IRISIN: A NEW MARKER OF SUBCLINICAL ATHEROSCLEROSIS, CARDIOVASCULAR RISK AND DISEASE ACTIVITY IN AXIAL SPONDYLOARTHRITIS?

BackgroundAxial spondyloarthritis (axSpA) is an inflammatory disease with detrimental effects on the health status of the individuals affected by this condition [1]. axSpA patients also exhibit high cardiovascular (CV) risk, mainly due to accelerated atherosclerosis [2]. Interestingly, the adipomyokine irisin was described to play a beneficial role in several physiological and pathophysiological processes such as inflammation, angiogenesis, oxidative stress, as well as lipid and bone metabolism [3]. However, studies on the role of irisin in CV risk in the setting of axSpA or in the pathogenesis of axSpA are limited [4].ObjectivesIn this study we evaluated the role of irisin as a genetic and serological biomarker of subclinical atherosclerosis and CV risk in a large cohort of patients with axSpA. We also assessed its role as a marker of axSpA susceptibility and severity.Methods725 patients who fulfilled the Assessment of SpondyloArthritis international Society classification criteria for axSpA were included in this study [5]. In these patients, the presence of subclinical atherosclerosis (plaques and/or abnormal carotid intima-media thickness values) was assessed by carotid ultrasound. Four irisin polymorphisms (rs16835198 G/T, rs3480 A/G, rs726344 G/A and rs1570569 G/T) were genotyped by TaqMan probes in all the patients and in 656 age, sex and ethnically-matched healthy controls. Additionally, serum irisin levels were determined by ELISA in all the patients. All analyses were performed using STATA v.11.1 statistical software, adjusting for potential confounding factors. The strength of associations is indicated as odds ratios (OR) [95% confidence intervals].ResultsLow levels of serum irisin were linked to the presence of plaques (p=0.002) and with atherogenic index values indicative of an adverse lipid profile (p=0.01). Serum irisin levels also negatively correlated with visual analogue scale (VAS) patient, VAS physician and Bath Ankylosing Spondylitis Metrology Index (BASMI) values (p<0.05). Moreover, the presence of sacroiliitis was related to lower serum irisin levels (p<0.001). Furthermore, the minor alleles of rs3480 (G) and rs1570569 (T) were associated with higher values of Ankylosing Spondylitis Disease Activity Score (ASDAS) in axSpA patients (p≤0.01 in both cases). In this line, the frequency of the minor allele of rs1570569 (T) was higher in patients with ASDAS values >2.1 (indicative of high disease activity) (OR: 1.46 [1.08-1.97], p=0.01), while the minor allele of rs16835198 (T) was less frequent in this group of patients (OR: 0.73 [0.57-0.92], p=0.01).ConclusionLow 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.References[1]Packham J. Rheumatology (Oxford). 2018;57(6):vi29-vi34.[2]Szabo SM, et al. Arthritis Rheum. 2011;63(11):3294–304.[3]Korta P, et al. Medicina (Kaunas). 2019;55(8):485.[4]Nam B, et al. Ann Rheum Dis. 2020;79:1358.[5]Sieper J, et al. Ann Rheum Dis. 2009;68(2):ii1–44.AcknowledgementsThis work was partially supported by grants from Instituto de Investigación Sanitaria IDIVAL (NVAL17/10), from the `Asociación Cántabra de Reumatología’ awarded to FG. FG and JR-G are beneficiaries of a grant funded by `Instituto de Salud Carlos III´ (ISCIII) (PI20/00059). SR-M is supported by funds of the RETICS Program (RD16/0012/0009) from ISCIII, co-funded by the European Regional Development Fund. VP-C is supported by a pre-doctoral grant from IDIVAL (PREVAL18/01). RL-M is a recipient of a Miguel Servet type I programme fellowship from ISCIII, co-funded by the European Social Fund, `Investing in your future´ (grant CP16/00033).Disclosure of InterestsSara Remuzgo-Martínez: None declared, Javier Rueda-Gotor: None declared, Verónica Pulito-Cueto: None declared, Raquel López-Mejías: None declared, Alfonso Corrales: None declared, Leticia Lera-Gómez: None declared, Raquel Pérez-Fernández: None declared, Virginia Portilla: None declared, Iñigo Gonzalez-Mazon: None declared, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Grant/research support from: Abbvie, MSD and Roche, Rosa Expósito: None declared, Cristina Mata: None declared, Javier Llorca: None declared, Vanessa Hernández-Hernández: None declared, Carlos Rodríguez-Lozano: None declared, Nuria Barbarroja Puerto: None declared, Rafaela Ortega Castro: None declared, Esther F. Vicente-Rabaneda: None declared, Cristina Fernández-Carballido: None declared, Maria Paz Martínez-Vidal: None declared, David Castro-Corredor: None declared, Joaquín Anino-Fernández: None declared, Diana Peiteado: None declared, Chamaida Plasencia: None declared, E Galindez: None declared, María L. García Vivar: None declared, Nuria Vegas-Revenga: None declared, Irati Urionaguena: None declared, Oreste Gualillo: None declared, Juan Carlos Quevedo-Abeledo: None declared, Santos Castañeda: None declared, Iván Ferraz-Amaro: None declared, Miguel A González-Gay Speakers bureau: Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene, MSD, GSK, Grant/research support from: Abbvie, MSD, Janssen, Roche, Fernanda Genre: None declared