Sex-specific impact of inflammation on traditional cardiovascular risk factors and atherosclerosis in axial spondyloarthritis. A multicentre study of 913 patients.

INTRODUCTION: The nature of the relationship between inflammation, cardiovascular (CV) risk factors and atherosclerosis in axial spondyloarthritis (axSpA) remains largely unknown and sex differences in this regard are yet to be assessed. METHODS: Study including 611 men and 302 women from the Spanish multicentre AtheSpAin cohort to assess CV disease in axSpA. Data on CV disease risk factors were collected both at disease diagnosis and at enrolment, and data on disease activity, functional indices and carotid ultrasonography only at enrolment. RESULTS: After a median disease duration of 9 years, patients of both sexes who at disease diagnosis had elevated acute phase reactants (APRs), more frequently had hypertension and obesity. The same occurred with dyslipidaemia in men and with diabetes mellitus in women. At enrolment, CV risk factors were independently associated with APR and with activity and functional indices, with various sex differences. C reactive protein (CRP) values were inversely associated with HDL-cholesterol in men (ß coefficient: -1.2 (95% CI: -0.3 to -0.07) mg/dL, p=0.001), while erythrocyte sedimentation rate values were positively associated with triglycerides in women (ß coefficient: 0.6 (95% CI: 0.04 to 1) mg/dL, p=0.035). Furthermore, only women showed an independent relationship between insulin resistance parameters and APR or disease activity. Both men and women with high-very high CV risk according to the Systematic Assessment of Coronary Risk Evaluation 2 and CRP levels higher than 3 mg/L at diagnosis of the disease presented carotid plaques significantly more frequently than those with normal CRP levels at disease diagnosis. CONCLUSION: Inflammation is associated with atherosclerosis and CV disease in axSpA. A gender-driven effect is observed in this relationship.

Sex differences in cardiovascular and disease-related features in axial spondyloarthritis. A multicenter study of 912 patients.

OBJECTIVES: To determine the potential impact of sex-specific disease-related characteristics on cardiovascular (CV) disease in axial spondyloarthritis (axSpA). METHODS: Cross-sectional study of the Spanish AtheSpAin cohort to study CV disease in axSpA. Data on carotid ultrasound and CV disease and disease-related features were collected. RESULTS: 611 men and 301 women were recruited. Classic CV risk factors were significantly less prevalent in women, who also showed a lower frequency of carotid plaques (p = 0.001), lower carotid intima-media thickness (IMT) values ​​(p<0.001) and CV events (p = 0.008). However, after adjustment for classic CV risk factors, only the differences with respect to carotid IMT remained statistically significant. Women showed higher ESR at diagnosis (p = 0.038), and more active disease (ASDAS, p = 0.012, and BASDAI, p<0.001). They had shorter disease duration (p<0.001), lower prevalence of psoriasis (p = 0.008), less structural damage (mSASSS, p<0.001), and less mobility limitation (BASMI, p = 0.033). To establish whether these findings could lead to sex differences in CV disease burden, we compared the prevalence of carotid plaques in men and women with the same level of CV risk stratified according to the Systematic Coronary Risk Evaluation (SCORE). Men included in the low-moderate CV risk SCORE category had more carotid plaques (p = 0.050), along with longer disease duration (p = 0.004), higher mSASSS (p = 0.001) and psoriasis (p = 0.023). In contrast, in the high-very high-risk SCORE category, carotid plaques were observed more frequently in women (p = 0.028), who were characterized as having worse BASFI (p = 0.011), BASDAI (p<0.001) and ASDAS (p = 0.027). CONCLUSION: Disease-related features may influence the expression of atherosclerosis in patients with axSpA. This may be especially applicable to women at high CV risk, characterized by greater disease severity and more severe subclinical atherosclerosis than men, suggesting a stronger interaction between disease activity and atherosclerosis in women with axSpA.

Circulating interleukin-6 and cardiovascular disease risk in patients with rheumatoid arthritis with low disease activity due to active therapy.

