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.

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.

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.

Potential relation of cardiovascular risk factors to disease activity in patients with axial spondyloarthritis.

BACKGROUND: Axial spondyloarthritis (axSpA) patients are known to have a higher prevalence of several comorbidities, including, among others, an increased risk of atherosclerosis, hypertension, dyslipidemia, and diabetes. The purpose of the present study was to determine whether the sum of traditional cardiovascular (CV) risk factors is related to disease characteristics, such as disease activity, in patients with axSpA. METHODS: A cross-sectional study that encompassed 804 patients with axSpA was conducted. Patients were assessed for the presence of five traditional CV risk factors (diabetes mellitus, dyslipidemia, hypertension, obesity, and smoking status), and disease activity measurements. A multivariable regression analysis was performed to evaluate whether the number of classic CV risk factors was independently associated with specific features of the disease, to include disease activity. RESULTS: A multivariable analysis showed that Ankylosing Spondylitis Disease Activity Score-C reactive protein (ASDAS-CRP) activity score was significantly higher in patients with 1 [beta coefficient 0.3 (95% confidence interval (CI) 0.1-0.5), p = 0.001] and ⩾2 [beta coefficient 0.5 (95% CI 0.3-0.7), p = 0.000] CV risk factors compared with those without CV risk factors. Similarly, patients with 1 [OR 2.00 (95%CI 0.99-4.02), p = 0.053] and ⩾2 [OR 3.39 (95%CI 1.82-6.31), p = 0.000] CV risk factors had a higher odds ratio for the presence of high disease activity compared with the zero CV category. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) activity score was significantly associated with the number of CV risk factors, being higher in patients with more CV risk factors. These relationships showed a CV risk factor-dependent effect being beta coefficients and ORs higher for the effect of ⩾2 over 1 CV risk factor. CONCLUSION: Among patients with axSpA, as the number of traditional CV risk factors increased, disease activity similarly increases in an independent manner.

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.

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.

Combined use of QRISK3 and SCORE as predictors of carotid plaques in patients with rheumatoid arthritis.

OBJECTIVE: Because carotid plaques predict the development of cardiovascular events in RA, we aimed to assess if the combined use of the systematic coronary risk evaluation (SCORE) and the QRISK3 algorithms allows for the identification of RA patients with carotid plaques in a defined population-based RA inception cohort. METHODS: A set of consecutive RA patients without a history of diabetes, chronic kidney disease or cardiovascular events were studied by carotid US between 2012 and 2019. Modified SCORE (mSCORE) for RA based on the 2015/2016 updated EULAR recommendations and QRISK3 algorithms were retrospectively tested using baseline data obtained at the time of the carotid US assessment. RESULTS: A total of 466 (54%) of 865 patients had carotid plaques. Using dichotomized QRISK3 and EULAR mSCORE, 73.2% (95% CI: 68.4.8, 77.6) of patients with QRISK ≥ 10% and EULAR mSCORE < 5% had plaque. In this group, the diagnostic odds ratio was 5.79 (95% CI: 4.14, 8.10). However, if both algorithms were above their thresholds of high cardiovascular risk (QRISK ≥ 10% and EULAR mSCORE ≥ 5%), the sensitivity increased up to 83.3% (95% CI: 72.1, 91.4) and the diagnostic odds ratio up to 10.6 (95% CI: 5.13, 22.0). When the risk charts scales were used as continuous variables, both QRISK3 and EULAR mSCORE were found positively associated with plaque. For each 1% QRISK3 or EULAR mSCORE increase, the probability of having plaques multiplied by 1.14 and 1.22, respectively. However, the effects of both algorithms did not multiply by each other. CONCLUSIONS: . The combined use of QRISK3 and EULAR mSCORE allows for the identification of most RA patients at high risk of carotid plaques.

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.

Carotid plaques as predictors of cardiovascular events in patients with Rheumatoid Arthritis. Results from a 5-year-prospective follow-up study.

