ventricular ejection fraction (LVEF) underwent coronariography previous to valve replacement. In those patients without obstructive coronary disease, an invasive physiological evaluation was performed to measure absolute coronary flow (Q) and microvascular resistances (R). Left anterior descending artery (LAD) was explored in all cases and, in a subgroup of patients, we also studied the circumflex (CX). Results 51 patients were included. 86% presenting with dyspnea, 26% also reported chest pain, and 11.8% syncope. No patient was admitted due to heart failure. Mean pressure gradient for AS was 52.44±15.41 mmHg with a mean aortic valve area of 0.76±0.17 cm2. Mean LVEF was 63±8.35%. The physiological study of LAD was successfully completed in all patients. 68.6% presented a normal / increased LAD-Q with a mean quantified flow of 262.118±161.99 mL/min. LAD-R proved normal in 56.9% of the cases and low in 13.7%. The quantified mean LAD-R was 400.78±195.89 UW. The physiological study of the CX was carried out in 34 patients. 82.3% presented normal / increased CX-Q, with a mean value of 201.82±117.91 mL/min. CX-R proved normal in 76.5% of the cases and low in 17.6%, with a mean value of 604.147±367.23 UW. Conclusion Invasive intracoronary measurements demonstrated most of patients with severe AS maintain normal values of Q and R Funding Acknowledgement Type of funding sources: None.

Background Traditional cardiovascular risk factors and a large number of biomarkers are well known in their association with the diagnosis and prognosis of coronary artery disease (CAD). Cyclophilin C (CypC) is a subfamily of immunophilins that modulates macrophage activation and redox homeostasis. Purpose This study is aimed at investigating the changes in serum CypC levels and their relationship with cardiovascular events at 12 months of follow-up in CAD patients. Methods The study included a total of 125 subjects (40 patients with acute CAD, 40 patients with chronic CAD and 45 control volunteers). We analyzed plasma CypC levels from baseline to 6 and 12 months for a better understanding of its behaviour in atherosclerosis. Results Serum CypC levels were shown to be gradually increased in CAD patients [(30.63 pg/mL ± 3.77 at baseline, 38.70 pg/mL ± 6.41 at 6 months (p=0.25) and 47.27 pg/mL ± 5.65 at 12 months (p=0.007)]. In addition, serum CypC levels during the follow-up were a significant predictor of CAD (c- statistic 0.76 at 6 months and 0.89 at 12 months; p2.3 mg/L plus NT-proBNP >300pg/mL together were significant predictors of cardiovascular events during the follow-up in CAD patients with CypC levels >17.5 pg/mL (p=0.048). Conclusions Taken together, our results suggest that serum CypC levels increase during the follow-up in CAD patients and could be a novel biomarker with a possible prognostic value in combination with hsCRP and NT-proBNP. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III. Spain

Aims To investigate a potential association between beta-blocker exposure and long-term survival in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). Methods Real world prospective registry of 128 consecutive patients with ATTR-CM recruited in 7 hospitals. The long-term survival of patients who were receiving beta-blockers (n=65) at baseline was compared with the one of untreated controls (n=63), by means of both unweighted and inverse probability of treatment weighting (IPTW) Cox's regression analyses. Tolerance and side effects of beta-blockers were recorded. Median study follow-up was 520 days. Results Patients with ATTR-CM who were receiving beta-blockers at baseline showed statistically significant lower all-cause mortality than untreated controls (figure 1), as compared either by means of unweighted Cox's regression (hazard ratio = 0.31; 95% CI 0.12–0.19; p=0.015), or by means of Cox's regression with IPTW (hazard-ratio = 0.18; 95% CI 0.08–0.41; p1000 pg/ml, and NYHA class III or IV (figure 2). The overall rate of beta-blocker suspension due to side effects in the study population was 25% (95% CI 15.5%–34.5%). Bradycardia and hypotension were the most frequent side effects leading to drug withdrawal. Conclusions In this real world, prospective, multi-institutional registry, patients with ATTR-CM who received beta-blockers presented lower all-cause mortality than untreated controls. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): PFIZERSOCIEDAD GALLEGA DE CARDIOLOGIA Figure 1. SurvivalFigure 2. Subgroup analysis