OBJECTIVES: Interleukin-6 (IL-6) has been implicated in the pathophysiology of rheumatoid arthritis (RA) and in the development of atherosclerosis in the general population. In the present work we aimed to study if IL-6 serum levels have an influence on factors associated with cardiovascular (CV) disease in a cohort of Spanish patients with RA. METHODS: Cross-sectional study that encompassed 407 patients with RA. Serum IL-6 levels were assessed. Multivariable analysis was performed to examine the relationship of IL-6 to subclinical carotid atherosclerosis and classic CV risk factors, including a comprehensive lipid molecule profile and indices of insulin resistance and beta-cell function. RESULTS: Circulating levels of IL-6 showed a correlation with acute phase reactants, disease activity, and other features of RA. However, classic CV risk factors, lipid profile and indices of insulin resistance, as well as subclinical carotid atherosclerosis, were not associated with serum IL-6 levels. CONCLUSIONS: Although a direct association between IL-6 levels and traditional CV risk factors and subclinical carotid atherosclerosis was not observed, circulating IL-6 was associated with disease activity and acute-phase reactants, which have been associated with an increased risk of CV in these patients.

Cardiovascular and disease-related features associated with extra-articular manifestations in axial spondyloarthritis. A multicenter study of 888 patients.

OBJECTIVES: To determine the potential impact of extra-articular manifestations (EAMs) on disease characteristics and cardiovascular (CV) risk in patients with axial spondylarthritis (axSpA). METHODS: This is a cross-sectional study from the AtheSpAin cohort, a Spanish multicenter cohort to study atherosclerosis in axSpA. Data on the history of CV events, subclinical carotid atherosclerosis, and disease-related features, including EAMs, were collected. RESULTS: 888 axSpA patients were recruited. Concomitant acute anterior uveitis (AAU), psoriasis (PSO), and inflammatory bowel disease (IBD) were present in 177 (19.9%), 96 (10.8%), and 57 (6.4%) patients, respectively. When compared with axSpA patients without EAMs, a significant increase in past CV events was observed in patients with PSO (9% versus 4%, p = 0.048) and in those with at least one EAM (7% versus 4%, p = 0.032) or with more than one EAM (11% versus 4%, p = 0.022). The frequency of carotid plaques and the values of cIMT were higher in patients with EAMs than in those without EAMs, although only the univariable analysis for carotid plaques in patients with PSO (39% versus 30%, p = 0.038) and for cIMT in patients with AAU (665 ± 156 µm versus 637 ± 139 µm, p = 0.042) and those with at least one EAM (661 ± 155 µm versus 637 ± 139 µm, p = 0.024) showed significant results. In addition, patients with PSO or IBD were found to have specific disease-related features, such as higher ESR at diagnosis, and more frequent use of glucocorticoids and TNF inhibitors than those without EAMs. Also, PSO patients had more commonly peripheral involvement and those with AAU more severe radiographic damage than those without EAMs. The frequency of HLA B27 was higher in patients with AAU and lower in those with PSO or IBD compared to those without EAMs. CONCLUSION: Patients with axSpA and EAMs, in addition to displaying their own disease-related features, are likely to have an increased CV risk that appears proportional to the number of EAMs and could be related to proatherogenic factors other than traditional CV risk factors, such as the inflammatory load and the use of glucocorticoids.

Interleukin 1 receptor antagonist relation to cardiovascular disease risk in patients with rheumatoid arthritis.

Interleukin (IL) 1, and its family member, IL-1 receptor antagonist (IL-1ra), are involved in the pathogenesis and inflammation perpetuation of patients with rheumatoid arthritis (RA). Besides, IL-1 has been linked to an increased risk and greater severity of cardiovascular (CV) disease. We aimed to study if IL-1ra is related to the CV manifestations-including lipid pattern and insulin resistance or subclinical atherosclerosis-that accompanies the disease in a large series of patients with RA. Cross-sectional study that encompassed 430 patients with RA. Serum IL-1ra levels were assessed. A multivariable analysis was performed to analyze the relation of IL-1ra to subclinical carotid atherosclerosis, and to traditional CV factors including a complete lipid molecules profile and insulin resistance or beta cell function indices. Body mass index, abdominal circumference, and the presence of obesity were significantly and positively associated with circulating IL-1ra. Similarly, erythrocyte sedimentation rate, and disease activity scores were significantly related to higher IL-1ra serum levels after adjustment for confounders. Neither carotid intima-media thickness nor the presence of carotid plaque were associated with serum levels of IL-1ra. However, after multivariable analysis circulating IL-1ra was independently and positively associated with higher serum levels of total cholesterol, triglycerides, and apolipoproteins B and C-III. Similarly, IL-1ra was related to higher levels of beta-cell function in the univariable analysis, although, in this case, significance was lost after adjustment. Among patients with RA, IL-1ra is associated with both disease activity and several traditional CV risk factors such as obesity and the presence of higher lipid levels. Our findings suggest that IL-1ra can represent a link between the inflammation and the CV disease risk that are present in patients with RA.