OBJECTIVE: To investigate if the Systematic Coronary Risk Evaluation (SCORE) and the QRISK3 algorithms as well as the carotid ultrasound are useful predictors of cardiovascular (CV) events and death in a prospectively defined population-based rheumatoid arthritis (RA) inception cohort. METHODS: A set of 327 consecutive RA patients without history of diabetes, chronic kidney disease or CV events were studied by carotid ultrasound between 2012 and 2013. At that time, CV risk was calculated according to the modified EULAR systematic coronary risk evaluation (mSCORE) for RA. A five-year prospective follow-up study was conducted by survival analysis models. The EULAR mSCORE based on the 2015/2016 updated EULAR recommendations and the QRISK3 algorithms were retrospectively tested using baseline data. RESULTS: After 1,984.25 patient-years of follow-up, 23 had died and 27 had experienced CV events. Linearized mortality rate was 1.16/100 patient-years (95% confidence interval [CI]: 0.74--1.73). Adjusting for age, gender and disease duration, a model with carotid plaques (Hazard ratio [HR]: 6.10 [95% CI:0.74--50.0]; p = 0.09) and another model with carotid plaques and QRISK3 (HR for carotid plaques: 6.12 [95% CI: 0.74--50.5]; p = 0.09 and HR for each 1% in QRISK3: 1.03 [95% CI: 0.99--1.07], p = 0.11, respectively were the best predictors of death whereas a model with carotid plaques (HR: 5.25 [95% CI:1.41--19.50]; p = 0.01) and another model with carotid plaques and QRISK3 (HR for carotid plaques: 5.13 [95% CI: 1.36--19.3]; p = 0.02 and HR for each 1% in QRISK3: 1.03 [95% CI: 0.99--1.07], p = 0.12, respectively, were the best predictors of CV events. In contrast, the mSCORE was a weaker predictor of the risk of death or CV events. CONCLUSIONS: The presence of carotid plaques predicts the development of CV events and death in patients with RA. The predictable capacity of carotid plaques and QRISK3 is higher than that of mSCORE in RA 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.

Disease Activity Influences Cardiovascular Risk Reclassification Based on Carotid Ultrasound in Patients with Psoriatic Arthritis.

OBJECTIVE: Because the addition of carotid ultrasound (US) into composite cardiovascular (CV) risk scores has been found effective for identifying patients with inflammatory arthritis and high CV risk, we aimed to determine whether its use would facilitate the reclassification of patients with psoriatic arthritis (PsA) into the very high Systematic Coronary Risk Evaluation (SCORE) risk category and whether this might be related to disease features. METHODS: This was a cross-sectional study involving 206 patients who fulfilled ClASsification for Psoriatic ARthritis criteria for PsA, and 179 controls. We assessed lipid profile, SCORE, disease activity measurements, and the presence of carotid plaques and carotid intima-media thickness by ultrasonography. A multivariable regression analysis, adjusted for classic CV risk factors, was performed to evaluate whether the risk of reclassification could be explained by disease-related features and to assess the most parsimonious combination of risk reclassification predictors. RESULTS: Forty-seven percent of patients were reclassified into a very high SCORE risk category after carotid US compared to 26% of controls (p < 0.001). Patients included in the low SCORE risk category were those who were more commonly reclassified (30% vs 14%, p = 0.002). The Disease Activity Index for PsA (DAPSA) score was associated with reclassification (ß 1.10, 95% CI 1.02-1.19; p = 0.019) after adjusting for age and traditional CV risk factors. A model containing SCORE plus age, statin use, and DAPSA score yielded the highest discriminatory accuracy compared to the SCORE-alone model (area under the receiver-operating characteristic curve 0.863, 95% CI 0.789-0.936 vs 0.716, 95% CI 0.668-0.764; p < 0.001). CONCLUSION: Patients with PsA are more frequently reclassified into the very high SCORE risk category following carotid US assessment than controls. This was independently explained by the disease activity.

