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Evidence for increased risk of cardiovascular morbidity and mortality in chronic inflammatory rheumatic diseases has accumulated during the last years. Traditional cardiovascular risk factors contribute in part to the excess of cardiovascular risk in these patients and several mechanisms, including precocious acceleration of subclinical atherosclerotic damage, inflammation, and immune system deregulation factors, have been demonstrated to strictly interplay in the induction and progression of atherosclerosis. In this setting, chronic inflammation is a cornerstone of rheumatic disease pathogenesis and exerts also a pivotal role in all stages of atherosclerotic damage. The strict link between inflammation and atherosclerosis suggests that cardiovascular risk may be reduced by rheumatic disease activity control. There are data to suggest that biologic therapies, in particular TNFα antagonists, may improve surrogate markers of cardiovascular disease and reduce CV adverse outcome. Thus, abrogation of inflammation is considered an important outcome for achieving not only control of rheumatic disease, but also reduction of cardiovascular risk. However, the actual effect of anti-rheumatic therapies on atherosclerosis progression and CV outcome in these patients is rather uncertain due to great literature inconsistency. In this paper, we will summarize some of the main mechanisms linking the inflammatory pathogenic background underlying rheumatic diseases and the vascular damage observed in these patients, with a particular emphasis on the pathways targeted by currently available therapies. Moreover, we will analyze current evidence on the potential atheroprotective effects of these treatments on cardiovascular outcome pointing out still unresolved questions.

ObjectiveTo define the role of ultrasound (US) for the assessment of patients with rheumatoid arthritis (RA) in clinical remission, including joint and tendon evaluation.MethodsA multicentre longitudinal study has been promoted by the US Study Group of the Italian Society for Rheumatology. 25 Italian centres participated, enrolling consecutive patients with RA in clinical remission. All patients underwent complete clinical assessment (demographic data, disease characteristics, laboratory exams, clinical assessment of 28 joints and patient/physician-reported outcomes) and Power Doppler (PD) US evaluation of wrist, metacarpalphalangeal joints, proximal interphalangeal joints and synovial tendons of the hands and wrists at enrolment, 6 and 12 months. The association between clinical and US variables with flare, disability and radiographic progression was evaluated by univariable and adjusted logistic regression models.Results361 patients were enrolled, the mean age was 56.20 (±13.31) years and 261 were women, with a mean disease duration of 9.75 (±8.07) years. In the 12 months follow-up, 98/326 (30.1%) patients presented a disease flare. The concurrent presence of PD positive tenosynovitis and joint synovitis predicted disease flare, with an OR (95% CI) of 2.75 (1.45 to 5.20) in crude analyses and 2.09 (1.06 to 4.13) in adjusted analyses. US variables did not predict the worsening of function or radiographic progression. US was able to predict flare at 12 months but not at 6 months.ConclusionsPD positivity in tendons and joints is an independent risk factor of flare in patients with RA in clinical remission. Musculoskeletal ultrasound evaluation is a valuable tool to monitor and help decision making in patients with RA in clinical remission.

Chronic inflammatory diseases (CID) are characterized by an increased risk of cardiovascular (CV) morbidity and mortality. Several mechanisms, including early acceleration of subclinical atherosclerotic damage, inflammatory markers and immune system deregulation factors, have been demonstrated to strictly interplay for development and progression of atherosclerosis. Moreover, traditional CV risk factors are likely to explain at least some of the excess of CV risk in these patients. Among traditional CV risk factors, compelling evidence suggests a higher incidence and prevalence of hypertension in patients with CID in comparison to the general population. Moreover, hypertension represents an important predictor of CV events in these patients. Pathogenic mechanisms underlying the rise of blood pressure in CID are multifactorial and still poorly investigated. Indeed, multiple disease-related factors may affect blood pressure control in these patients and hypertension may affect disease prognosis and increase CV risk. Better knowledge of the complex interplay between hypertension and CID will be important to elucidate pathogenic mechanisms and to improve CV outcome in these patients. Aim of this review is to highlight available evidence on the relationship between hypertension and CID and to elucidate the multiple factors that may affect blood pressure control in these disorders.