Irisin as a Novel Biomarker of Subclinical Atherosclerosis, Cardiovascular Risk and Severe Disease in Axial Spondyloarthritis.

Introduction: Patients with axial spondyloarthritis (axSpA) have a high disease burden mainly due to the rheumatic disease itself, and also exhibit accelerated atherosclerosis, that leads to a higher incidence of cardiovascular (CV) disease. Accordingly, the identification of biomarkers of CV risk and inflammation in axSpA patients is clinically relevant. In this sense, given the beneficial functions exerted by the adipomyokine irisin in processes related to CV disease and inflammation, our aim was to assess, for the first time, the role of irisin as a genetic and serological biomarker of subclinical atherosclerosis, CV risk and disease severity in axSpA patients. Methods: A large cohort of 725 Spanish patients with axSpA was included. Subclinical atherosclerosis (presence of plaques and abnormal carotid intima-media thickness values) was evaluated by carotid ultrasound. Four irisin polymorphisms (rs16835198 G/T, rs3480 A/G, rs726344 G/A, and rs1570569 G/T) were genotyped by TaqMan probes. Additionally, serum irisin levels were determined by ELISA. Results: Low irisin levels were linked to the presence of plaques (p=0.002) and atherogenic index values ≥4 (p=0.01). Serum irisin were positively correlated with C-peptide levels (p<0.001) and negatively correlated with visual analogue scale and Bath Ankylosing Spondylitis Metrology Index (p<0.05 in all the cases). Moreover, lower irisin levels were observed in patients with sacroiliitis and in those with a negative HLA-B27 status (p<0.001 and p=0.006, respectively), as well as in those treated with non-steroidal anti-inflammatory drugs and conventional disease-modifying antirheumatic drugs (p<0.001 and p=0.002, respectively). Interestingly, the TT genotype and the T allele of rs16835198 were less frequent in axSpA patients with ASDAS >2.1 (Odds Ratio (OR): 0.48 [0.28-0.83] and OR: 0.73 [0.57-0.92], respectively, p=0.01 in both cases). Additionally, the frequency of rs1570569 T allele was higher in these patients (OR: 1.46 [1.08-1.97], p=0.01). Furthermore, the GGGT haplotype was more frequent in patients with ASDAS values >2.1 (OR: 1.73 [1.13-2.66], p=0.01). Conclusions: Our results indicate that low serum irisin levels could be indicators of the presence of subclinical atherosclerosis, high CV risk and more severe disease in axSpA patients. In addition, irisin may also constitute a genetic biomarker of disease activity in axSpA.

Factors associated with atherosclerosis in radiographic and non-radiographic axial spondyloarthritis. A multicenter study on 838 patients.

OBJECTIVES: To identify disease-related factors associated with subclinical atherosclerosis and cardiovascular (CV) events in a large series of patients with axial spondyloarthritis (axSpA) and to identify possible differences in the effect of the potential pro-atherogenic factors between ankylosing spondylitis (AS) non-radiographic axSpA (nr-axSpA). METHODS: This is a cross-sectional observational study of the AtheSpAin cohort, a Spanish multicenter cohort to study atherosclerosis in axSpA. Subclinical atherosclerosis determined by carotid ultrasound included assessment of carotid intima-media thickness (cIMT) and plaque detection. RESULTS: 639 AS and 167 nr-axSpA patients were recruited. CV risk factors (CRF) and several disease-related factors showed a statistically significant association with subclinical atherosclerosis in the crude analysis. After adjustment for age, sex, and smoking (model 1), associations remained statistically significant for spinal mobility, inflammatory bowel disease, use of prednisone, and Disease-modifying antirheumatic drugs (DMARD) when assessing carotid plaques and for acute phase reactants (APR) at diagnosis, use of prednisone, DMARD, and TNF-inhibitors when measuring cIMT. In model 2, which also included classic CRF as confounding factors to identify axSpA features with a potential independent pro-atherogenic effect, the functional status was the only variable significantly associated with plaques and the use of prednisone and APR at diagnosis with cIMT. No association differences were found between both subtypes of patients. Besides, APR at diagnosis were also associated with subsequent development of CV events that had occurred in 33 patients. CONCLUSION: Apart from CRF, atherosclerotic disease in AxSpA is associated with disease-related factors such as inflammatory response and disease severity, with no differences between AS and nr-axSpA.