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Fundacion del Corazon Introduction COVID19 has emerged as a new disease, spreading around the world, leading to a complete lockdown. It is known that other infectious diseases can affect the heart inducing myocarditis. As a new entity, it was unknown if SARS-COV2 could provoke that cardiovascular manifestation. This national registry was created to describe COVID19 cardiac affection and its severity. Methods and results A multicenter registry was conducted, including 28 centers in Spain. Patients with COVID19 diagnosis presenting an acute cardiovascular event between March 1st and May 30th were included. Eighty-two patients were included. Of them, 9 (14,1%, excluding missing data) presented with acute myocarditis; the rest were diagnosed of acute myocardial infarction or stress cardiomyopathy. Baseline characteristics of these patients are summarised in Table 1. The 83,3% of patients with myocarditis presented with heart failure and 25% simulating an acute coronary syndrome. According to severity, 5 patients (62,5%) were admitted in the Intensive Care Unit, requiring orotracheal intubation 4 patients (57,1%). Left ventricle was affected in 66,7% of patients, whereas the remaining 33,3% presented biventricular failure. Mean left ventricle ejection fraction was 46% [30,0%-52%]. One patient developed refractory cardiogenic shock requiring implantation of both intra-aortic balloon pump and VA- ECMO. Three patients died during hospitalization. Cardiac magnetic resonance was conducted in 2 patients (28,6%), showing oedema and subepicardial enhacement in postero-lateral segments. Cardiac biopsy was performed in one patient showing significant lymphoid infiltration and intersticial oedema. Conclusions Patients with COVID 19 who develop acute myocarditis usually present with heart failure secondary to ventricular failure. This entity has a bad prognosis with high in-hospital mortality rate. Table 1. Baseline characteristics.n (%)Age65,0[47,0-77,0]Sex (female)3 (42,9%)Hypertension3 (42,9%)Dyslipidemia3 (42,9%)Diabetes mellitus2 (28,6%)Chronic coronary disease1 (14,3%)Previous stroke1 (14,3%)Cancer1 (14,3%)

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Fundación del Corazón Introduction COVID19 has spread uncontrollably all over the world through this 2020 year. As a new entity, we did not know the potential cardiovascular manifestations of this infectious disease. This national registry was created to describe the cardiac affection and its severity. Methods and results A multicenter registry was conducted, including 28 centers in Spain. Patients with COVID19 diagnosis presenting an acute cardiovascular event between March 1st and May 30th were included. Eighty-two patients were included. Of them, 49 (76,6%) presented with acute coronary syndrome; the rest were diagnosed of acute myocarditis or stress cardiomyopathy. The majority of cases were STEMI (n = 31), while the remaining 35,4% presented as NSTEMI. 29 patients (61,7%) underwent emergent percutaneous coronary intervention (PCI) (Figure 1). Anterior (n = 18) and inferior (n = 16) were the most frequent locations. Coronary angiogram showed total occlusion in 20 patients (55,6%); while 7 patients presented with non-obstructive coronary arteries. PCI was done in 31 patients. Eight patients (17,8%) developed Killip III-IV myocardial infarction. A total of 10 patients required endotracheal intubation and vasoactive agent were needed in 11 patients; none required IABP or ECMO. In-hospital mortality rate was 26,2%. Conclusions Patients with COVID19 may present with acute coronary syndromes. This entity has a poor prognosis, with noteworthy mortality. Table 1. Baseline characteristics.n (%)Age69,0[63,0-76,5]Sex (female)9 (19,1%)Hypertension28 (57,1%)Dyslipidemia25 (51,0%)Diabetes mellitus11 (22,4%)Chronic coronary disease10 (20,4%)Previous PCI10 (20,4%)Previous CABG0Previous AAS15 (30,6%)Smoking10 (20,4%)PCI percutaneous coronary intervention; CABG: coronary artery bypass graft; AAS: aspirin.Abstract Figure 1.