Background Subclinical synovial inflammation detected by ultrasonography (US) in patients with rheumatoid arthritis (RA) in clinical remission relates to disease flare. The impact of tenosynovitis in this context is not known. Objectives To evaluate the association between US-detected tenosynovitis and synovitis in RA patients in clinical remission and flare over 12-months. Methods STARTER is a multicentre cohort study of the US Study Group of the Italian Society for Rheumatology. Participants were selected on the basis of a reliability exercise and the availability of high-end equipment. Patients with RA in clinical remission underwent clinical evaluation and US synovitis (-S) and tenosynovitis (-T) were assessed categorically for Grey Scale (GS) and power Doppler (PD) at 11 joints, extensor and flexor tendons in both hands and wrists. Patients were seen at 6 and 12 months. Flare within 12 months was defined as increase of >1.2 or >0.6 if final DAS28>3.2. The relationship between the presence of GS-T/-S, PD-T/-S was evaluated by logistic models, presented as odds ratios (OR) and 95% confidence interval (CI), adjusted for pre-specified confounders. Results 361 patients (72.3% f, mean age (sd) 56.1 (13.3), median disease duration (IQR) 7.1 years (3.6–13.5)) were included. 98/326 (30.6%) patients had a flare within 12 months. Considering US variables separately, only PD-S significantly predicted flare (OR 1.87 (1.12,3.14)). When the model included both –T and –S, only the concurrent presence of –T and –S predicted flare (PD-T+-S: OR 2.06 (1.04, 4.07); GS-T+-S: OR 2.27, (1.01,5.10)), while isolated –S and –T did not. Conclusions In patients with RA in clinical remission, US-detected synovial and tenosynovial inflammation identifies patients at risk of flare. US might help decisions on management in this population. Disclosure of Interest None declared

This study was conducted to determine the prevalence of subclinical entheseal involvement at the greater trochanter level by ultrasound in patients with spondyloarthritis. Forty-six patients with spondyloarthritis and 46 healthy age- and sex-matched controls were studied. All patients with no clinical evidence of enthesopathy at the greater trochanter underwent an ultrasound examination. The following three entheses were scanned bilaterally: anterior insertion of gluteus minimus, anterior insertion of gluteus medius, and posterior insertion of gluteus medius. Ultrasound findings of enthesopathy were thickening, calcifications, bone erosions, enthesophytes, bursitis, and power Doppler signal. A total of 276 entheses were evaluated in spondyloarthritis patients. In 112 out of 276 (40.5%), grayscale ultrasound found enthesopathy. The enthesis with the highest number of signs of enthesopathy was the anterior insertion of gluteus medius (46/276) (16%), followed by posterior insertion of gluteus medius (37/276) (13.4%) and anterior insertion of gluteus minimus (29/276) (10.5%). In the healthy population, ultrasound found entesopathy in 80 out of 276 (29%) entheseal sites (p

Connective tissue diseases are associated with increased morbidity and mortality related to a higher rate of cardiovascular events and higher prevalence of subclinical atherosclerosis. Atherosclerosis is now considered a multifactorial process where autoimmunity and chronic inflammation play an important pathogenic role. In systemic autoimmune rheumatic diseases in general, and in systemic lupus erythematosus in particular, atherosclerosis cannot be explained by traditional cardiovascular risk factors alone. Cellular and humoral mechanisms, together with specific factors associated with the disease itself and/or its treatments, have been advocated to explain the acceleration of arterial wall organic damage in these patients. Endothelial dysfunction, carotid intima-media thickness and plaque evaluations provide accurate detection of atherosclerotic process at a preclinical stage, before appearance of clinical disease, allowing preventive measure introduction with the aim to modify the cardiovascular risk in subjects with systemic autoimmune rheumatic diseases.