The angiopoietin-like protein 4, apolipoprotein C3, and lipoprotein lipase axis is disrupted in patients with rheumatoid arthritis.

BACKGROUND: Modulators of triglyceride metabolism include lipoprotein lipase (LPL), angiopoietin-like protein 4 (ANGPTL4), and apolipoprotein C-3 (ApoC3). There is evidence on the influence of this triangle of molecules on an increased risk of atherosclerotic cardiovascular disease (CV) in the general population. Patients with rheumatoid arthritis (RA) present changes in lipid profiles and accelerated CV disease. In the present study, we set out to study whether the ANGPTL4, ApoC3, and LPL axis differs in subjects with RA compared to controls. In a further step, we investigated the relationship of this axis with subclinical atherosclerosis in patients with RA. METHODS: Cross-sectional study that included 569 individuals, 323 patients with RA and 246 age-matched controls. ANGPTL4, ApoC3 and LPL, and standard lipid profiles were analyzed in patients and controls. Carotid intima-media thickness (cIMT) and carotid plaques were assessed in RA patients. A multivariable analysis was performed to assess whether the ANGPTL4, ApoC3, and LPL axis was altered in RA and to study its relationship with RA dyslipidemia and subclinical carotid atherosclerosis. RESULTS: Most lipid profile molecules did not differ between patients and controls. Despite this, and after fully multivariable analysis including CV risk factors, use of statins, and changes in the lipid profile caused by the disease itself, patients with RA showed higher serum levels of ANGPTL4 (beta coef. 295 [95% CI 213-376] ng/ml, p<0.001) and ApoC3 (beta coef. 2.9 [95% CI 1.7-4.0] mg/dl, p<0.001), but lower circulating LPL (beta coef. -174 [95% CI -213 to -135] ng/ml, p<0.001). ANGPTL4 serum levels were positively and independently associated with a higher cIMT in patients with RA after fully multivariable adjustment. CONCLUSION: The axis consisting in ANGPTL4, ApoC3, and LPL is disrupted in patients with RA. ANGPTL4 serum levels are positively and independently associated with a higher cIMT in RA patients.

Vaspin in atherosclerotic disease and cardiovascular risk in axial spondyloarthritis: a genetic and serological study.

BACKGROUND: Vaspin is a novel anti-inflammatory adipokine associated with cardiovascular (CV) disease and inflammation in chronic inflammatory conditions different from axial spondyloarthritis (axSpA). Given the high incidence of CV disease (mainly due to accelerated atherosclerosis) exhibited by axSpA patients, we wondered if vaspin could also be a key molecule in this process. However, data on the role of vaspin regarding atherosclerotic disease in the context of axSpA is scarce. For this reason, we aimed to evaluate the implication of vaspin, at the genetic and serological level, in subclinical atherosclerosis and CV risk in axSpA. METHODS: This study included 510 patients diagnosed with axSpA. Carotid ultrasound (US) was performed to evaluate the presence of subclinical atherosclerosis. Three vaspin gene variants (rs2236242, rs7159023, and rs35262691) were genotyped by TaqMan probes. Serum vaspin levels were assessed by enzyme-linked immunosorbent assay. Statistical analysis was performed using STATA® v.11.1. RESULTS: Serum vaspin levels were significantly higher in female patients than in males and also in obese patients when compared to those with normal weight (p < 0.05). At the genetic level, we disclosed that the minor allele of rs2236242 (A) was associated with lower serum vaspin levels in axSpA, while the rs7159023 minor allele (A) was linked to higher serum levels (p < 0.05). When the three polymorphisms assessed were combined conforming haplotypes, we disclosed that the TGC haplotype related to high serum levels of vaspin (p = 0.01). However, no statistically significant association was observed between vaspin and markers of subclinical atherosclerosis, both at the genetic and serological level. CONCLUSIONS: Our results revealed that vaspin is linked to CV risk factors that may influence on the atherosclerotic process in axSpA. Additionally, we disclosed that serum vaspin concentration is genetically modulated in a large cohort of patients with axSpA.

HDL cholesterol efflux capacity and lipid profile in patients with systemic sclerosis.