Interobserver agreement using Schlapbach graded scale for diffuse idiopathic skeletal hyperostosis (DISH): can we reduce the cut-off point of vertebral affection?

Resnick-Niwayama criteria for diagnosing DISH depict an advanced stage, and a new reduced cut-off point with three contiguous vertebrae affected (two bone bridges) has been proposed. The aim has been to know the interobserver agreement by using a graded scale of DISH in which grade II matches with the new proposed cut-off point and grade III matches with the first criterion of Resnick-Niwayama. Males ≥ 50 years and postmenopausal women included in a population-based prospective study (the Camargo Cohort) were analyzed. Sample size was obtained according to an expected kappa of 0.95 and an accuracy of ± 8%. Three physicians applied independently Schlapbach graded scale (ranged from grade 0, no ossification, to grade III, ≥ 3 consecutive bone bridges) on the lateral radiographs of thoracic and lumbar spine of participants. We calculated inter- and intra-observer agreement and correlation. One hundred and fifty eight radiographs (79 patients, 68 ± 9 years) were assessed. Kappa values (95% confidence interval) for grades 0, I, II, and III were 0.63 (0.50-0.77), 0.49 (0.37-0.62), 0.32 (0.17-0.47), and 0.69 (0.60-0.77), respectively. Weighted kappa for the three pairs of raters were 0.87 (0.82-0.93), 0.84 (0.77-0.91), and 0.81 (0.72-0.90). Grade III was the image that generated greater agreement, while a significant decrease was noted in grade II, the new proposed criterion. The simultaneous presence of an incomplete DISH and osteoarthritis, in a thoracic spinal segment with peculiar anatomical characteristics (reduced disk spaces, kyphotic curve), is thought to be a major cause of variability in the results.

Association of circulating calprotectin with lipid profile in axial spondyloarthritis.

Calprotectin (CPT) is released during inflammation, also in the context of atherosclerosis. The link between CPT and the atherosclerotic process was evaluated in several diseases. However, studies in axial spondyloarthritis (axSpA), associated with a high incidence of subclinical atherosclerosis, are scarce. Therefore, we assessed the association of CPT with subclinical atherosclerosis and metabolic risk factors in axSpA. CPT serum levels were measured by enzyme-linked immunosorbent assay in 163 axSpA patients and 63 controls. Subclinical atherosclerosis was determined in patients by carotid ultrasonography (assessing the presence/absence of carotid plaques and carotid intima-media thickness [cIMT]). Data on inflammation, disease activity, lipid profile and treatment were collected to evaluate its relationship with CPT. axSpA patients evidenced lower CPT levels than controls. CPT showed no association with plaques or cIMT in axSpA. CPT and HDL-cholesterol negatively correlated, while a positive association of CPT with the atherogenic index was disclosed. Additionally, axSpA patients with C-reactive protein values at diagnosis higher than 3 mg/L displayed higher CPT levels. Our study shows no relationship between CPT and markers of subclinical atherosclerosis in axSpA. Nevertheless, it demonstrates an association of CPT with adverse lipid profiles and inflammatory biomarkers, which could further influence on the development of atherosclerosis.

Detection of high cardiovascular risk patients with ankylosing spondylitis based on the assessment of abdominal aortic calcium as compared to carotid ultrasound.