OBJECTIVE Chronic autoimmune diseases are associated with increased risk of cardiovascular death. Endothelial dysfunction represents the first stage of subclinical atherosclerosis and multiple factors contribute to endothelial injury. Among these, an altered balance between endothelial microparticle (EMP) release and endothelial progenitor cell (EPC) generation promotes endothelial dysfunction. The role of EMPs and EPCs in promoting endothelial damage in primary SS (pSS) has never been investigated. Our aim was to evaluate the role of EMPs and EPCs as markers of endothelial damage in pSS and their correlation with disease clinical and immunological features. METHODS Circulating EMPs (CD31(+)/CD42(-)), true EPCs (CD34(+)/KDR(+)/CD133(+)) and mature EPCs (CD34(+)/KDR(+)/CD133(-)) were quantified by FACS analysis in 34 pSS patients and 18 age- and sex-matched controls. Correlation between EMP and EPC levels and parameters of disease activity and damage, clinical features and markers of immunological dysfunction was performed. RESULTS Patients displayed higher EMP numbers with respect to healthy controls [HCs; mean 450 n/μl (S.D. 155) vs 231 (110), P < 0.0001]. EPC and mature EPC levels were higher in patients compared with HCs [mean 226 n/ml (S.D. 181) vs 69 (53), P < 0.001 and 166 (161) vs 36 (32), P < 0.0001, respectively). EMP levels directly correlated with disease duration from symptoms and diagnosis (ρ = 0.5, P < 0.01). Early EPCs inversely correlated with disease duration from symptoms (ρ = -0.5, P < 0.01) and diagnosis (ρ = -0.4, P < 0.05). CONCLUSION This is the first demonstration of chronic endothelial fragmentation characterizing pSS. The reparative potentiality of the endothelial layer appears to be preserved in the earliest stages of disease. During the course of the disease, progressive exhaustion of the precursor endothelial pool may be hypothesized, leading to defective vascular layer restoration and endothelial dysfunction.

Background Matrix metalloproteinaeses (MMPs) are a large family of zinc-dependent endoproteinases that cleave several components of the extracellular matrix (ECM) and that are tightly regulated by tissue type MMP inhibitors (TIMPs). The joint cartilage and bone degradation that occurs in osteoarthritis (OA) is in part the consequence of an imbalance between MMPs and TIMPs. MMPs are released by several cell types, including platelets that have been recently shown to participate in the inflammatory processes of arthritis. Among platelet-derived MMPs, MMP-2 is of particular potential relevance for OA. Hyaluronic acid (HA), a core component of ECM, is a critical constituent of normal synovial fluid and plays a pivotal role in joint homeostasis. In clinical practice, intra-articular injection of low molecular weight HA (LMW-HA) has been used as visco-supplementation for knee OA and its therapeutic efficacy has been verified in a number of studies. Objectives Aim of the present study was to investigate the effect of a short treatment with LMW-HA on platelet derived MMP-2 in the synovial fluid and possible correlations with clinical response. Methods Nineteen patients with knee OA were enrolled. Synovial fluid (SF) samples were collected before (T0) and after 5 weeks of intra-articular LMW-HA (T1) (4 injections, one week apart). Western Ontario and McMaster Universities Arthritis Index (WOMAC) and global pain visual analogic scale (VAS) were also collected at both time-points. MMP-2 measurement in SF was performed by zymography. SF inflammatory cell count was performed optically, by a Burker Chamber, while platelets were counted by flow cytometry. Results SF MMP-2 levels, platelet activation, platelet, monocyte and eosinophil numbers, were all significantly reduced at T1, while lymphocyte and synoviocyte number was not affected. A direct correlation between platelet number and MMP-2 concentration in SF was observed at both time-points (p

Objective Primary Sjogren's syndrome (SS) shares clinical and serologic features with rheumatoid arthritis and systemic lupus erythematosus, 2 diseases characterized by acceleration of atherosclerosis. Signs of precocious atherosclerosis have also been shown in SS, although the pathogenic basis of early arterial damage is unclear. The arterial wall was functionally evaluated in SS subjects with analysis of the role played by disease-related factors. Methods Endothelium-dependent flow-mediated vasodilation (FMV) and endothelium-independent nitrate-mediated vasodilation (NMV) were evaluated in 45 women with SS and 59 age-matched female controls. In addition, serum soluble intercellular adhesion molecule 1, soluble vascular cell adhesion molecule 1 (VCAM-1), and nitrotyrosine were detected. Results Although patient FMV values did not differ from those of control subjects (mean ± SD 7.4 ± 3.6 versus 7.7 ± 1.9; not significant), NMV was lower in SS patients than in controls (mean ± SD 8.1 ± 3.5 versus 10.3 ± 2.1; P ≤ 0.001). Patient NMV was inversely correlated with soluble VCAM-1 levels (r = −0.38, P = 0.001) and directly correlated with leukocyte count (r = 0.26, P = 0.03). An NMV decrease was confirmed in SS patient subsets with evidence of leukopenia, rheumatoid factor, anti-SSB antibodies, and joint involvement. However, patients with joint involvement or parotid enlargement, 2 of the sites mainly affected by chronic inflammation in SS, had an FMV lower than controls and patients without these clinical features. Conclusion Our results suggest that a functional impairment of the arterial wall may sustain early phases of atherosclerotic damage in SS. A combined effect of disease-related chronic inflammatory and immunologic factors appears to support dysfunction of endothelium and vascular smooth muscle cells, respectively.