OBJECTIVE: It is well established that patients with systemic sclerosis (SSc) have a disrupted lipid profile and an increased cardiovascular risk. Cholesterol efflux capacity (CEC), the ability of high-density lipoprotein (HDL)-cholesterol to accept cholesterol from macrophages, has been linked to cardiovascular events. The aim of this study was to establish whether CEC and lipid profile were impaired in SSc patients with respect to controls and whether these changes were associated with disease-related data. METHODS: Cross-sectional study encompassed 188 individuals: 73 SSc patients and 115 controls. CEC, using an in vitro assay, and lipoprotein serum concentrations were assessed in patients and controls. A multivariable analysis was performed to study the differences in CEC between patients and controls, and if SSc-related data could explain such differences. RESULTS: The multivariable analysis adjusted for demographic characteristics, cardiovascular risk factors, and lipid-related molecules showed that total cholesterol (beta coefficient: - 22 [95%CI - 37 to - 7], p = 0.004), triglycerides (beta coefficient: 24 [95%CI 2-47], p = 0.033), lipoprotein A (beta coefficient: 22 [95%CI 2-43], p = 0.033), and CEC (beta coefficient: - 6 [95%CI - 10 to - 2]%,p = 0.002) were significantly different between patients and controls. Skin thickness, as assessed by modified Rodnan skin score, was independently associated with a lower CEC (beta coefficient: - 0.21 [95%CI - 0.37 to - 0.05]%, p = 0.011) after multivariable adjustment. CONCLUSION: SSc patients show an abnormal lipid profile with respect to controls including CEC. Skin thickness is independent and inversely associated with CEC in SSc patients.

Subclinical atherosclerotic disease in ankylosing spondylitis and non-radiographic axial spondyloarthritis. A multicenter study on 806 patients.

OBJECTIVES: To compare the atherosclerosis disease burden between ankylosing spondylitis (AS) and non-radiographic (nr) axial spondyloarthritis (axSpA) and establish a model that allows to identify high-cardiovascular (CV) risk in axial spondyloarthritis patients. METHODS: Cross-sectional study from the AtheSpAin cohort, a Spanish multicenter cohort aimed to study atherosclerosis in axSpA. Carotid ultrasound (US) was performed to determine the carotid intima-media wall thickness (cIMT) and detect the presence of carotid plaques. The European cardiovascular disease risk assessment model, the Systematic COronary Risk Evaluation (SCORE), was also applied. RESULTS: A set of 639 patients with AS and 167 patients with nr-axSpA without history of CV events were recruited. AS patients were older showing more CV risk factors and higher values of C reactive protein and erythrocyte sedimentation rate (ESR) than those with nr-axSpA. However, no difference in the prevalence of carotid plaques or in the cIMT was found between both groups in the adjusted analysis. The percentage of patients reclassified from the low and moderate CV risk categories to the very high-risk category due to the presence of carotid plaques was comparable in AS and nr-axSpA (10.7% versus 10.1% and 40.5% versus 45.5%, respectively). A model containing age, BASFI and ESR applied to moderate risk axSpA patients identified 41% of these patients as having very high-risk patients with high specificity (88%). CONCLUSION: The atherosclerosis burden is similar in nr-axSpA and AS. As occurred for AS, more than 40% of axSpA patients included in the category of moderate CV risk according to the SCORE are reclassified into very high risk after carotid US, and a clinically relevant proportion of them can be detected by applying a model containing age, BASFI and ESR.

Omentin: a biomarker of cardiovascular risk in individuals with axial spondyloarthritis.

Cardiovascular (CV) disease is the main cause of mortality in axial spondyloarthritis (axSpA). CV risk is enhanced by dysregulation of adipokines. Low omentin levels were associated with metabolic dysfunction and CV disease in conditions different from axSpA. Accordingly, we evaluated the genetic and functional implication of omentin in CV risk and subclinical atherosclerosis in a cohort of 385 axSpA patients. Subclinical atherosclerosis was evaluated by carotid ultrasound. Omentin rs12409609, in linkage disequilibrium with a polymorphism associated with CV risk, was genotyped in 385 patients and 84 controls. Serum omentin levels were also determined. omentin mRNA expression was assessed in a subgroup of individuals. Serum and mRNA omentin levels were lower in axSpA compared to controls. Low serum omentin levels were related to male sex, obesity, inflammatory bowel disease (IBD) and high atherogenic index. rs12409609 minor allele was associated with low omentin mRNA expression in axSpA. No association was observed with subclinical atherosclerosis at the genetic or functional level. In conclusion, in our study low omentin serum levels were associated with CV risk factors in axSpA. Furthermore, rs12409609 minor allele may be downregulating the expression of omentin. These data support a role of omentin as a CV risk biomarker in axSpA.