Objectives:To determine the incidence and risk factors implicated in the development of first cardiovascular (CV) event (CVE) in patients with chronic inflammatory rheumatic diseases (CIRD) attending Spanish rheumatology clinics after 5 years of follow-upMethods:Analysis of data of patients included in an observational prospective study [CARdiovascular in rheuMAtology (CARMA) project] after 5 years of follow-up. The study includes a cohort of 2234 patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA), and another cohort of matched individuals (n=677) without CIRD from 67 hospitals in Spain. Cumulative incidence per 1000 patients of CVE was estimated in both cohorts at 5 years from the start. Weibull proportional hazard model was used to calculate the Hazard Ratio (HR) and 95% confidence intervals (CI) of the risk factors involved in the development of CV events. Losses to follow-up and their causes were also analyzed.Results:The total number patient who completed the follow-up visit at 5 years was 2.382 (81.9%). Fifteen patients died due to CVE and sixty due to non-CVE. The patients with CIRD showed higher cardiovascular cumulative incidence (40.5; 95% CI: 36.2-44.8) than controls (28.3; 95% CI: 21.8-34.8). The higher risk of developing a first CVE during the 5 years of follow-up was seen in patients with AS (HR: 4.60; 95% CI: 1.32-15.99; p=0.02), those with older age (HR:1.09; 95% CI: 1.05-1.13; pConclusion:Patients with AS prospectively followed-up at rheumatology outpatient clinics showed higher risk of developing a first CVE than those without CIRD. Besides traditional CV disease risk factors, a longer time course of the disease is a risk factor for the development of CV disease in patients with CIRD.Acknowledgments:This project has been supported by an unrestricted grant from Abbvie, Spain. The design, analysis, interpretation of results and preparation of the manuscript has been done independently of Abbvie.Disclosure of Interests:Maria Auxiliadora Martin-Martinez: None declared, Santos Castañeda: None declared, Fernando Sánchez-Alonso: None declared, Carmen García Gomez: None declared, Carlos Gonzalez Juanatey: None declared, Maria Angeles Belmonte: None declared, Jesús Tornero: None declared, José Santos Rey: None declared, CARMEN OLGA SANCHEZ GONZALEZ: None declared, Estefanía Quesada-Masachs: None declared, MARIA DELPUERTO MORENO GIL: None declared, Tatiana Cobo-Ibáñez: None declared, Jose Antonio Pinto Tasende: None declared, Jesús Babío: None declared, Gemma Bonilla: None declared, Antonio Juan Mas: None declared, Javier Manero: None declared, Montserrat Romera: None declared, Javier Bachiller-Corral: None declared, Eugenio Chamizo Carmona: None declared, Javier Calvo: None declared, Raimon Sanmarti: None declared, Maria Celia Erausquin: None declared, Rosario Garcia de Vicuna Grant/research support from: BMS, Lilly, MSD, Novartis, Roche, Consultant of: Abbvie, Biogen, BMS, Celltrion, Gebro, Lilly, Mylan, Pfizer, Sandoz, Sanofi, Paid instructor for: Lilly, Speakers bureau: BMS, Lilly, Pfizer, Sandoz, Sanofi, Carmen Barbadillo: None declared, Sergio Ros Exposito: None declared, Javier del Pino Grant/research support from: Roche, Bristol, Consultant of: Gedeon, MARIA JOSE GONZALEZ: None declared, José Manuel Pina Salvador: None declared, Javier Llorca: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD

Objectives:Since obesity has been associated with higher inflammatory burden and worse response to therapy in patients with chronic inflammatory joint diseases (CIJDs), we aimed to confirm the potential association between body mass index (BMI) and disease activity in a large series of patients with CIJDs included in the Spanish CARdiovascular in rheuMAtology (CARMA) registry.Methods:Baseline data assessment of patients included from the CARMA project, a 10-year prospective study of patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) attending outpatient rheumatology clinics from 67 Spanish hospitals. Obesity was defined when BMI (kg/m2) was>30 according to the WHO criteria. Scores used to evaluate disease activity were DAS28 in RA, BASDAI in AS, and modified DAS for PsA.Results:Data from 2,234 patients (775 RA, 738 AS and 721 PsA) were assessed. The mean±SD BMI at the baseline visit were: 26.9±4.8 in RA, 27.4±4.4 in AS and 28.2±4.7 in PsA. Multivariate analyses shown a positive association between BMI and disease activity in patients with RA (β-coefficient: 0.029; 95% CI: 0.01-0.05; p=0.007) and in those with PsA (β-coefficient: 0.036; 95% CI: 0.015-0.058; p=0.001). By contrast, there was no significant association between BMI and disease activity in patients with AS (β-coefficient: 0.001; 95% CI: -0.026-0.03; p=0.926).In patients with RA, female gender (β-coefficient: 0.546; 95% CI: 0.316-0.775; pBesides BMI, female gender (β-coefficient: 0.720; 95% CI: 0.524-0.916; pAs observed in RA and PsA, female gender was also associated with disease activity patients with AS (β-coefficient: 0.565; 95% CI: 0.299-0.832; pConclusion:BMI is associated with disease activity in RA and PsA but not in AS. Since obesity is a potentially modifiable factor, disease activity was associated with female gender and RF status in RA and with Psoriasis Area Severity Index and enthesitis in PsA. Adequate control over body weight may improve the outcome of patients with CIJDs and, therefore, weight control should be included in the strategy of management of these patients.Disclosure of Interests:Ruth López-González: None declared, Jesús Alejandro Valero Jaimes: None declared, Maria Auxiliadora Martin-Martinez: None declared, Santos Castañeda: None declared, Carmen García Gomez: None declared, Fernando Sánchez-Alonso: None declared, Carlos Gonzalez Juanatey: None declared, Eva Revuelta-Evrad: None declared, Carolina Perez-Garcia: None declared, Vicenç Torrente Segarra: None declared, Trinidad Pérez Sandoval: None declared, Javier Llorca: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD

To assess whether the polymorphism of the macrophage migration inhibitory factor (MIF) gene at the position -173 is implicated in the disease susceptibility, risk of cardiovascular (CV) events and presence of subclinical atherosclerosis in patients with rheumatoid arthritis (RA).A series of 293 unselected patients fulfilling the 1987 American College of Rheumatology classification criteria for RA seen at the rheumatology outpatient clinic of Hospital Xeral-Calde, Lugo, Spain and 526 matched controls were studied for differences in the MIF-173 G/C gene biallelic polymorphism. A total of 182 consecutive patients that had been periodically followed between March 1996 and September 1996 until patient's death or January 1, 2008 were assessed for the presence of CV events. 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=107) and the carotid artery intima-media thickness (IMT) (n=91) by ultrasonography studies. Patients and controls were genotyped for the MIF-173 G/C gene polymorphism using a PCR system with pre-developed TaqMan allelic discrimination assay.No significant differences in allele or genotype frequencies for the MIF-173 gene polymorphism between RA patients and controls were found. Forty-four of the 182 patients followed between 1996 and January 2008 experienced CV events. Although the frequency of MIF-173 GG homozygous was increased in those who had CV events (88.6%) compared to those who did not suffer these complication (73.2%), the difference was not statistically significant. It was also the case when we analyzed the potential influence of MIF-173 genotypes in the presence of endothelial dysfunction or increased carotid IMT of patients with RA.Our results do not show that MIF-173 gene polymorphism may infer a direct risk for disease susceptibility or CV disease in patients with RA.

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.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.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.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.

To determine whether the interleukin (IL)6 -174 gene polymorphism may influence the development of subclinical atherosclerosis manifested by the presence of endothelial dysfunction in RA patients.311 patients (228 [73.3%] women; 243 [78.1%] rheumatoid factor positive) who fulfilled the 1987 ACR classification criteria for RA seen at the Rheumatology outpatient clinic of Hospital Xeral-Calde, Lugo between March 1996 and December 2006 and 226 matched controls were included in this study. Between March and December 2007, a subgroup of 98 patients randomly selected was assessed for the presence of endothelial dysfunction. Patients and controls were genotyped for a single biallelic (G/C) nucleotide polymorphism (rs1800795) in the promoter region at the position -174 of the IL6 gene using a TaqMan 5' allele discrimination assay.No significant differences in the IL6 -174 allele or genotype frequency between RA patients and controls were found. However, RA patients homozygous for the IL6 -174 GG genotype had more severe endothelial dysfunction (flow-mediated endothelium-dependent vasodilatation-FMD%: 4.2 + or - 6.6) than those carrying the IL6 -174 GC (FMD%: 6.3 + or - 8.1) or IL6 -174 CC (FMD%: 6.0 + or - 3.3) genotypes. In this regard, significant differences were observed when FMD% values in RA patients carrying the IL6 -174 GG genotype were compared with that observed in those carrying the IL6 -174 GC and the IL6 -174 CC genotypes (FMD%: 6.3 + or - 4.6) (p=0.02).Our results support a role of IL6 -174 gene polymorphism in the development of subclinical atherosclerosis in patients with RA.