Background and aims: In advanced age, the influence of vertebral fractures on quality of life extends well beyond the usual sequelae of osteoporosis. In order to intercept older subjects’ distress associated with the clinical, functional, social and psychological consequences of the disease, we developed and validated a multidimensional instrument (the triple-Q questionnaire) tailored to older women with osteoporotic fractures. We also examined specific aspects of the questionnaire correlated with bone mineral density. Methods: 100 osteoporotic women with vertebral fractures and 100 controls aged >65 years, underwent a thorough examination, which also included X-ray of the thoraco-lumbar spine, hip densitometry, the triple-Q questionnaire, and five referral instruments evaluating function, cognition, perception of general health, mood and pain. Results: The questionnaire was repeatable and able to discriminate between older women with and without vertebral fractures. There was a strong association between referral instrument scores and the corresponding single domain score of the questionnaire. Femoral BMD was also associated with scores indicating fear of falling, fear of fracture, and pain. Conclusions: The questionnaire intercepted the influence of osteoporosis on the quality of life of elderly women with vertebral fractures. Subjects who suffered from severe pain and were more fearful of falling were most likely to be severely osteoporotic.

Rheumatoid arthritis is a chronic inflammatory disease characterized by a reduced life expectancy mainly due to cardiovascular disease. In long-standing disease, it has been widely demonstrated that both traditional cardiovascular risk and disease-related factors, including chronic inflammation and immune-mediated mechanisms, play a key role in accelerating atherosclerotic damage of the arterial wall. The short- and long-term effects of immunosuppressive treatment on cardiovascular disease outcome is, however, uncertain and a multidisciplinary approach appears to represent the best management of cardiovascular risk in these patients.

To compare ultrasonography (US) of salivary glands with contrast sialography and scintigraphy, in order to evaluate the diagnostic value of this method in primary SS (pSS).The diagnostic value of parotid gland US was studied in 77 patients with pSS (male/female ratio 3/74; mean age 54 yrs) and in 79 with sicca symptoms but without SS. The two groups were matched for sex and age. Imaging findings of US were graded using an ultrasonographic score ranging from 0 to 16, which was obtained by the sum of the scores for each parotid and submandibular gland. The sialographic and scintigraphic patterns were classified in four different stages. The area under receiver operating characteristic curve (AUC-ROC) was employed to evaluate the screening method's performance.Of the 77 patients with pSS, 66 had abnormal US findings. Mean US score in pSS patients was 9.0 (range from 3 to 16). Subjects without confirmed pSS had the mean US score 3.9 (range from 0 to 9) (P0.0001). Results of sialography showed that 59 pSS patients had abnormal findings at Stage 1 (n = 4), Stage 2 (n = 8), Stage 3 (n = 33) or Stage 4 (n = 14), and 58 patients had abnormal scintigraphic findings at Stage 1 (n = 11), Stage 2 (n = 18), Stage 3 (n = 25) or Stage 4 (n = 4). Through ROC curves US arose as the best performer (AUC = 0.863 +/- 0.030), followed by sialography (AUC = 0.804 +/- 0.035) and by salivary gland scintigraphy (AUC = 0.783 +/- 0.037). The difference between AUC-ROC curve of salivary gland US and scintigraphy was significant (P = 0.034). Setting the cut-off score6 US resulted in the best ratio of sensitivity (75.3%) to specificity (83.5%), with a likelihood ratio of 4.58. If a threshold8.0 was applied the test gained specificity, at the cost of a serious loss of sensitivity (sensitivity 54.5%, specificity 97.5%, likelihood ratio 21.5).Salivary gland US is a useful method in visualizing glandular structural changes in patients suspected of having pSS and it may represent a good option as a first-line imaging tool in the diagnostics of the disease.

