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

Abstract

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<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).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.

Increased visceral fat area to skeletal muscle mass ratio is positively associated with the risk of cardiometabolic diseases in a Chinese natural population: A cross‐sectional study

“…In addition, skeletal muscle is an endocrine organ that can produce and secrete myokines such as irisin and myonectin 20 . Irisin and myonectin are important myokines that have been proven to facilitate adipose tissue browning, promote thermogenesis, and increase the uptake and oxidation of NEFA in the liver and adipose tissue 21,22 . Therefore, impaired myokines secretion resulting from skeletal muscle loss may play a role in the development of insulin resistance and cardiometabolic diseases 23 …”

“… 20 Irisin and myonectin are important myokines that have been proven to facilitate adipose tissue browning, promote thermogenesis, and increase the uptake and oxidation of NEFA in the liver and adipose tissue. 21 , 22 Therefore, impaired myokines secretion resulting from skeletal muscle loss may play a role in the development of insulin resistance and cardiometabolic diseases. 23 …”

The correlation between visceral fat area to skeletal muscle mass ratio and multi-organ insulin resistance in Chinese population with obesity: a cross-sectional study

“…At the same time, IR contribute to reduced muscle protein synthesis and accelerated muscle protein catabolism, which promotes skeletal muscle loss and may eventually lead to type 2 diabetic sarcopenia [29] . Skeletal muscle is the target of obesity-induced in ammation, while the obesity-induced in ammation and IR can also cause the release of speci c skeletal muscle cytokines, such as IL-6, irisin, myostatin and muscle growth inhibitor [30,31] , etc. The release of these cytokines can increase or decrease the risk of obesity, in ammation, and IR [32,33] .…”

Irisin as a Novel Biomarker of Subclinical Atherosclerosis in Severe Obesity

“…The observed correlation between irisin and BMI suggests that irisin could also be a key molecule in atherosclerosis because most processes influenced by irisin are also disrupted in atherosclerosis. Indeed, low serum irisin levels have been linked to increased risk of CVD [27], and more recently, to the presence of plaques in patients with axial spondyloarthritis [28]. Despite these reports, little is known about the role of irisin in atherosclerosis and its exact mechanism of modulation.…”