TNF-alpha increases expression of inducible nitric oxide synthase (iNOS) in macrophages and vascular endothelial cells. Under normal conditions, iNOS activity is very low. However, iNOS activity is stimulated during inflammation by cytokines such as TNF-alpha and the amount of NO produced by iNOS may be a 1,000-fold greater than that produced by endothelial NOS. Since functional iNOS gene polymorphisms have been associated with susceptibility to rheumatoid arthritis (RA), drugs blocking TNF-alpha might decrease production of cytotoxic concentrations of NO leading to beneficial effect on RA or its complications. In the present study we investigated whether the infusion of the anti-TNF-alpha-infliximab may yield a short-term effect altering circulating NO oxidation products in patients with severe RA.We investigated 33 RA patients on periodical treatment with infliximab. Serum levels of nitrates, nitrites and NOx (nitrites+nitrates) were determined immediately prior to and after infliximab infusion. Correlation with clinical variables, laboratory markers of inflammation, metabolic syndrome features, adipokines and adhesion molecules was also assessed.Upon infliximab administration, serum NOx concentrations (microM) decreased significantly ([mean+/-SD: 15.0+/-8.8; median: 11.9; interquartile range: 9.2-18.5] before infliximab-time 0 (baseline) and [12.9+/-6.3; 10.9; 7.8-17.2] after infliximab infusion-time 120 minutes; p=0.03). It was also the case for nitrates (9.8+/- 8.3; 7.6; 5.5-10.2] before infliximab and [7.5+/-4.0; 6.6; 5.2-10.0] after infliximab infusion; p=0.008). There was a positive correlation between basal levels of nitrites and leptin concentration prior to infliximab administration. However, no significant correlations between NO oxidation products and clinical or other laboratory variables were found.Our results show, for the first time, a short-term effect of anti-TNF-alpha therapy on the levels of nitric oxide production.

The adipocytokine leptin regulates weight centrally and participates in the regulation of the immune and inflammatory responses. Chronic systemic inflammation is of major importance in the development of atherosclerosis in rheumatoid arthritis (RA). In the present study we investigated whether inflammation, obesity or both of these characteristics are potential determinants of circulating leptin 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 leptin concentrations in patients with severe RA.We investigated 33 patients with RA on periodical treatment with infliximab. Serum leptin levels were determined immediately prior to and after infliximab infusion.There was a positive correlation between body mass index of RA patients and baseline serum level of leptin (rho=0.665, p0.001). Apart from a significant correlation with VCAM-1 (rho=0.349, p=0.04), no significant correlations between baseline leptin 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, adhesion molecules, resistin, adiponectin, ghrelin or the cumulative prednisone dose at the time of the study were found. Leptin levels did not change upon infliximab infusion (p=0.48).In RA patients on TNF-alpha blocker treatment, circulating leptin levels are unrelated to disease activity but constitute a manifestation of adiposity. The beneficial effect of anti-TNF-alpha therapy on cardiovascular mortality in RA does not seem to be mediated by reduction in serum levels of leptin.

Complex interactions between environmental and genetic determinants in both the host immune system and the vasculature may operate modifying the vascular risk in rheumatoid arthritis (RA). An increased incidence of cardiovascular (CV) events in RA patients carrying HLA-DRB1 shared epitope alleles, in particular HLA-DRB1*0404, has recently been found. In the present study we have assessed the potential contribution of inducible and endothelial nitric oxide synthase (NOS2A and NOS3) gene polymorphisms to CV events in a cohort of patients with rheumatoid arthritis (RA). Also, interactions between NOS2A or NOS3 gene polymorphisms and HLA-DRB1 alleles for the risk of developing CV events were assessed.One hundred and eighty-two consecutive patients fulfilling the 1987 American College of Rheumatology classification criteria for RA seen at the Rheumatology outpatient clinic of Hospital Xeral Calde, Lugo, Northwest Spain, between March and September 1996 were included. Patients were genotyped by PCR based techniques for a multiallelic (CCTTT)n repeat in the promoter region of the NOS2A gene and for a T/C polymorphism at position -786 in the promoter region and a polymorphism in exon 7 (298Glu/Asp or 5557G/T) of the NOS3 gene. They were prospectively followed and clinical records were examined until patient's death or September 1, 2005. At the end of the study 39 (21%) patients had experienced CV events.No significant differences in allele or genotype frequencies for the NOS2A promoter CCTTT repeat microsatellite and NOS3 gene polymorphisms between RA patients with or without CV events were found. However, an increased frequency of CV events was observed in RA patients who carried the HLA-DRB1*0404 allele and were homozygous for the NOS3 (-786) TT genotype (OR: 9.06 [95% CI: 1.29-63.37]; p= 0.03) or for the presence of long NOS2A alleles (OR: 11.7 [95% CI: 1.53-88.4]); p= 0.02).Our results show that NOS2A or NOS3 gene polymorphisms do not infer a direct risk for CV events in RA. However, some interactions between NOS gene polymorphisms and HLA-DRB1 alleles confer and increased risk of developing CV events in patients with RA.