Background Tocilizumab (TCZ) is a humanized monoclonal antibody against interleukin (IL)-6 receptor employed in rheumatoid arthritis (RA). The inhibition of acute phase reactant liver production is associated with rapid normalization of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), often predating synovitis improvement. Thus, ESR and CRP are not suitable to assess drug efficacy. Joint ultrasonographic (US) examination is commonly employed to detect RA subclinical synovitis. However, US assessment of the whole articular sites may be time consuming. To overcome such limitation, a novel US score, the German US7 score, has been recently proposed as rapid method to assess synovitis, tenosynovitis, power Doppler (PD) signal and erosions by grey scale (GS) in seven joints. Objectives Since the strong effect of TCZ on acute phase reactants may underestimate disease activity, we investigated German US7 usefulness in detecting subclinical synovitis in TCZ-treated patients. Methods Sixteen RA patients diagnosed according the EULAR/ACR 2010 classification criteria and treated with TCZ since at least 3 months were enrolled. Disease activity was evaluated by DAS28 and HAQ. German US7 score assessment was performed by two blinded investigators (Esaote myLab 70; linear probe 10-18 Mhz). The following sites of the clinically dominant hand and foot were evaluated: wrist, 2nd and 3rd metacarpophalangeal and proximal interphalangeal, and 2nd and 5th metatarsophalangeal joints. Details of the score are provided in Table 1. Inter-observer agreement was very high (Cohen9s κ=0.9). Spearman correlation coefficient (rho, ρ) was assessed to evaluate correlation between clinic parameters, laboratory data and domains of German US7 score. Results As shown in Table, GSUS synovitis significantly correlated with DAS28-ESR (ρ=0.557; p Conclusions The present study suggests that German US7 score is a rapid tool to assess subclinical disease activity in RA patients receiving TCZ where ESR and CRP are not suitable to assess drug efficacy. US evaluation of TCZ-treated patients correlates with changing of clinical parameters, is able to detect subclinical activity and represents a prognostic parameter for new erosion development. In addition, our data, showing a strong correlation between number of tender and swollen joints and presence of PD signal, further support PD usefulness as independent diagnostic and prognostic tool in the evaluation of TCZ-treated patients. Despite limitations due to low number of enrolled patients and cross-sectional design, this study supports the role of German US7 score as a simple, reproducible and time-effective tool to monitor clinical and functional response in RA patients receiving TCZ. Disclosure of Interest None declared

Background Subclinical atherosclerosis can be considered a form of systemic involvement in patients with chronic inflammatory joint and connective tissue diseases. Multiple factors, including inflammatory and immune-mediated mechanisms, have been identified to promote atherosclerotic endothelial injury [1]. Recent studies focused on role played by the altered balance between endothelial microparticles (EMPs) release and endothelial progenitor cells (EPCs) generation in endothelial wall integrity disruption and subsequent endothelial dysfunction. EPCs represent a new marker of endothelial dysfunction cardiovascular (CV) disease patients and increased EMP levels have been demonstrated in diseases characterized by high inflammatory response, such as polymyalgia rheumatica [2]. There is evidence that primary Sjogren9s syndrome (pSS) patients, free of previous CV manifestations, display signs of subclinical atherosclerosis, suggesting a greater CV risk [3,4]. However, exact pathogenic mechanisms involved in vascular damage in SS are still unclear. Increased levels of leukocyte and platelet MPs, reflecting systemic cell activation, have been demonstrated in SS. On the other hand, the role of EMPs and EPCs in SS has been never investigated. Objectives To evaluate endothelial injury degree in SS by EMP quantification and their repair potential by EPC and mature EPC measurement and to analyze possible correlation with disease-specific clinical and immunologic features. Methods 34 female pSS patients and 18 age- and sex-matched normal controls (NC) were enrolled. Number of circulating EMPs (CD31 + /CD42 – ), EPCs (CD34 + /KDR + /CD133 + ) and mature EPCs (CD34 + /KDR + /CD133 – ) was quantified by FACS analysis. Parameters of disease activity and damage were measured by ESSDAI and SSDDI, respectively. Disease-related clinical features, laboratory markers of immunologic dysfunction and traditional CV risk factors were recorded. Results SS patients displayed higher EMP number with respect to NC (450±155 vs 231±110 n/μl mean ± SD; p Conclusions Present data highlight for the first time a chronic persistent endothelial fragmentation characterizing pSS patients. Endothelial layer reparative potentiality appears to be preserved in the earliest stages of disease. Following disease course, a progressive exhaustion of the precursor endothelial pool may be hypothesized, leading to defective vascular layer restoration and endothelial dysfunction. Further investigations are needed to ascertain the role of EMPs and EPCs in promoting subclinical atherosclerosis in pSS. References Bartoloni E et al. Arthritis Care Res 2011;63:178 Pirro M et al. J Intern Med 2012;272:177 Vaudo G et al. Arthritis Rheum 2005;52:3890 Gerli R et al. Arthritis Care Res 2010;62:712 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2887

