This cross-sectional study showed that median US EAT thickness was significantly higher in SpA patients than in the matched healthy controls (p = 0.001). This finding supports the hypothesis that SpA patients without CV risk factors display increased predicted subclinical coronary atherosclerosis. US assessment of epicardial fat in SpA has been little studied. To date, eight studies assessing US EAT thickness in SpA have been performed and demonstrated significantly higher values in SpA patients than in the control group, in agreement with our result. Table 6 summarizes the main patients’ characteristics and US findings of these studies, which included between 26 and 60 SpA patients. This is an additional argument in favor of the representative number of our sample of 47 SpA without CV risk factors.
The median EAT thickness in our SpA patients was the lowest value (3.1 mm (2.5-4)) compared with the EAT thickness measurements published in the literature data, which ranged between 4.35 mm and 7.3 mm (table 6). In fact, further analysis found that patients included in these studies were older than our SpA sample (mean age 38.6–46.6 years versus 36 years) [17–23] have higher values of BMI [17, 22, 23], higher levels of total cholesterol, LDL-C and triglyceride [17–21, 23–24] and higher disease activity [17, 19, 22, 24]. Moreover, smoking was not excluded in studies carried by Üstün et al, Çaglar et al and Öz et al [18, 22, 23]. Taking into account that (age, smoking, BMI and lipid profile) were known CV risk factors, this variation could be explained by differences in the clinical and biological characteristics of patients and selection criteria.
There is no consensus for the measurement of EAT thickness. MRI is considered the gold standard for the quantification of EAT thickness  but is limited by its high cost, cumbersomeness and limited availability. Recent data concluded that echocardiographic measurement is the best tool for assessment of EAT thickness considering its reproductibility, ease of application, cost-effectiveness and non-invasive nature compared to other imaging modalities and proposed it as a simple and reliable strategy for CV disease risk stratification and prediction of atherosclerotic burden [7, 9]. A recent meta-analysis confirmed that US EAT thickness was increased in CAD and the real challenge would be to determine the US threshold of EAT thickness at which there is a linear relationship with the risk of CAD . R Majumder et al suggested an US threshold of EAT thickness > 4.65 mm as an independent predictor of significant coronary stenosis confirmed by coronary angiography . In the light of these findings, EAT thickness is actually regarded as a surrogate marker of CV risk and increased EAT is an independent predictor of subclinical coronary atherosclerosis. EAT thickness was associated with the presence and severity of CAD [7, 26] independently of traditional CV risk factors , and correlated with high-risk and unstable coronary plaques [28, 29].
Although the present study included young SpA patients (≤ 50 years) without history of traditional CV risk factors, EAT thickness was positively correlated with age and SBP. In line with our result, Resorlu et al also reported significant association between EAT thickness and age as well as DBP in 40 SpA patients (19). Svanteson et al found that age was the strongest independent predictor of CAD in 86 patients with inflammatory joint disease (rheumatoid arthritis, SpA and psoriatic arthritis) . It seems that age leads to qualitative modifications of the EAT with reduced expression of adiponectin by the EAT .
In our study, triglyceride level was identified as an independent predictor of increased EAT thickness in multivariate analysis in SpA patients (β coefficient, 0.661; 95% confidence interval (95% CI), 0.168–1.143; p = 0.01) as it has been reported by Resorlu et al also . This association is explained by the pathophysiology of ectopic fat depositions. Ectopic lipid storage is associated with insulin resistance, which stimulates lipogenesis de novo and hepatic triglyceride production . The correlation between these patient-related parameters and increased EAT thickness highlights the importance of regular screening of traditional CV risk factors even in young patients with low disease activity.