To assess the potential influence of the age in the clinical spectrum of giant cell arteritis (GCA).The case records of all patients diagnosed with biopsy-proven GCA at the Department of Medicine of the Hospital Xeral-Calde (Lugo, Northwest Spain) between 1981 and 2006 were reviewed.During the period of study, 273 Lugo residents were diagnosed with biopsy-proven GCA. The mean age +/- standard deviation at the time of disease diagnosis was 75.1+/-6.8 years (median: 75 years; interquartile range 71-80 years). A longer delay to the diagnosis was observed in patients younger than 70 years of age (13.2+/-12.8 weeks) compared to those 70 years and older (9.4+/-10.2 weeks) (p=0.03). Patients younger than 70 years presented more frequently polymyalgia rheumatica (p=0.02), cerebrovascular accidents (p=0.004), peripheral arteriopathy of recent onset due to large artery stenosis (p=0.03) and high alkaline phosphatase values (p=0.001) than those 70 years and older. Individuals 70-79 years of age at the time of disease diagnosis had ESR values (90.2+/-22.8 mm/1st hour) lower than those observed in patients younger than 70 years (98.3+/-22.2 mm/1st hour) or 80 years and older (99.5+/-20.6 mm/1st hour) (p=0.005). However, no significant differences in the frequency of visual ischemic complications according to the age at the time of disease diagnosis were observed.The results from this study display differences in the clinical spectrum of the disease according to the age of disease onset.

Chronic systemic inflammation plays a pivotal role in the development of atherosclerosis in rheumatoid arthritis (RA). In the present study, we investigated whether anti-TNF-alpha antagonist-monoclonal antibody-infliximab administration alters circulating levels of resistin, a proinflammatory adipokine. We further assessed associations of circulating resistin concentrations with CRP and ESR levels, platelet counts and metabolic syndrome and demographic characteristics in RA patients on periodical treatment with infliximab.We investigated 33 patients with RA on periodical treatment with infliximab. Serum resistin levels were determined immediately prior to and after infliximab infusion.Upon infliximab administration, mean (SD) serum resistin concentrations (ng/ml) decreased from 21.9 (9.9) to 17.4 (8.9) (p=0.005). Also, a significant association between the mean ESR (r=0.405; p=0.03) and CRP (r=0.571; p=0.0005) from disease diagnosis and ESR (r=0.486; p=0.004), CRP (r=0.599; p=0.0005) and platelet count (r=0.559; p=0.0007) at the time of the study and baseline resistin levels was found.The present study shows that anti-TNF-alpha therapy results in a rapid reduction of serum resistin levels in patients with RA. It also confirms a close association between laboratory markers of inflammation, particularly CRP and resistin levels. These observations support a potential role of resistin in the inflammatory cascade in RA.

Secondary vasculitis resulting from unusual pathologic expressions of infections has been described and has important clinical significance. Infectious agents have also been implicated in the pathogenesis of different primary systemic necrotizing vasculitides. Infectious endocarditis is of particular importance in the differential diagnosis of a patient presenting with ANCA associated vasculitis. We report a well-documented case of a patient with recurrent Staphylococcus aureus bacteremia who developed bacterial endocarditis and also fulfilled the Chapel Hill Conference definitions for microscopic polyangiitis. To the best of our knowledge, it is the second case of bacterial endocarditis associated with both pANCA and anti-MPO specificity that fulfilled definitions for systemic necrotizing vasculitis. We emphasize the potential pathogenic role of infection as the trigger factor for the development of systemic vasculitis.

