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. Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that mainly affects the spine and pelvic joints. axSpA patients can also show a broad range of disease manifestations, including arthritis, enthesitis, dactylitis, psoriasis, uveitis and inflammatory bowel disease (IBD), among others. All this substantially affects the patient's quality of life and has important socioeconomic consequences 1. Besides, similarly to other chronic inflammatory rheumatic diseases, axSpA is also associated with a higher incidence of hypertension, obesity, dyslipidemia and smoking habit, which are considered classic risk factors for the development of cardiovascular (CV) disease. Moreover, the inflammatory status present in those patients further enhances their CV risk 2-4. In fact, CV disease is the main leading cause of mortality in patients with axSpA 4. 1 Research group on genetic epidemiology and atherosclerosis in systemic diseases and in metabolic diseases of the musculoskeletal system, IDIVAL, Santander, Spain.

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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.

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.

IntroductionPatients 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.MethodsA 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.ResultsLow 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&lt;0.001) and negatively correlated with visual analogue scale and Bath Ankylosing Spondylitis Metrology Index (p&lt;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&lt;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&lt;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 &gt;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 &gt;2.1 (OR: 1.73 [1.13-2.66], p=0.01).ConclusionsOur 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.