Background Although osteoarthritis (OA) is a degenerative joint disorder, it has been demonstrated that inflammation takes part in the development and progression of this condition. Matrix metalloproteinases (MMPs), including MMP-2, are involved in the cartilage breakdown observed in OA. Platelets (PLTs) are involved in different inflammatory conditions, including rheumatoid arthritis, contain and release several MMPs, including MMP-2, and enhance MMPs expression by other cell types. However, their role in OA has not been investigated yet. Hyaluronic acid (HA) is a normal component of extracellular matrix and synovial fluid (SF). Intra-articular (IA) administration of HA in OA is widely employed in clinical practice with good clinical efficacy. Objectives Aims of our study were to investigate the role of platelets and MMP-2 in the pathogenesis of OA, to test the biologic activity of IA-HA in OA patients and to analyze the effects of HA on the interaction between platelets and synoviocytes in vitro. Methods Thirty-eight patients with knee OA were screened and twenty-four patients were included in the study. Systemic therapy with non-steroidal anti-inflammatory drugs or corticosteroids and previous IA corticosteroid treatment represented exclusion criteria. Five injections of IA sodium hyaluronate (500-730 KDa) were administrated weekly. SF samples were collected prior to the first (T0) and at the last (T1) injection. Total cell and PLT count, platelet-leukocyte aggregates (PLT activation marker) and MMP-2 levels were measured in SF. For clinical assessment at T0, T1 and 3 months after the last injection (T3) the Western Ontario and Mc Masters University (WOMAC) scale and VAS for knee pain were employed. Fibroblast-like synoviocytes (FLS) were isolated from untreated OA-SF and cultured with PLTs in presence or absence of HA at different concentrations for 24 hours. Platelet P-selectin was measured by flow-cytometry and MMP-2 in culture supernatants was quantified by zymography. Results Total cell count in SF was significantly reduced after IA-HA (p Conclusions Our results show that PLTs, in addition to other inflammatory cells, participate in the pathogenesis of OA by the induction of MMP-2 release by FLS possibly via P-selectin, thus contributing to cartilage breakdown. Treatment with HA decreases count and activation of PLT and levels of MMP-2 in the SF. PLT and synoviocytes interaction leads to platelet activation and MMP-2 release enhancement. Hence, PLTs may represent a new therapeutic target in OA. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.4585