Objectives To study the association between vitamin D levels and the clinical characteristics of patients with chronic inflammatory rheumatic diseases (CIRD). Methods Analysis of data from the baseline visit of the CARMA project (CARdiovascular in rheuMAtology); a 10-year prospective study evaluating the risk of cardiovascular events in a cohort of rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) patients, and a cohort of unexposed matched individuals who attended rheumatology outpatient clinics from 67 hospitals in Spain. Sociodemographic characteristics, comorbidities, and disease activity of CIRD were analyzed. Patients were defined as having vitamin D deficiency if 25-OH vitamin D levels were Results 2.234 patients (775 RA, 738 AS and 721 PsA) and 677 unexposed subjects were assessed. The median [p25-p75] 25-OH vitamin D levels were: 20.4 [14.4-29.2] ng/ml in RA, 20.9 [13.1-29.0] in AS, 20.0 [14.0-28.8] in PsA and 24.8 [18.4-32.6] ng/ml in unexposed controls. Vitamin D deficiency was detected in 40.5% RA, 39.7% AS, 40.9% PsA and 26.7% unexposed cohort (p Conclusions Patients with CIRD show an increased risk of having vitamin D deficiency compared to unexposed matched individuals. ACPA and BASFI were the main factors associated with vitamin D deficiency in RA and AS, respectively Disclosure of Interest A. Urruticoechea Arana: None declared, M. A. Martin Martinez: None declared, S. Castaneda: None declared, C. A. Piedra: None declared, C. Gonzalez Juanatey: None declared, J. Llorca: None declared, F. Diaz Gonzalez: None declared, M. A. Gonzalez-Gay Grant/research support from: This project has been supported by an unrestricted grant from Abbvie, Spain. The design, analysis, interpretation of results and preparation of the manuscript has been done independently of Abbvie. Dr. Gonzalez-Gay9s studies have been supported by grants from “Fondo de Investigaciones Sanitarias” PI06/0024, PS09/00748 and PI12/00060, and RD12/0009/0013 (RIER) from “Instituto de Salud Carlos III” (ISCIII) (Spain).

Objectives To establish the cardiovascular (CV) morbidity and associated risk factors for CV disease (CVD) in Spanish patients with chronic inflammatory rheumatic diseases (CIRD) and unexposed individuals attending rheumatology clinics Methods Analysis of data from the baseline visit of a 10-year prospective study (CARdiovascular in rheuMAtology-CARMA-project) that includes a cohort of patients with CIRD [rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA)] and another cohort of matched individuals without CIRD attending outpatient rheumatology clinics from sixty-seven hospitals in Spain. Prevalence of CV morbidity, CV risk factors and systematic coronary risk evaluation (SCORE) assessment were analyzed Results 2,234 patients (775 RA, 738 AS and 721 PsA) and 677 unexposed subjects were included. A high percentage of patients had low disease activity at the time of recruitment. PsA patients had more commonly classic CV risk factors and metabolic syndrome features than did the remaining individuals. Prevalence of CVD was higher in RA (10.5%) than in AS (7.6%), PsA (7.2%) and unexposed individuals (6.4%). A multivariate analysis adjusted for the presence of classic CV risk factors and disease duration revealed a positive trend for CVD in RA (OR=1.58; 95%CI=0.90-2.76; p=0.10) and AS (OR=1.77; 95%CI=0.96-3.27; p=0.07). Disease duration in all CIRD groups (RA: OR=1.06; 95%CI=1.01-1.11; AS: OR=1.06; 95%CI=1.01-1.06; PsA: OR=1.15; 95%CI=1.07-1.23) and functional capacity (HAQ) in RA (OR=2.15; 95%CI=1.29-3.56; p=0.003) were associated with an increased risk of CVD. Most patients had a moderate CV risk according to the SCORE charts. Conclusions Despite recent advances in the management of CIRD, prevalence of CVD remains increased in Spanish subjects with CIRD attending outpatient rheumatology clinics. Disclosure of Interest S. Castaneda: None declared, M. A. Martin Martinez: None declared, C. Gonzalez Juanatey: None declared, J. Llorca: None declared, M. J. Garcia Yebenes: None declared, S. Perez Vicente: None declared, J. T. Sanchez Costa: None declared, F. Diaz Gonzalez: None declared, M. A. Gonzalez Gay Grant/research support from: This project has been supported by an unrestricted grant from Abbvie, Spain. The design, analysis, interpretation of results and preparation of the manuscript has been done independently of Abbvie. Dr. Gonzalez-Gay9s studies have been supported by grants from “Fondo de Investigaciones Sanitarias” PI06/0024, PS09/00748 and PI12/00060, and RD12/0009/0013 (RIER) from “Instituto de Salud Carlos III” (ISCIII) (Spain).