When looking at disease-related parameters, EAT thickness was correlated to age at onset of SpA, chest expansion and mSASSS. The association between EAT thickness and thoracic spinal mobility has not been studied. In our sample, reduced thoracic spinal mobility was correlated with increased CV risk. Similar to our finding, Hamdi et al and Bodnár et al demonstrated a negative correlation between carotid intima-media thickness and chest expansion in SpA patients, supporting the relationship between restriction of spinal mobility and subclinical atherosclerosis [33, 34]. However, it has been shown that spinal mobility impairment is independently determined both by irreversible spinal radiographic damage in later disease stages and in an early axial SpA by clinical disease activity and active spinal inflammation on MRI . Regarding disease duration, our finding were in contrast to those described by Surucu et al and Resorlu et al, who reported a significant association between EAT and disease duration [19, 24]. This may be due to the heterogeneity of disease duration distribution between patients which ranged between 1 and 32 years.
To our knowledge, for the first time in literature, our study determined a powerful association between EAT thickness and radiographic structural damage. EAT thickness was significantly increased in patients with spinal structural lesions (syndesmophytes, bony bridging, apophyseal joint arthritis) and the mSASSS score was identified as the strongest independent predictor of subclinical coronary atherosclerosis. Recent data have suggested a link between structural damage in SpA (syndesmophytes, bony bridging, mSASSS score) and accelerated atherosclerosis as assessed by the carotid intima-media thickness progression [36–37]. Similarly, Kang et al demonstrated that the number of syndesmophytes was independently associated with the Framingham risk score (FRS) estimating the 10-year CV disease risk in a cohort of 185 patients with axial SpA without CV risk factor . Coronary atherosclerosis and radiographic progression in SpA seem to share some common pathophysiological substrate. Age, sedentary lifestyle, smoking, and chronic inflammation are established CV risk factors, but also for structural damage. Chronic activation of the immune system and the inflammatory state underlie the pathophysiology of both atherosclerosis and structural damage. Ectopic fat tissue is the seat of increased secretion of pro-inflammatory molecules with local and systemic action. In fact, EAT over-expresses pro-inflammatory cytokines and pro-atherogenic factors including phospholipase sPLA2-IIA, IL6, adiponectin, and adipokines with an insulin-resistant effect such as resistin and visfatin leading to immune cell activation and inflammation, and contribute to the development and progression of atherosclerosis [6, 39, 40]. On the other hand, recent data show that adipokines were also correlated with an enhanced CV risk and the progression spinal progression in SpA [41–45]. The latest study of Rademacher J confirmed that new syndesmophyte formation and mSASSS progression after 4 years in SpA was significantly associated with increased levels of visfatin and leptin over the first 2 years .
Furthermore, we determined no significant association between EAT thickness and disease activity scores (BASDAI and ASDAS-CRP) as well as CRP level in agreement with findings of Surucu et al , Resorlu et al  and Üstün et al . In contrast, Büyükterzi et al have found ASDAS to be independently associated with EAT thickness in a cohort of 50 newly diagnosed SpA patients (p < 0.001) . This result may be explained by the low disease activity in the majority of patients and the relatively low CRP level (with a median of 6.45 mg/l).
One other important finding of our study is that patients treated with TNFi exhibited significantly higher values of EAT thickness than those treated with NSAIDs and csDMARDs (p = 0.007). Available data on the effect of TNFi on CV disease risk show discrepant findings. Some clinical studies have reported their effectiveness in improving carotid intima-media thickness, endothelial dysfunction and arterial stiffness in SpA patients [44, 47, 49], and have suggested their protective effect against CV events by dampening inflammation. However, Knowles et al in a recent systematic review of 60 studies examining the effect of TNFi on Flow-mediated dilation, carotid intima-media thickness and P-wave velocity (PWV) in chronic inflammatory diseases did not found a strong evidence for a beneficial effect on atherosclerosis and this hypothesis remains controversial . Given the small size of our study population (18/47 using TNFi) and its heterogeneity in terms of age and disease duration (with a significantly higher age (p = 0.009) and disease duration of SpA (p = 0.004) in the group using TNFi, no conclusions can be drawn.
Despite providing findings of absolute novelty, our study has some limitations. First, the heterogeneity of our study group in terms of age and disease duration (ranging between 18–50 years and 1–32 years, respectively) may lead to interpretation bias. Second limitation was the lack of standardized cut-off value for EAT thickness, therefore it was considered as a continuous variable. Establishing a reference threshold value in our population would be more relevant.