Background Patients with systemic inflammatory and autoimmune diseases display an increased risk of cardiovascular (CV) mortality. Inflammatory and immune-mediated mechanisms have been identified to promote induction and progression of atherosclerotic endothelial injury (1). Sjogren’s syndrome (SS) represents an interesting model to investigate pathogenetic mechanisms involved in atherosclerotic damage. Young SS patients are characterized by an accelerated subclinical atherosclerotic damage and disease-related immune mechanisms may be involved in this process (2,3). However, the exact pathogenetic mechanisms involved in the precocious vascular damage in SS are still unknown. Recent evidence suggests that endothelial integrity loss may involve defects in the vascular regenerative capacity provided by circulating endothelial progenitor cells (EPC) and generation of circulating microparticles (MPs). Endothelial (E) MPs represent an emerging marker of endothelial dysfunction in patients with CV diseases and an increased number of EMPs have been demonstrated in diseases characterized by high inflammatory response, as polymyalgia rheumatica (4). Increased levels of leukocyte and platelet MPs have been recently demonstrated in SS and have been identified as biomarkers reflecting systemic cell activation. On the other hand, the role of EMPs in SS has never been investigated. Objectives Evaluate the degree of endothelial injury in SS patients by measuring number of circulating EMPs and their repair potential by EPC measurement. Methods 31 SS patients (30 female, 1 male, mean age 52±12 SD) and 31 age- and sex-matched normal controls (NC) were enrolled. Number of circulating EMPs (CD31+/CD42-) and EPC (CD34+/KDR+) was quantified by FACS analysis. Parameters of disease activity and damage were measured by ESSDAI (inactive ≤2, active >2) and SSDDI, respectively. Disease-related clinical features, laboratory markers of immunologic dysfunction and traditional CV risk factors were recorded. Results SS patients displayed higher levels of EMPs and lower count of EPC than NC (634±21548 vs 399±28 n/microL: p Conclusions This is the first demonstration of a significant imbalance between endothelial injury and repair in SS, as demonstrated by increased number of EMPs associated with EPC count reduction. In this setting, increased endothelial fragmentation in association with a reduced endothelial repair may advocated as adjunctive potential pathogenic mechanism promoting subclinical atherosclerotic damage in SS. Among traditional CV risk factors, smoke may be associated with an higher risk of active disease. References Bartoloni E et al. Arthritis Care Res 2011;63:178 Vaudo G et al. Arthritis Rheum 2005;52:3890 Gerli R et al. Arthritis Care Res 2010;62:712 Pirro M et al. J Intern Med 2011 [Epub ahead of print] Disclosure of Interest None Declared

Background Patients with systemic autoimmune diseases display an increased risk of cardiovascular (CV) mortality. Inflammatory and immune-mediated mechanisms have been identified to promote atherosclerotic endothelial injury (1). Sjogren’s syndrome (SS) represents an interesting model to investigate pathogenetic mechanisms involved in atherosclerotic damage. Young SS patients are characterized by an accelerated subclinical atherosclerotic damage (2,3). However, exact pathogenic mechanisms involved in the precocious vascular damage in SS are still unclear. Recent evidence suggests that loss of endothelial integrity may involve defects in the vascular regenerative capacity provided by circulating endothelial progenitor cells (EPC) and generation of circulating microparticles (MPs). Endothelial (E) MPs represent an emerging marker of endothelial dysfunction in patients with CV diseases and increased numbers of EMPs have been demonstrated in diseases characterized by high inflammatory response, such as polymyalgia rheumatica (4). Increased levels of leukocyte and platelet MPs have been demonstrated in SS and have been identified as biomarkers of systemic cell activation. On the other hand, the role of EMPs in SS has been never investigated. Objectives To evaluate endothelial injury degreein SS by quantification of circulating EMPs and their repair potential by EPCmeasurement and to analyze possible correlation with disease-specific clinical and immunologic features. Methods 49 SS patients (48 female, 1 male) and 30 age- and sex-matched normal controls (NC) were enrolled. Number of circulating EMPs (CD31 + /CD42 - ) and EPC (CD34 + /CD133 + /KDR + and mature CD34 + /KDR + ) was quantified by FACS analysis. Parameters of disease activity and damage were measured by ESSDAI (inactive ≤ 2, active > 2) and SSDDI, respectively. Disease-related clinical features, laboratory markers of immunologic dysfunction and traditional CV risk factors were recorded. Results SS patients displayed higher levels of EMPs and triple positive EPCs than NC (mean±SD: 565±223 vs 399±28 and 144±117 vs 74±54 n/mL, respectively, p + /KDR + EPCs were inversely correlated with disease duration. Intriguingly, it was of interest the observation that, among patients, smokers displayed higher ESSDAI in comparison to non-smokers (p=0.004). Conclusions This is the first evidence that SS may be associated with endothelium integrity loss toward generation of EMPs. Progenitors seem to be adequately released, particularly in early stages of the disease, so suggesting an attempt at revascularization. However, their ability to mature differs from healthy subjects and this may contribute to endothelial dysfunction. Of interest, among traditional CV risk factors, smoking may be associated with an higher risk of active disease. Further investigations, however, are needed to ascertain the role of EMPs and EPCs in promoting subclinical atherosclerotic damage in SS. References Bartoloni E et al. Arthritis Care Res 2011;63:178 Vaudo G et al. Arthritis Rheum 2005;52:3890 Gerli R et al. Arthritis Care Res 2010;62:712 Pirro M et al. J Intern Med 2012;272:177 Disclosure of Interest None Declared