Chronic systemic inflammation plays a pivotal role in the development of atherosclerosis in rheumatoid arthritis (RA). Soluble (s) adhesion molecules were found significantly increased in RA patients with active disease. Since increased levels of some adhesion molecules were closely linked to the development of endothelial dysfunction and atherosclerosis and administration of anti-TNF-alpha-infliximab resulted in a rapid and dramatic improvement of endothelial function in long-term infliximab treated RA patients, we assessed whether infusion of the chimeric anti-TNF-alpha infliximab might also yield a rapid and favorable effect on serum levels of soluble adhesion molecules in RA patients periodically treated with this drug because of severe disease.We recruited patients with RA refractory to conventional therapy seen over a period of 2 months at Hospital Xeral-Calde, Lugo, Spain, who were on periodical treatment with infliximab for at least 14 weeks. Blood samples for determination of sICAM-1, sICAM-3, sVCAM-1, sE-selectin, and sP-selectin levels by ELISA were taken immediately before and after infliximab infusion.Thirty-four RA patients (25 women; mean age: 55.4 years; mean DAS28: 4.27) fulfilled the inclusion criteria. Following infliximab infusion a reduction of the overall mean values of the five adhesion molecules was observed. However, when a Wilcoxon signed-rank test was used, only significant differences for sICAM-3 and sP-selectin were observed. In this regard, sICAM-3 and sP-selectin levels fell in 26 (77%) and 28 (82%) of the 34 patients.Our study confirms a rapid and beneficial effect of infliximab infusion on expression of some adhesion molecules in RA patients treated periodically with this anti-TNF-alpha monoclonal antibody because of severe disease.

Endothelial dysfunction has been found in patients with rheumatoid arthritis (RA). In this study we aimed to assess whether adalimumab, a fully human monoclonal antibody directed against TNF-alpha, was able to improve endothelial function in RA patients with long-standing disease refractory to infliximab.Eight RA patients (7 women; range: 24- 74 years) were studied. They had been treated with the chimeric monoclonal anti-TNF-alpha antibody-infliximab for at least 1 year and were switched to adalimumab therapy because of loss of efficacy following periodical treatment with infliximab. Endothelial dependent (EDV) and independent vasodilatation (EIV) were measured by brachial ultrasonography. Patients were assessed prior to (day 0) and at day 2, and weeks 2 and 12 after the onset of adalimumab therapy.Following adalimumab administration a rapid increase in the percentage (%) of EDV was found in all patients (mean +/- SD: 10.1 +/- 5.1% at day 2 compared to 5.8 +/- 4.1% at day 0). At weeks 2 and 12 the %EDV was also significantly increased compared to day 0. All patients showed decrease in the disease activity score 28 and C-reactive protein levels (P = 0.012). Moreover, at week 12 the atherogenic index was reduced in all patients (P = 0.012).Our study confirms that short-term adalimumab therapy yields an active and positive effect on endothelial function in long-standing RA patients with severe disease. This observation emphasizes the potential role of the TNF-alpha blockade in the mechanisms implicated in the development of atherogenesis in RA.

Systemic inflammation, insulin resistance, and endothelial dysfunction have been implicated in the development of cardiovascular disease in rheumatoid arthritis (RA). Since insulin resistance can promote endothelial dysfunction and anti-TNF-alpha blockade yield a rapid improvement of endothelial function, we have sought to assess whether TNF-alpha blockade may also result in a reduction of insulin serum levels and improvement of insulin resistance in RA patients who require this therapy because of severe and refractory disease.We recruited patients with RA seen over a period of 1 month at Hospital Xeral-Calde, Lugo, Spain, that were on treatment with anti-TNF-alpha monoclonal antibody-infliximab. Patients with diabetes mellitus or plasma glucose110 mg/dl were excluded. Fasting blood samples were taken for determination of plasma glucose and serum insulin levels immediately prior to and after infliximab infusion.Twenty-seven RA patients (21 women; mean age: 57.1 years; mean DAS28: 4.43) fulfilled the inclusion criteria. Dramatic reduction in the serum insulin levels and insulin/glucose index was observed following infliximab infusion. Also, a significant improvement of insulin resistance and insulin sensitivity was found.Our study confirms a rapid beneficial effect of infliximab on insulin resistance and insulin sensitivity in RA patients treated periodically with this drug. It may support the long-term use of drugs that act blocking TNF-alpha function to reduce the mechanisms implicated in the development of atherosclerosis in patients with RA.