Proprotein convertase subtilisin/kexin type 9 in patients with systemic sclerosis.

OBJECTIVES: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that regulates cholesterol metabolism through low-density lipoprotein receptor degradation, and which has been linked to cardiovascular risk. The purpose of the present study was to examine whether PCSK9 serum levels are disrupted in patients with systemic sclerosis (SS) compared to controls, and if PCSK9 is related to disease-related data and the subclinical atherosclerosis that occurs in these patients. METHODS: Cross-sectional study that encompassed 146 individuals; 73 patients with SS and 73 age- and sex-matched controls. PCSK9, lipoproteins serum concentrations, and standard lipid profiles were assessed in patients and controls. Carotid intima-media thickness (cIMT) and the presence of carotid plaques were evaluated in SS patients. A multivariable analysis, adjusted for traditional cardiovascular risk factors, was performed to evaluate the differences in PCSK9 between patients and controls, the association of SS-related manifestations with PCSK9 levels, and if PCSK9 was associated with subclinical carotid atherosclerosis in SS patients. RESULTS: After multivariable analysis, PCSK9 was downregulated in SS patients compared to controls (beta coefficient -78 (95%CI -106 - -50) ng/ml, p=0.000) and skin thickness was associated with higher serum levels of PCSK9 (beta coef. 22 (7-37) units, p=0.005). PCSK9 was significantly and positively associated with cIMT (beta coef. 0.65 (0.06-1.24) ng/ml, p=0.031) in SS patients after multivariable adjustment. CONCLUSIONS: PCSK9 serum concentration is downregulated in SS patients compared to controls and is directly associated with disease severity subrogated parameters. PCSK9 was independently related to cIMT in SS patients.

Reclassification into very-high cardiovascular risk after carotid ultrasound in patients with axial spondyloarthritis.

OBJECTIVES: Subclinical atherosclerosis, defined as the presence of carotid plaques, is more frequently found in patients with axial spondyloarthritis (axSpA) than in healthy individuals. We sought to determine whether axSpA patients are more commonly reclassified into the very high cardiovascular risk category than controls after performing carotid ultrasound and if this can be linked to disease characteristics. METHODS: 343 patients diagnosed with axSpA according to ASAS criteria and 177 controls were studied. Disease characteristics and Systematic Coronary Risk Evaluation (SCORE) were assessed in patients and controls. Presence of plaques and intima-media thickness (cIMT) was determined by carotid ultrasound. Multivariable regression analysis was performed to identify differences in the frequency of reclassification between patients and controls, as well as factors associated with reclassification in axSpA. RESULTS: Carotid plaques (36% vs.25%, p=0.010) and higher cIMT (0.641± 0.121 vs. 0.602± 0.115 mm, p=0.001) were more common in patients than controls. Reclassification into the high-risk category was greater in patients (34% vs. 25%, p=0.037). Age (beta coefficient 2.74 [95%CI 1.34-5.62] vs. beta coef. 0.63 (95%CI 0.40-0.99) in patients, interaction p=0.001) and serum LDL-cholesterol (beta coef. 1.03 [95%CI 1.02-1.04] vs. beta coef. 1.00 [0.99-1.01], interaction p=0.029) showed a higher effect on reclassification in controls after multivariable analysis. Although reclassification in axSpA was associated with higher ASDAS-CRP, BASFI and BASMI scores, these associations were lost after adjusting for cardiovascular risk factors. CONCLUSIONS: Patients with axSpA are more likely to be reclassified into the very-high risk category after carotid ultrasound than controls. The influence of traditional cardiovascular risk factors on this reclassification differs between patients and controls.

Role of CXCL13 and CCL20 in the recruitment of B cells to inflammatory foci in chronic arthritis.