BACKGROUND: This study aimed to determine whether, besides carotid ultrasound (US), a lateral lumbar spine radiography may also help identify ankylosing spondylitis (AS) patients at high risk of cardiovascular (CV) disease. METHODS: A set of 125 AS patients older than 35 years without a history of CV events, diabetes mellitus, or chronic kidney disease was recruited. Carotid US and lateral lumbar spine radiography were performed in all of them. The CV risk was calculated according to the total cholesterol systematic coronary risk evaluation (TC-SCORE) algorithm. Presence of carotid plaques was defined following the Mannheim Carotid Intima-media Thickness and Plaque Consensus. Abdominal aortic calcium (AAC) in a plain radiography was defined as calcific densities visible in an area parallel and anterior to the lumbar spine. RESULTS: Carotid US showed higher sensitivity than lateral lumbar spine radiography to detect high CV risk in the 54 patients with moderate TC-SCORE (61% versus 38.9%). Using carotid plaques as the gold standard test, a predictive model that included a TC-SCORE ≥ 5% or the presence of AAC in the lateral lumbar spine radiography in patients with both moderate and low CV risk (< 5%) according to the TC-SCORE yielded a sensitivity of 50.9% with a specificity of 95.7% to identify high/very high CV-risk AS patients. A positive correlation between AAC and carotid plaques was observed (r2 = 0.49, p < 0.001). CONCLUSIONS: A lateral lumbar spine radiography is a useful tool to identify patients with AS at high risk of CV disease.

Relative Risk Chart Score for the Assessment of the Cardiovascular Risk in Young Patients with Ankylosing Spondylitis.

OBJECTIVE: To determine if the use of the relative risk (RR) chart score may help to identify young ankylosing spondylitis (AS) patients at high risk of cardiovascular (CV) disease. METHODS: 73 AS patients younger than 50 years were assessed. CV risk was calculated according to the total cholesterol systematic coronary risk evaluation (TC-SCORE) and the RR chart score. C-reactive protein (CRP) value at disease diagnosis and carotid ultrasound data were also analyzed. RESULTS: Twenty (27.4%) patients exhibited carotid plaques being classified into the category of very high CV risk. None of them was found to have a high/very high TC-SCORE. CRP > 3 mg/L at disease diagnosis was associated with the presence of carotid plaques (odds ratio 5.66, p = 0.03). Whereas only 5 (14.2%) of the 35 patients with RR = 1 had carotid plaques, 15 (39.5%) of 38 with RR > 1 showed plaques. A model that included the performance of carotid US in patients with RR > 1 who had CRP > 3 mg/L allowed us to identify 60% of very high risk patients, with a specificity of 77.4%. CONCLUSIONS: RR chart score assessment may help to identify young AS patients at high risk of CV disease.

Implication of osteoprotegerin and sclerostin in axial spondyloarthritis cardiovascular disease: study of 163 Spanish patients.

OBJECTIVES: Due to the high incidence of cardiovascular disease in axial spondyloarthritis (axSpA), the search of potential biomarkers that may help to identify patients with high cardiovascular risk is of main importance. Therefore, in this study we assessed the implication of osteoprotegerin (OPG) and sclerostin (SCL), two biomarkers associated with cardiovascular disease and bone metabolism, in the clinical spectrum and atherosclerotic disease of patients with axSpA. METHODS: OPG and SCL serum levels were determined in 163 axSpA Spanish patients (119 ankylosing spondylitis and 44 non-radiographic axSpA) and 63 healthy controls by enzyme-linked immunosorbent assay. Carotid ultrasound was performed in axSpA patients to determine the presence of subclinical atherosclerosis (by the identification of abnormally increased carotid intima-media thickness [cIMT] and presence of plaques). RESULTS: Patients displayed higher OPG but lower SCL levels than controls (p=0.02 and 0.001, respectively). Association of these molecules with some metabolic syndrome features was seen. In this regard, OPG negatively correlated with body mass index (p=0.04) whereas SCL levels were higher in hypertensive patients (p=0.01) and in men (p=0.002). However, serum OPG and SCL were not significantly correlated with cIMT values or presence of plaques when data were adjusted by age at the time of the study, sex, classic cardiovascular risk factors and anti-TNF therapy. CONCLUSIONS: Our results suggest an association of OPG and SCL in axSpA with some metabolic syndrome features that are associated with an increased risk of CV disease.