BACKGROUND: B cells exert their pathogenic action in rheumatoid arthritis (RA) locally in the synovium. This study was undertaken to elucidate the chemokines responsible for the recruitment of B cells in the inflamed synovium, taking into account that the rich chemokine milieu present in the synovial tissue can fine-tune modulate discrete chemokine receptors. METHODS: Expression levels of chemokine receptors from the CC and CXC family, as well as CD27, were assessed by flow cytometry in CD20+ mononuclear cells isolated from the peripheral blood (PB) and synovial fluid (SF) of RA and psoriatic arthritis patients. Transwell experiments were used to study migration of B cells in response to a chemokine or in the presence of multiple chemokines. RESULTS: B cells from the SF of arthritis patients showed a significant increase in the surface expression of CCR1, CCR2, CCR4, CCR5 and CXCR4 with respect to PB. Conversely, SF B cells expressed consistently lower amounts of CXCR5, CXCR7 and CCR6, independent of CD27 expression. Analysis of permeabilized B cells suggested internalization of CXCR5 and CCR6 in SF B cells. In Transwell experiments, CCL20 and CXCL13, ligands of CCR6 and CXCR5, respectively, caused a significantly higher migration of B cells from PB than of those from SF of RA patients. Together, these two chemokines synergistically increased B-cell migration from PB, but not from SF. CONCLUSIONS: These results suggest that CXCL13 and CCL20 might play major roles in RA pathogenesis by acting singly on their selective receptors and synergistically in the accumulation of B cells within the inflamed synovium.

Influence of disease activity on the physical activity of rheumatoid arthritis patients.

OBJECTIVES: The aims of this study were to study physical activity (PA) in patients with RA by accelerometry and to determine to what degree their mobility is affected by disease activity. METHODS: A group of 50 RA patients, without lower limb clinical disease, and 50 age- and sex-matched healthy controls were included in this cross-sectional study. PA was assessed by accelerometry and with the International Physical Activity Questionnaire (IPAQ). We performed multiple regression analysis not only to compare PA between groups, but also to explore the relation between RA features, including disease activity and cardiovascular risk parameters, and PA. In a randomized group of 30 RA patients a test-retest study was carried out in order to determine the correlation between variations in disease activity and PA. RESULTS: The number of minutes of moderate and vigorous activity per day, as evaluated by accelerometry, was significantly lower in RA patients than in healthy controls. In RA patients, accelerometry and IPAQ demonstrated concordance to a moderate degree [quadratic weighed kappa index 0.27 (0.06-0.48), P = 0.02]. HAQ negatively correlated with both IPAQ and accelerometry data. The 28-joint DAS using CRP (DAS28-CRP) was also inversely related with IPAQ. Framingham score and metabolic syndrome were inversely associated with PA in RA patients. Interestingly, variations in PA by accelerometry inversely correlated with changes in RA disease activity (r = -0.42, P = 0.02). CONCLUSION: In RA patients, accelerometry is a reliable technique to evaluate PA. This study not only showed that RA patients spend less time doing moderate and vigorous PA than healthy controls, but also PA, as assessed by accelerometry, was sensitive to any changes in disease activity.

Confirmation of association of the macrophage migration inhibitory factor gene with systemic sclerosis in a large European population.

OBJECTIVES: The aim of this study was to confirm the implication of macrophage migration inhibitory factor (MIF) gene in SSc susceptibility or clinical phenotypes in a large European population. METHODS: A total of 3800 SSc patients and 4282 healthy controls of white Caucasian ancestry from eight different European countries were included in the study. The MIF -173 single nucleotide polymorphism (SNP) was selected as genetic marker and genotyped using Taqman 5' allelic discrimination assay. RESULTS: The MIF -173 SNP showed association with SSc [P = 0.04, odds ratio (OR) = 1.10, 95% CI 1.00, 1.19]. Analysis of the MIF -173 polymorphism according to SSc clinical phenotype revealed that the frequency of the -173*C allele was significantly higher in the dcSSc group compared with controls (P = 5.30E-03, OR = 1.21, 95% CI 1.07, 1.38). Conversely, the frequency of the MIF -173*C allele was significantly underrepresented in the lcSSc group compared with dcSSc patients, supporting previous findings [(P = 0.04, OR = 0.86, 95% CI 0.75, 0.99); meta-analysis including previous results (P = 0.005, OR = 0.83, 95% CI 0.73, 0.94)]. CONCLUSION: Our results confirm the role of MIF -173 promoter polymorphism in SSc, and provide evidence of a strong association with the dcSSc subgroup of patients. Hence, the MIF -173 variant is confirmed as a promising clinical phenotype genetic marker.

Mujer con artralgias y aumento de tamaño de miembros superiores / No disponible

No disponible